Low Resistance to Adefovir Combined With Lamivudine

A 3-Year Study of 145 Lamivudine-Resistant Hepatitis B Patients

Pietro Lampertico, Mauro Viganò, Elena Manenti, Massimo Iavarone, Erwin Sablon, Massimo Colombo

Research output: Contribution to journalArticle

294 Citations (Scopus)

Abstract

Background & Aims: Adefovir monotherapy is an established treatment modality for lamivudine-experienced patients with chronic hepatitis B, but it carries a significant risk of resistance in the long term. We assessed whether this risk could be overcome by adefovir-lamivudine combination therapy. Methods: A total of 145 lamivudine-resistant patients with chronic hepatitis B (73% cirrhotics, 86% hepatitis B e antigen negative, 92% genotype D) were treated with adefovir 10 mg in addition to lamivudine 100 mg. Liver function tests and hepatitis B virus (HBV) DNA (Versant 3.0) were assessed bimonthly, whereas adefovir-related mutations were searched by INNO-LiPA assay at baseline and at yearly intervals. Results: During 42 months (range, 12-74), 116 patients (80%) cleared serum HBV DNA, 67 (84%) had normalized alanine aminotransferase levels, and 145 (100%) remained free of virologic and clinical breakthroughs, independently of the degree of HBV suppression. The rtA181V/T was the only adefovir-related mutation detected, which occurred in 6 patients at baseline (4%; 1 rtA181V and 5 rtA181T) and in an additional 3 patients (2%; all rtA181T) during treatment. In all these 9 patients, HBV DNA levels progressively declined during therapy to become undetectable in 7 (78%). The 1-, 2-, 3-, and 4-year cumulative rates of de novo rtA181T were 1%, 2%, 4%, and 4%, respectively. None of the cirrhotic patients clinically decompensated, but 11 (12%) developed hepatocellular carcinoma. Conclusions:: Under prolonged adefovir-lamivudine therapy, patients with lamivudine-resistant hepatitis B were unlikely to develop genotypic resistance to adefovir and had durable prevention of virologic and clinical breakthrough.

Original languageEnglish
Pages (from-to)1445-1451
Number of pages7
JournalGastroenterology
Volume133
Issue number5
DOIs
Publication statusPublished - Nov 2007

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Lamivudine
Hepatitis B
Hepatitis B virus
Chronic Hepatitis B
DNA
Therapeutics
Mutation
Hepatitis B e Antigens
adefovir
Liver Function Tests
Alanine Transaminase
Hepatocellular Carcinoma
Genotype
Serum

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Low Resistance to Adefovir Combined With Lamivudine : A 3-Year Study of 145 Lamivudine-Resistant Hepatitis B Patients. / Lampertico, Pietro; Viganò, Mauro; Manenti, Elena; Iavarone, Massimo; Sablon, Erwin; Colombo, Massimo.

In: Gastroenterology, Vol. 133, No. 5, 11.2007, p. 1445-1451.

Research output: Contribution to journalArticle

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abstract = "Background & Aims: Adefovir monotherapy is an established treatment modality for lamivudine-experienced patients with chronic hepatitis B, but it carries a significant risk of resistance in the long term. We assessed whether this risk could be overcome by adefovir-lamivudine combination therapy. Methods: A total of 145 lamivudine-resistant patients with chronic hepatitis B (73{\%} cirrhotics, 86{\%} hepatitis B e antigen negative, 92{\%} genotype D) were treated with adefovir 10 mg in addition to lamivudine 100 mg. Liver function tests and hepatitis B virus (HBV) DNA (Versant 3.0) were assessed bimonthly, whereas adefovir-related mutations were searched by INNO-LiPA assay at baseline and at yearly intervals. Results: During 42 months (range, 12-74), 116 patients (80{\%}) cleared serum HBV DNA, 67 (84{\%}) had normalized alanine aminotransferase levels, and 145 (100{\%}) remained free of virologic and clinical breakthroughs, independently of the degree of HBV suppression. The rtA181V/T was the only adefovir-related mutation detected, which occurred in 6 patients at baseline (4{\%}; 1 rtA181V and 5 rtA181T) and in an additional 3 patients (2{\%}; all rtA181T) during treatment. In all these 9 patients, HBV DNA levels progressively declined during therapy to become undetectable in 7 (78{\%}). The 1-, 2-, 3-, and 4-year cumulative rates of de novo rtA181T were 1{\%}, 2{\%}, 4{\%}, and 4{\%}, respectively. None of the cirrhotic patients clinically decompensated, but 11 (12{\%}) developed hepatocellular carcinoma. Conclusions:: Under prolonged adefovir-lamivudine therapy, patients with lamivudine-resistant hepatitis B were unlikely to develop genotypic resistance to adefovir and had durable prevention of virologic and clinical breakthrough.",
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