Semin Liver Dis 2004; 24(1): 3-20
DOI: 10.1055/s-2004-823098
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Nonalcoholic Steatohepatitis

Elizabeth M. Brunt1
  • 1Associate Professor of Pathology, Saint Louis University Liver Center, Saint Louis University Health Sciences Center, Department of Pathology, St. Louis, Missouri
Further Information

Publication History

Publication Date:
13 April 2004 (online)

Nonalcoholic fatty liver disease (NAFLD) is being increasingly recognized as a common liver disorder that represents the hepatic manifestation of the metabolic syndrome, a variably defined aggregate of disorders related to obesity, insulin resistance, type II diabetes, hypertension and hyperlipidemia. Nonalcoholic steatohepatitis (NASH) is the progressive form of liver injury that carries a risk for progressive fibrosis, cirrhosis, and end-stage liver disease. Hepatocellular carcinoma (HCC) is a documented complication in an as yet unknown percentage of cases of NASH cirrhosis. The diagnosis of nonalcoholic steatohepatitis requires histopathologic evaluation because the lesions of parenchymal injury and fibrosis cannot be detected by imaging studies or laboratory tests. This article will briefly discuss prevalence studies and the pathophysiology of NAFLD and focus on current discussions related to the specific lesions in the pathology of NASH, including the challenges of pediatric NASH and NASH-related cirrhosis.

REFERENCES

  • 1 Sanyal A J. AGA technical review on nonalcoholic fatty liver disease.  Gastroenterology. 2002;  123 1705-1725
  • 2 Neuschwander-Tetri B A, Caldwell S H. Nonalcoholic steatohepatitis: summary of an AASLD single topic conference.  Hepatology. 2003;  37 1202-1219
  • 3 McCullough A J. Update on nonalcoholic fatty liver disease.  J Clin Gastroenterol. 2002;  34 255-262
  • 4 Dixon J B, O'Brien P E, Bhatal P S. A wider view on diagnostic criteria of nonalcoholic steatohepatitis (reply).  Gastroenterology. 2002;  122 841-842
  • 5 Brunt E M. Nonalcoholic steatohepatitis: definition and pathology.  Semin Liver Dis. 2001;  21 3-16
  • 6 Ludwig J, Viggiano T R, McGill D B, Oh B J. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease.  Mayo Clin Proc. 1980;  55 434-438
  • 7 Adler M, Schaffner F. Fatty liver hepatitis and cirrhosis in obese patients.  Am J Med. 1979;  67 811-816
  • 8 Nasrallah S M, Wills C E, Galambos J T. Hepatic morphology in obesity.  Dig Dis Sci. 1981;  26 325-327
  • 9 Silverman J F, O'Brien K F, Long S et al.. Liver pathology in morbidly obese patients with and without diabetes.  Am J Gastroenterol. 1990;  85 1349-1355
  • 10 Silverman E M, Sapala J A, Appelman H D. Regression of hepatic steatosis in morbidly obese persons after gastric bypass.  Am J Clin Pathol. 1995;  104 23-31
  • 11 Teli M R, James O FW, Burt A D, Bennett M K, Day C P. The natural history of nonalcoholic fatty liver-a follow-up study.  Hepatology. 1995;  22 1714-1719
  • 12 Falck-Ytter Y, Younossi Z M, Marchesini G, McCullough A J. Clinical features and natural history of nonalcoholic steatosis syndromes.  Semin Liver Dis. 2001;  21 17-26
  • 13 Matteoni C A, Younossi Z M, Gramlich T et al.. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.  Gastroenterology. 1999;  116 1413-1419
  • 14 Clark J M, Brancati F L, Diehl A M. Nonalcoholic fatty liver disease.  Gastroenterology. 2002;  122 1649-1657
  • 15 Clark J M, Diehl A M. Defining nonalcoholic fatty liver disease: implications for epidemiologic studies.  Gastroenterology. 2003;  124 248-250
  • 16 Dixon J B, Bhathal P S, O'Brien P E. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese.  Gastroenterology. 2001;  121 91-100
  • 17 Wigg A J, Roberts-Thomson I C, Dymock R B et al.. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis.  Gut. 2001;  48 206-211
  • 18 Farrell G C. Is bacterial ash the flash that ignites NASH?.  Gut. 2001;  48 148-149
  • 19 Lonardo A, Bellini M, Tartoni P, Tondelli E. The bright liver syndrome-prevalence and determinants of a “bright” liver echopattern.  Ital J Gastroenterol Hepatol. 1997;  29 351-356
  • 20 Bellentani S, Sacciccio G, Masutti F et al.. Prevalence of and risk factors for hepatic steatosis in northern Italy.  Ann Intern Med. 2000;  132 112-117
  • 21 Bellentani S, Tiribelli C. The spectrum of liver disease in the general population: lesson from the Dionysos study.  J Hepatol. 2001;  35 531-537
  • 22 Saadeh S, Younossi Z M, Remer E M et al.. The utility of radiological imaging in nonalcoholic fatty liver disease.  Gastroenterology. 2002;  123 745-750
  • 23 Ruhl C E, Everhart J E. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States.  Gastroenterology. 2003;  124 71-79
  • 24 Prati D, Taioli E, Zanella A et al.. Updated definitions of healthy ranges for serum alanine aminotransferase levels.  Ann Intern Med. 2002;  137 1-9
  • 25 Expert panel on Detection . Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP).  JAMA. 2001;  285 2486-2497
  • 26 Clark J M, Brancati F L, Diehl A M. The prevalence and etiology of elevated aminotransferase levels in the United States.  Am J Gastroenterol. 2003;  98 960-967
  • 27 Kim W R, Brown R S, Terrault N A, El-Serag H. Burden of liver disease in the United States: summary of a workshop.  Hepatology. 2002;  36 227-242
  • 28 Yu A S, Keefe E B. Elevated AST or ALT to nonalcoholic fatty liver disease: accurate predictor of disease prevalence? (editorial).  Am J Gastroenterol. 2003;  98 955-956
  • 29 Clinical Practice Committee AGA . AGA medical position statement: evaluation of liver chemistry tests.  Gastroenterology. 2003;  123 1364-1366
  • 30 Mofrad P, Contos M J, Haque M et al.. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values.  Hepatology. 2003;  37 1286-1292
  • 31 Mulhall B P, Ong J P, Younossi Z M. Non-alcoholic fatty liver disease: an overview.  J Gastroenterol Hepatol. 2002;  17 1136-1143
  • 32 Hilden M, Christoffersen P, Juhl E, Dalgaard J B. Liver histology in a “normal” population-examinations of 503 consecutive fatal traffic casualties.  Scand J Gastroenterol. 1977;  12 593-597
  • 33 Wanless I R, Lentz J S. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors.  Hepatology. 1990;  12 1106-1110
  • 34 Charlton M, Kasparova P, Weston S et al.. Frequency of nonalcoholic steatohepatitis as a cause of advanced liver disease.  Liver Transpl. 2001;  7 608-614
  • 35 Youssef W I, McCullough A J. Diabetes mellitus, obesity, and hepatic steatosis.  Semin Gastrointest Dis. 2002;  13 17-30
  • 36 Marchesini G, Bugianesi E, Forlani G et al.. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome.  Hepatology. 2003;  37 917-923
  • 37 Roberts E A. Steatohepatitis in children.  Best Pract Res Clin Gastroenterol. 2002;  16 749-765
  • 38 Caldwell S H, Oelsner D H, Iezzoni J C et al.. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease.  Hepatology. 1999;  29 664-669
  • 39 Bacon B R, Farahvash M J, Janney C G, Neuschwandertetri B A. Nonalcoholic steatohepatitis-an expanded clinical entity.  Gastroenterology. 1994;  107 1103-1109
  • 40 Chitturi S, Farrell G C. Etiopathogenesis of nonalcoholic steatohepatitis.  Semin Liver Dis. 2001;  21 27-41
  • 41 Farrell G C. Drugs and steatohepatitis.  Semin Liver Dis. 2002;  22 185-194
  • 42 Garcia-Monzon C, Fernandez-Bermejo M. A wider view of diagnostic criteria of nonalcoholic steatohepatitis (letter to the editor).  Gastroenterology. 2002;  122 840-841
  • 43 Garcia-Monzon C, Martin-Perez E, Lo Iacono O et al.. Characterization of pathogenic and prognostic factors of nonalcoholic steatohepatitis associated with obesity.  J Hepatol. 2000;  33 716-724
  • 44 Angulo P. Nonalcoholic fatty liver disease.  N Engl J Med. 2002;  346 1221-1231
  • 45 Neuschwander-Tetri B A. Evolving pathophysiologic concepts in nonalcoholic steatohepatitis.  Curr Gastroenterol Rep. 2002;  4 31-36
  • 46 Skelly M M, James P D, Ryder S D. Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology.  J Hepatol. 2001;  35 195-199
  • 47 Marceau P, Biron S, Hould F S et al.. Liver pathology and the metabolic syndrome X in severe obesity.  J Clin Endocrinol Metab. 1999;  84 1513-1517
  • 48 Cortez-Pinto H, Camilo M E, Baptista A, De Oliveira A G, De Moura M C. Non-alcoholic fatty liver: another feature of the metabolic syndrome?.  Clin Nutr. 1999;  18 353-358
  • 49 Marchesini G, Brizi M, Morselli-Labate A M et al.. Association of nonalcoholic fatty liver disease with insulin resistance.  Am J Med. 1999;  107 450-455
  • 50 Marchesini G, Brizi M, Bianchi G et al.. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome.  Diabetes. 2001;  50 1844-1850
  • 51 Pagano G, Pacini G, Musso G et al.. Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association.  Hepatology. 2002;  35 367-372
  • 52 Chitturi S, Abeygunasekera S, Farrell G C et al.. NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome.  Hepatology. 2002;  35 373-379
  • 53 Youssef W I, McCullough A J. Steatohepatitis in obese individuals (review).  Best Pract Res Clin Gastroenterol. 2002;  16 733-747
  • 54 Neuschwander-Tetri B A, Brunt E M, Wehmeier K R, Oliver D, Bacon B R. Improved nonalcoholic steatohepatitis following 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone.  Hepatology. 2003;  38 1008-1017
  • 55 Neuschwander-Tetri B A, Brunt E M, Wehmeier K R et al.. Interim results of a pilot study demonstrating the early effects of the PPAR-g ligand rosiglitazone on insulin sensitivity, aminotransferases, hepatic steatosis and body weight in patients with non-alcoholic steatohepatitis.  J Hepatol. 2003;  38 434-440
  • 56 Marchesini G, Brizi M, Bianchi G et al.. Metformin in non-alcoholic steatohepatitis.  Lancet. 2001;  358 893-894
  • 57 Caldwell S H, Hespenheide E E, Redick J A et al.. A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis.  Am J Gastroenterol. 2001;  96 519-525
  • 58 Pessayre D, Berson A, Fromenty B, Mansouri A. Mitochondria in steatohepatitis.  Semin Liver Dis. 2001;  21 57-69
  • 59 Day C P, Saksena S. Nonalcoholic steatohepatitis: definitions and pathogenesis.  J Gastroenterol Hepatol. 2002;  17 S377-S384
  • 60 Day C P. Pathogenesis of steatohepatitis.  Best Pract Res Clin Gastroenterol. 2002;  16 663-678
  • 61 Lebovitz H E. The relationship of obesity to the metabolic syndrome.  Int J Clin Pract Suppl. 2003;  134 18-27
  • 62 Paradis V, Perlemuter G, Bonvoust F et al.. High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis.  Hepatology. 2001;  34 738-744
  • 63 Leclercq I A, Farrell G C, Schriemer R, Robertson G R. Leptin is essential for the hepatic fibrogenic response to chronic liver injury.  J Hepatol. 2002;  37 206-213
  • 64 Angulo P, Lindor K D. Treatment of nonalcoholic fatty liver: present and emerging therapies.  Semin Liver Dis. 2001;  21 81-88
  • 65 Angulo P, Lindor K D. Treatment of non-alcoholic steatohepatitis.  Best Pract Res Clin Gastroenterol. 2002;  16 797-810
  • 66 O'Brien P E, Dixon J B. The extent of the problem of obesity.  Am J Surg. 2002;  184 4S-8S
  • 67 Korner J, Leibel R L. To eat or not to eat-how the gut talks to the brain.  N Engl J Med. 2003;  349 926-928
  • 68 McCullough A J, Falck-Ytter Y. Body composition and hepatic steatosis as precursors for fibrotic liver disease.  Hepatology. 1999;  29 1328-1330
  • 69 Arner P. The adipocyte in insulin resistance: key molecules and the impact of the thiazolidinediones.  Trends Endocrinol Metab. 2003;  14 137-145
  • 70 Prins J B. Adipose tissue as an endocrine organ.  Best Pract Res Clin Endocrinol Metab. 2002;  16 639-651
  • 71 Kern P A, Di Gregorio G B, Lu T, Rassouli N, Ranganathan G. Adiponectin exprssion from human adipose tissue. Relation to obesity, insulin resistance, and tumor necrosis factor-α expression.  Diabetes. 2003;  52 1779-1785
  • 72 Stumvoll M. Thiazolidinediones-some recent developments.  Expert Opin Investig Drugs. 2003;  12 1179-1187
  • 73 Das U N. Is metabolic syndrome X an inflammatory condition? (Review).  Exp Biol Med (Maywood). 2002;  227 989-997
  • 74 Xu A, Wang Y, Keshaw H et al.. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice.  J Clin Invest. 2003;  112 91-100
  • 75 Sreekumar R, Rosado B, Rasmussen D, Charlton M. Hepatic gene expression in histologically progressive nonalcoholic steatohepatitis.  Hepatology. 2003;  38 244-251
  • 76 Ludwig J, McGill D B, Lindor K D. Review: nonalcoholic steatohepatitis.  J Gastroenterol Hepatol. 1997;  12 398-403
  • 77 Lee R G. Nonalcoholic steatohepatitis: a study of 49 patients.  Hum Pathol. 1989;  20 594-598
  • 78 Diehl A M, Goodman Z, Ishak K G. Alcohol-like liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury.  Gastroenterology. 1988;  95 1056-1062
  • 79 Itoh S, Yougel T, Kawagoe K. Comparison between nonalcoholic steatohepatitis and alcoholic hepatitis.  Am J Gastroenterol. 1987;  82 650-654
  • 80 Brunt E M. Alcoholic and nonalcoholic steatohepatitis.  Clin Liver Dis. 2002;  6 399-420
  • 81 Brunt E M, Tiniakos D G. Pathology of steatohepatitis (review).  Best Pract Res Clin Gastroenterol. 2002;  16 691-707
  • 82 Burt A D, Mutton A, Day C P. Diagnosis and interpretation of steatosis and steatohepatitis.  Semin Diagn Pathol. 1998;  15 246-258
  • 83 Garg A, Misra A. Hepatic steatosis, insulin resistance and adipose tissue disorders (editorial).  J Clin Endocrinol Metab. 2002;  87 3019-3022
  • 84 Ishak K G. Light microscopic morphology of viral hepatitis.  Am J Clin Pathol. 1976;  65 787-827
  • 85 Natori S, Rust C, Stadheim L M et al.. Hepatocyte apoptosis is a pathologic feature of human alcoholic hepatitis.  J Hepatol. 2001;  34 248-253
  • 86 Ziol M, Tepper M, Lohez M et al.. Clinical and biological relevance of hepatocyte apoptosis in alcoholic hepatitis.  J Hepatol. 2001;  34 254-260
  • 87 Canbay A, Tamir P, Torok N J et al.. Apoptotic body engulfment by a human stellate cell line is profibrogenic.  Lab Invest. 2003;  83 655-663
  • 88 Feldstein A E, Canbay A, Angulo P et al.. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis.  Gastroenterology. 2003;  125 437-443
  • 89 Nanki T, Koike R, Miyasaka N. Subacute severe steatohepatitis during prednisolone therapy for systemic lupus erythematosis (letter to editor).  Am J Gastroenterol. 1999;  94 3379
  • 90 Dourakis S P, Sevastinaos V A, Kaliopi P. Acute severe steatohepatitis related to prednisolone therapy (letter to editor).  Am J Gastroenterol. 2002;  97 1074-1075
  • 91 Caldwell S H, Hespenheide E E. Subacute liver failure in obese women.  Am J Gastroenterol. 2002;  97 2058-2062
  • 92 Brunt E M, Ramrakhiani S, Cordes B G et al.. Concurrence of histologic features of steathepatitis with other forms of chronic liver disease.  Mod Pathol. 2003;  16 49-56
  • 93 Brunt E M, Tiniakos D G. Steatosis, steatohepatitis: review of effects on chronic hepatitis C.  Current Hepatitis Reports. 2002;  1 38-44
  • 94 Clouston A D, Powell E E. Interaction of non-alcoholic fatty liver disease with other liver diseases.  Best Pract Res Clin Gastroenterol. 2002;  16 767-781
  • 95 Ong J P, Younossi Z M, Speer C et al.. Chronic hepatitis C and superimposed nonalcoholic fatty liver disease.  Liver. 2001;  21 266-271
  • 96 Washington K, Wright K, Shyr Y et al.. Hepatic stellate cell activation in nonalcoholic steatohepatitis and fatty liver.  Hum Pathol. 2000;  31 822-828
  • 97 Cortez-Pinto H, Baptista A, Camilo M E, de Moura M C. Hepatic stellate cell activation occurs in nonalcoholic steatohepatitis.  Hepatogastroenterol. 2001;  48 87-90
  • 98 Denk H, Stumptner C, Zatloukal K. Mallory bodies revisited.  J Hepatol. 2000;  32 689-702
  • 99 Ludwig J, McGill D B, Lindor K D. Nonalcoholic steatohepatitis.  J Gastroenterol Hepatol. 1997;  12 398-403
  • 100 Brunt E M, Janney C G, Di Bisceglie A M, Neuschwander-Tetri B A, Bacon B R. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions.  Am J Gastroenterol. 1999;  94 2467-2474
  • 101 Stumptner C, Fuchsbichler A, Heid H, Zatloukal K, Denk H. Mallory body-a disease-associated type of sequestosome.  Hepatology. 2002;  35 1053-1062
  • 102 Savas M C, Koruk M, Pirim I et al.. Serum ubiquitin levels in patients with nonalcoholic steatohepatitis.  Hepatogastroenterology. 2003;  50 738-741
  • 103 Teli M R, Day C P, Burt A D, Bennett M J, James O F. Determinants of progression to cirrhosis or fibrosis in pure alcoholic fatty liver.  Lancet. 1995;  346 987-990
  • 104 Caldwell S H, Swerdlow R H, Khan E M et al.. Mitochondrial abnormalities in non-alcoholic steatohepatitis.  J Hepatol. 1999;  31 430-434
  • 105 Sanyal A J, Campbell-Sargent C, Mirshahi F et al.. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities.  Gastroenterology. 2001;  120 1183-1192
  • 106 George D K, Goldwurm S, MacDonald G A et al.. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis.  Gastroenterology. 1998;  114 311-318
  • 107 Younossi Z M, Gramlich T, Bacon B R et al.. Hepatic iron and nonalcoholic fatty liver disease.  Hepatology. 1999;  30 847-850
  • 108 Bonkovsky H L, Jawaid Q, Tortorelli K et al.. Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis.  J Hepatol. 1999;  31 421-429
  • 109 Chitturi S, Weltman M, Farrell G C et al.. HFE Mutations, hepatic iron, and fibrosis: Ethnic-specific association of NASH with C282Y but not with fibrotic severity.  Hepatology. 2002;  36 142-149
  • 110 Cortez-Pinto H, Baptista A, Camilo M E et al.. Nonalcoholic steatohepatitis-clinicopathological comparison with alcoholic hepatitis in ambulatory and hospitalized patients.  Dig Dis Sci. 1996;  41 172-179
  • 111 Abdelmalek M, Angulo P, Jorgensen R A, Sylvestre P B, Lindor K. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study.  Am J Gastroenterol. 2001;  96 2711-2717
  • 112 Laurin J, Lindor K D, Crippin J S et al.. Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis-a pilot study.  Hepatology. 1996;  23 1464-1467
  • 113 Andersen T, Gluud C, Franzmann M-B, Christoffersen P. Hepatic effects of dietary weight loss in morbidly obese subjects.  J Hepatol. 1991;  12 224-229
  • 114 Angulo P, Keach J C, Batts K P, Lindor K D. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis.  Hepatology. 1999;  30 1356-1362
  • 115 Ratziu V, Giral P, Charlotte F et al.. Liver fibrosis in overweight patients.  Gastroenterology. 2000;  118 1117-1123
  • 116 Dixon J B, Bhatal P S, O'Brien P E. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese.  Gastroenterology. 2001;  121 91-100
  • 117 Shimada M, Hashimoto E, Kaneda H, Noguchi S, Hayashi N. Nonalcoholic steatohepatitis: risk factors for liver fibrosis.  Hepatol Res. 2002;  24 429-438
  • 118 Evans C DJ, Oien K A, MacSween R NM, Mills P R. Nonalcoholic steatohepatitis: a common cause of advanced liver injury?.  J Clin Pathol. 2002;  55 689-692
  • 119 Brunt E M. Grading and staging the histopathologcial lesions of chronic hepatitis: the Knodell histology activity index and beyond.  Hepatology. 2000;  31 241-246
  • 120 Abdelmalek M, Ludwig J, Lindor K D. Two cases from the spectrum of nonalcoholic steatohepatitis.  J Clin Gastroenterol. 1995;  20 127-130
  • 121 Contos M J, Cales W, Sterling R K et al.. Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis.  Liver Transpl. 2001;  7 363-373
  • 122 Shimada M, Hashimoto E, Taniai M et al.. Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis.  J Hepatol. 2002;  37 154-160
  • 123 Hui J M, Kench J G, Chitturi S et al.. Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C.  Hepatology. 2003;  38 420-427
  • 124 Calle E E, Rodriguez C, Walker-Thurmond K, Thun M J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults.  N Engl J Med. 2003;  348 1625-1638
  • 125 Nair S, Mason A, Eason J, Loss G, Perillo R P. Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis?.  Hepatology. 2002;  36 150-155
  • 126 Marrero J A, Fontana R J, Su G L et al.. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States.  Hepatology. 2002;  36 1349-1354
  • 127 Ratziu V, Bonyhay L, Di Martino V et al.. Survival, liver failure and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis.  Hepatology. 2002;  35 1485-1493
  • 128 Balkau B, Kahn H S, Courbon D, Eschwege E, Ducimetiere P. Hyperinsulinemia predicts fatal liver cancer but is inversely associated with fatal cancer at some other sites.  Diabetes Care. 2001;  24 843-849
  • 129 Yang S, Lin H Z, Hwang J, Chacko V P, Diehl A M. Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition?.  Cancer Res. 2001;  61 5016-5023

Elizabeth M BruntM.D. 

4th Floor FDT, Saint Louis University Hospital

3635 Vista Avenue at Grand Boulevard

St. Louis, MO 63110

Email: bruntem@slu.edu