Digestive Diseases and Sciences

, Volume 52, Issue 2, pp 570–578

Clinical Implications of Hepatic Steatosis in Patients with Chronic Hepatitis C: A Multicenter Study of U.S. Veterans

  • Ke-Qin Hu
  • Sue L. Currie
  • Hui Shen
  • Ramsey C. Cheung
  • Samuel B. Ho
  • Edmund J. Bini
  • John D. McCracken
  • Tim Morgan
  • Norbert Bräu
  • Warren N. Schmidt
  • Lennox Jeffers
  • Teresa L. Wright
  • for the VA HCV-001 Study Grouptitle
Original Paper


Studies have indicated a high prevalence of hepatic steatosis in patients with chronic hepatitis C (CHC). To address the impact of steatosis on the clinical course of CHC and treatment response requires large multicenter studies. The present study analyzed hepatitis C virus (HCV)-infected veterans enrolled in a U.S. Veteran Administration multicenter study of the epidemiology and response to interferon α-2b and ribavirin treatment. Of the 357 patients, 97.1% were males, with a mean age of 48.7±6.4 years, and 184 (51.5%) had hepatic steatosis. The mean body mass index (BMI) was 29.3±5.2 kg/m2, including 37.1% who were obese (BMI, ≥30 kg/m2). Stage III–IV fibrosis was present in 111 of 334 (33.3%) of the patients. After adjusting for age, race, and history of alcohol use in the past 12 months, only stage III–IV fibrosis was independently and significantly associated with hepatic steatosis (P=0.03). There was a trend of association between obesity and steatosis independent of the other factors. Only HCV genotype was independently associated with a sustained virological response (SVR) to interferon α-2b and ribavirin treatment after adjusting for age, alcohol use, steatosis, BMI, stage III–IV fibrosis, serum AFP, and HCV load. In conclusion, analyses of our multicenter trial data demonstrated that the prevalence of hepatic steatosis is 51.5% in HCV-infected U.S. veterans. We found that steatosis is independently associated with stage III–IV fibrosis. However, only HCV genotype, and not steatosis, obesity, or stage III–IV fibrosis, was associated with SVR to interferon α-2b and ribavirin treatment.


Hepatitis C virus Chronic hepatitis C Hepatic steatosis Obesity Body mass index Hepatic fibrosis 


  1. 1.
    Madhava V, Burgess C, Drucker E (2002) Epidemiology of chronic hepatitis C infection in sub-Saharan Africa. Lancet Infect Dis 2:293–302PubMedCrossRefGoogle Scholar
  2. 2.
    Alter MJ, Kruszon-Moran D, Nainan OV, et al. (1999) Prevalence of hepatitis C virus infection in the United States. N Eng J Med 341:556–562CrossRefGoogle Scholar
  3. 3.
    NIH (2003) National institutes of health consensus development conference statement. Management of Hepatitis C: June 10–12, 2002. Hepatology 36:S3–S20Google Scholar
  4. 4.
    Di Bsceglie AM (2000) Natural history of hepatitis C: its impact on clinical management. Hepatology 31:1014–1018CrossRefGoogle Scholar
  5. 5.
    Seeff LB (2002) Natural history of hepatitis C. Hepatology 36:S35–S46PubMedCrossRefGoogle Scholar
  6. 6.
    Hu KQ, Tong MJ (1999) The long-term outcomes of patients with compensated hepatitis C virus-related cirrhosis and history of parenteral exposure in the United States. Hepatology 29:1311–1316PubMedCrossRefGoogle Scholar
  7. 7.
    Fattovich G, Giustina G, Degos F, et al. (1997) Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology 112:463–472PubMedCrossRefGoogle Scholar
  8. 8.
    Poynard T, Ratziu V, McHutchison JG, et al. (2003) Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C. Hepatology 38:75–85PubMedCrossRefGoogle Scholar
  9. 9.
    Bressler BL, Guindi M, Tomlinson G, Heathcote J (2003) High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C. Hepatology 38:557–559CrossRefGoogle Scholar
  10. 10.
    Cheung RC, Currie S, Shen H, et al. (2005) Chronic hepatitis C in Latinos: Natural history, treatment, eligibility, acceptance, and outcomes. Am J Gastroenterol 100:2186–2193PubMedCrossRefGoogle Scholar
  11. 11.
    Hourigan LF, Macdonald GA, Purdie D, et al. (1999) Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. Hepatology 29:1215–1219PubMedCrossRefGoogle Scholar
  12. 12.
    Adinolfi LE, Gambardella M, Andreana A, Tripodi M-F, Utili R, Ruggiero G (2001) Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology 33:1358–1364PubMedCrossRefGoogle Scholar
  13. 13.
    Czaja AJ, Carpenter HA, Santrach PJ, Moore SB (1998) Host- and disease-specific factors affecting steatosis in chronic hepatitis C. J Hepatol 29:198–206PubMedCrossRefGoogle Scholar
  14. 14.
    Hwang SJ, Luo JC, Chu CW, et al. (2001) Hepatic steatosis in chronic hepatitis C virus infection: prevalence and clinical correlation. J Gastroenterol Hepatol 16:190–195PubMedCrossRefGoogle Scholar
  15. 15.
    Giannini E, Geppa P, Botta F, et al. (1999) Steatosis and bile duct damage in chronic hepatitis C: distribution and relationships in a group of Nothern Italian patients. Liver 19:432–427PubMedGoogle Scholar
  16. 16.
    Clouston AD, Jonsson JR, Purdie DM, et al. (2001) Steatosis and chronic hepatitis C: analysis of fibrosis and stellate cell activation. J Hepatol 34:314–320PubMedCrossRefGoogle Scholar
  17. 17.
    Hu K-Q, Kyulo N, Esrailian E, Thompson K, Chase R, Hillebrand DJ, Runyon BA (2004) Overweight and obesity, hepatic steatosis, and progression of chronic hepatitis c: a large cohort study in the United States. J Hepatol 40:147–154PubMedCrossRefGoogle Scholar
  18. 18.
    Kumar D, Farrell GC, Fung C, George J (2002) Hepatitis C virus genotype 3 is cytopathic to hepatocytes: reversal of hepatic steatosis after sustained therapeutic response. Hepatology 36:1266–1272PubMedCrossRefGoogle Scholar
  19. 19.
    Negro F (2002) Hepatitis C virus and liver steatosis: Is it the virus? Yes it is, but not always. Hepatology 36:1050–1052PubMedCrossRefGoogle Scholar
  20. 20.
    Contos MJ, Garcia N, Sterling RK, et al. (2001) The impact of nonalcoholic fatty liver disease on the progression of hepatitis C. Hepatology (Suppl) 34:A1139 (abstr)Google Scholar
  21. 21.
    Sumida Y, Nakashima T, Yoh T, et al. (2001) Independent predictors of hepatic steatosis and fibrosis in Japanese patients with chronic hepatitis C. Gastroenterology 120:A381CrossRefGoogle Scholar
  22. 22.
    Monto A, Alonzo J, Watson JJ, Grunfeld G, Wright T (2002) Steatosis in chronic hepatitis: relative contribution of obesity, diabetes mellitus, and alcohol. Hepatology 36:729–736PubMedCrossRefGoogle Scholar
  23. 23.
    Patton HM, Patel K, Behling C, et al. (2004) The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis c patients. J Hepatol 40:484–490PubMedCrossRefGoogle Scholar
  24. 24.
    Castera L, Chouteau P, Hezode C, Zafrani E-S, Dhumeaux D, Pawlotsky J-M (2005) Hepatitis C virus-induced hepatocellular steatosis. Am J Gastroenterol 100:711–715PubMedCrossRefGoogle Scholar
  25. 25.
    Patel K, Zekry A, McHutchison JG (2005) Steatosis and chronic hepatitis C virus infection: Mechanisams and significance. Clin Liv Dis 9:399–410CrossRefGoogle Scholar
  26. 26.
    Rubbia-Brandt L, Giostra E, Quadri R, et al. (1999) Evidence that liver steatosis is virally mediated in a subset of patients infected by hepatitis C virus genotype 3. J Hepatol (Suppl) 30:133A (abstr)Google Scholar
  27. 27.
    Rubbia-Brandt L, Quadri R, Abid K, et al. (2000) Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3. J Hepatol 33:106–115PubMedCrossRefGoogle Scholar
  28. 28.
    Cheung RC (2000) Epidemiology of hepatitis C virus infection in American veterans. Am J Gastroenterol 95:740–747PubMedCrossRefGoogle Scholar
  29. 29.
    Briggs ME, Baker C, Hall R, et al. (2001) Prevalence and risk factors for hepatitis C virus infection at an urban Veterans Administrtation Medical Center. Hepatology 34:1200–1205PubMedCrossRefGoogle Scholar
  30. 30.
    Bini EJ, Brau N, Currie S, et al. (2005) Prospective multicenter study of eligibility for antiviral therapy among 4,084 U.S. Veterans with chronic hepatitis C virus infection. Am J Gastroenterol 100:1772–1779PubMedCrossRefGoogle Scholar
  31. 31.
    Bräu N, Bini EJ, Currie S, et al. (2006) Black patients with chronic hepatitis C have a lower sustained viral response rate than non-Blacks with genotype 1, but the same with genotypes 2/3, and this is not explained by more frequent dose reductions of interferon and ribavirin J of Viral Hepatitis 13:242–249Google Scholar
  32. 32.
    Donato KA (1998) Executive summary of the clinical guidelines on the identification, evaluation, and treatment of obesity in adults. Arch Intern Med 158:1855–1867CrossRefGoogle Scholar
  33. 33.
    Knodell RG, Ishak KG, Black WC, et al. (1981) Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1:431–435PubMedGoogle Scholar
  34. 34.
    Brunt EM, Janney CG, et al. (1999) Nonalcoholic steatohepatitis: a proposal for grading and staging the histologic lesions. Am J Gastroenterol 94:2467–2474PubMedCrossRefGoogle Scholar
  35. 35.
    Hu K-Q, Yang HY, Lin YS, Lindsay KL, Redeker AG (2004) The clinical profile of chronic hepatitis C in a major county medical center outpatient setting in the United States. Int J Med Sci 1:92–100PubMedGoogle Scholar
  36. 36.
    Hu K-Q, Kyulo N, Lim N, et al. (2004) Clinical significance of elevated alpha fetoprotein (AFP) in patients with chronic hepatitis C, but not hepatocellular carcinoma. Am J Gastroenterol 99:860–865PubMedCrossRefGoogle Scholar
  37. 37.
    Sanyal AJ, Contos MJ, Sterling RK, Luketic VA, Shiffman ML, Stravitz RT, Mills AS (2003) Non-alcoholic fatty liver disease in patients with hepatitis C is associated with features of the metabolic syndrome. Am J Gastroenterol 98:2064–2071PubMedCrossRefGoogle Scholar
  38. 38.
    Moriya K, Yotsuyanagi H, Shintani Y, et al. (1997) Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. J Gen Virol 78:1527–1531PubMedGoogle Scholar
  39. 39.
    Lerat H, Honda M, Beard MR, et al. (2002) Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus. Gastroenterology 122:352–365PubMedCrossRefGoogle Scholar
  40. 40.
    Perlemuter G, Sabile A, Letteron P, et al. (2002) Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipiprotein secretion: a model of viral-related steatosis. FASEB J 16:185–194PubMedCrossRefGoogle Scholar
  41. 41.
    Domitrovich AM, Felmlee DJ, Siddiqui A (2005) Hepatitis C virus nonstructural prteins inhibit apilipoprotein B100 secretion. J Biol Chem 180:39802–39808Google Scholar
  42. 42.
    Abid K, Pazienza V, de Gottarsi A, et al. (2005) An in vitro model of hepatitis C virus genotype 3a-associated triglycerides accumulation. J Hepatol 42:744–751Google Scholar
  43. 43.
    McHutchison JG, Gordon S, Schiff E, et al. (1998) Interferon alfa 2b alone or in combination of with rabavirin as initial treatment for chronic hepatitis C. N Engl J Med 339:1485–1492PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • Ke-Qin Hu
    • 1
    • 2
  • Sue L. Currie
    • 3
  • Hui Shen
    • 3
  • Ramsey C. Cheung
    • 4
  • Samuel B. Ho
    • 5
  • Edmund J. Bini
    • 6
  • John D. McCracken
    • 7
    • 8
  • Tim Morgan
    • 9
  • Norbert Bräu
    • 10
  • Warren N. Schmidt
    • 11
  • Lennox Jeffers
    • 12
  • Teresa L. Wright
    • 3
  • for the VA HCV-001 Study Grouptitle
  1. 1.Contributed to this study when he was the staff hepatologist at Loma Linda VA Medical CenterLoma LindaUSA
  2. 2.Division of Gastroenterology/HepatologyUniversity of California, Irvine, 101 The City DriveOrangeUSA
  3. 3.Veteran Affairs Medical CenterSan FranciscoUSA
  4. 4.Veteran Affairs Medical CenterPalo AltoUSA
  5. 5.Veteran Affairs Medical CenterMinneapolisUSA
  6. 6.Veteran Affairs Medical CenterNew YorkUSA
  7. 7.Contributed to this study when he was the staff Gastroenterologist at Loma Linda VA Medical CenterLoma LindaUSA
  8. 8.Kaiser Permanente 2025 Morse Avenue SacramentoSacramentoUSA
  9. 9.Veteran Affairs Medical CenterLong BeachUSA
  10. 10.Veteran Affairs Medical CenterThe BronxUSA
  11. 11.Veteran Affairs Medical CenterIowa CityUSA
  12. 12.Veteran Affairs Medical CenterMiamiUSA

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