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Predictors for early HBeAg loss during lamivudine therapy in HBeAg-positive chronic hepatitis B patients with acute exacerbation

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Abstract

Purpose

To examine the rate of early HBeAg loss and predictors of HBeAg loss in HBeAg-positive chronic hepatitis B (CHB) patients with acute exacerbation (AE) treated with lamivudine.

Methods

A total of 146 patients diagnosed with CHB and AEs were included in this retrospective study. Patients were divided into two groups: decompensated and compensated.

Results

The mean treatment duration for the decompensated and compensated groups was 18.1 and 19.9 months, respectively. Decompensated patients were significantly older and had a higher prevalence of cirrhosis and genotype B infection than compensated patients. Compared to compensated patients, decompensated patients achieved a higher rate of HBeAg loss (25.8 vs. 14.3%; P = 0.0805) at 3 months of therapy, a higher rate of serum HBV DNA negativity (53.2 vs. 29.8%; P = 0.0042), and a lower rate of rtM204V/I mutation (3.2 vs. 16.7%; P = 0.0139) after 12 months of lamivudine therapy. The rates of HBeAg loss after 6 and 12 months of lamivudine therapy were similar between the two groups. Logistic regression analysis revealed that female gender and baseline ALT level ≥1,000 IU/L, but not decompensations, were significant predictors of HBeAg loss at 3 months; however, only female gender was a significant predictor of HBeAg loss after 6 and 12 months of lamivudine therapy. The early HBeAg losers showed a significantly higher sustained remission rate off lamivudine therapy.

Conclusions

Female gender and baseline serum ALT level ≥1,000 IU/L were independent predictors of early HBeAg loss during lamivudine therapy in HBeAg-positive CHB patients with AE.

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Abbreviations

AE:

Acute exacerbation

ALT:

Alanine aminotransferase

AFP:

Alpha-fetoprotein

AST:

Aspartate aminotransferase

CHB:

Chronic hepatitis B

CI:

Confidence interval

HAV:

Hepatitis A virus

HBeAg:

Hepatitis B e antigen

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HDV:

Hepatitis D virus

OR:

Odds ratio

PT:

Prothrombin time

RFLP:

Restriction fragment length polymorphism

rtM204V/I:

Reverse transcriptase domain 204 methionine-to-valine/isoleucine mutation

SD:

Standard deviation

ULN:

Upper limit of normal

References

  1. Fattovich G. Natural history and prognosis of hepatitis B. Semin Liver Dis 2003;23:47–58

    Article  PubMed  Google Scholar 

  2. Chu CM, Liaw YF. Chronic hepatitis B virus infection acquired in childhood: special emphasis on prognostic and therapeutic implication of delayed HBeAg seroconversion. J Viral Hepat 2007;14:147–152

    Article  PubMed  Google Scholar 

  3. Liaw YF. Hepatitis flares and hepatitis B e antigen seroconversion: implication in anti-hepatitis B virus therapy. J Gastroenterol Hepatol 2003;18:246–252

    Article  CAS  PubMed  Google Scholar 

  4. Sheen IS, Liaw YF, Tai DI, et al. Hepatic decompensation associated with hepatitis B e antigen clearance in chronic type B hepatitis. Gastroenterology 1985;89:732–735

    CAS  PubMed  Google Scholar 

  5. Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol 2005;5:215–229

    Article  CAS  PubMed  Google Scholar 

  6. Tsai SL, Chen PJ, Lai MY, et al. Acute exacerbations of chronic type B hepatitis are accompanied by increased T cell responses to hepatitis B core and e antigens. Implications for hepatitis B e antigen seroconversion. J Clin Invest 1992;89:87–96

    Article  CAS  PubMed  Google Scholar 

  7. Shimada N, Yamamoto K, Kuroda MJ, et al. HBcAg-specific CD8 T cells play an important role in virus suppression, and acute flare-up is associated with the expansion of activated memory T cells. J Clin Immunol 2003;23:223–232

    Article  CAS  PubMed  Google Scholar 

  8. Nicoll A, Locarnini S. Review: present and future directions in the treatment of chronic hepatitis B infection. J Gastroenterol Hepatol 1997;12:843–854

    Article  CAS  PubMed  Google Scholar 

  9. Tsang SWC, Chan HLY, Leung NWY, et al. Lamivudine treatment for fulminant hepatic failure due to acute exacerbation of chronic hepatitis B infection. Aliment Pharmacol Ther 2001;15:1737–1744

    Article  CAS  PubMed  Google Scholar 

  10. Chan HL, Tsang SW, Hui Y, et al. The role of lamivudine and predictors of mortality in severe flare-up of chronic hepatitis B with jaundice. J Viral Hepat 2002;9:424–428

    Article  PubMed  Google Scholar 

  11. Chien RN, Lin CH, Liaw YF. The effect of lamivudine therapy in hepatic decompensation during acute exacerbation of chronic hepatitis B. J Hepatol 2003;38:322–327

    Article  CAS  PubMed  Google Scholar 

  12. Yuen MF, Sablon E, Hui CK, et al. Prognostic factors in severe exacerbation of chronic hepatitis B. Clin Infect Dis 2003;36:979–984

    Article  PubMed  Google Scholar 

  13. Tsubota A, Arase Y, Suzuki Y, et al. Lamivudine monotherapy for spontaneous severe acute exacerbation of chronic hepatitis B. J Gastroenterol Hepatol 2005;20:426–432

    Article  CAS  PubMed  Google Scholar 

  14. Dai CY, Yu ML, Hsieh MY, et al. Early response to lamivudine therapy in clinically non-cirrhotic chronic hepatitis B patients with decompensation. Liver Int 2007;27:1364–1370

    Article  CAS  PubMed  Google Scholar 

  15. Chien RN, Liaw YF, Atkins M. Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion during lamivudine therapy in patients with chronic hepatitis B. Hepatology 1999;30:770–774

    Article  CAS  PubMed  Google Scholar 

  16. Perrillo RP, Lai CL, Liaw YF, et al. Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B. Hepatology 2002;36:186–194

    Article  CAS  PubMed  Google Scholar 

  17. Akuta N, Tsubota A, Suzuki F, et al. Long-term prognosis by lamivudine monotherapy for severe acute exacerbation in chronic hepatitis B infection: emergence of YMDD motif mutant and risk of breakthrough hepatitis––an open-cohort study. J Hepatol 2003;38:91–97

    Article  CAS  PubMed  Google Scholar 

  18. Tsubota A, Arase Y, Suzuki F, et al. Severe acute exacerbation of liver disease may reduce or delay emergence of YMDD motif mutants in long-term lamivudine therapy for hepatitis B e antigen-positive chronic hepatitis B. J Med Virol 2004;73:7–12

    Article  CAS  PubMed  Google Scholar 

  19. Wong VW, Wong GL, Tsang SW, et al. Long-term follow-up of lamivudine treatment in patients with severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. Antivir Ther 2008;13:571–579

    PubMed  Google Scholar 

  20. Lin DY, Sheen IS, Chiu CT, et al. Ultrasonographic changes of early liver cirrhosis in chronic hepatitis B: a longitudinal study. J Clin Ultrasound 1993;21:303–308

    Article  CAS  PubMed  Google Scholar 

  21. Dai MS, Wu PF, Shyu RY, et al. Hepatitis B virus reactivation in breast cancer patients undergoing cytotoxic chemotherapy and the role of preemptive lamivudine administration. Liver Int 2004;24:540–546

    Article  CAS  PubMed  Google Scholar 

  22. Mizokami M, Nakano T, Orito E, et al. Hepatitis B virus genotype assignment using restriction fragment length polymorphism patterns. FEBS Lett 1999;450:66–71

    Article  CAS  PubMed  Google Scholar 

  23. Tseng TC, Liu CJ, Wang CC, et al. A higher alanine aminotransferase level correlates with earlier hepatitis B e antigen seroconversion in lamivudine-treated chronic hepatitis B patients. Liver Int 2008;28:1034–1041

    Article  CAS  PubMed  Google Scholar 

  24. Stevens CE, Beasley RP, Tsui J, et al. Vertical transmission of hepatitis B antigen in Taiwan. N Engl J Med 1975;292:771–774

    Article  CAS  PubMed  Google Scholar 

  25. Hsu HY, Chang MH, Chen DS, et al. Baseline seroepidemiology of hepatitis B virus infection in children in Taipei, 1984: a study just before mass hepatitis B vaccination program in Taiwan. J Med Virol 1986;18:301–307

    Article  CAS  PubMed  Google Scholar 

  26. Liaw YF, Chu CM, Huang MJ, et al. Determinants for hepatitis B e antigen clearance in chronic type B hepatitis. Liver 1984;4:301–306

    CAS  PubMed  Google Scholar 

  27. Chu CM, Sheen IS, Lin SM, et al. Sex difference in chronic hepatitis B virus infection: studies of serum HBeAg and alanine aminotransferase levels in 10, 431 asymptomatic Chinese HBsAg carriers. Clin Infect Dis 1993;16:709–713

    CAS  PubMed  Google Scholar 

  28. Chu CM, Hung SJ, Lin J, et al. Natural history of hepatitis B e antigen to antibody seroconversion in patients with normal serum aminotransferase levels. Am J Med 2004;116:829–834

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Professor Yun-Fan Liaw for his insightful comments on the manuscript. This study was supported by the grants DMR-94-001, DMR-96-021 and DMR-96-105 from China Medical University Hospital, Taichung, Taiwan, and by the Liver Disease Prevention and Treatment Research Foundation.

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Authors and Affiliations

  1. Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan

    Cheng-Yuan Peng, Chih-Bin Chen, Hsueh-Chou Lai, Wen-Pang Su & Po-Heng Chuang

  2. Department of Applied Mathematics, Institute of Statistics, National Chung-Hsing University, 250, Kuo Kuang Road, Taichung, 402, Taiwan

    Hong-Dar Isaac Wu

  3. Department of Surgery, China Medical University Hospital, No 2, Yuh-Der Road, Taichung, 404, Taiwan

    Long-Bin Jeng

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  1. Cheng-Yuan Peng
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Correspondence to Cheng-Yuan Peng.

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Peng, CY., Chen, CB., Lai, HC. et al. Predictors for early HBeAg loss during lamivudine therapy in HBeAg-positive chronic hepatitis B patients with acute exacerbation. Hepatol Int 5, 586–596 (2011). https://doi.org/10.1007/s12072-010-9227-x

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  • DOI: https://doi.org/10.1007/s12072-010-9227-x

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