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Objective: Adefovir dipivoxil (ADV) is a nucleoside analogue that inhibits wild-type hepatitis B virus (HBV) and lamivudine-resistant HBV mutants in vitro and in vivo. The aim of this study was to evaluate the efficacy of ADV against lamivudine-resistant mutants and of adefovir and interferon (IFN) add-on to lamivudine for patients with severe acute exacerbation of hepatitis caused by lamivudine-resistant mutants. Methods: Fourteen patients with breakthrough hepatitis were treated with ADV. Four of the 14 patients also received IFN as combined treatment for severe acute exacerbation of hepatitis. Results: At week 24, serum HBV DNA levels had significantly decreased by a median of over 4.8 log copies/ml in the ADV group and over 5.9 log copies/ml in the ADV + IFN group compared to baseline. The median decrease in alanine aminotransferase (ALT) levels from baseline to week 24 was –1.05 times the upper limit of normal (ULN) in the ADV group [significant at week 24 compared with baseline (p = 0.012)] and –22.3 times the ULN in the ADV + IFN group. Conclusions: Administration of ADV add-on to lamivudine for patients with breakthrough hepatitis reduced HBV DNA and ALT levels. ADV and IFN add-on to lamivudine could prevent a fatal course in patients with severe acute exacerbation of hepatitis.Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The purpose of this clinical study was to determine the effect of long-term interferon (IFN) administration on the incidence of hepatocellular carcinomas (HCC) in chronic hepatitis C patients, without eradication of hepatitis C virus (HCV) by IFN therapy. Methods: The number of patients with biopsy-proven chronic hepatitis with moderate or severe staging, HCV genotype 1b, a high viral load exceeding 1 MEq/ml (mega equivalents per milliliter), who received 6 MU of natural IFN-α daily for 2–8 weeks, followed by three times/week for 16–22 weeks, as initial IFN therapy, and positivity for HCV RNA during IFN administration was 131. 47 of the 131 patients continued to be treated with IFN (long-term IFN group, dose 3 or 6 MU twice or three times weekly for 1.5–10.5 years, median 4.0 years) after initial IFN therapy, while 84 patients did not receive any IFN therapy apart from the initial 6-month course (no-add-IFN group). The patients were prospectively monitored, and the cumulative incidence of HCC and risk factors for HCC were examined. Results: The 5- and 10-year cumulative rates of HCC were 1.9 and 6.4% and 1.9 and 26.8% for long-term IFN and no-add-IFN groups, respectively. Cox regression analysis indicated that the relative risk of HCC in the patients of the no-add-IFN group was 8.72 times of that in patients of the long-term IFN group. Conclusion: Long-term IFN therapy in patients with chronic HCV infection is effective in preventing hepatocarcinogenesis.Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: During the course of chronic hepatitis B virus (HBV) infection, severe acute exacerbations of the infection often occur spontaneously and follow a fulminating progression to fatal hepatic failure. The aim of this study was to clarify potential factors, including benefit of lamivudine therapy, which could influence clinical course of the serious disease in an area of intermediate HBV endemicity. Methods and Results: Using a database of 3,163 chronically HBV-infected patients, 418 (13.2%) developed acute exacerbation of hepatitis B. Of the 418 patients, 52 (12.4%) spontaneously developed severe acute exacerbation and were included in this study. Of the 52 patients, 23 were treated with lamivudine. In multivariate analyses, fulminating progression to hepatic failure (odds ratio, 15.45; 95% confidence interval, 3.71–64.41; p = 0.0002) was a significantly independent predictor of patient survival. Three variables were independently associated with fulminating development of hepatic failure: presence of cirrhosis (29.06, 1.74–85.56, 0.019, respectively), higher baseline bilirubin level (14.89, 1.31–52.91, 0.029, respectively), and genotype B (22.14, 1.59–29.68, 0.021, respectively). Treatment lacking lamivudine was a significant factor that contributed to shorter survival time, development of hepatic failure, and progression to cirrhosis in univariate analyses (p = 0.014, 0.012 and 0.0030, respectively). Conclusion: In an area of intermediate HBV endemicity, certain proportion of chronic hepatitis B patients could spontaneously develop the serious disease. Factors influencing clinical course of the disease should be identified to improve prognosis and establish more rational and effective therapeutic strategies. Lamivudine therapy could potentially benefit the serious disease, although larger series of patients and longer follow-up periods are needed.Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

AbstractBackground: To elucidate the influence of serum hepatitis B virus (HBV) load on hepatocellular carcinogenesis in cirrhotic patients, HBV-DNA was sequentially measured. Patients and Methods: Among 160 consecutive patients with HBV-related cirrhosis who received no anti-viral therapy, serial assay of HBV-DNA concentration was available in 146 (91.3%): 48 developed hepatocellular carcinoma (HCC) and 98 did not during a median of 11.7 years. HBV-DNA of 103.7 copies/ml or less was considered as low. Results: Of the 48 cases with eventual HCC development (group A), 9 showed intermittently high HBV-DNA, and the other 39 persistently high values. Among 48 age- and sex-matched control patients (group B) selected from the 98 HCC-free patients, 9 had continuously low HBV-DNA, 13 showed a settled down course of HBV-DNA, 9 intermittently high, and the remaining 17 patients demonstrated continuously high HBV-DNA. High HBV-DNA in the last 3 years was significantly associated with carcinogenesis (group A; 0/48 vs. group B; 22/48, p < 0.0001). No patient with a continuously low HBV-DNA for the last 3 years developed HCC. Conclusion: Persistence of high HBV-DNA concentration suggested an increased risk of carcinogenesis. Sequential analysis of HBV-DNA is important in the assessment of the carcinogenesis risk.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]