Aktualisierte S2k-Leitlinie nicht-alkoholische Fettlebererkrankung der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – April 2022 – AWMF-Registernummer: 021–025

E. Roeb; A. Canbay; H. Bantel; J. Bojunga; J. de Laffolie; M. Demir; U. W. Denzer; A. Geier; W. P. Hofmann; C. Hudert; T. Karlas; M. Krawczyk; T. Longerich; T. Luedde; M. Roden; J. Schattenberg; M. Sterneck; A. Tannapfel; P. Lorenz; F. Tacke; Collaborators:

doi:10.1055/a-1880-2283

Zeitschrift für Gastroenterologie, Table of Contents

Z Gastroenterol 2022; 60(09): 1346-1421
DOI: 10.1055/a-1880-2283

Leitlinie

Aktualisierte S2k-Leitlinie nicht-alkoholische Fettlebererkrankung der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – April 2022 – AWMF-Registernummer: 021–025

Authors

E. Roeb‡

¹Gastroenterologie, Medizinische Klinik II, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
A. Canbay‡

²Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
H. Bantel

³Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
J. Bojunga

⁴Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin., Universitätsklinikum Frankfurt, Frankfurt, Deutschland
J. de Laffolie

⁵Allgemeinpädiatrie und Neonatologie, Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
M. Demir

⁶Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
U. W. Denzer

⁷Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Marburg, Deutschland
A. Geier

⁸Medizinische Klinik und Poliklinik II, Schwerpunkt Hepatologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
W. P. Hofmann

⁹Gastroenterologie am Bayerischen Platz – Medizinisches Versorgungszentrum, Berlin, Deutschland
C. Hudert

¹⁰Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum – Universitätsmedizin Berlin, Berlin, Deutschland
T. Karlas

¹¹Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
M. Krawczyk

¹²Klinik für Innere Medizin II, Gastroent., Hepat., Endokrin., Diabet., Ern.med., Universitätsklinikum des Saarlandes, Homburg, Deutschland
T. Longerich

¹³Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
T. Luedde

¹⁴Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
M. Roden

¹⁵Klinik für Endokrinologie und Diabetologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
J. Schattenberg

¹⁶I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
M. Sterneck

¹⁷Klinik für Hepatobiliäre Chirurgie und Transplantationschirurgie, Universitätsklinikum Hamburg, Hamburg, Deutschland
A. Tannapfel

¹⁸Institut für Pathologie, Ruhr-Universität Bochum, Bochum, Deutschland
P. Lorenz

¹⁹Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
F. Tacke‡

⁶Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland

Literatur
1 Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell 2021; 184: 2537-2564
2 Morita Y, Ueno T, Sasaki N. et al. Comparison of liver histology between patients with non-alcoholic steatohepatitis and patients with alcoholic steatohepatitis in Japan. Alcohol Clin Exp Res 2005; 29: 277S-281S
3 Edmondson HA, Peters RL, Reynolds TB. et al. Sclerosing hyaline necrosis of the liver in the chronic alcoholic. A recognizable clinical syndrome. Ann Intern Med 1963; 59: 646-673
4 Ye Q, Zou B, Yeo YH. et al. Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2020; 5: 739-752
5 Young S, Tariq R, Provenza J. et al. Prevalence and Profile of Nonalcoholic Fatty Liver Disease in Lean Adults: Systematic Review and Meta-Analysis. Hepatol Commun 2020; 4: 953-972
6 Eslam M, Sanyal AJ, George J. et al. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology 2020; 158: 1999-2014
7 Fouad Y, Waked I, Bollipo S. et al. Whatʼs in a name? Renaming “NAFLD” to “MAFLD”. Liver Int 2020; 40: 1254-1261
8 Roeb E. Excess Body Weight and Metabolic (Dysfunction)-Associated Fatty Liver Disease (MAFLD). Visceral Medicine 2021;
9 Loomba R, Lim JK, Patton H. et al. AGA Clinical Practice Update on Screening and Surveillance for Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: Expert Review. Gastroenterology 2020; 158: 1822-1830
10 Petrick JL, Thistle JE, Zeleniuch-Jacquotte A. et al. Body Mass Index, Diabetes and Intrahepatic Cholangiocarcinoma Risk: The Liver Cancer Pooling Project and Meta-analysis. Am J Gastroenterol 2018; 113: 1494-1505
11 [Diagnostik und Therapie des hepatozellulären Karzinoms]. Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): Langversion1.0, AWMF Registrierungsnummer: 032-053OL. https://www.leitlinienprogramm-onkologie.de/Leitlinien.7.0.html
12 Cairns SR, Peters TJ. Micromethods for quantitative lipid analysis of human liver needle biopsy specimens. Clin Chim Acta 1983; 127: 373-382
13 Bedossa P, Poitou C, Veyrie N. et al. Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients. Hepatology 2012; 56: 1751-1759
14 Kleiner DE, Brunt EM, Van Natta M. et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313-1321
15 Flechtenmacher C, Schirmacher P, Schemmer P. Donor liver histology – a valuable tool in graft selection. Langenbecks Arch Surg 2015; 400: 551-557
16 Xiao H, Shi M, Xie Y. et al. Comparison of diagnostic accuracy of magnetic resonance elastography and Fibroscan for detecting liver fibrosis in chronic hepatitis B patients: A systematic review and meta-analysis. PLoS One 2017; 12: e0186660
17 Dulai PS, Singh S, Patel J. et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology 2017; 65: 1557-1565
18 Vilar-Gomez E, Calzadilla-Bertot L, Wai-Sun Wong V. et al. Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease: A Multi-National Cohort Study. Gastroenterology 2018; 155: 443-457
19 Xiao G, Zhu S, Xiao X. et al. Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis. Hepatology 2017; 66: 1486-1501
20 Ooi GJ, Mgaieth S, Eslick GD. et al. Systematic review and meta-analysis: non-invasive detection of non-alcoholic fatty liver disease related fibrosis in the obese. Obes Rev 2018; 19: 281-294
21 Bedossa P, Consortium FP. Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatology 2014; 60: 565-575
22 Lackner C. Hepatocellular ballooning in nonalcoholic steatohepatitis: the pathologistʼs perspective. Expert Rev Gastroenterol Hepatol 2011; 5: 223-231
23 Davison BA, Harrison SA, Cotter G. et al. Suboptimal reliability of liver biopsy evaluation has implications for randomized clinical trials. J Hepatol 2020; 73: 1322-1332
24 Longerich T, Schirmacher P. Determining the reliability of liver biopsies in NASH clinical studies. Nat Rev Gastroenterol Hepatol 2020; 17: 653-654
25 Alberti KG, Zimmet P, Shaw J. Metabolic syndrome – a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 2006; 23: 469-480
26 Alberti KG, Zimmet P, Shaw J. The metabolic syndrome – a new worldwide definition. Lancet 2005; 366: 1059-1062
27 Strobel D, Bernatik T, Blank W. et al. Incidence of bleeding in 8172 percutaneous ultrasound-guided intraabdominal diagnostic and therapeutic interventions – results of the prospective multicenter DEGUM interventional ultrasound study (PIUS study). Ultraschall in Med 2015; 36: 122-131
28 Crawford AR, Lin XZ, Crawford JM. The normal adult human liver biopsy: a quantitative reference standard. Hepatology 1998; 28: 323-331
29 Rockey DC, Caldwell SH, Goodman ZD. et al. Liver biopsy. Hepatology 2009; 49: 1017-1044
30 Colloredo G, Guido M, Sonzogni A. et al. Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease. J Hepatol 2003; 39: 239-244
31 Chalasani N, Younossi Z, Lavine JE. et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology 2018; 67: 328-357
32 Brunetti E, Silini E, Pistorio A. et al. Coarse vs. fine needle aspiration biopsy for the assessment of diffuse liver disease from hepatitis C virus-related chronic hepatitis. J Hepatol 2004; 40: 501-506
33 Palmer T, Georgiades I, Treanor D. et al. Improved tissue sections for medical liver biopsies: a comparison of 16 vs 18g biopsy needles using digital pathology. J Clin Pathol 2014; 67: 415-419
34 Aribaş BK, Arda K, Ciledağ N. et al. Accuracy and safety of percutaneous US-guided needle biopsies in specific focal liver lesions: comparison of large and small needles in 1300 patients. Panminerva Med 2012; 54: 233-239
35 Vijayaraghavan GR, Vedantham S, Rangan V. et al. Effect of needle gauge and lobe laterality on parenchymal liver biopsy outcome: a retrospective analysis. Abdom Imaging 2015; 40: 1223-1229
36 Hall TC, Deakin C, Atwal GS. et al. Adequacy of percutaneous non-targeted liver biopsy under real-time ultrasound guidance when comparing the Biopince and Achieve biopsy needle. Br J Radiol 2017; 90: 20170397
37 Forssell PL, Bonkowsky HL, Anderson PB. et al. Intrahepatic hematoma after aspiration liver biopsy. A prospective randomized trial using two different needles. Dig Dis Sci 1981; 26: 631-635
38 Tublin ME, Blair R, Martin J. et al. Prospective Study of the Impact of Liver Biopsy Core Size on Specimen Adequacy and Procedural Complications. Am J Roentgenol 2018; 210: 183-188
39 Kleiner DE, Bedossa P. Liver histology and clinical trials for nonalcoholic steatohepatitis-perspectives from 2 pathologists. Gastroenterology 2015; 149: 1305-1308
40 Neuberger J, Patel J, Caldwell H. et al. Guidelines on the use of liver biopsy in clinical practice from the British Society of Gastroenterology, the Royal College of Radiologists and the Royal College of Pathology. Gut 2020; 69: 1382-1403
41 Ratziu V, Charlotte F, Heurtier A. et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005; 128: 1898-1906
42 Merriman RB, Ferrell LD, Patti MG. et al. Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease. Hepatology 2006; 44: 874-880
43 Larson SP, Bowers SP, Palekar NA. et al. Histopathologic variability between the right and left lobes of the liver in morbidly obese patients undergoing Roux-en-Y bypass. Clin Gastroenterol Hepatol 2007; 5: 1329-1332
44 Ooi GJ, Clouston A, Johari Y. et al. Evaluation of the histological variability of core and wedge biopsies in nonalcoholic fatty liver disease in bariatric surgical patients. Surg Endosc 2021; 35: 1210-1218
45 Vuppalanchi R, Unalp A, Van Natta ML. et al. Effects of liver biopsy sample length and number of readings on sampling variability in nonalcoholic Fatty liver disease. Clin Gastroenterol Hepatol 2009; 7: 481-486
46 Perrault J, McGill DB, Ott BJ. et al. Liver biopsy: complications in 1000 inpatients and outpatients. Gastroenterology 1978; 74: 103-106
47 Maharaj B, Bhoora IG. Complications associated with percutaneous needle biopsy of the liver when one, two or three specimens are taken. Postgrad Med J 1992; 68: 964-967
48 Chi H, Hansen BE, Tang WY. et al. Multiple biopsy passes and the risk of complications of percutaneous liver biopsy. Eur J Gastroenterol Hepatol 2017; 29: 36-41
49 Schirmacher P, Fleig WE, Tannapfel A. et al. [Bioptic diagnosis of chronic hepatitis. Results of an evidence-based consensus conference of the German Society of Pathology, of the German Society for Digestive and Metabolic Diseases and of Compensated Hepatitis (HepNet)]. Pathologe 2004; 25: 337-348
50 Einaga N, Yoshida A, Noda H. et al. Assessment of the quality of DNA from various formalin-fixed paraffin-embedded (FFPE) tissues and the use of this DNA for next-generation sequencing (NGS) with no artifactual mutation. PLoS One 2017; 12: e0176280
51 Roeb E, Steffen HM, Bantel H. et al. S2k-Leitlinie nicht alkoholische Fettlebererkrankungen. Z Gastroenterol 2015; 53: 668-723
52 Wong VW, Chan WK, Chitturi S. et al. Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-Part 1: Definition, risk factors and assessment. J Gastroenterol Hepatol 2018; 33: 70-85
53 Mueller S, Nahon P, Rausch V. et al. Caspase-cleaved keratin-18 fragments increase during alcohol withdrawal and predict liver-related death in patients with alcoholic liver disease. Hepatology 2017; 66: 96-107
54 Mueller J, Raisi H, Rausch V. et al. Sensitive and non-invasive assessment of hepatocellular iron using a novel room-temperature susceptometer. J Hepatol 2017; 67: 535-542
56 Larsson SC, Wallin A, Wolk A. et al. Differing association of alcohol consumption with different stroke types: a systematic review and meta-analysis. BMC Med 2016; 14: 178
57 Stubbs MA, Morgan MY. Managing alcohol dependence and alcohol-related liver disease: a problem for the hepatologist, psychiatrist or economist?. Clin Med (Lond) 2011; 11: 189-193
58 Åberg F, Puukka P, Salomaa V. et al. Risks of Light and Moderate Alcohol Use in Fatty Liver Disease: Follow-Up of Population Cohorts. Hepatology 2020; 71: 835-848
59 Younossi ZM, Stepanova M, Ong J. et al. Effects of Alcohol Consumption and Metabolic Syndrome on Mortality in Patients With Nonalcoholic and Alcohol-Related Fatty Liver Disease. Clin Gastroenterol Hepatol 2019; 17: 1625-1633.e1621
60 Li J, Zou B, Yeo YH. et al. Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999–2019: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2019; 4: 389-398
61 Younossi ZM, Koenig AB, Abdelatif D. et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64: 73-84
62 Allen AM, Therneau TM, Larson JJ. et al. Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: A 20 year-community study. Hepatology 2018; 67: 1726-1736
63 Estes C, Anstee QM, Arias-Loste MT. et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016–2030. J Hepatol 2018; 69: 896-904
64 Kabbany MN, Conjeevaram Selvakumar PK, Watt K. et al. Prevalence of Nonalcoholic Steatohepatitis-Associated Cirrhosis in the United States: An Analysis of National Health and Nutrition Examination Survey Data. Am J Gastroenterol 2017; 112: 581-587
65 Hofmann WP, Buggisch P, Schubert L. et al. The Fatty Liver Assessment in Germany (FLAG) cohort study identifies large heterogeneity in NAFLD care. JHEP Rep 2020; 2: 100168
66 Singh S, Allen AM, Wang Z. et al Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol 2015; 13: 643-654 e641–649; quiz e639–640
67 McPherson S, Hardy T, Henderson E. et al. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. J Hepatol 2015; 62: 1148-1155
68 Hagström H, Nasr P, Ekstedt M. et al. Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. J Hepatol 2017; 67: 1265-1273
69 Sanyal AJ, Harrison SA, Ratziu V. et al. The Natural History of Advanced Fibrosis Due to Nonalcoholic Steatohepatitis: Data From the Simtuzumab Trials. Hepatology 2019; 70: 1913-1927
70 Long MT, Zhang X, Xu H. et al. Hepatic Fibrosis Associates With Multiple Cardiometabolic Disease Risk Factors: The Framingham Heart Study. Hepatology 2021; 73: 548-559
71 Angulo P, Kleiner DE, Dam-Larsen S. et al. Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 2015; 149: 389-397.e310
72 Bengtsson B, Stål P, Wahlin S. et al. Characteristics and outcome of hepatocellular carcinoma in patients with NAFLD without cirrhosis. Liver Int 2019; 39: 1098-1108
73 Bhala N, Angulo P, van der Poorten D. et al. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Hepatology 2011; 54: 1208-1216
74 Dyson J, Jaques B, Chattopadyhay D. et al. Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team. J Hepatol 2014; 60: 110-117
75 Younossi ZM. Non-alcoholic fatty liver disease – A global public health perspective. J Hepatol 2019; 70: 531-544
76 Kanwal F, Kramer JR, Mapakshi S. et al. Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease. Gastroenterology 2018; 155: 1828-1837
77 Piscaglia F, Svegliati-Baroni G, Barchetti A. et al. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study. Hepatology 2016; 63: 827-838
78 Cholankeril G, Wong RJ, Hu M. et al. Liver Transplantation for Nonalcoholic Steatohepatitis in the US: Temporal Trends and Outcomes. Dig Dis Sci 2017; 62: 2915-2922
79 Tacke F, Kroy DC, Barreiros AP. et al. Liver transplantation in Germany. Liver Transpl 2016; 22: 1136-1142
80 Kim D, Kim WR, Kim HJ. et al. Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology 2013; 57: 1357-1365
81 Nasr P, Ignatova S, Kechagias S. et al. Natural history of nonalcoholic fatty liver disease: A prospective follow-up study with serial biopsies. Hepatol Commun 2018; 2: 199-210
82 Ekstedt M, Hagström H, Nasr P. et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 2015; 61: 1547-1554
83 Shen H, Lipka S, Kumar A. et al. Association between nonalcoholic fatty liver disease and colorectal adenoma: a systemic review and meta-analysis. J Gastrointest Oncol 2014; 5: 440-446
84 Kim GA, Lee HC, Choe J. et al. Association between non-alcoholic fatty liver disease and cancer incidence rate. J Hepatol 2017;
85 Bertot LC, Jeffrey GP, Wallace M. et al. Nonalcoholic fatty liver disease-related cirrhosis is commonly unrecognized and associated with hepatocellular carcinoma. Hepatol Commun 2017; 1: 53-60
86 Iqbal U, Perumpail BJ, Akhtar D. et al. The Epidemiology, Risk Profiling and Diagnostic Challenges of Nonalcoholic Fatty Liver Disease. Medicines (Basel) 2019; 6
87 Younossi Z, Anstee QM, Marietti M. et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2018; 15: 11-20
88 de Vries M, Westerink J, Kaasjager K. et al. Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) in Patients With Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis. J Clin Endocrinol Metab 2020; 105: 3842-3853
89 Jarvis H, Craig D, Barker R. et al. Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies. PLoS Med 2020; 17: e1003100
90 Sookoian S, Pirola CJ. Systematic review with meta-analysis: risk factors for non-alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients. Aliment Pharmacol Ther 2017; 46: 85-95
91 Hu XY, Li Y, Li LQ. et al. Risk factors and biomarkers of non-alcoholic fatty liver disease: an observational cross-sectional population survey. BMJ Open 2018; 8: e019974
92 Golabi P, Otgonsuren M, de Avila L. et al. Components of metabolic syndrome increase the risk of mortality in nonalcoholic fatty liver disease (NAFLD). Medicine (Baltimore) 2018; 97: e0214
93 Labenz C, Huber Y, Kalliga E. et al. Predictors of advanced fibrosis in non-cirrhotic non-alcoholic fatty liver disease in Germany. Aliment Pharmacol Ther 2018; 48: 1109-1116
94 Rinella ME. Screening for nonalcoholic fatty liver disease in patients with atherosclerotic coronary disease? – In principle yes, in practice not yet. Hepatology 2016; 63: 688-690
95 Noureddin M, Jones C, Alkhouri N. et al. Screening for Nonalcoholic Fatty Liver Disease in Persons with Type 2 Diabetes in the United States Is Cost-effective: A Comprehensive Cost-Utility Analysis. Gastroenterology 2020; 159: 1985-1987.e1984
96 Nones RB, Ivantes CP, Pedroso MLA. Can FIB4 and NAFLD fibrosis scores help endocrinologists refer patients with non-alcoholic fat liver disease to a hepatologist?. Arch Endocrinol Metab 2017; 61: 276-281
97 Ciardullo S, Muraca E, Perra S. et al. Screening for non-alcoholic fatty liver disease in type 2 diabetes using non-invasive scores and association with diabetic complications. BMJ Open Diabetes Res Care 2020; 8
98 Castera L. Non-invasive tests for liver fibrosis in NAFLD: Creating pathways between primary healthcare and liver clinics. Liver Int 2020; 40 (Suppl. 01) 77-81
99 Pandyarajan V, Gish RG, Alkhouri N. et al. Screening for Nonalcoholic Fatty Liver Disease in the Primary Care Clinic. Gastroenterol Hepatol (N Y) 2019; 15: 357-365
100 [Anonymous]. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Diabetologia 2016; 59: 1121-1140
101 Berzigotti A, Boursier J, Castera L. et al. Easl Clinical Practice Guidelines (Cpgs) On Non-Invasive Tests For Evaluation Of Liver Disease Severity And Prognosis- 2020 Update. J Hepatol 2021;
102 Younossi ZM, Corey KE, Alkhouri N. et al. Clinical assessment for high-risk patients with non-alcoholic fatty liver disease in primary care and diabetology practices. Aliment Pharmacol Ther 2020; 52: 513-526
103 Grecian SM, McLachlan S, Fallowfield JA. et al. Non-invasive risk scores do not reliably identify future cirrhosis or hepatocellular carcinoma in Type 2 diabetes: The Edinburgh type 2 diabetes study. Liver Int 2020; 40: 2252-2262
104 Mofrad P, Contos MJ, Haque M. et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 2003; 37: 1286-1292
105 Verma S, Jensen D, Hart J. et al. Predictive value of ALT levels for non-alcoholic steatohepatitis (NASH) and advanced fibrosis in non-alcoholic fatty liver disease (NAFLD). Liver Int 2013; 33: 1398-1405
106 Lee TY, Wu JC, Yu SH. et al. The occurrence of hepatocellular carcinoma in different risk stratifications of clinically noncirrhotic nonalcoholic fatty liver disease. Int J Cancer 2017; 141: 1307-1314
107 Fedchuk L, Nascimbeni F, Pais R. et al. Performance and limitations of steatosis biomarkers in patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther 2014; 40: 1209-1222
108 Cheung CL, Lam KS, Wong IC. et al. Non-invasive score identifies ultrasonography-diagnosed non-alcoholic fatty liver disease and predicts mortality in the USA. BMC Med 2014; 12: 154
109 Lind L, Johansson L, Ahlström H. et al. Comparison of four non-alcoholic fatty liver disease detection scores in a Caucasian population. World J Hepatol 2020; 12: 149-159
110 Boursier J, Vergniol J, Guillet A. et al. Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease. J Hepatol 2016; 65: 570-578
111 Demir M, Lang S, Nierhoff D. et al. Stepwise combination of simple noninvasive fibrosis scoring systems increases diagnostic accuracy in nonalcoholic fatty liver disease. J Clin Gastroenterol 2013; 47: 719-726
112 Lee J, Vali Y, Boursier J. et al. Prognostic accuracy of FIB-4, NAFLD fibrosis score and APRI for NAFLD-related events: A systematic review. Liver Int 2021; 41: 261-270
113 Yoneda M, Imajo K, Eguchi Y. et al. Noninvasive scoring systems in patients with nonalcoholic fatty liver disease with normal alanine aminotransferase levels. J Gastroenterol 2013; 48: 1051-1060
114 Hagström H, Talbäck M, Andreasson A. et al. Ability of Noninvasive Scoring Systems to Identify Individuals in the Population at Risk for Severe Liver Disease. Gastroenterology 2020; 158: 200-214
115 McPherson S, Hardy T, Dufour JF. et al. Age as a Confounding Factor for the Accurate Non-Invasive Diagnosis of Advanced NAFLD Fibrosis. Am J Gastroenterol 2017; 112: 740-751
116 Wentworth BJ, Caldwell SH. Pearls and pitfalls in nonalcoholic fatty liver disease: tricky results are common. Metabolism and Target Organ Damage 2021; 1: 2
117 EASL-Guideline. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016; 64: 1388-1402
118 Hernaez R, Lazo M, Bonekamp S. et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology 2011; 54: 1082-1090
119 Bril F, Ortiz-Lopez C, Lomonaco R. et al. Clinical value of liver ultrasound for the diagnosis of nonalcoholic fatty liver disease in overweight and obese patients. Liver Int 2015; 35: 2139-2146
120 Kromrey ML, Ittermann T, Berning M. et al. Accuracy of ultrasonography in the assessment of liver fat compared with MRI. Clin Radiol 2019; 74: 539-546
121 Iwasaki M, Takada Y, Hayashi M. et al. Noninvasive evaluation of graft steatosis in living donor liver transplantation. Transplantation 2004; 78: 1501-1505
122 Hyodo T, Yada N, Hori M. et al. Multimaterial Decomposition Algorithm for the Quantification of Liver Fat Content by Using Fast-Kilovolt-Peak Switching Dual-Energy CT: Clinical Evaluation. Radiology 2017; 283: 108-118
123 Tang A, Tan J, Sun M. et al. Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis. Radiology 2013; 267: 422-431
124 Tang A, Desai A, Hamilton G. et al. Accuracy of MR imaging-estimated proton density fat fraction for classification of dichotomized histologic steatosis grades in nonalcoholic fatty liver disease. Radiology 2015; 274: 416-425
125 Caussy C, Johansson L. Magnetic resonance-based biomarkers in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Endocrinol Diabetes Metab 2020; 3: e00134
126 Choi SJ, Kim SM, Kim YS. et al. Magnetic Resonance-Based Assessments Better Capture Pathophysiologic Profiles and Progression in Nonalcoholic Fatty Liver Disease. Diabetes Metab J 2020;
127 Yokoo T, Serai SD, Pirasteh A. et al. Linearity, Bias, and Precision of Hepatic Proton Density Fat Fraction Measurements by Using MR Imaging: A Meta-Analysis. Radiology 2018; 286: 486-498
128 Park CC, Nguyen P, Hernandez C. et al. Magnetic Resonance Elastography vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients With Biopsy-Proven Nonalcoholic Fatty Liver Disease. Gastroenterology 2017; 152: 598-607.e592
129 Bastati N, Feier D, Wibmer A. et al. Noninvasive differentiation of simple steatosis and steatohepatitis by using gadoxetic acid-enhanced MR imaging in patients with nonalcoholic fatty liver disease: a proof-of-concept study. Radiology 2014; 271: 739-747
130 Kim JW, Lee YS, Park YS. et al. Multiparametric MR Index for the Diagnosis of Non-Alcoholic Steatohepatitis in Patients with Non-Alcoholic Fatty Liver Disease. Sci Rep 2020; 10: 2671
131 Kaswala DH, Lai M, Afdhal NH. Fibrosis Assessment in Nonalcoholic Fatty Liver Disease (NAFLD) in 2016. Dig Dis Sci 2016; 61: 1356-1364
132 Vali Y, Lee J, Boursier J. et al. Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: A systematic review and meta-analysis. Journal of hepatology 2020; 73: 252-262
133 Bedogni G, Bellentani S, Miglioli L. et al. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol 2006; 6: 33
134 Koehler EM, Schouten JN, Hansen BE. et al. External validation of the fatty liver index for identifying nonalcoholic fatty liver disease in a population-based study. Clin Gastroenterol Hepatol 2013; 11: 1201-1204
135 Kwok R, Tse YK, Wong GL. et al. Systematic review with meta-analysis: non-invasive assessment of non-alcoholic fatty liver disease--the role of transient elastography and plasma cytokeratin-18 fragments. Aliment Pharmacol Ther 2014; 39: 254-269
136 Krawczyk M, Liebe R, Lammert F. Toward Genetic Prediction of Nonalcoholic Fatty Liver Disease Trajectories: PNPLA3 and Beyond. Gastroenterology 2020; 158: 1865-1880.e1861
137 Sookoian S, Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 2011; 53: 1883-1894
138 Trépo E, Valenti L. Update on NAFLD genetics: From new variants to the clinic. J Hepatol 2020; 72: 1196-1209
139 Bianco C, Jamialahmadi O, Pelusi S. et al. Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores. J Hepatol 2020;
140 Chernbumroong S, Grove JI, Astbury S. et al. Advanced machine learning techniques to identify a panel of biomarkers that identify nonalcoholic steatohepatitis. Hepatology (Baltimore, MD) 2017; 66: 53A-54A
141 Zhu L, Baker SS, Gill C. et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology 2013; 57: 601-609
142 Boursier J, Mueller O, Barret M. et al. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology 2016; 63: 764-775
143 Lang S, Demir M, Martin A. et al. Intestinal Virome Signature Associated With Severity of Nonalcoholic Fatty Liver Disease. Gastroenterology 2020; 159: 1839-1852
144 Rau M, Rehman A, Dittrich M. et al. Fecal SCFAs and SCFA-producing bacteria in gut microbiome of human NAFLD as a putative link to systemic T-cell activation and advanced disease. United European Gastroenterol J 2018; 6: 1496-1507
145 Demir M, Lang S, Martin A. et al. Phenotyping non-alcoholic fatty liver disease by the gut microbiota: Ready for prime time?. J Gastroenterol Hepatol 2020; 35: 1969-1977
146 Lang S, Farowski F, Martin A. et al. Prediction of advanced fibrosis in non-alcoholic fatty liver disease using gut microbiota-based approaches compared with simple non-invasive tools. Sci Rep 2020; 10: 9385
147 Castera L, Friedrich-Rust M, Loomba R. Noninvasive Assessment of Liver Disease in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 2019; 156: 1264-1281.e1264
148 Ballestri S, Nascimbeni F, Lugari S. et al. A critical appraisal of the use of ultrasound in hepatic steatosis. Expert Rev Gastroenterol Hepatol 2019; 13: 667-681
149 Petzold G, Lasser J, Rühl J. et al. Diagnostic accuracy of B-Mode ultrasound and Hepatorenal Index for graduation of hepatic steatosis in patients with chronic liver disease. PLoS One 2020; 15: e0231044
150 Sasso M, Beaugrand M, de Ledinghen V. et al. Controlled attenuation parameter (CAP): a novel VCTE™ guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes. Ultrasound Med Biol 2010; 36: 1825-1835
151 Karlas T, Petroff D, Sasso M. et al. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol 2017; 66: 1022-1030
152 Eddowes PJ, Sasso M, Allison M. et al. Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 2019; 156: 1717-1730
153 Petroff D, Blank V, Newsome PN. et al. Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes: an individual patient data meta-analysis. Lancet Gastroenterol Hepatol 2021;
154 Semmler G, Wöran K, Scheiner B. et al. Novel reliability criteria for controlled attenuation parameter assessments for non-invasive evaluation of hepatic steatosis. United European Gastroenterol J 2020; 8: 321-331
155 Agarwal L, Aggarwal S, Shalimar S. et al. Bariatric Surgery in Nonalcoholic Fatty Liver Disease (NAFLD): Impact Assessment Using Paired Liver Biopsy and Fibroscan. Obes Surg 2020;
156 Wong VW. Predicting NASH response with liver fat: Are we back to square one?. J Hepatol 2020; 72: 386-388
157 Ferraioli G, Maiocchi L, Savietto G. et al. Performance of the Attenuation Imaging Technology in the Detection of Liver Steatosis. J Ultrasound Med 2020;
158 Jesper D, Klett D, Schellhaas B. et al. Ultrasound-Based Attenuation Imaging for the Non-Invasive Quantification of Liver Fat – A Pilot Study on Feasibility and Inter-Observer Variability. IEEE J Transl Eng Health Med 2020; 8: 1800409
159 Stern C, Castera L. Non-invasive diagnosis of hepatic steatosis. Hepatol Int 2017; 11: 70-78
160 Caussy C, Reeder SB, Sirlin CB. et al. Noninvasive, Quantitative Assessment of Liver Fat by MRI-PDFF as an Endpoint in NASH Trials. Hepatology 2018; 68: 763-772
161 Caussy C, Alquiraish MH, Nguyen P. et al. Optimal threshold of controlled attenuation parameter with MRI-PDFF as the gold standard for the detection of hepatic steatosis. Hepatology 2018; 67: 1348-1359
162 Karlas T, Petroff D, Wiegand J. Collaboration, Not Competition: The Role of Magnetic Resonance, Transient Elastography, and Liver Biopsy in the Diagnosis of Nonalcoholic Fatty Liver Disease. Gastroenterology 2017; 152: 479-481
163 Stine JG, Munaganuru N, Barnard A. et al. Change in MRI-PDFF and Histologic Response in Patients with Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol 2020;
164 Angulo P, Hui JM, Marchesini G. et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007; 45: 846-854
165 Shah AG, Lydecker A, Murray K. et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009; 7: 1104-1112
166 Piscaglia F, Salvatore V, Mulazzani L. et al. Ultrasound Shear Wave Elastography for Liver Disease. A Critical Appraisal of the Many Actors on the Stage. Ultraschall in Med 2016; 37: 1-5
167 Wong VW, Vergniol J, Wong GL. et al. Liver stiffness measurement using XL probe in patients with nonalcoholic fatty liver disease. Am J Gastroenterol 2012; 107: 1862-1871
168 Wong VW, Vergniol J, Wong GL. et al. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology 2010; 51: 454-462
169 Papatheodoridi M, Hiriart JB, Lupsor-Platon M. et al. Refining the Baveno VI elastography criteria for the definition of compensated advanced chronic liver disease. J Hepatol 2021; 74: 1109-1116
170 Berger A, Shili S, Zuberbuhler F. et al. Liver Stiffness Measurement With FibroScan: Use the Right Probe in the Right Conditions!. Clin Transl Gastroenterol 2019; 10: e00023
171 Greten TF, Malek NP, Schmidt S. et al. [Diagnosis of and therapy for hepatocellular carcinoma]. Z Gastroenterol 2013; 51: 1269-1326
172 Pfeifer L, Goertz RS, Sturm J. et al. Acoustic radiation force impulse (ARFI) and high-frequency ultrasound of the liver surface for the diagnosis of compensated liver cirrhosis. Ultraschall in Med 2014; 35: 44-50
173 Dietrich CF, Bamber J, Berzigotti A. et al. EFSUMB-Leitlinien und Empfehlungen zur klinischen Anwendung der Leberelastographie, Update 2017 (Langversion). Ultraschall in Med 2017; 38: e48
174 EASL-Guideline. EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015; 63: 237-264
175 Herrmann E, de Lédinghen V, Cassinotto C. et al. Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography: An individual patient data-based meta-analysis. Hepatology 2018; 67: 260-272
176 Erman A, Sathya A, Nam A. et al. Estimating chronic hepatitis C prognosis using transient elastography-based liver stiffness: A systematic review and meta-analysis. J Viral Hepat 2018; 25: 502-513
177 Nierhoff J, Chávez Ortiz AA, Herrmann E. et al. The efficiency of acoustic radiation force impulse imaging for the staging of liver fibrosis: a meta-analysis. Eur Radiol 2013; 23: 3040-3053
178 Tapper EB, Challies T, Nasser I. et al. The Performance of Vibration Controlled Transient Elastography in a US Cohort of Patients With Nonalcoholic Fatty Liver Disease. Am J Gastroenterol 2016; 111: 677-684
179 Karlas T, Dietrich A, Peter V. et al. Evaluation of Transient Elastography, Acoustic Radiation Force Impulse Imaging (ARFI), and Enhanced Liver Function (ELF) Score for Detection of Fibrosis in Morbidly Obese Patients. PLoS One 2015; 10: e0141649
180 Siddiqui MS, Vuppalanchi R, Van Natta ML. et al. Vibration-Controlled Transient Elastography to Assess Fibrosis and Steatosis in Patients With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol 2019; 17: 156-163.e152
181 Jiang W, Huang S, Teng H. et al. Diagnostic accuracy of point shear wave elastography and transient elastography for staging hepatic fibrosis in patients with non-alcoholic fatty liver disease: a meta-analysis. BMJ Open 2018; 8: e021787
182 Hsu C, Caussy C, Imajo K. et al. Magnetic Resonance vs Transient Elastography Analysis of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Pooled Analysis of Individual Participants. Clin Gastroenterol Hepatol 2019; 17: 630-637.e638
183 Wan T, Köhn N, Kröll D. et al. Applicability and Results of Liver Stiffness Measurement and Controlled Attenuation Parameter Using XL Probe for Metabolic-Associated Fatty Liver Disease in Candidates to Bariatric Surgery. A Single-Center Observational Study. Obes Surg 2020;
184 Chuah KH, Lai LL, Vethakkan SR. et al. Liver stiffness measurement in non-alcoholic fatty liver disease: Two is better than one. J Gastroenterol Hepatol 2020; 35: 1404-1411
185 Ozturk A, Mohammadi R, Pierce TT. et al. Diagnostic Accuracy of Shear Wave Elastography as a Non-invasive Biomarker of High-Risk Non-alcoholic Steatohepatitis in Patients with Non-alcoholic Fatty Liver Disease. Ultrasound Med Biol 2020; 46: 972-980
186 Jamialahmadi T, Nematy M, Jangjoo A. et al. Measurement of Liver Stiffness with 2D-Shear Wave Elastography (2D-SWE) in Bariatric Surgery Candidates Reveals Acceptable Diagnostic Yield Compared to Liver Biopsy. Obes Surg 2019; 29: 2585-2592
187 Giuffrè M, Giuricin M, Bonazza D. et al. Optimization of Point-Shear Wave Elastography by Skin-to-Liver Distance to Assess Liver Fibrosis in Patients Undergoing Bariatric Surgery. Diagnostics (Basel) 2020; 10
188 Cassinotto C, Boursier J, Paisant A. et al. Transient Versus 2-Dimensional Shear-Wave Elastography in a Multistep Strategy to Detect Advanced Fibrosis in NAFLD. Hepatology 2020;
189 Furlan A, Tublin ME, Yu L. et al. Comparison of 2D Shear Wave Elastography, Transient Elastography, and MR Elastography for the Diagnosis of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Am J Roentgenol 2020; 214: W20-W26
190 Leong WL, Lai LL, Nik Mustapha NR. et al. Comparing point shear wave elastography (ElastPQ) and transient elastography for diagnosis of fibrosis stage in non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2020; 35: 135-141
191 Ferraioli G, Barr RG. Ultrasound liver elastography beyond liver fibrosis assessment. World J Gastroenterol 2020; 26: 3413-3420
192 Karlas T, Petroff D, Sasso M. et al. Impact of controlled attenuation parameter on detecting fibrosis using liver stiffness measurement. Aliment Pharmacol Ther 2018; 47: 989-1000
193 Ferraioli G. Review of Liver Elastography Guidelines. J Ultrasound Med 2019; 38: 9-14
194 Barr RG, Wilson SR, Rubens D. et al. Update to the Society of Radiologists in Ultrasound Liver Elastography Consensus Statement. Radiology 2020; 296: 263-274
195 Jung J, Loomba RR, Imajo K. et al. MRE combined with FIB-4 (MEFIB) index in detection of candidates for pharmacological treatment of NASH-related fibrosis. Gut 2020;
196 Boursier J, Guillaume M, Leroy V. et al. New sequential combinations of non-invasive fibrosis tests provide an accurate diagnosis of advanced fibrosis in NAFLD. J Hepatol 2019; 71: 389-396
197 Petta S, Wong VW, Cammà C. et al. Serial combination of non-invasive tools improves the diagnostic accuracy of severe liver fibrosis in patients with NAFLD. Aliment Pharmacol Ther 2017; 46: 617-627
198 Vali Y, Lee J, Boursier J. et al. Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: A systematic review and meta-analysis. J Hepatol 2020; 73: 252-262
199 Harrison SA, Ratziu V, Boursier J. et al. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol 2020; 5: 970-985
200 Eslam M, Wong GL, Hashem AM. et al. A Sequential Algorithm Combining ADAPT and Liver Stiffness Can Stage Metabolic-Associated Fatty Liver Disease in Hospital-Based and Primary Care Patients. Am J Gastroenterol 2021; 116: 984-993
201 Sugimoto K, Moriyasu F, Oshiro H. et al. The Role of Multiparametric US of the Liver for the Evaluation of Nonalcoholic Steatohepatitis. Radiology 2020; 296: 532-540
202 Lee DH, Cho EJ, Bae JS. et al. Accuracy of Two-Dimensional Shear Wave Elastography and Attenuation Imaging for Evaluation of Patients With Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol 2020;
203 Newsome PN, Sasso M, Deeks JJ. et al. FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol 2020; 5: 362-373
204 Puri P, Jain S, Fuchs M. Use of FibroScan-AST Score to Stratify High-Risk Nonalcoholic Steatohepatitis in US Veterans. Clin Gastroenterol Hepatol 2020; 18: 3060-3061
205 McDonald N, Eddowes PJ, Hodson J. et al. Multiparametric magnetic resonance imaging for quantitation of liver disease: a two-centre cross-sectional observational study. Sci Rep 2018; 8: 9189
206 Dennis A, Mouchti S, Kelly M. et al. A composite biomarker using multiparametric magnetic resonance imaging and blood analytes accurately identifies patients with non-alcoholic steatohepatitis and significant fibrosis. Sci Rep 2020; 10: 15308
207 Feldstein AE, Wieckowska A, Lopez AR. et al. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology 2009; 50: 1072-1078
208 Bantel H, Lugering A, Heidemann J. et al. Detection of apoptotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury. Hepatology 2004; 40: 1078-1087
209 Bechmann LP, Kocabayoglu P, Sowa JP. et al. Free fatty acids repress small heterodimer partner (SHP) activation and adiponectin counteracts bile acid-induced liver injury in superobese patients with nonalcoholic steatohepatitis. Hepatology 2013; 57: 1394-1406
210 Bantel H, John K, Schulze-Osthoff K. Robust detection of liver steatosis and staging of NAFLD by an improved ELISA for serum cytokeratin-18 fragments. Am J Gastroenterol 2014; 109: 140-141
211 Diab DL, Yerian L, Schauer P. et al. Cytokeratin 18 fragment levels as a noninvasive biomarker for nonalcoholic steatohepatitis in bariatric surgery patients. Clin Gastroenterol Hepatol 2008; 6: 1249-1254
212 Shen J, Chan HL, Wong GL. et al. Non-invasive diagnosis of non-alcoholic steatohepatitis by combined serum biomarkers. J Hepatol 2012; 56: 1363-1370
213 Tamimi TI, Elgouhari HM, Alkhouri N. et al. An apoptosis panel for nonalcoholic steatohepatitis diagnosis. J Hepatol 2011; 54: 1224-1229
214 Musso G, Gambino R, Cassader M. et al. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med 2011; 43: 617-649
215 Feldstein AE, Alkhouri N, De Vito R. et al. Serum cytokeratin-18 fragment levels are useful biomarkers for nonalcoholic steatohepatitis in children. Am J Gastroenterol 2013; 108: 1526-1531
216 Cusi K, Chang Z, Harrison S. et al. Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with non-alcoholic fatty liver disease. J Hepatol 2014; 60: 167-174
217 Liebig S, Stoeckmann N, Geier A. et al. Multicenter Validation Study of a Diagnostic Algorithm to Detect NASH and Fibrosis in NAFLD Patients With Low NAFLD Fibrosis Score or Liver Stiffness. Clin Transl Gastroenterol 2019; 10: e00066
218 Canbay A, Kälsch J, Neumann U. et al. Non-invasive assessment of NAFLD as systemic disease-A machine learning perspective. PLoS One 2019; 14: e0214436
219 Boursier J, Anty R, Vonghia L. et al. Screening for therapeutic trials and treatment indication in clinical practice: MACK-3, a new blood test for the diagnosis of fibrotic NASH. Aliment Pharmacol Ther 2018; 47: 1387-1396
220 Lonardo A, Bellentani S. Non-alcoholic Fatty Liver Disease Study G. et al. Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups. Dig Liver Dis 2015; 47: 997-1006
221 Miyake T, Kumagi T, Hirooka M. et al. Body mass index is the most useful predictive factor for the onset of nonalcoholic fatty liver disease: a community-based retrospective longitudinal cohort study. J Gastroenterol 2013; 48: 413-422
222 Subichin M, Clanton J, Makuszewski M. et al. Liver disease in the morbidly obese: a review of 1000 consecutive patients undergoing weight loss surgery. Surg Obes Relat Dis 2015; 11: 137-141
223 Younossi ZM, Golabi P, de Avila L. et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. J Hepatol 2019; 71: 793-801
224 Meex RCR, Watt MJ. Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance. Nat Rev Endocrinol 2017; 13: 509-520
225 Aneni EC, Oni ET, Martin SS. et al. Blood pressure is associated with the presence and severity of nonalcoholic fatty liver disease across the spectrum of cardiometabolic risk. J Hypertens 2015; 33: 1207-1214
226 Wu KT, Kuo PL, Su SB. et al. Nonalcoholic fatty liver disease severity is associated with the ratios of total cholesterol and triglycerides to high-density lipoprotein cholesterol. J Clin Lipidol 2016; 10: 420-425.e421
227 Koehler EM, Schouten JN, Hansen BE. et al. Prevalence and risk factors of non-alcoholic fatty liver disease in the elderly: results from the Rotterdam study. J Hepatol 2012; 57: 1305-1311
228 Caballería L, Pera G, Auladell MA. et al. Prevalence and factors associated with the presence of nonalcoholic fatty liver disease in an adult population in Spain. Eur J Gastroenterol Hepatol 2010; 22: 24-32
229 Eguchi Y, Hyogo H, Ono M. et al. Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study. J Gastroenterol 2012; 47: 586-595
230 Summart U, Thinkhamrop B, Chamadol N. et al. Gender differences in the prevalence of nonalcoholic fatty liver disease in the Northeast of Thailand: A population-based cross-sectional study. F1000Res 2017; 6: 1630
231 Rich NE, Oji S, Mufti AR. et al. Racial and Ethnic Disparities in Nonalcoholic Fatty Liver Disease Prevalence, Severity, and Outcomes in the United States: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2018; 16: 198-210.e192
232 Loomba R, Schork N, Chen CH. et al. Heritability of Hepatic Fibrosis and Steatosis Based on a Prospective Twin Study. Gastroenterology 2015; 149: 1784-1793
233 Schwimmer JB, Celedon MA, Lavine JE. et al. Heritability of nonalcoholic fatty liver disease. Gastroenterology 2009; 136: 1585-1592
234 Mantovani A, Zaza G, Byrne CD. et al. Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and meta-analysis. Metabolism 2018; 79: 64-76
235 Mantovani A, Nascimbeni F, Lonardo A. et al. Association Between Primary Hypothyroidism and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Thyroid 2018; 28: 1270-1284
236 Musso G, Cassader M, Olivetti C. et al. Association of obstructive sleep apnoea with the presence and severity of non-alcoholic fatty liver disease. A systematic review and meta-analysis. Obes Rev 2013; 14: 417-431
237 Candia R, Ruiz A, Torres-Robles R. et al. Risk of non-alcoholic fatty liver disease in patients with psoriasis: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol 2015; 29: 656-662
238 Ramezani-Binabaj M, Motalebi M, Karimi-Sari H. et al. Are women with polycystic ovarian syndrome at a high risk of non-alcoholic Fatty liver disease; a meta-analysis. Hepat Mon 2014; 14: e23235
239 Li M, Xu Y, Xu M. et al. Association between nonalcoholic fatty liver disease (NAFLD) and osteoporotic fracture in middle-aged and elderly Chinese. J Clin Endocrinol Metab 2012; 97: 2033-2038
240 Adams LA, Anstee QM, Tilg H. et al. Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut 2017; 66: 1138-1153
241 Adams LA, Waters OR, Knuiman MW. et al. NAFLD as a risk factor for the development of diabetes and the metabolic syndrome: an eleven-year follow-up study. Am J Gastroenterol 2009; 104: 861-867
242 Ampuero J, Aller R, Gallego-Durán R. et al. Significant fibrosis predicts new-onset diabetes mellitus and arterial hypertension in patients with NASH. J Hepatol 2020; 73: 17-25
243 Leite NC, Salles GF, Araujo AL. et al. Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Int 2009; 29: 113-119
244 Park SK, Seo MH, Shin HC. et al. Clinical availability of nonalcoholic fatty liver disease as an early predictor of type 2 diabetes mellitus in Korean men: 5-year prospective cohort study. Hepatology 2013; 57: 1378-1383
245 Portillo-Sanchez P, Bril F, Maximos M. et al. High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels. J Clin Endocrinol Metab 2015; 100: 2231-2238
246 Targher G, Bertolini L, Padovani R. et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007; 30: 1212-1218
247 Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 2011; 34: 274-285
248 Leung JC, Loong TC, Wei JL. et al. Histological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients. Hepatology 2017; 65: 54-64
249 Vos B, Moreno C, Nagy N. et al. Lean non-alcoholic fatty liver disease (Lean-NAFLD): a major cause of cryptogenic liver disease. Acta Gastroenterol Belg 2011; 74: 389-394
250 Younossi ZM, Stepanova M, Negro F. et al. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine (Baltimore) 2012; 91: 319-327
251 Kim D, Kim W, Joo SK. et al. Subclinical Hypothyroidism and Low-Normal Thyroid Function Are Associated With Nonalcoholic Steatohepatitis and Fibrosis. Clin Gastroenterol Hepatol 2018; 16: 123-131.e121
252 Kim D, Vazquez-Montesino LM, Escober JA. et al. Low Thyroid Function in Nonalcoholic Fatty Liver Disease Is an Independent Predictor of All-Cause and Cardiovascular Mortality. Am J Gastroenterol 2020; 115: 1496-1504
253 Yan F, Wang Q, Lu M. et al. Thyrotropin increases hepatic triglyceride content through upregulation of SREBP-1c activity. J Hepatol 2014; 61: 1358-1364
254 Maratou E, Hadjidakis DJ, Kollias A. et al. Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol 2009; 160: 785-790
255 Tan S, Bechmann LP, Benson S. et al. Apoptotic markers indicate nonalcoholic steatohepatitis in polycystic ovary syndrome. J Clin Endocrinol Metab 2010; 95: 343-348
256 Liebe R, Esposito I, Bock HH. et al. Diagnosis and management of secondary causes of steatohepatitis. J Hepatol 2021; 74: 1455-1471
257 EASL-Guideline. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. J Hepatol 2018; 69: 154-181
258 S3-Leitlinie-Alkoholkrankheiten. S3 Leitlinie Screening, Diagnose und Behandlung alkoholbezogener Störungen. Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF). 2020 https://www.awmf.org/leitlinien/detail/ll/076-001.html Zugriff am 02.02.2022
259 OʼShea RS, Dasarathy S, McCullough AJ. Alcoholic liver disease. Hepatology 2010; 51: 307-328
260 Farrell GC, Chitturi S, Lau GK. et al. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary. J Gastroenterol Hepatol 2007; 22: 775-777
261 Lucey MR, Mathurin P, Morgan TR. Alcoholic hepatitis. N Engl J Med 2009; 360: 2758-2769
262 Mueller S, Englert S, Seitz HK. et al. Inflammation-adapted liver stiffness values for improved fibrosis staging in patients with hepatitis C virus and alcoholic liver disease. Liver Int 2015; 35: 2514-2521
263 Dunn W, Angulo P, Sanderson S. et al. Utility of a new model to diagnose an alcohol basis for steatohepatitis. Gastroenterology 2006; 131: 1057-1063
264 Wang RT, Koretz RL, Yee HF. et al. Is weight reduction an effective therapy for nonalcoholic fatty liver? A systematic review. Am J Med 2003; 115: 554-559
265 Plauth M, Bernal W, Dasarathy S. et al. ESPEN guideline on clinical nutrition in liver disease. Clin Nutr 2019; 38: 485-521
266 Chalasani N, Younossi Z, Lavine JE. et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012; 55: 2005-2023
267 Burza MA, Romeo S, Kotronen A. et al. Long-term effect of bariatric surgery on liver enzymes in the Swedish Obese Subjects (SOS) study. PLoS One 2013; 8: e60495
268 Parry SA, Hodson L. Managing NAFLD in Type 2 Diabetes: The Effect of Lifestyle Interventions, a Narrative Review. Adv Ther 2020; 37: 1381-1406
269 Koutoukidis DA, Koshiaris C, Henry JA. et al. The effect of the magnitude of weight loss on non-alcoholic fatty liver disease: A systematic review and meta-analysis. Metabolism 2021; 115: 154455
270 Harrison SA, Fincke C, Helinski D. et al. A pilot study of orlistat treatment in obese, non-alcoholic steatohepatitis patients. Aliment Pharmacol Ther 2004; 20: 623-628
271 Stratopoulos C, Papakonstantinou A, Terzis I. et al. Changes in liver histology accompanying massive weight loss after gastroplasty for morbid obesity. Obes Surg 2005; 15: 1154-1160
272 Barker KB, Palekar NA, Bowers SP. et al. Non-alcoholic steatohepatitis: effect of Roux-en-Y gastric bypass surgery. Am J Gastroenterol 2006; 101: 368-373
273 Dixon JB, Bhathal PS, OʼBrien PE. Weight loss and non-alcoholic fatty liver disease: falls in gamma-glutamyl transferase concentrations are associated with histologic improvement. Obes Surg 2006; 16: 1278-1286
274 Tendler D, Lin S, Yancy Jr WS. et al. The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study. Dig Dis Sci 2007; 52: 589-593
275 Harrison SA, Fecht W, Brunt EM. et al. Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial. Hepatology 2009; 49: 80-86
276 Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L. et al Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis. Gastroenterology 2015; 149: 367-378 e365; quiz e314–365
277 Lassailly G, Caiazzo R, Buob D. et al Bariatric Surgery Reduces Features of Nonalcoholic Steatohepatitis in Morbidly Obese Patients. Gastroenterology 2015; 149: 379-388 ; quiz e315–376
278 Lee Y, Doumouras AG, Yu J. et al. Complete Resolution of Nonalcoholic Fatty Liver Disease After Bariatric Surgery: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2019; 17: 1040-1060.e1011
279 Katsagoni CN, Papatheodoridis GV, Ioannidou P. et al. Improvements in clinical characteristics of patients with non-alcoholic fatty liver disease, after an intervention based on the Mediterranean lifestyle: a randomised controlled clinical trial. Br J Nutr 2018; 120: 164-175
280 Fakhry TK, Mhaskar R, Schwitalla T. et al. Bariatric surgery improves nonalcoholic fatty liver disease: a contemporary systematic review and meta-analysis. Surg Obes Relat Dis 2019; 15: 502-511
281 Caiazzo R, Lassailly G, Leteurtre E. et al Roux-en-Y gastric bypass versus adjustable gastric banding to reduce nonalcoholic fatty liver disease: a 5-year controlled longitudinal study. Ann Surg 2014; 260: 893-898 ; discussion 898–899
282 Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol 2017; 67: 829-846
283 Younossi ZM, Corey KE, Lim JK. AGA Clinical Practice Update on Lifestyle Modification Using Diet and Exercise to Achieve Weight Loss in the Management of Nonalcoholic Fatty Liver Disease: Expert Review. Gastroenterology 2021; 160: 912-918
284 Huang MA, Greenson JK, Chao C. et al. One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study. Am J Gastroenterol 2005; 100: 1072-1081
285 Zelber-Sagi S, Kessler A, Brazowsky E. et al. A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2006; 4: 639-644
286 Promrat K, Kleiner DE, Niemeier HM. et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010; 51: 121-129
287 Haufe S, Engeli S, Kast P. et al. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects. Hepatology 2011; 53: 1504-1514
288 Wong VW, Wong GL, Chan RS. et al. Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease. J Hepatol 2018; 69: 1349-1356
289 Berzigotti A, Albillos A, Villanueva C. et al. Effects of an intensive lifestyle intervention program on portal hypertension in patients with cirrhosis and obesity: The SportDiet study. Hepatology 2017; 65: 1293-1305
290 Mazzotti A, Caletti MT, Brodosi L. et al. An internet-based approach for lifestyle changes in patients with NAFLD: Two-year effects on weight loss and surrogate markers. J Hepatol 2018; 69: 1155-1163
291 Huber Y, Pfirrmann D, Gebhardt I. et al. Improvement of non-invasive markers of NAFLD from an individualised, web-based exercise program. Aliment Pharmacol Ther 2019; 50: 930-939
292 Axley P, Kodali S, Kuo YF. et al. Text messaging approach improves weight loss in patients with nonalcoholic fatty liver disease: A randomized study. Liver Int 2018; 38: 924-931
293 Sumida Y, Yoshikawa T, Tanaka S. et al. The “donations for decreased ALT (D4D)” prosocial behavior incentive scheme for NAFLD patients. J Public Health (Oxf) 2014; 36: 629-634
294 Johnson NA, Sachinwalla T, Walton DW. et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology 2009; 50: 1105-1112
295 Hallsworth K, Fattakhova G, Hollingsworth KG. et al. Resistance exercise reduces liver fat and its mediators in non-alcoholic fatty liver disease independent of weight loss. Gut 2011; 60: 1278-1283
296 Sullivan S, Kirk EP, Mittendorfer B. et al. Randomized trial of exercise effect on intrahepatic triglyceride content and lipid kinetics in nonalcoholic fatty liver disease. Hepatology 2012; 55: 1738-1745
297 Houghton D, Thoma C, Hallsworth K. et al. Exercise Reduces Liver Lipids and Visceral Adiposity in Patients With Nonalcoholic Steatohepatitis in a Randomized Controlled Trial. Clin Gastroenterol Hepatol 2017; 15: 96-102.e103
298 Thoma C, Day CP, Trenell MI. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol 2012; 56: 255-266
299 Orci LA, Gariani K, Oldani G. et al. Exercise-based Interventions for Nonalcoholic Fatty Liver Disease: A Meta-analysis and Meta-regression. Clin Gastroenterol Hepatol 2016; 14: 1398-1411
300 Katsagoni CN, Georgoulis M, Papatheodoridis GV. et al. Effects of lifestyle interventions on clinical characteristics of patients with non-alcoholic fatty liver disease: A meta-analysis. Metabolism 2017; 68: 119-132
301 Hashida R, Kawaguchi T, Bekki M. et al. Aerobic vs. resistance exercise in non-alcoholic fatty liver disease: A systematic review. J Hepatol 2017; 66: 142-152
302 Garvey WT, Mechanick JI, Brett EM. et al. American Association of Clinical Endocrinologists And American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Endocr Pract 2016; 22 (Suppl. 03) 1-203
303 Wirth A, Wabitsch M, Hauner H. The prevention and treatment of obesity. Dtsch Arztebl Int 2014; 111: 705-713
304 Hickman IJ, Jonsson JR, Prins JB. et al. Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut 2004; 53: 413-419
305 Thomas EL, Brynes AE, Hamilton G. et al. Effect of nutritional counselling on hepatic, muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease. World J Gastroenterol 2006; 12: 5813-5819
306 Larson-Meyer DE, Newcomer BR, Heilbronn LK. et al. Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function. Obesity (Silver Spring) 2008; 16: 1355-1362
307 Gerber L, Otgonsuren M, Mishra A. et al. Non-alcoholic fatty liver disease (NAFLD) is associated with low level of physical activity: a population-based study. Aliment Pharmacol Ther 2012; 36: 772-781
308 Stewart KE, Haller DL, Sargeant C. et al. Readiness for behaviour change in non-alcoholic fatty liver disease: implications for multidisciplinary care models. Liver Int 2015; 35: 936-943
309 Baldry EL, Aithal GP, Kaye P. et al. Effects of short-term energy restriction on liver lipid content and inflammatory status in severely obese adults: Results of a randomized controlled trial using 2 dietary approaches. Diabetes Obes Metab 2017; 19: 1179-1183
310 Deibert P, Lazaro A, Schaffner D. et al. Comprehensive lifestyle intervention vs soy protein-based meal regimen in non-alcoholic steatohepatitis. World J Gastroenterol 2019; 25: 1116-1131
311 Hohenester S, Christiansen S, Nagel J. et al. Lifestyle intervention for morbid obesity: effects on liver steatosis, inflammation, and fibrosis. Am J Physiol Gastrointest Liver Physiol 2018; 315: G329-G338
312 Markova M, Pivovarova O, Hornemann S. et al. Isocaloric Diets High in Animal or Plant Protein Reduce Liver Fat and Inflammation in Individuals With Type 2 Diabetes. Gastroenterology 2017; 152: 571-585.e578
313 Bray GA, Nielsen SJ, Popkin BM. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 2004; 79: 537-543
314 Roeb E, Weiskirchen R. Fructose and Non-Alcoholic Steatohepatitis. Front Pharmacol 2021; 12: 634344
315 Stanhope KL, Schwarz JM, Keim NL. et al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest 2009; 119: 1322-1334
316 Jensen T, Abdelmalek MF, Sullivan S. et al. Fructose and sugar: A major mediator of non-alcoholic fatty liver disease. J Hepatol 2018; 68: 1063-1075
317 Chung M, Ma J, Patel K. et al. Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis. Am J Clin Nutr 2014; 100: 833-849
318 Chiu S, Sievenpiper JL, de Souza RJ. et al. Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials. Eur J Clin Nutr 2014; 68: 416-423
319 Stricker S, Rudloff S, Geier A. et al. Fructosekonsum & freie Zucker und ihr Einfluss auf die Gesundheit. Dtsch Arztebl International 2021; 118: 71-80
320 Johnston RD, Stephenson MC, Crossland H. et al. No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. Gastroenterology 2013; 145: 1016-1025.e1012
321 Shai I, Schwarzfuchs D, Henkin Y. et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med 2008; 359: 229-241
322 Pérez-Guisado J, Muñoz-Serrano A. The effect of the Spanish Ketogenic Mediterranean Diet on nonalcoholic fatty liver disease: a pilot study. J Med Food 2011; 14: 677-680
323 Ryan MC, Itsiopoulos C, Thodis T. et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol 2013; 59: 138-143
324 Trovato FM, Catalano D, Martines GF. et al. Mediterranean diet and non-alcoholic fatty liver disease: the need of extended and comprehensive interventions. Clin Nutr 2015; 34: 86-88
325 Misciagna G, Del Pilar Díaz M, Caramia DV. et al. Effect of a Low Glycemic Index Mediterranean Diet on Non-Alcoholic Fatty Liver Disease. A Randomized Controlled Clinici Trial. J Nutr Health Aging 2017; 21: 404-412
326 Gelli C, Tarocchi M, Abenavoli L. et al. Effect of a counseling-supported treatment with the Mediterranean diet and physical activity on the severity of the non-alcoholic fatty liver disease. World J Gastroenterol 2017; 23: 3150-3162
327 Tzima N, Pitsavos C, Panagiotakos DB. et al. Adherence to the Mediterranean diet moderates the association of aminotransferases with the prevalence of the metabolic syndrome; the ATTICA study. Nutr Metab (Lond) 2009; 6: 30
328 Kontogianni MD, Tileli N, Margariti A. et al. Adherence to the Mediterranean diet is associated with the severity of non-alcoholic fatty liver disease. Clin Nutr 2014; 33: 678-683
329 Aller R, Izaola O, de la Fuente B. et al. Mediterranean Diet is Associated with Liver Histology in Patients with Non Alcoholic Fatty Liver Disease. Nutr Hosp 2015; 32: 2518-2524
330 Trovato FM, Martines GF, Brischetto D. et al. Fatty liver disease and lifestyle in youngsters: diet, food intake frequency, exercise, sleep shortage and fashion. Liver Int 2016; 36: 427-433
331 Abenavoli L, Milic N, Peta V. et al. Alimentary regimen in non-alcoholic fatty liver disease: Mediterranean diet. World J Gastroenterol 2014; 20: 16831-16840
332 Suárez M, Boqué N, Del Bas JM. et al. Mediterranean Diet and Multi-Ingredient-Based Interventions for the Management of Non-Alcoholic Fatty Liver Disease. Nutrients 2017; 9
333 Ma J, Hennein R, Liu C. et al. Improved Diet Quality Associates With Reduction in Liver Fat, Particularly in Individuals With High Genetic Risk Scores for Nonalcoholic Fatty Liver Disease. Gastroenterology 2018; 155: 107-117
334 Velasco N, Contreras A, Grassi B. The Mediterranean diet, hepatic steatosis and nonalcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care 2014; 17: 453-457
335 Gepner Y, Shelef I, Schwarzfuchs D. et al. Effect of Distinct Lifestyle Interventions on Mobilization of Fat Storage Pools: CENTRAL Magnetic Resonance Imaging Randomized Controlled Trial. Circulation 2018; 137: 1143-1157
336 Stefan N, Häring HU, Schulze MB. Metabolically healthy obesity: the low-hanging fruit in obesity treatment?. Lancet Diabetes Endocrinol 2018; 6: 249-258
337 Štefan L, Čule M, Milinović I. et al. The Relationship between Lifestyle Factors and Body Compositionin Young Adults. Int J Environ Res Public Health 2017; 14
338 Buzzetti E, Linden A, Best LM. et al. Lifestyle modifications for nonalcohol-related fatty liver disease: a network meta-analysis. Cochrane Database Syst Rev 2021; 6: Cd013156
339 Yaskolka Meir A, Rinott E, Tsaban G. et al. Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial. Gut 2021;
340 Zelber-Sagi S, Buch A, Yeshua H. et al. Effect of resistance training on non-alcoholic fatty-liver disease a randomized-clinical trial. World J Gastroenterol 2014; 20: 4382-4392
341 Shojaee-Moradie F, Cuthbertson DJ, Barrett M. et al. Exercise Training Reduces Liver Fat and Increases Rates of VLDL Clearance But Not VLDL Production in NAFLD. J Clin Endocrinol Metab 2016; 101: 4219-4228
342 Cotrim HP, Freitas LA, Alves E. et al. Effects of light-to-moderate alcohol consumption on steatosis and steatohepatitis in severely obese patients. Eur J Gastroenterol Hepatol 2009; 21: 969-972
343 Hajifathalian K, Torabi Sagvand B, McCullough AJ. Effect of Alcohol Consumption on Survival in Nonalcoholic Fatty Liver Disease: A National Prospective Cohort Study. Hepatology 2019; 70: 511-521
344 Mueller S, Seitz HK. Alkoholsucht und Leber: Wie wichtig ist ein Leberscreening auch für Suchttherapeuten?. Suchtmedizin 2018; 20: 1-9
345 Nascimento AF, Ip BC, Luvizotto RA. et al. Aggravation of nonalcoholic steatohepatitis by moderate alcohol consumption is associated with decreased SIRT1 activity in rats. Hepatobiliary Surg Nutr 2013; 2: 252-259
346 Seitz HK, Mueller S, Hellerbrand C. et al. Effect of chronic alcohol consumption on the development and progression of non-alcoholic fatty liver disease (NAFLD). Hepatobiliary Surg Nutr 2015; 4: 147-151
347 Wang Y, Seitz HK, Wang XD. Moderate alcohol consumption aggravates high-fat diet induced steatohepatitis in rats. Alcohol Clin Exp Res 2010; 34: 567-573
348 Xu J, Lai KKY, Verlinsky A. et al. Synergistic steatohepatitis by moderate obesity and alcohol in mice despite increased adiponectin and p-AMPK. J Hepatol 2011; 55: 673-682
349 Ekstedt M, Franzén LE, Holmqvist M. et al. Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease. Scand J Gastroenterol 2009; 44: 366-374
350 Ascha MS, Hanouneh IA, Lopez R. et al. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 2010; 51: 1972-1978
351 Roerecke M, Vafaei A, Hasan OSM. et al. Alcohol Consumption and Risk of Liver Cirrhosis: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2019; 114: 1574-1586
352 Blomdahl J, Nasr P, Ekstedt M. et al. Moderate alcohol consumption is associated with advanced fibrosis in non-alcoholic fatty liver disease and shows a synergistic effect with type 2 diabetes mellitus. Metabolism 2021; 115: 154439
353 Bhurwal A, Rattan P, Yoshitake S. et al. Inverse Association of Coffee with Liver Cancer Development: An Updated Systematic Review and Meta-analysis. J Gastrointestin Liver Dis 2020; 29: 421-428
354 Zhao LG, Li ZY, Feng GS. et al. Coffee drinking and cancer risk: an umbrella review of meta-analyses of observational studies. BMC Cancer 2020; 20: 101
355 Godos J, Micek A, Marranzano M. et al. Coffee Consumption and Risk of Biliary Tract Cancers and Liver Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies. Nutrients 2017; 9
356 Poole R, Kennedy OJ, Roderick P. et al. Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes. BMJ 2017; 359: j5024
357 Hayat U, Siddiqui AA, Okut H. et al. The effect of coffee consumption on the non-alcoholic fatty liver disease and liver fibrosis: A meta-analysis of 11 epidemiological studies. Ann Hepatol 2021; 20: 100254
358 Sanyal AJ, Chalasani N, Kowdley KV. et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010; 362: 1675-1685
359 Bjelakovic G, Nikolova D, Gluud LL. et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 2012;
360 Miller 3rd ER, Pastor-Barriuso R. et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005; 142: 37-46
361 Klein EA, Thompson Jr IM, Tangen CM. et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011; 306: 1549-1556
362 Scorletti E, Bhatia L, McCormick KG. et al. Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the Welcome* study. Hepatology 2014; 60: 1211-1221
363 Scorletti E, West AL, Bhatia L. et al. Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: Results from the WELCOME trial. J Hepatol 2015; 63: 1476-1483
364 Argo CK, Patrie JT, Lackner C. et al. Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial. J Hepatol 2015; 62: 190-197
365 Dasarathy S, Dasarathy J, Khiyami A. et al. Double-blind randomized placebo-controlled clinical trial of omega 3 fatty acids for the treatment of diabetic patients with nonalcoholic steatohepatitis. J Clin Gastroenterol 2015; 49: 137-144
366 Chen LH, Wang YF, Xu QH. et al. Omega-3 fatty acids as a treatment for non-alcoholic fatty liver disease in children: A systematic review and meta-analysis of randomized controlled trials. Clin Nutr 2018; 37: 516-521
367 Yan JH, Guan BJ, Gao HY. et al. Omega-3 polyunsaturated fatty acid supplementation and non-alcoholic fatty liver disease: A meta-analysis of randomized controlled trials. Medicine (Baltimore) 2018; 97: e12271
368 Parker HM, Cohn JS, OʼConnor HT. et al. Effect of Fish Oil Supplementation on Hepatic and Visceral Fat in Overweight Men: A Randomized Controlled Trial. Nutrients 2019; 11
369 Reja M, Makar M, Visaria A. et al. Increased serum selenium levels are associated with reduced risk of advanced liver fibrosis and all-cause mortality in NAFLD patients: National Health and Nutrition Examination Survey (NHANES) III. Ann Hepatol 2020; 19: 635-640
370 Wong VW, Wong GL, Chan AW. et al. Treatment of non-alcoholic steatohepatitis with Phyllanthus urinaria: a randomized trial. J Gastroenterol Hepatol 2013; 28: 57-62
371 Navarro VJ, Belle SH, DʼAmato M. et al. Silymarin in non-cirrhotics with non-alcoholic steatohepatitis: A randomized, double-blind, placebo controlled trial. PLoS One 2019; 14: e0221683
372 Geier A, Eichinger M, Stirnimann G. et al. Treatment of non-alcoholic steatohepatitis patients with vitamin D: a double-blinded, randomized, placebo-controlled pilot study. Scand J Gastroenterol 2018; 53: 1114-1120
373 Barchetta I, Del Ben M, Angelico F. et al. No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. BMC Med 2016; 14: 92
374 Behrouz V, Aryaeian N, Zahedi MJ. et al. Effects of probiotic and prebiotic supplementation on metabolic parameters, liver aminotransferases, and systemic inflammation in nonalcoholic fatty liver disease: A randomized clinical trial. J Food Sci 2020; 85: 3611-3617
375 Sepideh A, Karim P, Hossein A. et al. Effects of Multistrain Probiotic Supplementation on Glycemic and Inflammatory Indices in Patients with Nonalcoholic Fatty Liver Disease: A Double-Blind Randomized Clinical Trial. J Am Coll Nutr 2016; 35: 500-505
376 Scorletti E, Afolabi PR, Miles EA. et al. Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 2020; 158: 1597-1610.e1597
377 Mofidi F, Poustchi H, Yari Z. et al. Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease: a pilot, randomised, double-blind, placebo-controlled, clinical trial. Br J Nutr 2017; 117: 662-668
378 Sharpton SR, Maraj B, Harding-Theobald E. et al. Gut microbiome-targeted therapies in nonalcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression. Am J Clin Nutr 2019; 110: 139-149
379 Cosentino F, Grant PJ, Aboyans V. et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2020; 41: 255-323
380 Armstrong MJ, Gaunt P, Aithal GP. et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 2016; 387: 679-690
381 Newsome PN, Buchholtz K, Cusi K. et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med 2020;
382 Cusi K, Bril F, Barb D. et al. Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes. Diabetes Obes Metab 2019; 21: 812-821
383 Eriksson JW, Lundkvist P, Jansson PA. et al. Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study. Diabetologia 2018; 61: 1923-1934
384 Kahl S, Gancheva S, Straßburger K. et al. Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial. Diabetes Care 2020; 43: 298-305
385 Latva-Rasku A, Honka MJ, Kullberg J. et al. The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity: A Randomized, Double-Blind, Placebo-Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients. Diabetes Care 2019; 42: 931-937
386 Belfort R, Harrison SA, Brown K. et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355: 2297-2307
387 Cusi K, Orsak B, Bril F. et al. Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus: A Randomized Trial. Ann Intern Med 2016; 165: 305-315
388 Fujiwara N, Friedman SL, Goossens N. et al. Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol 2018; 68: 526-549
389 Vilar-Gomez E, Calzadilla-Bertot L, Wong VW. et al. Type 2 Diabetes and Metformin Use Associate With Outcomes of Patients With Nonalcoholic Steatohepatitis-Related, Child-Pugh A Cirrhosis. Clin Gastroenterol Hepatol 2021; 19: 136-145.e136
390 Kaplan DE, Serper M, John BV. et al. Effects of Metformin Exposure on Survival in a Large National Cohort of Patients With Diabetes and Cirrhosis. Clin Gastroenterol Hepatol 2020;
391 Bril F, Biernacki DM, Kalavalapalli S. et al. Role of Vitamin E for Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes: A Randomized Controlled Trial. Diabetes Care 2019; 42: 1481-1488
392 Dormandy JA, Charbonnel B, Eckland DJ. et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005; 366: 1279-1289
393 Marso SP, Daniels GH, Brown-Frandsen K. et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375: 311-322
394 Marso SP, Bain SC, Consoli A. et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2016; 375: 1834-1844
395 Zinman B, Wanner C, Lachin JM. et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015; 373: 2117-2128
396 Wiviott SD, Raz I, Bonaca MP. et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2019; 380: 347-357
397 Stefan N, Haring HU, Cusi K. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol 2019; 7: 313-324
398 Dongiovanni P, Petta S, Mannisto V. et al. Statin use and non-alcoholic steatohepatitis in at risk individuals. J Hepatol 2015; 63: 705-712
399 Kamal S, Khan MA, Seth A. et al. Beneficial Effects of Statins on the Rates of Hepatic Fibrosis, Hepatic Decompensation, and Mortality in Chronic Liver Disease: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2017; 112: 1495-1505
400 Lee JI, Lee HW, Lee KS. et al. Effects of Statin Use on the Development and Progression of Nonalcoholic Fatty Liver Disease: A Nationwide Nested Case-Control Study. Am J Gastroenterol 2021; 116: 116-124
401 Pose E, Trebicka J, Mookerjee RP. et al. Statins: Old drugs as new therapy for liver diseases?. J Hepatol 2019; 70: 194-202
402 Munoz AE, Pollarsky F, Marino M. et al. Safety of Chronic Simvastatin Treatment in Patients with Decompensated Cirrhosis: Many Adverse Events but No Liver Injury. Dig Dis Sci 2020;
403 Islam MM, Poly TN, Walther BA. et al. Statin Use and the Risk of Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies. Cancers (Basel) 2020; 12
404 Bosch J, Gracia-Sancho J, Abraldes JG. Cirrhosis as new indication for statins. Gut 2020; 69: 953-962
405 Mantovani A, Petracca G, Beatrice G. et al. Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials. Metabolites 2021; 11
406 Bajaj HS, Burrows M, Blavignac J. et al. Extended-release naltrexone/bupropion and liver health: Pooled, post hoc analysis from four randomized controlled trials. Diabetes Obes Metab 2020;
407 Pan CS, Stanley TL. Effect of Weight Loss Medications on Hepatic Steatosis and Steatohepatitis: A Systematic Review. Front Endocrinol (Lausanne) 2020; 11: 70
408 Dietrich CG, Rau M, Jahn D. et al. Changes in drug transport and metabolism and their clinical implications in non-alcoholic fatty liver disease. Expert Opin Drug Metab Toxicol 2017; 13: 625-640
409 Vildhede A, Kimoto E, Pelis RM. et al. Quantitative Proteomics and Mechanistic Modeling of Transporter-Mediated Disposition in Nonalcoholic Fatty Liver Disease. Clin Pharmacol Ther 2020; 107: 1128-1137
410 Pierre V, Johnston CK, Ferslew BC. et al. Population Pharmacokinetics of Morphine in Patients With Nonalcoholic Steatohepatitis (NASH) and Healthy Adults. CPT Pharmacometrics Syst Pharmacol 2017; 6: 331-339
411 Sundelin EIO, Gormsen LC, Heeboll S. et al. Hepatic exposure of metformin in patients with non-alcoholic fatty liver disease. Br J Clin Pharmacol 2019; 85: 1761-1770
412 Tirona RG, Kassam Z, Strapp R. et al. Apixaban and Rosuvastatin Pharmacokinetics in Nonalcoholic Fatty Liver Disease. Drug Metab Dispos 2018; 46: 485-492
413 Rinella ME, Tacke F, Sanyal AJ. et al. Report on the AASLD/EASL joint workshop on clinical trial endpoints in NAFLD. J Hepatol 2019; 71: 823-833
414 Anania FA, Dimick-Santos L, Mehta R. et al. Nonalcoholic Steatohepatitis: Current Thinking from the Division of Hepatology and Nutrition at the Food and Drug Administration. Hepatology 2020;
415 Han MAT, Altayar O, Hamdeh S. et al. Rates of and Factors Associated With Placebo Response in Trials of Pharmacotherapies for Nonalcoholic Steatohepatitis: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2019; 17: 616-629.e626
416 Friedman SL, Neuschwander-Tetri BA, Rinella M. et al. Mechanisms of NAFLD development and therapeutic strategies. Nat Med 2018; 24: 908-922
417 Konerman MA, Jones JC, Harrison SA. Pharmacotherapy for NASH: Current and emerging. J Hepatol 2018; 68: 362-375
418 Lambrecht J, van Grunsven LA, Tacke F. Current and emerging pharmacotherapeutic interventions for the treatment of liver fibrosis. Expert Opin Pharmacother 2020; 21: 1637-1650
419 Roeb E, Geier A. Nonalcoholic steatohepatitis (NASH) – current treatment recommendations and future developments. Z Gastroenterol 2019; 57: 508-517
420 Younossi ZM, Ratziu V, Loomba R. et al. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 2019; 394: 2184-2196
421 Francque SM, Bedossa P, Ratziu V. et al. A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH. N Engl J Med 2021; 385: 1547-1558
422 Mullard A. FDA rejects NASH drug. Nat Rev Drug Discov 2020; 19: 501
423 Loomba R, Noureddin M, Kowdley KV. et al. Combination Therapies Including Cilofexor and Firsocostat for Bridging Fibrosis and Cirrhosis Attributable to NASH. Hepatology 2021; 73: 625-643
424 Rau M, Geier A. An update on drug development for the treatment of nonalcoholic fatty liver disease – from ongoing clinical trials to future therapy. Expert Rev Clin Pharmacol 2021; 14: 333-340
425 Taylor RS, Taylor RJ, Bayliss S. et al. Association Between Fibrosis Stage and Outcomes of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Gastroenterology 2020; 158: 1611-1625.e1612
426 Acharya C, Bajaj JS. Chronic Liver Diseases and the Microbiome: Translating Our Knowledge of Gut Microbiota to Management of Chronic Liver Disease. Gastroenterology 2020;
427 Lindén D, Ahnmark A, Pingitore P. et al. Pnpla3 silencing with antisense oligonucleotides ameliorates nonalcoholic steatohepatitis and fibrosis in Pnpla3 I148M knock-in mice. Mol Metab 2019; 22: 49-61
428 Schwartz BE, Rajagopal V, Smith C. et al. Discovery and Targeting of the Signaling Controls of PNPLA3 to Effectively Reduce Transcription, Expression, and Function in Pre-Clinical NAFLD/NASH Settings. Cells 2020; 9
429 DGAV D, DDG, DGEM, DGE-BV, DGPM, DGPRÄC, DKPM, VDBD, VDOE. S3-Leitlinie: Chirurgie der Adipositas und metabolischer Erkrankungen In. Version 2.3 (Februar 2018) AWMF-Register Nr. 088-001 ed: AWMF. 2018
430 Lassailly G, Caiazzo R, Ntandja-Wandji LC. et al. Bariatric Surgery Provides Long-term Resolution of Nonalcoholic Steatohepatitis and Regression of Fibrosis. Gastroenterology 2020;
431 Kwak M, Mehaffey JH, Hawkins RB. et al. Bariatric surgery is associated with reduction in non-alcoholic steatohepatitis and hepatocellular carcinoma: A propensity matched analysis. Am J Surg 2019;
432 Wirth KM, Sheka AC, Kizy S. et al. Bariatric Surgery is Associated With Decreased Progression of Nonalcoholic Fatty Liver Disease to Cirrhosis: A Retrospective Cohort Analysis. Ann Surg 2020;
433 Klebanoff MJ, Corey KE, Chhatwal J. et al. Bariatric surgery for nonalcoholic steatohepatitis: A clinical and cost-effectiveness analysis. Hepatology 2017; 65: 1156-1164
434 Alam S, Jahid Hasan M, Khan MAS. et al. Effect of Weight Reduction on Histological Activity and Fibrosis of Lean Nonalcoholic Steatohepatitis Patient. J Transl Int Med 2019; 7: 106-114
435 Panunzi S, Maltese S, Verrastro O. et al. Pioglitazone and bariatric surgery are the most effective treatments for non-alcoholic steatohepatitis: A hierarchical network meta-analysis. Diabetes, obesity & metabolism 2020;
436 Mosko JD, Nguyen GC. Increased perioperative mortality following bariatric surgery among patients with cirrhosis. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 2011; 9: 897-901
437 Younus H, Sharma A, Miquel R. et al. Bariatric Surgery in Cirrhotic Patients: Is It Safe?. Obesity surgery 2020; 30: 1241-1248
438 Quezada N, Maturana G, Irarrazaval MJ. et al. Bariatric Surgery in Cirrhotic Patients: a Matched Case-Control Study. Obesity surgery 2020; 30: 4724-4731
439 Vuppalanchi R, McCabe MEt, Tandra SR. et al. Safety and Efficacy of Bariatric Surgery in Cirrhosis Patients With Extreme Obesity. Ann Surg 2020;
440 Goh GB, Schauer PR, McCullough AJ. Considerations for bariatric surgery in patients with cirrhosis. World journal of gastroenterology: WJG 2018; 24: 3112-3119
441 Hanipah ZN, Punchai S, McCullough A. et al. Bariatric Surgery in Patients with Cirrhosis and Portal Hypertension. Obesity surgery 2018; 28: 3431-3438
442 Sharpton SR, Terrault NA, Posselt AM. Outcomes of Sleeve Gastrectomy in Obese Liver Transplant Candidates. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2019; 25: 538-544
443 Peterli R, Wolnerhanssen BK, Peters T. et al. Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized Clinical Trial. Jama 2018; 319: 255-265
444 Salminen P, Helmiö M, Ovaska J. et al. Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss at 5 Years Among Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial. Jama 2018; 319: 241-254
445 Robert M, Espalieu P, Pelascini E. et al. Efficacy and safety of one anastomosis gastric bypass versus Roux-en-Y gastric bypass for obesity (YOMEGA): a multicentre, randomised, open-label, non-inferiority trial. The Lancet 2019; 393: 1299-1309
446 Colquitt JL, Pickett K, Loveman E. et al. Surgery for weight loss in adults. Cochrane Database Syst Rev 2014; 8: CD003641
447 Froylich D, Corcelles R, Daigle C. et al. Effect of Roux-en-Y gastric bypass and sleeve gastrectomy on nonalcoholic fatty liver disease: a comparative study. Surgery for obesity and related diseases: official journal of the American Society for Bariatric Surgery 2015;
448 von Schonfels W, Beckmann JH, Ahrens M. et al. Histologic improvement of NAFLD in patients with obesity after bariatric surgery based on standardized NAS (NAFLD activity score). Surgery for obesity and related diseases: official journal of the American Society for Bariatric Surgery 2018; 14: 1607-1616
449 Eilenberg M, Langer FB, Beer A. et al. Significant Liver-Related Morbidity After Bariatric Surgery and Its Reversal-a Case Series. Obesity surgery 2018; 28: 812-819
450 Mahawar KK. Liver Dysfunction with Both Roux-en-Y and One-Anastomosis Gastric Bypass Is Almost Exclusively Seen with Longer Than Standard Limb Lengths. Obesity surgery 2018; 28: 548-549
451 Agarwal L, Sahu AK, Baksi A. et al. Safety of metabolic and bariatric surgery in obese patients with liver cirrhosis: a systematic review and meta-analysis. Surgery for obesity and related diseases: official journal of the American Society for Bariatric Surgery 2020;
452 Dietrich A, Aberle J, Wirth A. et al. Adipositaschirurgie und Therapie metabolischer Erkrankungen. Dtsch Arztebl International 2018; 115: 705-711
453 Kotinda A, de Moura DTH, Ribeiro IB. et al. Efficacy of Intragastric Balloons for Weight Loss in Overweight and Obese Adults: a Systematic Review and Meta-analysis of Randomized Controlled Trials. Obes Surg 2020; 30: 2743-2753
454 Imaz I, Martínez-Cervell C, García-Alvarez EE. et al. Safety and effectiveness of the intragastric balloon for obesity. A meta-analysis. Obes Surg 2008; 18: 841-846
455 Lee Y, Dang JT, Switzer N. et al. Bridging interventions before bariatric surgery in patients with BMI ≥ 50 kg/m(2): a systematic review and meta-analysis. Surg Endosc 2019; 33: 3578-3588
456 Lee YM, Low HC, Lim LG. et al. Intragastric balloon significantly improves nonalcoholic fatty liver disease activity score in obese patients with nonalcoholic steatohepatitis: a pilot study. Gastrointest Endosc 2012; 76: 756-760
457 Bazerbachi F, Vargas EJ, Rizk M. et al. Intragastric Balloon Placement Induces Significant Metabolic and Histologic Improvement in Patients With Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol 2021; 19: 146-154.e144
458 Frutos MD, Morales MD, Luján J. et al. Intragastric balloon reduces liver volume in super-obese patients, facilitating subsequent laparoscopic gastric bypass. Obes Surg 2007; 17: 150-154
459 Forlano R, Ippolito AM, Iacobellis A. et al. Effect of the BioEnterics intragastric balloon on weight, insulin resistance, and liver steatosis in obese patients. Gastrointest Endosc 2010; 71: 927-933
460 Folini L, Veronelli A, Benetti A. et al. Liver steatosis (LS) evaluated through chemical-shift magnetic resonance imaging liver enzymes in morbid obesity; effect of weight loss obtained with intragastric balloon gastric banding. Acta Diabetol 2014; 51: 361-368
461 Due-Petersson R, Poulsen IM, Hedbäck N. et al Effect and safety of endoscopic sleeve gastroplasty for treating obesity – a systematic review. Dan Med J 2020; 67 (11) A05200359 . PMID: 33215606
462 Sharaiha RZ, Kumta NA, Saumoy M. et al. Endoscopic Sleeve Gastroplasty Significantly Reduces Body Mass Index and Metabolic Complications in Obese Patients. Clin Gastroenterol Hepatol 2017; 15: 504-510
463 Hajifathalian K, Mehta A, Ang B. et al. Improvement in insulin resistance and estimated hepatic steatosis and fibrosis after endoscopic sleeve gastroplasty. Gastrointest Endosc 2020;
464 Rohde U, Hedbäck N, Gluud LL. et al. Effect of the EndoBarrier Gastrointestinal Liner on obesity and type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab 2016; 18: 300-305
465 Gollisch KS, Lindhorst A, Raddatz D. EndoBarrier Gastrointestinal Liner in Type 2 Diabetic Patients Improves Liver Fibrosis as Assessed by Liver Elastography. Exp Clin Endocrinol Diabetes 2017; 125: 116-121
466 van Baar ACG, Beuers U, Wong K. et al. Endoscopic duodenal mucosal resurfacing improves glycaemic and hepatic indices in type 2 diabetes: 6-month multicentre results. JHEP Rep 2019; 1: 429-437
467 van Baar ACG, Holleman F, Crenier L. et al. Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: one year results from the first international, open-label, prospective, multicentre study. Gut 2020; 69: 295-303
468 Machytka E, Bužga M, Zonca P. et al. Partial jejunal diversion using an incisionless magnetic anastomosis system: 1-year interim results in patients with obesity and diabetes. Gastrointest Endosc 2017; 86: 904-912
469 Axley P, Ahmed Z, Arora S. et al. NASH Is the Most Rapidly Growing Etiology for Acute-on-Chronic Liver Failure-Related Hospitalization and Disease Burden in the United States: A Population-Based Study. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2019; 25: 695-705
470 Holmer M, Melum E, Isoniemi H. et al. Nonalcoholic fatty liver disease is an increasing indication for liver transplantation in the Nordic countries. Liver international: official journal of the International Association for the Study of the Liver 2018; 38: 2082-2090
471 Samji NS, Heda R, Satapathy SK. Peri-transplant management of nonalcoholic fatty liver disease in liver transplant candidates Translational gastroenterology and hepatology. Transl Gastroenterol Hepatol 2020; 5: 10
472 Thuluvath PJ, Hanish S, Savva Y. Liver Transplantation in Cryptogenic Cirrhosis: Outcome Comparisons Between NASH, Alcoholic, and AIH Cirrhosis. Transplantation 2018; 102: 656-663
473 Haldar D, Kern B, Hodson J. et al. Outcomes of liver transplantation for non-alcoholic steatohepatitis: A European Liver Transplant Registry study. J Hepatol 2019; 71: 313-322
474 EASL clinical practical guidelines: management of alcoholic liver disease. Journal of hepatology 2012; 57: 399-420
475 Beckmann S, Drent G, Ruppar T. et al. Body Weight Parameters are Related to Morbidity and Mortality After Liver Transplantation: A Systematic Review and Meta-analysis. Transplantation 2019; 103: 2287-2303
476 Schlansky B, Naugler WE, Orloff SL. et al. Higher Mortality and Survival Benefit in Obese Patients Awaiting Liver Transplantation. Transplantation 2016; 100: 2648-2655
477 Leonard J, Heimbach JK, Malinchoc M. et al. The impact of obesity on long-term outcomes in liver transplant recipients-results of the NIDDK liver transplant database. American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2008; 8: 667-672
478 Sourianarayanane A, Arikapudi S, McCullough AJ. et al. Nonalcoholic steatohepatitis recurrence and rate of fibrosis progression following liver transplantation. European journal of gastroenterology & hepatology 2017; 29: 481-487
479 Tokodai K, Karadagi A, Kjaernet F. et al. Characteristics and risk factors for recurrence of nonalcoholic steatohepatitis following liver transplantation. Scandinavian journal of gastroenterology 2019; 54: 233-239
480 Bhati C, Idowu MO, Sanyal AJ. et al. Long-term Outcomes in Patients Undergoing Liver Transplantation for Nonalcoholic Steatohepatitis-Related Cirrhosis. Transplantation 2017; 101: 1867-1874
481 Kakar S, Dugum M, Cabello R. et al. Incidence of Recurrent NASH-Related Allograft Cirrhosis. Digestive diseases and sciences 2019; 64: 1356-1363
482 van den Berg EH, Douwes RM, de Meijer VE. et al. Liver transplantation for NASH cirrhosis is not performed at the expense of major post-operative morbidity. Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2018; 50: 68-75
483 Kalaitzakis E, Björnsson E. Coronary artery disease in liver cirrhosis: does the aetiology of liver disease matter?. Journal of hepatology 2009; 51: 962-963 ; author reply 963–964
484 Nair S, Verma S, Thuluvath PJ. Obesity and its effect on survival in patients undergoing orthotopic liver transplantation in the United States. Hepatology (Baltimore, Md) 2002; 35: 105-109
485 Nicolau-Raducu R, Gitman M, Ganier D. et al. Adverse cardiac events after orthotopic liver transplantation: a cross-sectional study in 389 consecutive patients. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2015; 21: 13-21
486 Wang X, Li J, Riaz DR. et al. Outcomes of liver transplantation for nonalcoholic steatohepatitis: a systematic review and meta-analysis. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 2014; 12: 394-402.e391
487 Vanwagner LB, Bhave M, Te HS. et al. Patients transplanted for nonalcoholic steatohepatitis are at increased risk for postoperative cardiovascular events. Hepatology (Baltimore, Md) 2012; 56: 1741-1750
488 VanWagner LB, Serper M, Kang R. et al. Factors Associated With Major Adverse Cardiovascular Events After Liver Transplantation Among a National Sample. American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2016; 16: 2684-2694
489 Barone M, Viggiani MT, Losurdo G. et al. Systematic review with meta-analysis: post-operative complications and mortality risk in liver transplant candidates with obesity. Alimentary pharmacology & therapeutics 2017; 46: 236-245
490 Hogan BJ, Gonsalkorala E, Heneghan MA. Evaluation of coronary artery disease in potential liver transplant recipients. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2017; 23: 386-395
491 Malik SM, deVera ME, Fontes P. et al. Outcome after liver transplantation for NASH cirrhosis. Am J Transplant 2009; 9: 782-793
492 European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Liver transplantation. Journal of hepatology 2016; 64: 433-485
493 Collins BH, Pirsch JD, Becker YT. et al. Long-term results of liver transplantation in older patients 60 years of age and older. Transplantation 2000; 70: 780-783
494 Kappus M, Abdelmalek M. De Novo and Recurrence of Nonalcoholic Steatohepatitis After Liver Transplantation. Clinics in liver disease 2017; 21: 321-335
495 Finkenstedt A, Auer C, Glodny B. et al. Patatin-like phospholipase domain-containing protein 3 rs738409-G in recipients of liver transplants is a risk factor for graft steatosis. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 2013; 11: 1667-1672
496 Richards J, Gunson B, Johnson J. et al. Weight gain and obesity after liver transplantation. Transplant international: official journal of the European Society for Organ Transplantation 2005; 18: 461-466
497 Germani G, Laryea M, Rubbia-Brandt L. et al. Management of Recurrent and De Novo NAFLD/NASH After Liver Transplantation. Transplantation 2019; 103: 57-67
498 Dick AA, Spitzer AL, Seifert CF. et al. Liver transplantation at the extremes of the body mass index. Liver Transpl 2009; 15: 968-977
499 Haldar D, Kern B, Hodson J. et al. Outcomes of liver transplantation for non-alcoholic steatohepatitis: A European Liver Transplant Registry study. J Hepatol 2019; 71: 313-322
500 Conzen KD, Vachharajani N, Collins KM. et al. Morbid obesity in liver transplant recipients adversely affects longterm graft and patient survival in a single-institution analysis. HPB (Oxford) 2015; 17: 251-257
501 Martin P, DiMartini A, Feng S. et al. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology 2014; 59: 1144-1165
502 Hakeem AR, Cockbain AJ, Raza SS. et al. Increased morbidity in overweight and obese liver transplant recipients: a single-center experience of 1325 patients from the United Kingdom. Liver Transpl 2013; 19: 551-562
503 Fujikawa T, Fujita S, Mizuno S. et al. Clinical and financial impact of obesity on the outcome of liver transplantation. Transplant Proc 2006; 38: 3612-3614
504 Pelletier SJ, Schaubel DE, Wei G. et al. Effect of body mass index on the survival benefit of liver transplantation. Liver Transpl 2007; 13: 1678-1683
505 Lai JC, Rahimi RS, Verna EC. et al. Frailty Associated With Waitlist Mortality Independent of Ascites and Hepatic Encephalopathy in a Multicenter Study. Gastroenterology 2019; 156: 1675-1682
506 Czigany Z, Kramp W, Bednarsch J. et al. Myosteatosis to predict inferior perioperative outcome in patients undergoing orthotopic liver transplantation. Am J Transplant 2020; 20: 493-503
507 Ney M, Haykowsky MJ, Vandermeer B. et al. Systematic review: pre- and post-operative prognostic value of cardiopulmonary exercise testing in liver transplant candidates. Aliment Pharmacol Ther 2016; 44: 796-806
508 Montano-Loza AJ, Angulo P, Meza-Junco J. et al. Sarcopenic obesity and myosteatosis are associated with higher mortality in patients with cirrhosis. J Cachexia Sarcopenia Muscle 2016; 7: 126-135
509 Carias S, Castellanos AL, Vilchez V. et al. Nonalcoholic steatohepatitis is strongly associated with sarcopenic obesity in patients with cirrhosis undergoing liver transplant evaluation. J Gastroenterol Hepatol 2016; 31: 628-633
510 van Vugt JLA, Alferink LJM, Buettner S. et al. A model including sarcopenia surpasses the MELD score in predicting waiting list mortality in cirrhotic liver transplant candidates: A competing risk analysis in a national cohort. J Hepatol 2018; 68: 707-714
511 Vidot H, Kline K, Cheng R. et al. The Relationship of Obesity, Nutritional Status and Muscle Wasting in Patients Assessed for Liver Transplantation. Nutrients 2019; 11
512 Della Corte C, Mosca A, Vania A. et al. Good adherence to the Mediterranean diet reduces the risk for NASH and diabetes in pediatric patients with obesity: The results of an Italian Study. Nutrition 2017; 39/40: 8-14
513 Kawaguchi T, Izumi N, Charlton MR. et al. Branched-chain amino acids as pharmacological nutrients in chronic liver disease. Hepatology 2011; 54: 1063-1070
514 Park JG, Tak WY, Park SY. et al. Effects of Branched-Chain Amino Acid (BCAA) Supplementation on the Progression of Advanced Liver Disease: A Korean Nationwide, Multicenter, Prospective, Observational, Cohort Study. Nutrients 2020; 12
515 Chen CJ, Wang LC, Kuo HT. et al. Significant effects of late evening snack on liver functions in patients with liver cirrhosis: A meta-analysis of randomized controlled trials. J Gastroenterol Hepatol 2019; 34: 1143-1152
516 Plank LD, Gane EJ, Peng S. et al. Nocturnal nutritional supplementation improves total body protein status of patients with liver cirrhosis: a randomized 12-month trial. Hepatology 2008; 48: 557-566
517 Tsien CD, McCullough AJ, Dasarathy S. Late evening snack: exploiting a period of anabolic opportunity in cirrhosis. J Gastroenterol Hepatol 2012; 27: 430-441
518 easloffice@easloffice.eu EAftSotLEa, Liver EAftSot. EASL Clinical Practice Guidelines on nutrition in chronic liver disease. J Hepatol 2019; 70: 172-193
519 Iwasa M, Iwata K, Hara N. et al. Nutrition therapy using a multidisciplinary team improves survival rates in patients with liver cirrhosis. Nutrition 2013; 29: 1418-1421
520 Yumuk V, Tsigos C, Fried M. et al. European Guidelines for Obesity Management in Adults. Obes Facts 2015; 8: 402-424
521 Durrer Schutz D, Busetto L, Dicker D. et al. European Practical and Patient-Centred Guidelines for Adult Obesity Management in Primary Care. Obes Facts 2019; 12: 40-66
522 Sutin AR, Stephan Y, Terracciano A. Weight Discrimination and Risk of Mortality. Psychol Sci 2015; 26: 1803-1811
523 Wharton S, Lau DCW, Vallis M. et al. Obesity in adults: a clinical practice guideline. CMAJ 2020; 192: E875-E891
524 Debette-Gratien M, Tabouret T, Antonini MT. et al. Personalized adapted physical activity before liver transplantation: acceptability and results. Transplantation 2015; 99: 145-150
525 Zenith L, Meena N, Ramadi A. et al. Eight weeks of exercise training increases aerobic capacity and muscle mass and reduces fatigue in patients with cirrhosis. Clin Gastroenterol Hepatol 2014; 12: 1920-1926.e1922
526 Duarte-Rojo A, Ruiz-Margáin A, Montaño-Loza AJ. et al. Exercise and physical activity for patients with end-stage liver disease: Improving functional status and sarcopenia while on the transplant waiting list. Liver Transpl 2018; 24: 122-139
527 Brustia R, Savier E, Scatton O. Physical exercise in cirrhotic patients: Towards prehabilitation on waiting list for liver transplantation. A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2018; 42: 205-215
528 Mantovani A, Byrne CD, Bonora E. et al. Nonalcoholic Fatty Liver Disease and Risk of Incident Type 2 Diabetes: A Meta-analysis. Diabetes Care 2018; 41: 372-382
529 Hoehn RS, Singhal A, Wima K. et al. Effect of pretransplant diabetes on short-term outcomes after liver transplantation: a national cohort study. Liver Int 2015; 35: 1902-1909
530 Davies MJ, DʼAlessio DA, Fradkin J. et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018; 41: 2669-2701
531 Buse JB, Wexler DJ, Tsapas A. et al. 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2020; 43: 487-493
532 Landgraf R, Aberle J, Birkenfeld AL. et al. Therapy of Type 2 Diabetes. Exp Clin Endocrinol Diabetes 2019; 127: S73-S92
533 Gangopadhyay KK, Singh P. Consensus Statement on Dose Modifications of Antidiabetic Agents in Patients with Hepatic Impairment. Indian J Endocrinol Metab 2017; 21: 341-354
534 Maruthur NM, Tseng E, Hutfless S. et al. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Ann Intern Med 2016; 164: 740-751
535 Chen HP, Shieh JJ, Chang CC. et al. Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies. Gut 2013; 62: 606-615
536 Donadon V, Balbi M, Mas MD. et al. Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease. Liver Int 2010; 30: 750-758
537 Singh S, Singh PP, Singh AG. et al. Anti-diabetic medications and the risk of hepatocellular cancer: a systematic review and meta-analysis. Am J Gastroenterol 2013; 108: 881-891; quiz 892
538 Zhang X, Harmsen WS, Mettler TA. et al. Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatology 2014; 60: 2008-2016
539 Vilar-Gomez E, Vuppalanchi R, Desai AP. et al. Long-term metformin use may improve clinical outcomes in diabetic patients with non-alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis. Aliment Pharmacol Ther 2019; 50: 317-328
540 Nkontchou G, Cosson E, Aout M. et al. Impact of metformin on the prognosis of cirrhosis induced by viral hepatitis C in diabetic patients. J Clin Endocrinol Metab 2011; 96: 2601-2608
541 Richy FF, Sabidó-Espin M, Guedes S. et al. Incidence of lactic acidosis in patients with type 2 diabetes with and without renal impairment treated with metformin: a retrospective cohort study. Diabetes Care 2014; 37: 2291-2295
542 Salpeter SR, Greyber E, Pasternak GA. et al. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus: systematic review and meta-analysis. Arch Intern Med 2003; 163: 2594-2602
543 Smith FC, Stocker SL, Danta M. et al. The safety and pharmacokinetics of metformin in patients with chronic liver disease. Aliment Pharmacol Ther 2020; 51: 565-575
544 Renda F, Mura P, Finco G. et al. Metformin-associated lactic acidosis requiring hospitalization. A national 10 year survey and a systematic literature review. Eur Rev Med Pharmacol Sci 2013; 17 (Suppl. 01) 45-49
545 Grancini V, Resi V, Palmieri E. et al. Management of diabetes mellitus in patients undergoing liver transplantation. Pharmacol Res 2019; 141: 556-573
546 Hydes TJ, Summers N, Brown E. et al. Mechanisms, screening modalities and treatment options for individuals with non-alcoholic fatty liver disease and type 2 diabetes. Diabet Med 2020; 37: 1793-1806
547 Yilmaz Y, Yonal O, Deyneli O. et al. Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis. Acta Gastroenterol Belg 2012; 75: 240-244
548 Alam S, Ghosh J, Mustafa G. et al. Effect of sitagliptin on hepatic histological activity and fibrosis of nonalcoholic steatohepatitis patients: a 1-year randomized control trial. Hepat Med 2018; 10: 23-31
549 Nesto RW, Bell D, Bonow RO. et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Diabetes Care 2004; 27: 256-263
550 Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ 2009; 180: 32-39
551 Flint A, Nazzal K, Jagielski P. et al. Influence of hepatic impairment on pharmacokinetics of the human GLP-1 analogue, liraglutide. Br J Clin Pharmacol 2010; 70: 807-814
552 Arase Y, Suzuki F, Kobayashi M. et al. Efficacy and safety in sitagliptin therapy for diabetes complicated by chronic liver disease caused by hepatitis C virus. Hepatol Res 2011; 41: 524-529
553 He YL, Sabo R, Campestrini J. et al. The influence of hepatic impairment on the pharmacokinetics of the dipeptidyl peptidase IV (DPP-4) inhibitor vildagliptin. Eur J Clin Pharmacol 2007; 63: 677-686
554 Graefe-Mody U, Rose P, Retlich S. et al. Pharmacokinetics of linagliptin in subjects with hepatic impairment. Br J Clin Pharmacol 2012; 74: 75-85
555 Boulton DW, Li L, Frevert EU. et al. Influence of renal or hepatic impairment on the pharmacokinetics of saxagliptin. Clin Pharmacokinet 2011; 50: 253-265
556 Gentile S, Turco S, Guarino G. et al. Effect of treatment with acarbose and insulin in patients with non-insulin-dependent diabetes mellitus associated with non-alcoholic liver cirrhosis. Diabetes Obes Metab 2001; 3: 33-40
557 Gentile S, Guarino G, Romano M. et al. A randomized controlled trial of acarbose in hepatic encephalopathy. Clin Gastroenterol Hepatol 2005; 3: 184-191
558 Schopman JE, Simon AC, Hoefnagel SJ. et al. The incidence of mild and severe hypoglycaemia in patients with type 2 diabetes mellitus treated with sulfonylureas: a systematic review and meta-analysis. Diabetes Metab Res Rev 2014; 30: 11-22
559 Lee JY, Jang SY, Nam CM. et al. Incident Hepatocellular Carcinoma Risk in Patients Treated with a Sulfonylurea: A Nationwide, Nested, Case-Control Study. Sci Rep 2019; 9: 8532
560 Home PD. The pharmacokinetics and pharmacodynamics of rapid-acting insulin analogues and their clinical consequences. Diabetes Obes Metab 2012; 14: 780-788
561 Elkrief L, Rautou PE, Sarin S. et al. Diabetes mellitus in patients with cirrhosis: clinical implications and management. Liver Int 2016; 36: 936-948
562 Grancini V, Trombetta M, Lunati ME. et al. Central role of the β-cell in driving regression of diabetes after liver transplantation in cirrhotic patients. J Hepatol 2019; 70: 954-962
563 Grancini V, Trombetta M, Lunati ME. et al. Contribution of β-cell dysfunction and insulin resistance to cirrhosis-associated diabetes: Role of severity of liver disease. J Hepatol 2015; 63: 1484-1490
564 Silva TE, Ronsoni MF, Schiavon LL. Challenges in diagnosing and monitoring diabetes in patients with chronic liver diseases. Diabetes Metab Syndr 2018; 12: 431-440
565 Nadelson J, Satapathy SK, Nair S. Glycated Hemoglobin Levels in Patients with Decompensated Cirrhosis. Int J Endocrinol 2016; 2016: 8390210
566 Diwan TS, Lee TC, Nagai S. et al. Obesity, transplantation, and bariatric surgery: An evolving solution for a growing epidemic. American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2020; 20: 2143-2155
567 Kardashian AA, Dodge JL, Roberts J. et al. Weighing the risks: Morbid obesity and diabetes are associated with increased risk of death on the liver transplant waiting list. Liver international: official journal of the International Association for the Study of the Liver 2018; 38: 553-563
568 Barone M, Viggiani MT, Avolio AW. et al. Obesity as predictor of postoperative outcomes in liver transplant candidates: Review of the literature and future perspectives. Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2017; 49: 957-966
569 Aller R, Fernandez-Rodriguez C, Lo Iacono O. et al. Consensus document. Management of non-alcoholic fatty liver disease (NAFLD). Clinical practice guideline. Gastroenterol Hepatol 2018; 41: 328-349
570 Tsochatzis E, Coilly A, Nadalin S. et al. International Liver Transplantation Consensus Statement on End-stage Liver Disease Due to Nonalcoholic Steatohepatitis and Liver Transplantation. Transplantation 2019; 103: 45-56
571 Ratziu V, Ghabril M, Romero-Gomez M. et al. Recommendations for Management and Treatment of Nonalcoholic Steatohepatitis. Transplantation 2019; 103: 28-38
572 Idriss R, Hasse J, Wu T. et al. Impact of Prior Bariatric Surgery on Perioperative Liver Transplant Outcomes. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2019; 25: 217-227
573 Nicoll A. Surgical risk in patients with cirrhosis. Journal of gastroenterology and hepatology 2012; 27: 1569-1575
574 de Goede B, Klitsie PJ, Lange JF. et al. Morbidity and mortality related to non-hepatic surgery in patients with liver cirrhosis: a systematic review. Best Pract Res Clin Gastroenterol 2012; 26: 47-59
575 Newman KL, Johnson KM, Cornia PB. et al. Perioperative Evaluation and Management of Patients With Cirrhosis: Risk Assessment, Surgical Outcomes, and Future Directions. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 2020; 18: 2398-2414.e2393
576 Schmitz A, Haste P, Johnson MS. Transjugular Intrahepatic Portosystemic Shunt (TIPS) Creation Prior to Abdominal Operation: a Retrospective Analysis. J Gastrointest Surg 2020; 24: 2228-2232
577 Kim JJ, Dasika NL, Yu E. et al. Cirrhotic patients with a transjugular intrahepatic portosystemic shunt undergoing major extrahepatic surgery. Journal of clinical gastroenterology 2009; 43: 574-579
578 Heimbach JK, Watt KD, Poterucha JJ. et al. Combined liver transplantation and gastric sleeve resection for patients with medically complicated obesity and end-stage liver disease. American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2013; 13: 363-368
579 Zamora-Valdes D, Watt KD, Kellogg TA. et al. Long-term outcomes of patients undergoing simultaneous liver transplantation and sleeve gastrectomy. Hepatology 2018; 68: 485-495
580 Merli M, Lattanzi B, Aprile F. Sarcopenic obesity in fatty liver. Current opinion in clinical nutrition and metabolic care 2019; 22: 185-190
581 Pais R, Barritt ASt, Calmus Y. et al. NAFLD and liver transplantation: Current burden and expected challenges. Journal of hepatology 2016; 65: 1245-1257
582 Osseis M, Lazzati A, Salloum C. et al. Sleeve Gastrectomy After Liver Transplantation: Feasibility and Outcomes. Obesity surgery 2018; 28: 242-248
583 Tsamalaidze L, Stauffer JA, Arasi LC. et al. Laparoscopic Sleeve Gastrectomy for Morbid Obesity in Patients After Orthotopic Liver Transplant: a Matched Case-Control Study. Obesity surgery 2018; 28: 444-450
584 Dziodzio T, Biebl M, Ollinger R. et al. The Role of Bariatric Surgery in Abdominal Organ Transplantation-the Next Big Challenge?. Obesity surgery 2017; 27: 2696-2706
585 Lazzati A, Iannelli A, Schneck AS. et al. Bariatric surgery and liver transplantation: a systematic review a new frontier for bariatric surgery. Obesity surgery 2015; 25: 134-142
586 El Atrache MM, Abouljoud MS, Divine G. et al. Recurrence of non-alcoholic steatohepatitis and cryptogenic cirrhosis following orthotopic liver transplantation in the context of the metabolic syndrome. Clinical transplantation 2012; 26: E505-512
587 Butte JM, Devaud N, Jarufe NP. et al. Sleeve gastrectomy as treatment for severe obesity after orthotopic liver transplantation. Obesity surgery 2007; 17: 1517-1519
588 Choudhary NS, Puri R, Saraf N. et al. Intragastric balloon as a novel modality for weight loss in patients with cirrhosis and morbid obesity awaiting liver transplantation. Indian J Gastroenterol 2016; 35: 113-116
589 Baba HA, Theurer S, Canbay A. et al. [Liver transplantation. Current aspects of pretransplantation diagnosis and rejection]. Pathologe 2020; 41: 505-514
590 Chu MJ, Dare AJ, Phillips AR. et al. Donor Hepatic Steatosis and Outcome After Liver Transplantation: a Systematic Review. J Gastrointest Surg 2015; 19: 1713-1724
591 Dutkowski P, Schlegel A, Slankamenac K. et al The use of fatty liver grafts in modern allocation systems: risk assessment by the balance of risk (BAR) score. Ann Surg 2012; 256: 861-868 ; discussion 868–869
592 Nasralla D, Coussios CC, Mergental H. et al. A randomized trial of normothermic preservation in liver transplantation. Nature 2018; 557: 50-56
593 Mergental H, Laing RW, Kirkham AJ. et al. Transplantation of discarded livers following viability testing with normothermic machine perfusion. Nat Commun 2020; 11: 2939
594 Jassem W, Xystrakis E, Ghnewa YG. et al. Normothermic Machine Perfusion (NMP) Inhibits Proinflammatory Responses in the Liver and Promotes Regeneration. Hepatology 2019; 70: 682-695
595 Lee SG. A complete treatment of adult living donor liver transplantation: a review of surgical technique and current challenges to expand indication of patients. Am J Transplant 2015; 15: 17-38
596 Jin YJ, Kim KM, Hwang S. et al. Exercise and diet modification in non-obese non-alcoholic fatty liver disease: analysis of biopsies of living liver donors. J Gastroenterol Hepatol 2012; 27: 1341-1347
597 Rinella ME, Alonso E, Rao S. et al. Body mass index as a predictor of hepatic steatosis in living liver donors. Liver Transpl 2001; 7: 409-414
598 Younossi ZM, Tampi RP, Racila A. et al. Economic and Clinical Burden of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes in the U.S. Diabetes Care 2020; 43: 283-289
599 Schattenberg JM. [Non-alcoholic fatty liver disease (NAFLD)]. MMW Fortschr Med 2020; 162: 56-62
600 Labenz C, Huber Y, Michel M. et al. Impact of NAFLD on the Incidence of Cardiovascular Diseases in a Primary Care Population in Germany. Dig Dis Sci 2020; 65: 2112-2119
601 Hagstrom H, Elfwen O, Hultcrantz R. et al. Steatohepatitis Is Not Associated with an Increased Risk for Fibrosis Progression in Nonalcoholic Fatty Liver Disease. Gastroenterol Res Pract 2018; 2018: 1942648
602 Vergniol J, Boursier J, Coutzac C. et al. Evolution of noninvasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C. Hepatology 2014; 60: 65-76
603 Chalasani N, Abdelmalek MF, Loomba R. et al. Relationship between three commonly used non-invasive fibrosis biomarkers and improvement in fibrosis stage in patients with non-alcoholic steatohepatitis. Liver Int 2019; 39: 924-932
604 Hagstrom H, Talback M, Andreasson A. et al. Repeated FIB-4 measurements can help identify individuals at risk of severe liver disease. J Hepatol 2020; 73: 1023-1029
605 Loomba R, Neuschwander-Tetri BA, Sanyal A. et al. Multicenter Validation of Association Between Decline in MRI-PDFF and Histologic Response in NASH. Hepatology 2020;
606 Allen AM, Hicks SB, Mara KC. et al. The risk of incident extrahepatic cancers is higher in non-alcoholic fatty liver disease than obesity – A longitudinal cohort study. J Hepatol 2019; 71: 1229-1236
607 Huber Y, Labenz C, Michel M. et al. Tumor incidence in patients with non-alcoholic fatty liver disease. Deutsches Ärzteblatt 2020; 117: 719-724
608 Ioannou GN, Green P, Kerr KF. et al. Models estimating risk of hepatocellular carcinoma in patients with alcohol or NAFLD-related cirrhosis for risk stratification. J Hepatol 2019; 71: 523-533
609 Kansagara D, Papak J, Pasha AS. et al. Screening for hepatocellular carcinoma in chronic liver disease: a systematic review. Ann Intern Med 2014; 161: 261-269
610 Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med 2014; 11: e1001624
611 Andersson KL, Salomon JA, Goldie SJ. et al. Cost effectiveness of alternative surveillance strategies for hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol 2008; 6: 1418-1424
612 Colombo M. Screening and diagnosis of hepatocellular carcinoma. Liver Int 2009; 29 (Suppl. 01) 143-147
613 Sarasin FP, Giostra E, Hadengue A. Cost-effectiveness of screening for detection of small hepatocellular carcinoma in western patients with Child-Pugh class A cirrhosis. Am J Med 1996; 101: 422-434
614 Moon AM, Weiss NS, Beste LA. et al. No Association Between Screening for Hepatocellular Carcinoma and Reduced Cancer-Related Mortality in Patients With Cirrhosis. Gastroenterology 2018; 155: 1128-1139.e1126
615 Nurnberg D, Jung A, Schmieder C. et al. [Whatʼs the price of routine sonography – results of an analysis of costs and processes in a district hospital]. Ultraschall in Med 2008; 29: 405-417
616 Schuler A, Reuss J, Delorme S. et al. [Costs of clinical ultrasound examinations – an economical cost calculation and analysis]. Ultraschall in Med 2010; 31: 379-386
617 Zoli M, Magalotti D, Bianchi G. et al. Efficacy of a surveillance program for early detection of hepatocellular carcinoma. Cancer 1996; 78: 977-985
618 Kim SY, An J, Lim YS. et al. MRI With Liver-Specific Contrast for Surveillance of Patients With Cirrhosis at High Risk of Hepatocellular Carcinoma. JAMA Oncol 2017; 3: 456-463
619 Shah TU, Semelka RC, Pamuklar E. et al. The risk of hepatocellular carcinoma in cirrhotic patients with small liver nodules on MRI. Am J Gastroenterol 2006; 101: 533-540
620 Tzartzeva K, Obi J, Rich NE. et al. Surveillance Imaging and Alpha Fetoprotein for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis: A Meta-analysis. Gastroenterology 2018; 154: 1706-1718.e1701
621 Best J, Bechmann LP, Sowa JP. et al. GALAD Score Detects Early Hepatocellular Carcinoma in an International Cohort of Patients With Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol 2020; 18: 728-735.e724
622 Li T, Yin J, Yuan L. et al. Downregulation of microRNA-139 is associated with hepatocellular carcinoma risk and short-term survival. Oncol Rep 2014; 31: 1699-1706
623 Mourad L, El-Ahwany E, Zoheiry M. et al. Expression analysis of liver-specific circulating microRNAs in HCV-induced hepatocellular Carcinoma in Egyptian patients. Cancer Biol Ther 2018; 19: 400-406
624 Chen L, Chu F, Cao Y. et al. Serum miR-182 and miR-331-3p as diagnostic and prognostic markers in patients with hepatocellular carcinoma. Tumour Biol 2015; 36: 7439-7447
625 Shaheen NMH, Zayed N, Riad NM. et al. Role of circulating miR-182 and miR-150 as biomarkers for cirrhosis and hepatocellular carcinoma post HCV infection in Egyptian patients. Virus Res 2018; 255: 77-84
626 Loosen SH, Wirtz TH, Roy S. et al. Circulating levels of microRNA193a-5p predict outcome in early stage hepatocellular carcinoma. PLoS One 2020; 15: e0239386
627 Younossi ZM, Otgonsuren M, Henry L. et al. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology 2015; 62: 1723-1730
628 Marrero JA, Kulik LM, Sirlin CB. et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2018; 68: 723-750
629 Ertle J, Dechene A, Sowa JP. et al. Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. Int J Cancer 2011; 128: 2436-2443
630 Grimaudo S, Pipitone RM, Pennisi G. et al. Association Between PNPLA3 rs738409 C>G Variant and Liver-Related Outcomes in Patients With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol 2020; 18: 935-944.e933
631 Liu YL, Patman GL, Leathart JB. et al. Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol 2014; 61: 75-81
632 Kawamura Y, Arase Y, Ikeda K. et al. Large-scale long-term follow-up study of Japanese patients with non-alcoholic Fatty liver disease for the onset of hepatocellular carcinoma. Am J Gastroenterol 2012; 107: 253-261
633 Yang JD, Ahmed F, Mara KC. et al. Diabetes Is Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Cirrhosis From Nonalcoholic Fatty Liver Disease. Hepatology 2020; 71: 907-916
634 Benhammou JN, Lin J, Hussain SK. et al. Emerging risk factors for nonalcoholic fatty liver disease associated hepatocellular carcinoma. Hepatoma Res 2020; 6
635 Kozlitina J, Smagris E, Stender S. et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2014; 46: 352-356
636 Mancina RM, Dongiovanni P, Petta S. et al. The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent. Gastroenterology 2016; 150: 1219-1230.e1216
637 Donati B, Dongiovanni P, Romeo S. et al. MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals. Sci Rep 2017; 7: 4492
638 Behary J, Amorim N, Jiang XT. et al. Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma. Nat Commun 2021; 12: 187
639 Götz M, Anders M, Biecker E. et al. [S2k Guideline Gastrointestinal Bleeding – Guideline of the German Society of Gastroenterology DGVS]. Z Gastroenterol 2017; 55: 883-936
640 de Franchis R, Baveno VIF. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol 2015; 63: 743-752
641 Garcia-Tsao G, Abraldes JG, Berzigotti A. et al. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology 2017; 65: 310-335
642 Zheng KI, Liu C, Li J. et al. Validation of Baveno VI and expanded Baveno VI criteria to identify high-risk varices in patients with MAFLD-related compensated cirrhosis. J Hepatol 2020; 73: 1571-1573
643 Rubino F, Puhl RM, Cummings DE. et al. Joint international consensus statement for ending stigma of obesity. Nat Med 2020; 26: 485-497
644 Hales CM, Carroll MD, Fryar CD. et al. Prevalence of Obesity Among Adults and Youth: United States, 2015–2016. NCHS Data Brief 2017; 288: 1-8
645 Schienkiewitz A, Mensink GB, Scheidt-Nave C. Comorbidity of overweight and obesity in a nationally representative sample of German adults aged 18–79 years. BMC Public Health 2012; 12: 658
646 Meixner L, Cohrdes C, Schienkiewitz A. et al. Health-related quality of life in children and adolescents with overweight and obesity: results from the German KIGGS survey. BMC Public Health 2020; 20: 1722
647 Kleiser C, Schienkiewitz A, Schaffrath Rosario A. et al. Indicators of overweight and cardiovascular disease risk factors among 11- to 17-year-old boys and girls in Germany. Obes Facts 2011; 4: 379-385
648 Wiegand S, Keller KM, Robl M. et al. Obese boys at increased risk for nonalcoholic liver disease: evaluation of 16,390 overweight or obese children and adolescents. Int J Obes (Lond) 2010; 34: 1468-1474
649 Schwimmer JB, Deutsch R, Kahen T. et al. Prevalence of fatty liver in children and adolescents. Pediatrics 2006; 118: 1388-1393
650 Mencin AA, Lavine JE. Advances in pediatric nonalcoholic fatty liver disease. Pediatr Clin North Am 2011; 58: 1375-1392, x
651 Mencin AA, Lavine JE. Nonalcoholic fatty liver disease in children. Curr Opin Clin Nutr Metab Care 2011; 14: 151-157
652 Newton KP, Hou J, Crimmins NA. et al. Prevalence of Prediabetes and Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease. JAMA Pediatr 2016; 170: e161971
653 Kohli R, Boyd T, Lake K. et al. Rapid progression of NASH in childhood. J Pediatr Gastroenterol Nutr 2010; 50: 453-456
654 Mann JP, De Vito R, Mosca A. et al. Portal inflammation is independently associated with fibrosis and metabolic syndrome in pediatric nonalcoholic fatty liver disease. Hepatology 2016; 63: 745-753
655 Hagstrom H, Stal P, Hultcrantz R. et al. Overweight in late adolescence predicts development of severe liver disease later in life: A 39years follow-up study. J Hepatol 2016; 65: 363-368
656 Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S. et al. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut 2009; 58: 1538-1544
657 Nogrady B. Childhood obesity: A growing concern. Nature 2017; 551: S96
658 Della Corte C, Mosca A, Majo F. et al. Nonalcoholic fatty pancreas disease and Nonalcoholic fatty liver disease: more than ectopic fat. Clin Endocrinol (Oxf) 2015; 83: 656-662
659 Dunn W, Sanyal AJ, Brunt EM. et al. Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD). J Hepatol 2012; 57: 384-391
660 Abeysekera KWM, Fernandes GS, Hammerton G. et al. Prevalence of steatosis and fibrosis in young adults in the UK: a population-based study. Lancet Gastroenterol Hepatol 2020; 5: 295-305
661 Bruce KD, Cagampang FR, Argenton M. et al. Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression. Hepatology 2009; 50: 1796-1808
662 Bugianesi E, Bizzarri C, Rosso C. et al. Low Birthweight Increases the Likelihood of Severe Steatosis in Pediatric Non-Alcoholic Fatty Liver Disease. Am J Gastroenterol 2017; 112: 1277-1286
663 Newton KP, Feldman HS, Chambers CD. et al. Low and High Birth Weights Are Risk Factors for Nonalcoholic Fatty Liver Disease in Children. J Pediatr 2017; 187: 141-146.e141
664 Liu CH, Ampuero J, Gil-Gomez A. et al. miRNAs in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Hepatol 2018; 69: 1335-1348
665 Nobili V, Donati B, Panera N. et al. A 4-polymorphism risk score predicts steatohepatitis in children with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 2014; 58: 632-636
666 Valenti L, Alisi A, Galmozzi E. et al. I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease. Hepatology 2010; 52: 1274-1280
667 Hudert CA, Selinski S, Rudolph B. et al. Genetic determinants of steatosis and fibrosis progression in paediatric non-alcoholic fatty liver disease. Liver Int 2019; 39: 540-556
668 Larrieta-Carrasco E, Acuna-Alonzo V, Velazquez-Cruz R. et al. PNPLA3 I148M polymorphism is associated with elevated alanine transaminase levels in Mexican Indigenous and Mestizo populations. Mol Biol Rep 2014; 41: 4705-4711
669 Teo K, Abeysekera KWM, Adams L. et al. rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis. J Hepatol 2021; 74: 20-30
670 Di Sessa A, Umano GR, Cirillo G. et al. The rs72613567: TA Variant in the Hydroxysteroid 17-beta Dehydrogenase 13 Gene Reduces Liver Damage in Obese Children. J Pediatr Gastroenterol Nutr 2020; 70: 371-374
671 Nobili V, Liccardo D, Bedogni G. et al. Influence of dietary pattern, physical activity, and I148M PNPLA3 on steatosis severity in at-risk adolescents. Genes Nutr 2014; 9: 392
672 Eng K, Lopez R, Liccardo D. et al. A non-invasive prediction model for non-alcoholic steatohepatitis in paediatric patients with non-alcoholic fatty liver disease. Dig Liver Dis 2014; 46: 1008-1013
673 Schwimmer JB, Dunn W, Norman GJ. et al SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology 2010; 138: 1357-1364 , 1364 e1351-1352
674 Younossi ZM, Gramlich T, Liu YC. et al. Nonalcoholic fatty liver disease: assessment of variability in pathologic interpretations. Mod Pathol 1998; 11: 560-565
675 Schwimmer JB, Behling C, Newbury R. et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 2005; 42: 641-649
676 Africa JA, Behling CA, Brunt EM. et al. In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis. Clin Gastroenterol Hepatol 2018; 16: 438-446.e431
677 Mameli C, Zuccotti GV, Carnovale C. et al. An update on the assessment and management of metabolic syndrome, a growing medical emergency in paediatric populations. Pharmacol Res 2017; 119: 99-117
678 van der Heijden LB, Feskens EJM, Janse AJ. Maintenance interventions for overweight or obesity in children: a systematic review and meta-analysis. Obes Rev 2018; 19: 798-809
679 Utz-Melere M, Targa-Ferreira C, Lessa-Horta B. et al. Non-Alcoholic Fatty Liver Disease in Children and Adolescents: Lifestyle Change – a Systematic Review and Meta-Analysis. Ann Hepatol 2018; 17: 345-354
680 Katsagoni CN, Papachristou E, Sidossis A. et al. Effects of Dietary and Lifestyle Interventions on Liver, Clinical and Metabolic Parameters in Children and Adolescents with Non-Alcoholic Fatty Liver Disease: A Systematic Review. Nutrients 2020; 12
681 Golabi P, Locklear CT, Austin P. et al. Effectiveness of exercise in hepatic fat mobilization in non-alcoholic fatty liver disease: Systematic review. World J Gastroenterol 2016; 22: 6318-6327
682 Goss AM, Dowla S, Pendergrass M. et al. Effects of a carbohydrate-restricted diet on hepatic lipid content in adolescents with non-alcoholic fatty liver disease: A pilot, randomized trial. Pediatr Obes 2020; 15: e12630
683 Africa JA, Newton KP, Schwimmer JB. Lifestyle Interventions Including Nutrition, Exercise, and Supplements for Nonalcoholic Fatty Liver Disease in Children. Dig Dis Sci 2016; 61: 1375-1386
684 Kwon Y, Jeong SJ. Relative Skeletal Muscle Mass Is an Important Factor in Non-Alcoholic Fatty Liver Disease in Non-Obese Children and Adolescents. J Clin Med 2020; 9
685 Nobili V, Vajro P, Dezsofi A. et al. Indications and limitations of bariatric intervention in severely obese children and adolescents with and without nonalcoholic steatohepatitis: ESPGHAN Hepatology Committee Position Statement. J Pediatr Gastroenterol Nutr 2015; 60: 550-561
686 Pratt JSA, Browne A, Browne NT. et al. ASMBS pediatric metabolic and bariatric surgery guidelines, 2018. Surg Obes Relat Dis 2018; 14: 882-901
687 Arbeitsgemeinschaft Adipositas im Kindes- und Jugendalter B. Bariatrisch-chirurgische Maßnahmen bei Jugendlichen mit extremer Adipositas. Monatsschr Kinderheilkd 2012; 160: 1123-1128
688 Weihe P, Weihrauch-Bluher S. Metabolic Syndrome in Children and Adolescents: Diagnostic Criteria, Therapeutic Options and Perspectives. Curr Obes Rep 2019; 8: 472-479
689 Bolling CF, Armstrong SC, Reichard KW. et al. Metabolic and Bariatric Surgery for Pediatric Patients With Severe Obesity. Pediatrics 2019; 144
690 Corey KE, Stanley TL, Misdraji J. et al. Prevalence and outcome of non-alcoholic fatty liver disease in adolescents and young adults undergoing weight loss surgery. Pediatr Obes 2014; 9: e91-e93
691 Loy JJ, Youn HA, Schwack B. et al. Improvement in nonalcoholic fatty liver disease and metabolic syndrome in adolescents undergoing bariatric surgery. Surg Obes Relat Dis 2015; 11: 442-449
692 Nobili V, Carpino G, De Peppo F. et al. Laparoscopic Sleeve Gastrectomy Improves Nonalcoholic Fatty Liver Disease-Related Liver Damage in Adolescents by Reshaping Cellular Interactions and Hepatic Adipocytokine Production. J Pediatr 2018; 194: 100-108.e103
693 Franchitto A, Carpino G, Alisi A. et al. The Contribution of the Adipose Tissue-Liver Axis in Pediatric Patients with Nonalcoholic Fatty Liver Disease after Laparoscopic Sleeve Gastrectomy. J Pediatr 2020; 216: 117-127.e112
694 Jones RE, Yeh AM, Kambham N. et al. Intraoperative Liver Biopsy During Adolescent Bariatric Surgery: Is It Really Necessary?. Obes Surg 2020; 30: 69-76
695 Lavine JE, Schwimmer JB, Van Natta ML. et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA 2011; 305: 1659-1668
696 Nobili V, Alisi A, Valenti L. et al. NAFLD in children: new genes, new diagnostic modalities and new drugs. Nat Rev Gastroenterol Hepatol 2019; 16: 517-530
697 Janczyk W, Lebensztejn D, Wierzbicka-Rucinska A. et al Omega-3 Fatty acids therapy in children with nonalcoholic Fatty liver disease: a randomized controlled trial. J Pediatr 2015; 166: 1358-1363 e1351–1353
698 Pacifico L, Bonci E, Di Martino M. et al. A double-blind, placebo-controlled randomized trial to evaluate the efficacy of docosahexaenoic acid supplementation on hepatic fat and associated cardiovascular risk factors in overweight children with nonalcoholic fatty liver disease. Nutr Metab Cardiovasc Dis 2015; 25: 734-741
699 Nobili V, Alisi A, Della Corte C. et al. Docosahexaenoic acid for the treatment of fatty liver: randomised controlled trial in children. Nutr Metab Cardiovasc Dis 2013; 23: 1066-1070
700 Nobili V, Bedogni G, Donati B. et al. The I148M variant of PNPLA3 reduces the response to docosahexaenoic acid in children with non-alcoholic fatty liver disease. J Med Food 2013; 16: 957-960
701 Zohrer E, Alisi A, Jahnel J. et al. Efficacy of docosahexaenoic acid-choline-vitamin E in paediatric NASH: a randomized controlled clinical trial. Appl Physiol Nutr Metab 2017; 42: 948-954
702 Schwimmer JB, Lavine JE, Wilson LA. et al. In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores. Gastroenterology 2016; 151: 1141-1154.e1149
703 Vajro P, Mandato C, Licenziati MR. et al. Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease. J Pediatr Gastroenterol Nutr 2011; 52: 740-743
704 Alisi A, Bedogni G, Baviera G. et al. Randomised clinical trial: The beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2014; 39: 1276-1285
705 Williams CD, Stengel J, Asike MI. et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 2011; 140: 124-131
706 Caussy C, Chen J, Alquiraish MH. et al. Association Between Obesity and Discordance in Fibrosis Stage Determination by Magnetic Resonance vs Transient Elastography in Patients With Nonalcoholic Liver Disease. Clin Gastroenterol Hepatol 2018; 16: 1974-1982.e1977
707 Jayakumar S, Middleton MS, Lawitz EJ. et al. Longitudinal correlations between MRE, MRI-PDFF, and liver histology in patients with non-alcoholic steatohepatitis: Analysis of data from a phase II trial of selonsertib. J Hepatol 2019; 70: 133-141
708 Hudert CA, Tzschatzsch H, Rudolph B. et al. Tomoelastography for the Evaluation of Pediatric Nonalcoholic Fatty Liver Disease. Invest Radiol 2019; 54: 198-203
709 Yang HR, Kim HR, Kim MJ. et al. Noninvasive parameters and hepatic fibrosis scores in children with nonalcoholic fatty liver disease. World J Gastroenterol 2012; 18: 1525-1530
710 Mansoor S, Yerian L, Kohli R. et al. The evaluation of hepatic fibrosis scores in children with nonalcoholic fatty liver disease. Dig Dis Sci 2015; 60: 1440-1447
711 Jackson JA, Konomi JV, Mendoza MV. et al. Performance of fibrosis prediction scores in paediatric non-alcoholic fatty liver disease. J Paediatr Child Health 2018; 54: 172-176
712 Alkhouri N, Mansoor S, Giammaria P. et al. The development of the pediatric NAFLD fibrosis score (PNFS) to predict the presence of advanced fibrosis in children with nonalcoholic fatty liver disease. PLoS One 2014; 9: e104558
713 Nobili V, Alisi A, Vania A. et al. The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease. BMC Med 2009; 7: 21
714 Nobili V, Vizzutti F, Arena U. et al. Accuracy and reproducibility of transient elastography for the diagnosis of fibrosis in pediatric nonalcoholic steatohepatitis. Hepatology 2008; 48: 442-448
715 Garcovich M, Veraldi S, Di Stasio E. et al. Liver Stiffness in Pediatric Patients with Fatty Liver Disease: Diagnostic Accuracy and Reproducibility of Shear-Wave Elastography. Radiology 2017; 283: 820-827
716 Hudert CA, Tzschatzsch H, Guo J. et al. US Time-Harmonic Elastography: Detection of Liver Fibrosis in Adolescents with Extreme Obesity with Nonalcoholic Fatty Liver Disease. Radiology 2018; 288: 99-106
717 Schwimmer JB, Behling C, Angeles JE. et al. Magnetic resonance elastography measured shear stiffness as a biomarker of fibrosis in pediatric nonalcoholic fatty liver disease. Hepatology 2017; 66: 1474-1485
718 Castera L, Foucher J, Bernard PH. et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13369 examinations. Hepatology 2010; 51: 828-835

Supplementary Material

Supplementary Material (PDF)