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Background/Aims : To study the outcome and the virologic profiles of severe hepatitis exacerbations due to YMDD mutants in lamivudine-treated patients. Methods : Eighteen lamivudine-treated patients with severe hepatitis exacerbations due to YMDD mutants were recruited. Laboratory and clinical parameters were monitored. Viral genotypes and YMDD mutations were determined. Results : None of the 18 patients had YMDD wild-type during exacerbations. Three (17%) and 15 (83%) patients had genotypes B and C, respectively. Elevated bilirubin levels and prolonged prothrombin time were found in 11 (61%) and six patients (33%) respectively. Three patients (17%) had adverse outcome with the development of ascites and/or encephalopathy. One of these patients required liver transplantation and one died. Both patients had evidence of cirrhosis before treatment and hepatitis B e antigen (HBeAg) seroreversion from anti-HBe positivity. The remaining 16 patients (89%) have no evidence of pre-existing cirrhosis. Thirty seven percent of patients had normal alanine aminotransferase levels at the last follow-up. The median HBV DNA level at the last follow-up was significantly lower than the pre-treatment level ( P = 0.009 ). Conclusions : Though the majority of patients with severe hepatitis exacerbations due to YMDD mutants had uneventful course, early liver transplantation should be considered in patients with pre-existing cirrhosis and HBeAg seroreversion.

The significance of early HBV DNA suppression during telbivudine treatment in predicting long-term outcomes needs further investigation.We determined the cumulative rates of HBeAg seroconversion, ALT normalization, HBV DNA suppression (12IU/ml) and telbivudine resistant mutations (using the highly sensitive line probe assay) for 117 treatment-native chronic hepatitis B (CHB) patients (61.5% HBeAg-positive) on telbivudine for 3years. The significance of serum HBV DNA at week 12 and 24 was compared.The median age and duration of follow-up were 39years and 24.2months, respectively. 117, 105, 69, and 43 patients had been followed up for at least 6months and 1, 2, and 3years, respectively. The cumulative rates of HBeAg seroconversion, ALT normalization, HBV DNA undetectability were 46.8%, 80.5%, and 51.2%, respectively, at 3years. There was an incremental increase in virologic breakthroughs to 39.5% by year 3. The cumulative rate of telbivudine resistant mutations was 4.8%, 17.6%, and 34.0% for year 1, 2, and 3, respectively. Week 12 HBV DNA of200IU/ml was predictive of a higher chance of HBV DNA undetectability (p=0.022) and lower chance of resistance (p=0.001) by year 3. Undetectable HBV DNA at week 24 was predictive of viral suppression at year 2 (p0.001) but not at year 3 (p=0.241).Continuous telbivudine resulted in improved biochemical and virologic outcomes, although there was an incremental increase in cumulative rate of resistance up to year 3. Week 12 HBV DNA of200IU/ml was predictive of favorable long-term outcomes.

Background/Aims This study aimed to measure the intrahepatic total hepatitis B virus (HBV) DNA and covalently closed circular DNA (cccDNA) levels in tumor and non-tumor tissues in hepatocellular carcinoma (HCC) patients. Methods Intrahepatic total HBV DNA and cccDNA were measured in 25 HCC patients (21 hepatitis B surface antigen [HBsAg]-positive and 4 HBsAg-negative) by the Invader ® assay. Results A low level of intrahepatic HBV DNA was detectable in all HBsAg-negative patients. For HBsAg-positive patients, the intrahepatic total HBV DNA levels in the tumor and non-tumor tissues were comparable ( P =0.903). However, the tumor tissues had significantly higher levels of cccDNA (0.35 vs. 0.16copies/cell, P =0.030) and higher proportion of intrahepatic HBV DNA in the form of cccDNA (100% vs. 84%, P =0.004) than the non-tumor tissues. Seventeen out of 21 (81%) tumor tissues had intrahepatic HBV DNA solely in cccDNA form. Analysis of HBV mRNA expression indicated that HBV replication appeared to be lower in the tumor tissues than the non-tumor tissues. Conclusions Compared to the non-tumor tissues, the levels of HBV replication in the tumor tissues appeared to be lower, and cccDNA was the predominant form of HBV DNA in the tumor tissues.

This journal suppl. entitled: Abstracts of the 42nd Annual Meeting of the European Association for the Study of the Liver ... 2007