Gastroenterology

Gastroenterology

Volume 119, Issue 1, July 2000, Pages 172-180
Gastroenterology

Liver, Pancreas, and Biliary Tract
Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B,☆☆,

https://doi.org/10.1053/gast.2000.8559Get rights and content

Abstract

Background & Aims: One-year lamivudine therapy significantly suppressed hepatitis B virus (HBV) replication, improved hepatic necroinflammatory activity, and prevented progression of fibrosis. However, the effects of prolonged therapy are unknown. Methods: A total of 334 Asian patients with chronic hepatitis B from a previously reported 1-year study were randomized to receive either lamivudine (100 or 25 mg) or placebo for another year. The effects of treatment on serum HBV-DNA suppression, alanine transaminase (ALT) normalization, and hepatitis B e antigen (HBeAg) seroconversion were measured. The presence of YMDD variant HBV and its effect were also determined. Results: A significantly greater proportion of patients achieved sustained HBV-DNA suppression and ALT normalization with 100 mg lamivudine daily for 2 years compared with lamivudine for 1 year followed by placebo for the second year (P < 0.001). Daily lamivudine therapy for 2 years was safe and resulted in incremental HBeAg seroconversion from 17% at week 52 to 27% at week 104. HBeAg seroconversion during continued lamivudine therapy increased linearly with increasing pretherapy ALT levels (P < 0.001). Despite the emergence of YMDD mutant in 38% of the patients, they continued to clear serum HBeAg and maintain lower median serum HBV-DNA and ALT levels than baseline values. In contrast, ALT levels increased 8-12 weeks after switching from lamivudine to placebo, but returned to normal once lamivudine treatment was resumed. Conclusions: Treatment with lamivudine for 2 years is both well tolerated and efficacious in patients with chronic hepatitis B.

GASTROENTEROLOGY 2000;119:172-180

Section snippets

Study design

A total of 358 Chinese patients with chronic HBV infection were recruited into the first year of the study between July 1994 and July 1995 from 7 centers in Taiwan, Singapore, and Hong Kong, as reported previously.10 In the first year of the trial, patients were randomized to receive either 25 or 100 mg lamivudine daily or placebo. To ensure blinding of the first year data and continuity of the study, patients were randomized again before the first year randomization codes were broken. Patients

Study population

Of the 358 patients enrolled in the first year of the study, 24 patients withdrew and/or declined to participate in the second year of the study after rerandomization. The intent-to-treat population for the follow-up study, therefore, consisted of 334 Chinese patients with chronic hepatitis B (Figure 1).

. Study design and patient disposition. After randomization by the end of week 52, 334 of the 358 year 1 patients entered the second year of the study with 93 and 101 patients continuing to

Discussion

This study is a 1-year follow-up study from a previous 1-year study that showed that lamivudine therapy induced suppression of HBV replication for up to 1 year, and was significantly associated with normalization of ALT levels, HBeAg seroconversion, reduction in liver necroinflammatory activity, and reduced progression of hepatic fibrosis.10 The current follow-up study shows that 100 mg lamivudine once daily for 2 years continues to suppress viral replication in association with ALT level

Acknowledgements

The authors thank Lynn Condreay, Ph.D., for the evaluation of genotypic resistance to lamivudine, and the study monitors Maggie Yang, Hilary Lau, See-Wah Loke, Stephen-Loucian Lowe, and Carmen Sephton.

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Address requests for reprints to: Yun-Fan Liaw, M.D., Liver Research Unit, Chang Gung Memorial Hospital, 199, Tung Hwa North Road, Taipei, Taiwan 105. e-mail: [email protected]; fax: (886) 3-328-2824.

☆☆

Supported by Glaxo Wellcome Research and Development, England.

In addition to the authors, the members of the Asia Hepatitis Lamivudine Study Group were: Clinical Group: Y. T. Lee, Steve W. C. Tsang, Henry L. Y. Chan, Sara Cheung, and Yolanda Yan, Department of Medicine, Prince of Wales Hospital, Hong Kong; W. M. Wong and M. F. Yuen, Department of Medicine, Queen Mary Hospital, Hong Kong; Lim Seng Gee, Yeoh Khay Guan, and Dede Selamat Sutedja, Department of Medicine, National University Hospital, Singapore; Chuah Khoon Beng and Ng Han Seong, Department of Gastroenterology, Singapore General Hospital, Singapore; Chuan-Mo Lee, Liver Unit, Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Mei-Feng Ke, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; and Mark Atkins and Fraser Gray, Glaxo Wellcome.

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