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Goals of Antiviral Therapy for Hepatitis B: HBeAg Seroconversion, HBsAg Seroconversion, Histologic Improvement, and Possible Impact on Risk of Hepatocellular Carcinoma

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Abstract

A major goal of antiviral therapy in patients with chronic hepatitis B (CHB) is to achieve durable suppression of viral replication. By maintaining undetectable serum HBV DNA levels, one hopes to improve the clinical outcome of these CHB patients. Recent studies have demonstrated that prolonged viral suppression using first-line antiviral medications such as entecavir or tenofovir is associated with a significant reduction in necroinflammation, fibrosis, and even reversal of cirrhosis. Thus, durable suppression of viral replication might decrease the rates of developing cirrhosis, hepatocellular carcinoma, and most importantly, the mortality from complications associated with HBV-related liver diseases. The first-line medications, entecavir, tenofovir and pegylated interferon α-2a, may help to achieve such outcome with potency and lack or minimal chance of developing antiviral resistance to them. Achieving HBeAg loss and seroconversion in patients with HBeAg-positive CHB is another major goal of antiviral therapy. However, the possibility of HBsAg loss and seroconversion albeit uncommon, represents the holy grail of successful HBV treatment and remains the best predictor of durable viral suppression in patients with CHB.

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References

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

  1. Reijnders JG, Perquin MJ, Zhang N, et al. Nucleos(t)ide analogues only induce temporary hepatitis B e antigen seroconversion in most patients with chronic hepatitis B. Gastroenterology. 2010;139(2):491–8.

    Article  PubMed  CAS  Google Scholar 

  2. Sonneveld MJ. Chronic hepatitis B: peginterferon or nucleos(t)ide analogues? Liver Int. 2011;31 Suppl 1:78–84.

    Article  PubMed  Google Scholar 

  3. Hsu YS. Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology. 2002;35(6):1522–7.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  6. Woo G. Tenofovir and entecavir are the most effective antiviral agents for chronic hepatitis B: a systematic review and Bayesian meta-analyses. Gastroenterology. 2010;139(4):1218–29.

    Article  PubMed  CAS  Google Scholar 

  7. Liaw YF. Hepatitis B e antigen seroconversion: a critical event in chronic hepatitis B virus infection. Dig Dis Sci. 2010;55(10):2727–34.

    Article  PubMed  CAS  Google Scholar 

  8. Wiegand J. Management of chronic hepatitis B: status and challenges beyond treatment guidelines. Semin Liver Dis. 2010;30(4):361–77.

    Article  PubMed  CAS  Google Scholar 

  9. Lin SM, Yu ML, Lee CM, et al. Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol. 2007;46(1):45–52.

    Article  PubMed  CAS  Google Scholar 

  10. Hadziyannis SJ. Milestones and perspectives in viral hepatitis B. Liver Int. 2011;31 Suppl 1:129–34.

    Article  PubMed  Google Scholar 

  11. Da Silva LC, Madruga CL, Carrilho FJ, et al. Spontaneous hepatitis B surface antigen clearance in a long-term follow-up study of patients with chronic type B hepatitis. Lack of correlation with hepatitis C and D virus superinfection. J Gastroenterol. 1996;31:696–701.

    Article  PubMed  Google Scholar 

  12. Kim JH, Lee YS, Lee HJ, et al. HBsAg seroclearance in chronic hepatitis B: implications for hepatocellular carcinoma. J Clin Gastroenterol. 2011;45(1):64–8.

    Article  PubMed  CAS  Google Scholar 

  13. • Lee JM, Ahn SH, Kim HS, et al. Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir. Hepatology. 2011;53(5):1486–93. This study confirms that although the clinical outcomes after HBsAg seroclearance in CHB patients are favorable HCC, even the patients with HBsAg seroclearance may develop hepatocellular carcinoma, particularly those with evidence of cirrhosis at the time of HBsAg seroclearance.

    Article  PubMed  Google Scholar 

  14. •• Chang TT, Liaw YF, Wu SS, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010;52(3):886–93. The latest study confirming the reversal of fibrosis, even cirrhosis, in patients with chronic HBV infection, with a long-term antiviral therapy. This is most likely a class effect, associated with rare or no occurrence of antiviral resistance when using first-line therapeutic options such as entecavir or tenofovir.

    Article  PubMed  CAS  Google Scholar 

  15. Schiff ER. Long-term treatment with entecavir induces reversal of advanced fibrosis or cirrhosis in patients with chronic hepatitis B. Clin Gastroenterol Hepatol. 2011;9(3):274–6.

    Article  PubMed  CAS  Google Scholar 

  16. Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295(1):65–73.

    Article  PubMed  CAS  Google Scholar 

  17. Loomba R, Yang Hi, Su J, et al. Obesity and alcohol synergize to increase the risk of incident hepatocellular carcinoma in men. Clin Gastroenterol Hepatol. 2010;8(10):891–8.

    Article  PubMed  Google Scholar 

  18. Iloeje UH, Yang HI, Su J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130:678–86.

    Article  PubMed  Google Scholar 

  19. •• Liu J, Yang HL, Lee MH, et al. Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance: a community-based follow-up study. Gastroenterology. 2010;139:474–482. The paper’s follow-up analysis on data stemming from the REVEAL study carried out in Taiwan suggests that low HBV DNA levels are an important factor affecting the natural seroclearance of HBsAg.

    Article  PubMed  Google Scholar 

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Disclosure

Albert D. Min received payment for consultancy, development of educational materials, and honoraria from Bristol-Myers Squibb, Gilead, and Roche/Genentech; Petros C. Benias reported no potential conflicts of interest relevant to this article.

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  1. Division of Digestive Diseases, Beth Israel Medical Center, First Avenue at 16th Street, New York, NY, 10003, USA

    Petros C. Benias & Albert D. Min

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  1. Petros C. Benias
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  2. Albert D. Min
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Correspondence to Albert D. Min.

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Benias, P.C., Min, A.D. Goals of Antiviral Therapy for Hepatitis B: HBeAg Seroconversion, HBsAg Seroconversion, Histologic Improvement, and Possible Impact on Risk of Hepatocellular Carcinoma. Curr Hepatitis Rep 10, 292–296 (2011). https://doi.org/10.1007/s11901-011-0112-4

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