A prospective and comparative cohort study on efficacy and drug resistance during long-term lamivudine treatment for various stages of chronic hepatitis B and cirrhosis

Tomohiro Nishida, Haruhiko Kobashi, Shin Ichi Fujioka, Kozo Fujio, Kouichi Takaguchi, Hiroshi Ikeda, Mitsuhiko Kawaguchi, Masaharu Ando, Yasuyuki Araki, Toshihiro Higashi, Bon Shoji, Akinobu Takaki, Yoshiaki Iwasaki, Kohsaku Sakaguchi, Yasushi Shiratori, Kazuhide Yamamoto

Research output: Contribution to journalArticle

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Abstract

Background and Aims: A prospective, non-randomized cohort study on long-term lamivudine treatment, comparing efficacy, drug resistance, and prognosis for various stages of chronic hepatitis B virus (HBV)-related liver disease was performed to elucidate the significance and indication of lamivudine for individual patients at each stage of disease. Methods: A total of 158 cases consisting of 87 chronic hepatitis, 28 compensated cirrhosis, and 43 decompensated cirrhosis, with serum HBV-DNA > 5 log10 copies/mL and with elevated alanine aminotransferase (ALT) over twice the upper normal limit or complications of hepatic insufficiency, were administered 100 mg of lamivudine daily and monitored for HBV markers, biochemistry, and prognosis. Results: Lamivudine reduced HBV-DNA and ALT equally in all groups. Serum albumin, prothrombin time (%), and platelet count increased in all groups. The increased margin of albumin was the highest in the decompensated cirrhosis and higher in the compensated cirrhosis than the chronic hepatitis groups. Cumulative incidence of virologic breakthrough was 16%, 42%, 49%, and 53% at 12, 24, 36, and 48 months, respectively, and the strongest predictive factor for lamivudine resistance was persistent HBV-DNA at 3 months. Ascites, encephalopathy, and jaundice improved in the majority of patients with decompensated cirrhosis. On the other hand, hepatic failure developed or deteriorated in 10 patients after virologic breakthrough, and nine of them had decompensated cirrhosis. Conclusions: Lamivudine was effective in reducing HBV-DNA and improving hepatic reserve at all stages and was most beneficial and significant for decompensated cirrhosis. Meanwhile, close monitoring of viral load and immediate rescue treatment for lamivudine resistance is necessary to prevent hepatic failure in decompensated cirrhosis.

Original languageEnglish
Pages (from-to)794-803
Number of pages10
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume23
Issue number5
DOIs
Publication statusPublished - 2008

Fingerprint

Lamivudine
Chronic Hepatitis B
Drug Resistance
Fibrosis
Cohort Studies
Hepatitis B virus
DNA
Liver Failure
Chronic Hepatitis
Therapeutics
Alanine Transaminase
Hepatic Insufficiency
R Factors
Prothrombin Time
Brain Diseases
Jaundice
Viral Load
Platelet Count
Ascites
Serum Albumin

Keywords

  • Adefovir dipivoxil
  • Chronic hepatitis B
  • Cirrhosis
  • Drug resistance
  • Efficacy
  • HBV-DNA
  • Hepatitis B virus
  • Hepatocellular carcinoma
  • Lamivudine
  • Nucleoside analog

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

A prospective and comparative cohort study on efficacy and drug resistance during long-term lamivudine treatment for various stages of chronic hepatitis B and cirrhosis. / Nishida, Tomohiro; Kobashi, Haruhiko; Fujioka, Shin Ichi; Fujio, Kozo; Takaguchi, Kouichi; Ikeda, Hiroshi; Kawaguchi, Mitsuhiko; Ando, Masaharu; Araki, Yasuyuki; Higashi, Toshihiro; Shoji, Bon; Takaki, Akinobu; Iwasaki, Yoshiaki; Sakaguchi, Kohsaku; Shiratori, Yasushi; Yamamoto, Kazuhide.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 23, No. 5, 2008, p. 794-803.

Research output: Contribution to journalArticle

Nishida, T, Kobashi, H, Fujioka, SI, Fujio, K, Takaguchi, K, Ikeda, H, Kawaguchi, M, Ando, M, Araki, Y, Higashi, T, Shoji, B, Takaki, A, Iwasaki, Y, Sakaguchi, K, Shiratori, Y & Yamamoto, K 2008, 'A prospective and comparative cohort study on efficacy and drug resistance during long-term lamivudine treatment for various stages of chronic hepatitis B and cirrhosis', Journal of Gastroenterology and Hepatology (Australia), vol. 23, no. 5, pp. 794-803. https://doi.org/10.1111/j.1440-1746.2007.05240.x
Nishida, Tomohiro ; Kobashi, Haruhiko ; Fujioka, Shin Ichi ; Fujio, Kozo ; Takaguchi, Kouichi ; Ikeda, Hiroshi ; Kawaguchi, Mitsuhiko ; Ando, Masaharu ; Araki, Yasuyuki ; Higashi, Toshihiro ; Shoji, Bon ; Takaki, Akinobu ; Iwasaki, Yoshiaki ; Sakaguchi, Kohsaku ; Shiratori, Yasushi ; Yamamoto, Kazuhide. / A prospective and comparative cohort study on efficacy and drug resistance during long-term lamivudine treatment for various stages of chronic hepatitis B and cirrhosis. In: Journal of Gastroenterology and Hepatology (Australia). 2008 ; Vol. 23, No. 5. pp. 794-803.
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AU - Kobashi, Haruhiko

AU - Fujioka, Shin Ichi

AU - Fujio, Kozo

AU - Takaguchi, Kouichi

AU - Ikeda, Hiroshi

AU - Kawaguchi, Mitsuhiko

AU - Ando, Masaharu

AU - Araki, Yasuyuki

AU - Higashi, Toshihiro

AU - Shoji, Bon

AU - Takaki, Akinobu

AU - Iwasaki, Yoshiaki

AU - Sakaguchi, Kohsaku

AU - Shiratori, Yasushi

AU - Yamamoto, Kazuhide

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N2 - Background and Aims: A prospective, non-randomized cohort study on long-term lamivudine treatment, comparing efficacy, drug resistance, and prognosis for various stages of chronic hepatitis B virus (HBV)-related liver disease was performed to elucidate the significance and indication of lamivudine for individual patients at each stage of disease. Methods: A total of 158 cases consisting of 87 chronic hepatitis, 28 compensated cirrhosis, and 43 decompensated cirrhosis, with serum HBV-DNA > 5 log10 copies/mL and with elevated alanine aminotransferase (ALT) over twice the upper normal limit or complications of hepatic insufficiency, were administered 100 mg of lamivudine daily and monitored for HBV markers, biochemistry, and prognosis. Results: Lamivudine reduced HBV-DNA and ALT equally in all groups. Serum albumin, prothrombin time (%), and platelet count increased in all groups. The increased margin of albumin was the highest in the decompensated cirrhosis and higher in the compensated cirrhosis than the chronic hepatitis groups. Cumulative incidence of virologic breakthrough was 16%, 42%, 49%, and 53% at 12, 24, 36, and 48 months, respectively, and the strongest predictive factor for lamivudine resistance was persistent HBV-DNA at 3 months. Ascites, encephalopathy, and jaundice improved in the majority of patients with decompensated cirrhosis. On the other hand, hepatic failure developed or deteriorated in 10 patients after virologic breakthrough, and nine of them had decompensated cirrhosis. Conclusions: Lamivudine was effective in reducing HBV-DNA and improving hepatic reserve at all stages and was most beneficial and significant for decompensated cirrhosis. Meanwhile, close monitoring of viral load and immediate rescue treatment for lamivudine resistance is necessary to prevent hepatic failure in decompensated cirrhosis.

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KW - Hepatocellular carcinoma

KW - Lamivudine

KW - Nucleoside analog

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