Response to adefovir depends on mutation patterns in precore region, basal core promoter and reverse transcriptase, and on-treatment responses in Lamivudine-resistant chronic hepatitis B patients.

OBJECTIVE: In vitro studies showed that mutations in the basal core promoter (BCP) or precore (PC) region restore the replication inefficiency of the lamivudine-resistant mutant. The aim of this study was to clarify the effect of molecular characteristics on the antiviral response to adefovir in patients with lamivudine-resistant chronic hepatitis B (CHB). METHODS: Sixty-six lamivudine-resistant patients who were treated with adefovir monotherapy were studied. Sequences of BCP, PC region and reverse transcriptase were determined before adefovir therapy. In patients with virologic breakthrough, reverse transcriptase sequencing was performed. RESULTS: The cumulative probabilities of virologic response were 23.3, 46, 52.7 and 59.5% at years 1, 2, 3 and 4, respectively. PC mutation, the absence of compensatory mutations (rtL80I/V or rtV173L), and a decrease in serum hepatitis B virus (HBV) DNA by 3 log or greater at 6 months were independent predictors of virologic response. The cumulative probabilities of virologic breakthrough were 0, 12.9, 30.7 and 44.5% at years 1, 2, 3 and 4, respectively. BCP mutation and a less than 3 log decrease in serum HBV DNA at 6 months were 2 independent risk factors for virologic breakthrough. CONCLUSION: Response to adefovir depends on mutation patterns in the BCP, PC region and reverse transcriptase, and on-treatment decreases in serum HBV DNA in lamivudine-resistant CHB patients.

New scoring system for predicting relapse after lamivudine-induced hepatitis B e-antigen loss in chronic hepatitis B patients.

AIM: In endemic areas of hepatitis B virus (HBV) infection, lamivudine-induced hepatitis B e-antigen (HBeAg) loss is not durable. We developed a scoring system to predict the relapse after lamivudine-induced HBeAg loss. METHODS: Of 93 HBeAg-positive chronic hepatitis B patients receiving lamivudine therapy, we studied the 30 patients who achieved HBeAg loss. Qualitative polymerase chain reaction assays for HBV DNA were performed after HBeAg loss; if results were negative on two consecutive occasions, lamivudine treatment was stopped. Serum HBV DNA levels at the time of HBeAg loss were determined using stored serum by the Cobas Amplicor HBV Monitor Kit. RESULTS: Cumulative relapse rates were 44%, 55.8% and 59.8%, after 1, 2 and 5 years, respectively. Univariate analysis showed that the risk factors for relapse were age (>/= 30 years), HBV DNA level (>/= 60 IU/mL) at the time of HBeAg loss and liver cirrhosis. Independent risk factors for relapse were age (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.2-17.6) and serum HBV DNA level at the time of HBeAg loss (OR, 5.1; 95% CI, 1.3-21.6). We developed a scoring system based on these independent risk factors. No relapse was observed for patients with a risk score of 0. For patients with a risk score of 1, the relapse rates were 41%, 49% and 56% at 1, 2 and 5 years, respectively. All patients with a risk score of 2 relapsed (P = 0.01). CONCLUSION: Our new scoring system may be useful for predicting relapses in patients with lamivudine-induced HBeAg loss. Treatment strategies should be individualized according to risk score.

[Distribution of hepatitis C virus genotypes in Jeju Island].

BACKGROUNDS/AIMS: The hepatitis C virus (HCV) genotype affects clinical outcomes of HCV infection, in terms of the response to antiviral therapy and progression of chronic liver diseases, and shows geographic differences in distribution. The aim of this study was to elucidate the HCV genotypes in patients with chronic HCV infection in Jeju, which is an island off the Korean peninsula. METHODS: The study population consisted of 162 patients with anti-HCV antibodies and HCV-RNA. HCV genotypes were determined using genotype specific primers. RESULTS: HCV genotype 2a predominated (62.3%), followed by genotype 1b (34.0%) and 2b (3.7%). The prevalence of genotypes differed significantly with age, with HCV genotypes 1 and 2 being more frequent in older and younger subjects (P=0.035), respectively. HCV-RNA levels were higher in patients with genotype 1 than in those with genotype 2 (P=0.001). HCV genotype was not significantly related to sex, clinical diagnosis and potential risk factors. CONCLUSIONS: HCV genotype 2a is most common in Jeju, followed by genotype 1b. Our results suggest that the distribution of the HCV genotype differs between regions in Korea.