Gastroenterologie up2date, Table of Contents Gastroenterologie up2date 2018; 14(03): 231-246DOI: 10.1055/a-0600-9040 Leber/Galle/Pankreas Georg Thieme Verlag KG Stuttgart · New York Erhöhte Leberwerte Axel Holstege Recommend Article Abstract Buy Article All articles of this category Erhöhte Leberwerte weisen meist auf Lebererkrankungen hin – sie können aber auch extrahepatische oder sogar physiologische Ursachen haben. Dieser Beitrag erläutert, welche Konsequenzen das Muster der Leberwerterhöhung für die weitere differenzialdiagnostische Abklärung haben sollte. Im Anschluss werden die infrage kommenden Krankheitsbilder anhand der für sie typischen Laborkonstellationen näher dargestellt. Schlüsselwörter SchlüsselwörterLeberkrankheiten - Cholestase - Transaminasen - alkalische Phosphatase - γ-Glutamyltranspeptidase Full Text References Literatur 1 Holstege A. Erhöhte Leberwerte. Dtsch Med Wochenschr 2016; 141: 1640-1646 2 Vogt W, Holstege A. Problem: Abklärung mäßig erhöhter Transaminasen und γ-GT. In: Schölmerich J, Bischoff SC, Manns MP. Hrsg. Diagnostik in der Gastroenterologie und Hepatologie. Stuttgart: Thieme; 1997: 151-160 3 Moriyama T, Tamura S, Nakano K. et al. Laboratory and clinical features of abnormal macroenzymes found in human sera. Biochim Biophys Acta 2015; 1854: 658-667 4 van Wijk XMR, Magee CA, Wu AHB. et al. A comparison of methods for evaluation of a case of suspected macro-aspartate aminotransferase. Clin Chim Acta 2016; 463: 1-3 5 Thomas L. Hrsg. Labor und Diagnose: Indikation und Bewertung von Laborbefunden für die medizinische Diagnostik. 8. Aufl.. Frankfurt: TH-Books-Verlagsgesellschaft; 2012 6 Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol 2017; 112: 18-35 7 Shield KD, Gmel G, Gmel G. et al. Life-time risk of mortality due to different levels of alcohol consumption in seven European countries: implications for low-risk drinking guidelines. Addiction 2017; 112: 1535-1544 8 Wood AM, Kaptoge S, Butterworth AS. et al. Emerging Risk Factors Collaboration/EPIC-CVD/UK Biobank Alcohol Study Group. Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies. Lancet 2018; 391: 1513-1523 9 Ruhl CE, Everhart JE. Upper limits of normal for alanine aminotransferase activity in the United States population. Hepatology 2012; 55: 447-454 10 von Herbay A, Strohmeyer G. Die erhöhte γ-GT. Dtsch Med Wochenschr 1994; 119: 1041-1044 11 Arndt V, Brenner H, Rothenbacher D. et al. Elevated liver enzyme activity in construction workers: prevalence and impact on early retirement and all-cause mortality. Int Arch Occup Environ Health 1998; 71: 405-412 12 Willson RA, Clayson KJ, Leon S. Unmeasurable serum alkaline phosphatase activity in Wilsonʼs disease associated with fulminant hepatic failure and hemolysis. Hepatology 1987; 7: 613-615 13 Williams AL, Hoofnagle JH. Ratio of serum aspartate to alanine aminotransferase in chronic hepatitis. Relationship to cirrhosis. Gastroenterology 1988; 95: 734-739 14 Torruellas C, French SW, Medici V. Diagnosis of alcoholic liver disease. World J Gastroenterol 2014; 20: 11684-11699 15 Singal AK, Bataller R, Ahn J. et al. ACG Clinical Guideline: Alcoholic Liver Disease. Am J Gastroenterol 2018; 113: 175-194 16 Patel K, Bedossa P, Castera L. Diagnosis of liver fibrosis: present and future. Semin Liver Dis 2015; 35: 166-183 17 Triger DR, Wright R. Hyperglobulinaemia in liver disease. Lancet 1973; 1: 1494-1496 18 Wedemeyer H, Pischke S, Manns MP. Pathogenesis and treatment of hepatitis E virus infection. Gastroenterology 2012; 142: 1388-1397 19 Strassburg CP, Beckebaum S, Geier A. et al. S2k Leitlinie Autoimmune Lebererkrankungen. Z Gastroenterol 2017; 55: 1135-1226 20 Manns MP, Lohse AW, Vergani D. Autoimmune hepatitis – Update 2015. J Hepatol 2015; 62 (Suppl. 01) S100-S111 21 Bacon BR, Adams PC, Kowdley KV. et al. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 2011; 54: 328-343 22 Ioannou GN, Dominitz JA, Weiss NS. et al. The effect of alcohol consumption on the prevalence of iron overload, iron deficiency, and iron deficiency anemia. Gastroenterology 2004; 126: 1293-1301 23 Bomford A. Genetics of haemochromatosis. Lancet 2002; 360: 1673-1681 24 Sarigianni M, Liakos A, Vlachaki E. et al. Accuracy of magnetic resonance imaging in diagnosis of liver iron overload: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2015; 13: 55-63 25 European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Wilsonʼs disease. J Hepatol 2012; 56: 671-685 26 Ferenci P, Caca K, Loudianos G. et al. Diagnosis and phenotypic classification of Wilson disease. Liver Int 2003; 23: 139-142 27 Hedera P. Update on the clinical management of Wilsonʼs disease. Appl Clin Genet 2017; 10: 9-19 28 Fontana RJ, Seeff LB, Andrade RJ. et al. Standardization of nomenclature and causality assessment in drug-induced liver injury: summary of a clinical research workshop. Hepatology 2010; 52: 730-742 29 Holstege A. Leberschäden durch Medikamente. In: Messmann H. Hrsg. Klinische Gastroenterologie. Stuttgart: Thieme; 2012: 599-605 30 Chalasani NP, Hayashi PH, Bonkowsky HL. et al. Practice Parameters Committee of the American College of Gastroenterology. ACG clinical guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol 2014; 109: 950-966 31 Li J, Zhang YL, Chen R. et al. Elevated serum liver enzymes in patients with obstructive sleep apnea-hypopnea syndrome. Chin Med J 2015; 128: 2983-2987 32 Kiladjian JJ, Cervantes F, Leebeek FW. et al. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases. Blood 2008; 111: 4922-4929 33 McDonald GB, Hinds MS, Fisher LD. et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med 1993; 118: 255-267 34 Kechagias S, Ernersson A, Dahlqvist O. et al. Fast Food Study Group. Fast-food-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects. Gut 2008; 57: 649-654 35 Rogal SS, Ukomadu C, Levy BD. et al. A sweet source of abdominal pain. N Engl J Med 2011; 364: 1762-1767 36 Stoller JK, Lacbawan FL, Aboussouan LS. Alpha-1 Antitrypsin deficiency. 2017. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A. eds. Gene Reviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993. – 2018 37 Beuers U, Gershwin ME, Gish RG. et al. Changing nomenclature for PBC: From ‘cirrhosis’ to ‘cholangitis’. Clin Res Hepatol Gastroenterol 2015; 39: e57-59 38 Marzorati S, Invernizzi P, Lleo A. Making sense of autoantibodies in cholestatic liver diseases. Clin Liver Dis 2016; 20: 33-46 39 Schwarze C, Terjung B, Lilienweiss P. et al. IgA class antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis and autoimmune hepatitis. Clin Exp Immunol 2003; 133: 283-289 40 Holstege A, Zolinski P, Woidy L. et al. The patient with unexplained elevated serum liver enzymes. Best Pract Res Clin Gastroenterol 2007; 21: 535-550 41 Boonstra K, Culver EL, de Buy Wenniger LM. et al. Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis. Hepatology 2014; 59: 1954-1963 42 Beuers U, Hubers LM, Doorenspleet M. et al. IgG4-associated cholangitis – a mimic of PSC. Dig Dis 2015; 33 (Suppl. 02) 176-180 43 Ziol M, Barbu V, Rosmorduc O. et al. ABCB4 heterozygous gene mutations associated with fibrosing cholestatic liver disease in adults. Gastroenterology 2008; 135: 131-141 44 Boyer JL. Bile formation and secretion. Compr Physiol 2013; 3: 1035-1078 45 Jangouk P, Hashash JG. An unusual cause of painless jaundice. Renal cell carcinoma (Stauffer syndrome). Gastroenterology 2014; 146: 913 1138 46 Jenniskens M, Langouche L, Van den Berghe G. Cholestatic alterations in the critically ill: some new light on an old problem. Chest 2018; 153: 733-743 47 Chand N, Sanyal AJ. Sepsis-induced cholestasis. Hepatology 2007; 45: 230-241 48 Kirchner GI, Rümmele P. Update on sclerosing cholangitis in critically ill patients. Viszeralmedizin 2015; 31: 178-184 49 Gutt C, Jenssen C, Barreiros AP. et al. Aktualisierte S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV) zur Prävention, Diagnostik und Behandlung von Gallensteinen (AWMF-Register-Nr. 021/008). Überarbeitung von 11/2017. Im Internet: http://www.awmf.org/leitlinien/detail/ll/021-008.html Stand: 04.07.2018 50 Zimmer V, Lammert F. Acute bacterial cholangitis. Viszeralmedizin 2015; 31: 166-172 51 Roeb E, Steffen HM, Bantel H. et al. S2k Guideline non-alcoholic fatty liver disease. Z Gastroenterol 2015; 53: 668-723 52 Burt AD, Lackner C, Tiniakos DG. Diagnosis and assessment of NAFLD: definitions and histopathological classification. Semin Liver Dis 2015; 35: 207-220 53 Masarone M, Rosato V, Aglitti A. et al. Liver biopsy in type 2 diabetes mellitus: Steatohepatitis represents the sole feature of liver damage. PLoS One 2017; 12: e0178473 54 Tannapfel A, Denk H, Dienes HP. et al. Histopathologische Diagnose der nicht alkoholischen und alkoholischen Fettlebererkrankung. Z Gastroenterol 2010; 48: 486-498 55 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 56 Younossi ZM, Loomba R, Anstee QM. et al. Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and associated fibrosis. Hepatology 2018; 68: 349-360 57 Cassinotto C, Boursier J, de Lédinghen V. et al. Liver stiffness in nonalcoholic fatty liver disease: A comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy. Hepatology 2016; 63: 1817-1827 58 Petta S, Maida M, Macaluso FS. et al. The severity of steatosis influences liver stiffness measurement in patients with nonalcoholic fatty liver disease. Hepatology 2015; 62: 1101-1110 59 Tapper EB, Castera L, Afdhal NH. FibroScan (vibration-controlled transient elastography): where does it stand in the United States practice. Clin Gastroenterol Hepatol 2015; 13: 27-36 60 Holstege A. Leberschäden durch Alkohol. In: Messmann H. Hrsg. Klinische Gastroenterologie. Stuttgart: Thieme; 2012: 594-599 61 John U, Seitz HK. Alkoholumgang: Konsum bedeutet immer Risiko. Dtsch Arztebl 2018; 115: A-640/B-556/C-556 62 Alte D, Luedemann J, Rose HJ. et al. Laboratory markers carbohydrate-deficient transferrin, gamma-glutamyltransferase, and mean corpuscular volume are not useful as screening tools for high-risk drinking in the general population: results from the Study of Health in Pomerania (SHIP). Alcohol Clin Exp Res 2004; 28: 931-940 63 Strobel D, Bernatik T, Blank W. et al. Diagnostic accuracy of CEUS in the differential diagnosis of small (≤ 20 mm) and subcentimetric (≤ 10 mm) focal liver lesions in comparison with histology. Results of the DEGUM multicenter trial. Ultraschall Med 2011; 32: 593-597 64 Lazo M, Selvin E, Clark JM. Brief communication: clinical implications of short-term variability in liver function test results. Ann Intern Med 2008; 148: 348-352 65 Pratt DS, Kaplan MM. Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med 2000; 342: 1266-1271