Skip to main content

Advertisement

SpringerLink
Log in

The Role of Hepatic Steatosis in Chronic Hepatitis B Infection

  • Published:
Current Hepatitis Reports Aims and scope Submit manuscript

Abstract

Chronic hepatitis B (CHB) infection is a global public health burden, and is associated with substantial morbidity and mortality. Although viral factors such as hepatitis B virus (HBV) DNA, hepatitis B e antigen, and genotype are known determinants of risk for histologic progression and hepatocellular carcinoma (HCC), other host factors can also play key roles. Hepatic steatosis (fatty liver) is increasingly common in the general population as a reflection of a rising prevalence of obesity in both Western and Eastern countries. Whereas the impact of superimposed hepatic steatosis on chronic hepatitis C infection is well-described, its role in the natural history, management, and clinical outcomes of CHB remains less defined. This article summarizes existing evidence on the prevalence and risk factors for hepatic steatosis in CHB, proposed pathogenetic links between HBV and hepatic steatosis, impact on the risk for liver fibrosis and HCC, and implications for antiviral therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11:97–107.

    Article  PubMed  CAS  Google Scholar 

  2. •• Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009;373:582–92. This article is an authoritative review of the epidemiology, natural history, and treatment of hepatitis B.

    Article  PubMed  CAS  Google Scholar 

  3. Kim WR. Epidemiology of hepatitis B in the United States. Hepatology. 2009;49:S28–34.

    Article  PubMed  Google Scholar 

  4. Welch S, Chiang B, Shadday P, Brosgart CL. Estimated prevalence of chronic hepatitis B in foreign-born persons living in the United States by country/region of origin [abstract 853]. Hepatology. 2008;48:687A.

    Google Scholar 

  5. McQuillan GM, Coleman PJ, Kruszon-Moran D, et al. Prevalence of hepatitis B virus infection in the United States: the National Health and Nutrition Examination Surveys, 1976 through 1994. Am J Public Health. 1999;89:14–8.

    PubMed  CAS  Google Scholar 

  6. Fattovich G, Pantalena M, Zagni I, et al. Effect of hepatitis B and C virus infections on the natural history of compensated cirrhosis: a cohort study of 297 patients. Am J Gastroenterol. 2002;97:2886–95.

    Article  PubMed  Google Scholar 

  7. Chu CM, Liaw YF. Hepatitis B virus-related cirrhosis: natural history and treatment. Semin Liver Dis. 2006;26:142–52.

    Article  PubMed  CAS  Google Scholar 

  8. Chen YC, Yeh ChuCM, CT LYF. Natural course following the onset of cirrhosis in patients with chronic hepatitis B: a long-term follow-up study. Hepatol Int. 2007;1:267–73.

    Article  PubMed  Google Scholar 

  9. Tran TT, Martin P. Hepatitis B: epidemiology and natural history. Clin Liver Dis. 2004;8:255–66.

    Article  PubMed  Google Scholar 

  10. Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–95.

    Article  PubMed  Google Scholar 

  11. Schuppan D, Gorrell MD, Klein T, et al. The challenge of developing novel pharmacological therapies for non-alcoholic steatohepatitis. Liver International. 2010;30:795–808.

    Article  PubMed  CAS  Google Scholar 

  12. Persico M, Iolascon A. Steatosis as a co-factor in chronic liver diseases. World J Gastroenterol. 2010;16:1171–6.

    Article  PubMed  Google Scholar 

  13. Powell EE, Jonsson JR, Clouston AD. Steatosis: co-factor in other liver diseases. Hepatology. 2005;42:5–13.

    Article  PubMed  CAS  Google Scholar 

  14. Kim KH, Shin HJ, Kim K, et al. Hepatitis B virus X protein induces hepatic steatosis via transcriptional activation of SREBP1 and PPARγ. Gastroenterology. 2007;132:1955–67.

    Article  PubMed  CAS  Google Scholar 

  15. Kim KJ, Kim KH, Kim HH, et al. Hepatitis B virus X protein induces lipogenic transcription factor SREBP-1 and fatty acid synthase through the activation of nuclear receptor LXRα. Biochem J. 2008;416:219–30.

    Article  PubMed  CAS  Google Scholar 

  16. • Wong GL, Wong VW, Choi PC, et al. Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B. Gut. 2009;58:111–7. This article describes an original analysis examining the relationship between metabolic syndrome and liver cirrhosis.

    Article  PubMed  Google Scholar 

  17. Chen CL, Yang HI, Yang WS, et al. Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C: a follow-up study in Taiwan. Gastroenterology. 2008;135:111–21.

    Article  PubMed  CAS  Google Scholar 

  18. • Stepanova M, Rafiq N, Younossi ZM. Components of metabolic syndrome are independent predictors of mortality in patients with chronic liver disease: a population-based study. Gut. 2010;59:1410–5. This article describes an original study with an analysis of the relationship between metabolic syndrome and liver-related mortality.

    Article  PubMed  Google Scholar 

  19. Altiparmak E, Koklu S, Yalinkilic M, et al. Viral and host causes of fatty liver in chronic hepatitis B. World J Gastroenterol. 2005;11:3056–9.

    CAS  Google Scholar 

  20. Bondini S, Kallman J, Wheeler A, et al. Impact of non-alcoholic fatty liver disease on chronic hepatitis B. Liver Int. 2007;27:607–11.

    Article  PubMed  Google Scholar 

  21. Cindoruk M, Karakan T, Unal S. Hepatic steatosis has no impact on the outcome of treatment in patients with chronic hepatitis B infection. J Clin Gastroenterol. 2007;41:513–7.

    Article  PubMed  Google Scholar 

  22. Czaja AJ, Carpenter HA, Santrach PJ, et al. Host and disease-specific factors affecting steatosis in chronic hepatitis C. J Hepatol. 1998;29:198–206.

    Article  PubMed  CAS  Google Scholar 

  23. Demir K, Akyuz F, Ozdil S, et al. What is the reason of elevated alanine aminotransferase level in HBeAg negative patients with low viremia: NAFLD or chronic hepatitis? Ann Hepatol. 2007;6:92–6.

    PubMed  CAS  Google Scholar 

  24. Giannattasio A, Cirillo F, Terlizzi V, et al. Hepatic steatosis is uncommon in children with chronic hepatitis B. J Clin Virol. 2009;46:360–2.

    Article  PubMed  Google Scholar 

  25. Gordon A, McLean CA, Pedersen JS, et al. Hepatic steatosis in chronic hepatitis B and C: predictors, distribution and effect on fibrosis. J Hepatol. 2005;43:38–44.

    Article  PubMed  CAS  Google Scholar 

  26. Hung CH, Lee CM, Lu SN, et al. Hepatic steatosis with hepatitis B virus/hepatitis C virus dual infection. Hepatology. 2010;52:1521–2.

    Article  PubMed  Google Scholar 

  27. Lin YC, Hsiao ST, Chen JD. Sonographic fatty liver and hepatitis B virus carrier status: synergistic effect on liver damage in Taiwanese adults. World J Gastroenterol. 2007;13:1805–10.

    PubMed  Google Scholar 

  28. Mellen JS, Xia VW, Hashemzadeh M, et al. The clinical presentation of chronic hepatitis B virus infection in Asian Americans. J Clin Gastroenterol. 2010;44:364–70.

    PubMed  Google Scholar 

  29. Minakari M, Molaei M, Shalmani HM, et al. Liver steatosis in patients with chronic hepatitis B infection: host and viral risk factors. J Gastroenterol Hepatol. 2009;21:512–6.

    Article  Google Scholar 

  30. • Park SH, Kim DJ, Lee HY. Insulin resistance is not associated with histologic severity in nondiabetic, noncirrhotic patients with chronic hepatitis B virus infection. Am J Gastroenterol. 2009;104:1135–9. This article describes an original study with analysis of metabolic and histologic parameters in a well-characterized nondiabetic cohort.

    Article  PubMed  CAS  Google Scholar 

  31. Peng D, Han Y, Ding H. Hepatic steatosis in chronic hepatitis B patients is associated with metabolic factors more than viral factors. J Gastroenterol Hepatol. 2008;23:1082–8.

    Article  PubMed  CAS  Google Scholar 

  32. Persico M, Masarone M, La Mura V, et al. Clinical expression of insulin resistance in hepatitis C and B virus-related chronic hepatitis: differences and similarities. World J Gastroenterol. 2009;15:462–6.

    Article  PubMed  CAS  Google Scholar 

  33. • Shi JP, Fan JG, Wu R, et al. Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese patients with chronic hepatitis B infection. J Gastroenterol Hepatol. 2008;23:1419–25. This article describes an original study with an analysis of the largest reported cohort of patients with chronic HBV infection undergoing liver biopsy with assessement of hepatic steatosis.

    Article  PubMed  Google Scholar 

  34. Siagris D, Vafiadis G, Michalaki M, et al. Serum adinopectin in chronic hepatitis C and B. J Viral Hepatitis. 2007;14:577–83.

    Article  CAS  Google Scholar 

  35. Thomopoulos KC, Arvaniti V, Tsamantas AC, et al. Prevalence of hepatic steatosis in patients with chronic hepatitis B: a study of associated factors and of relationship with fibrosis. Eur J Gastroenterol Hepatol. 2006;18:233–7.

    Article  PubMed  Google Scholar 

  36. Tsochatzis E, Papatheodoridis GV, Manesis EK. Hepatic steatosis in chronic hepatitis B develop due to host metabolic factors: a comparative approach with genotype 1 chronic hepatitis C. Dig Liver Dis. 2007;39:936–42.

    Article  PubMed  CAS  Google Scholar 

  37. Wang CC, Hsu CS, Liu CJ, et al. Association of chronic hepatitis B virus infection with insulin resistance and hepatic steatosis. J Gastroenterol Hepatol. 2008;23:779–82.

    Article  PubMed  Google Scholar 

  38. Yun JW, Cho YK, Park JH, et al. Hepatic steatosis and fibrosis in young men with treatment-naïve chronic hepatitis B. Liver Int. 2009;29:878–83.

    Article  PubMed  CAS  Google Scholar 

  39. Zheng RD, Xu CR, Jiang L, et al. Predictors of hepatic steatosis in HBeAg-negative chronic hepatitis B patients and their diagnostic values in hepatic fibrosis. Int J Med Sci. 2010;7:272–7.

    PubMed  CAS  Google Scholar 

  40. Brunt EM, Janney CG, DiBisceglie AM, et al. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94:2467–74.

    Article  PubMed  CAS  Google Scholar 

  41. 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;22:775–7.

    Article  PubMed  Google Scholar 

  42. Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–21.

    Article  PubMed  Google Scholar 

  43. Chu CM, Lin DY, Liaw YF. Does increased body mass index with hepatic steatosis contribute to seroclearance of hepatitis B (HBV) surface antigen in chronic HBV infection? Int J Obes. 2007;31:871–5.

    Google Scholar 

  44. WHO Expert Panel. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363:157–63.

    Article  Google Scholar 

  45. Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. New Engl J Med. 2008;359:2442–55.

    Article  PubMed  CAS  Google Scholar 

  46. Lai CL, Gane E, Liaw YF, et al. Telbivudine versus lamivudine in patients with chronic hepatitis B. New Engl J Med. 2007;357:2576–88.

    Article  PubMed  CAS  Google Scholar 

  47. Marcellin P, Chang TT, Lim SG, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. New Engl J Med. 2003;348:808–16.

    Article  PubMed  CAS  Google Scholar 

  48. Lai CL, Shouval D, Lok AS, et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. New Engl J Med. 2006;354:1011–20.

    Article  PubMed  CAS  Google Scholar 

  49. Lim JK, Ayoub WS, Nguyen MH. Histologic disease in patients with chronic hepatitis B, hig HBV DNA, and normal alanine aminotransferase levels. Curr Hepatitis Rep. 2010;9:65–74.

    Article  Google Scholar 

Download references

Disclosure

Conflicts of interest: J.K. Lim—consultancy and grants, Bristol-Myers Squibb, grants and honoraria, Gilead; M.H. Nguyen—none.

Author information

Authors and Affiliations

  1. Section of Digestive Diseases and Yale Liver Center, Yale University School of Medicine, New Haven, CT, USA

    Joseph K. Lim

  2. Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA, 94304-1509, USA

    Mindie H. Nguyen

Authors
  1. Joseph K. Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mindie H. Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mindie H. Nguyen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lim, J.K., Nguyen, M.H. The Role of Hepatic Steatosis in Chronic Hepatitis B Infection. Curr Hepatitis Rep 10, 134–141 (2011). https://doi.org/10.1007/s11901-011-0090-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11901-011-0090-6

Keywords

Search

Navigation