A prospective and comparative cohort study on efficacy and drug resistance during long-term lamivudi

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Journal of Gastroenterology and Hepatology 23 (5) , 794–803

doi:10.1111/j.1440-1746.2007.05240.x

Abstract

HEPATOLOGY

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,**Department of Gastroenterology and Hepatology, Okayama

University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,

Okayama, Haruhiko Kobashi,**Department of Gastroenterology and Hepatology,

Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical

Sciences, Okayama, Dr Haruhiko Kobashi, Department of Gastroenterology and

Hepatology, Okayama University Graduate School of Medicine, Dentistry and

Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama-city, Okayama 700-8558,

Japan. Email: hkobashi@... Shin-ichi Fujioka,††Department of

Medicine, Okayama Saiseikai General Hospital, Okayama, Kozo Fujio,‡‡Department

of Medicine, Fukuyama City Hospital, Fukuyama, Kouichi Takaguchi,§§Department of

Medicine, Kagawa Prefectural Central Hospital, Takamatsu, Hiroshi

Ikeda,¶¶Department of Gastroenterology, Kurashiki Central Hospital, Kurashiki,

Mitsuhiko Kawaguchi,††Department of Medicine, Okayama Saiseikai General

Hospital, Okayama, Masaharu Ando,****Department of Medicine, Mitoyo General

Hospital, Mitoyo, Yasuyuki Araki,††††Department of Medicine, Hiroshima City

Hospital, Hiroshima, and Toshihiro Higashi,‡‡‡‡Department of Medicine, Okayama

Citizens' Hospital, Okayama, Japan Bon Shoji,**Department of Gastroenterology

and Hepatology, Okayama University Graduate School of Medicine, Dentistry and

Pharmaceutical Sciences, Okayama, Akinobu Takaki,**Department of

Gastroenterology and Hepatology, Okayama University Graduate School of Medicine,

Dentistry and Pharmaceutical Sciences, Okayama, Yoshiaki Iwasaki,**Department of

Gastroenterology and Hepatology, Okayama University Graduate School of Medicine,

Dentistry and Pharmaceutical Sciences, Okayama, Kohsaku Sakaguchi,**Department

of Gastroenterology and Hepatology, Okayama University Graduate School of

Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Yasushi

Shiratori**Department of Gastroenterology and Hepatology, Okayama University

Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, and

Kazuhide Yamamoto**Department of Gastroenterology and Hepatology, Okayama

University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,

Okayama, *Department of Gastroenterology and Hepatology, Okayama University

Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama,

†Department of Medicine, Okayama Saiseikai General Hospital, Okayama,

‡Department of Medicine, Fukuyama City Hospital, Fukuyama, §Department of

Medicine, Kagawa Prefectural Central Hospital, Takamatsu, ¶Department of

Gastroenterology, Kurashiki Central Hospital, Kurashiki, **Department of

Medicine, Mitoyo General Hospital, Mitoyo, ††Department of Medicine, Hiroshima

City Hospital, Hiroshima, and ‡‡Department of Medicine, Okayama Citizens'

Hospital, Okayama, Japan

Dr Haruhiko Kobashi, Department of Gastroenterology and Hepatology, Okayama

University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,

2-5-1 Shikata-cho, Okayama-city, Okayama 700-8558, Japan. Email:

hkobashi@...

See J. Gastroenterol. Hepatol. 2008; 23: 681–682 for Editorial Comment on this

article.

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.

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1440-1746.2007.05240.x

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