Continued Lamivudine Therapy in Patients with Chronic Hepatitis B

Abstract

From September 1995 through April 2002, 286 patients with chronic hepatitis B were started on lamivudine at the Toranomon Hospital in Tokyo, Japan, and most of them continued with it. At present, 16 patients received lamivudine for 5 years, 7 of whom for 7 years or longer. YMDD mutants increased gradually and developed in 69% of them during the 7 years on lamivudine. Biochemical and virological responses were achieved in 9 of the 16 patients (56%) at 5 years, and in 4 of the 7 patients (57%) at 7 years. Histological assessments were performed at 3 years in the 16 patients and further at 4 and 7 years in the 7 patients. Necroinflammatory changes improved remarkably with a decrease in the total histological activity score from 11.3 ± 3.0 to 4.1 ± 1.7 (p < 0.0001) at 3 years in the 16 patients. Histological improvements continued in 4 of the 7 patients (57%) at 7 years on lamivudine, while the pathology was unchanged in 2 patients (29%) and aggravated in the remaining 1 patient (14%). Severe acute exacerbation of hepatitis developed in 1 patient, who received additional interferon-α therapy to cope with it. Based on my experience, the continuation of lamivudine in patients with chronic hepatitis B benefits approximately two thirds of them with persistent virological and biochemical responses accompanied by histological improvements. Breakthrough hepatitis induced by YMDD mutants along the way in a small number of patients needs to be diagnosed promptly by regular monitoring for transaminases and, if it develops, it can be treated with interferon or other antiviral agents.

Response to long‐term lamivudine treatment in patients infected with hepatitis B virus genotypes A, B, and C

“…In accordance with a poor virological response, YMDD mutants developed more frequently in patients with genotype A than B or C, both in those with (82% [9/ 11] In multivariate analysis, pretreatment HBeAg and genotype A were significant predictive factors for the emergence of YMDD mutants. In confirmation of previous results Liaw, 2002; Kumada, 2003], low ALT levels, HBeAg, severe liver disease, and high HBV DNA at the baseline independently enhanced the development of breakthrough hepatitis (Table III). Breakthrough hepatitis was not influenced by HBV genotypes, however, probably because of the patients with genotype A were fewer than those with genotype B or C (15 vs. 38 or 449).…”

“…Long-term lamivudine therapy is beneficial for patients with chronic hepatitis B [Lok and McMahon, 2001;Dienstag et al, 2003;Kumada, 2003;Lok et al, 2003], and can retard the progression of fibrosis [Lai et al, 1998;Dienstag et al, 2003;Suzuki et al, 2003b]. Remarkably, treatment decreased the incidence of hepatocellular carcinoma from 7.4% to 3.9% during the median of 2.7 years [Liaw et al, 2004] and from 13.3% to 1.1% during 2.7 years or longer in a multicenter retrospective study [Matsumoto et al, 2005].…”

Antiviral therapies: Focus on hepatitis B reverse transcriptase

“…In a study that followed LVD-treated patients for 5 years or longer, there was virological and biochemical response in 67% of patients infected with genotype B and in 54% of patients infected with genotype C (Kumada, 2003). In a separate study, Kao et al reported significant differences in the response to LVD treatment among patients infected with genotype B compared to those infected with genotype C (23% vs. 11%) (Kao et al, 2002).…”

Virological outcomes in patients infected chronically with hepatitis B virus genotype A in comparison with genotypes B and C

“…HBV infection prevails among homosexuals in Western countries where genotype A is frequent, who poorly respond to vaccines [Goilav and Piot, 1989]. Genotype A infection in Japan has a propensity to become chronic and tends to respond to antiviral therapies better than genotype B or C infection [Kobayashi et al, 2002, 2003Suzuki et al, 2005.…”

“…Hence seroconversion was achieved in 14 of the 19 (74%) patients with genotype A. In view of lamivudine, adefovir dipivoxil, and pegylated interferon that are reported efficacious in treatment of chronic hepatitis B [Perrillo et al, 2000;Hadziyannis et al, 2003;Kumada, 2003;Janssen et al, 2005], it would be unethical to evaluate genotypedependent differences in the natural course of persistent HBV infection.…”