Liver histology of Asian patients with chronic hepatitis B on prolonged lamivudine therapy

Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Alimentary Pharmacology & Therapeutics (Impact Factor: 5.73). 05/2005; 21(7):841-9. DOI: 10.1111/j.1365-2036.2005.02410.x
Source: PubMed


Long-term effect of YMDD mutations on liver histology in Chinese hepatitis B patients is unknown.
To examine the effect of prolonged lamivudine treatment on liver histology in Chinese patients with and without YMDD mutations.
Liver histology was assessed in 85 patients on long-term lamivudine at baseline and year 1, and at year 3 for 25 patients.
Comparing patients with and without YMDD mutations at year 1, the former had higher baseline median necroinflammatory (11 vs. six respectively, P = 0.014) and fibrosis scores (three vs. one respectively, P = 0.001). The proportion of patients with improvement in necroinflammation and worsening of fibrosis was comparable for patients with and without YMDD mutations at year 1 (57.1%, 14.3% vs. 55%, 15% respectively) and year 3 (57.9%, 26.3% vs. 50%, 16.7% respectively). Comparing the histology at year 1 and 3, more patients with YMDD mutations developing after year 1 had worsening of necroinflammation than patients with persistent YMDD wild type (53.8% vs. 25% respectively).
Patients who developed YMDD mutations had higher baseline histological scores. With YMDD mutations, the liver histology became less favourable after 3 years than at the first year, although there was still improvement when compared with that at baseline.

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    • "For HBeAg-negative disease, increased HBV DNA levels were independently associated with significant fibrosis. The findings are in line with the suggestion of suppressing HBV DNA permanently as a treatment end point [30], especially when long-term viral suppression has been shown to reverse histologic damage [31], [32]. Serum HBV DNA levels had no association with fibrosis in the immune clearance phase, which can be explained by an extensive immune-mediated response leading to low viremic levels despite significant abnormalities on histology [33]. "
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    ABSTRACT: To evaluate histological changes with interferon monotherapy or interferon plus lamivudine combination therapy in children with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. 31 children aged 2-13 years were randomly treated with interferon (IFN) (group 1, n = 16) or IFN plus simultaneously started lamivudine (group 2, n = 15). IFN-alpha 2a was given 9 MU/m2 3 times per week for 6 months in each group; lamivudine was given 4 mg x kg(-1) x day(-1) for 24 months. Liver biopsy specimens were evaluated according to the Knodell score before therapy and after 24 months of therapy. Histological response was defined as a decrease in the histological activity index (HAI) score by at least 2 points. Efficacy of therapy was evaluated at 24 months of therapy in all children. Alanine aminotransferase normalization, HbeAg, and hepatitis B virus DNA clearance were not different. Complete response and histological response were 37.5%/62.5% and 40%/46.7% in groups 1 and 2, respectively (P = NS). At baseline and at 24 months of therapy, total HAI and components of HAI were not different in the 2 groups. In comparison with baseline, a significant decrease in scores of periportal +/- bridging necrosis was observed in group 1 (P = 0.01); periportal +/- bridging necrosis, intralobular degeneration, focal necrosis, and necroinflammation scores significantly decreased in group 2 (P = 0.04 and P = 0.02) at 24 months of therapy. The addition of lamivudine to IFN-alpha did not increase the effectiveness of the treatment in terms of complete and histological responses. Both therapies seemed to be effective in the regression of periportal +/- bridging necrosis. In addition, combination therapy was also effective in the regression of intralobular degeneration, focal necrosis, and necroinflammatory activity index.
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