Steatosis is the predictor of relapse in HCV genotype 3- but not 2-infected patients treated with 12 weeks of pegylated interferon-α-2a plus ribavirin and RVR.

HCV genotypes 2- or 3-infected patients with a rapid virological response (RVR) to therapy with pegylated interferon and ribavirins who have a low viral load, noncirrhotic and nonobese may be considered for a shorter course of treatment. However, no studies have assessed host-viral factors associated with relapse in genotype 2 and 3 separately. Accordingly, we assessed whether 12 weeks of pegylated interferon and ribavirin was an optimized regimen for treatment of HCV genotype 2 and 3 with positive predictors of response. Power and sample size were a priori calculated and 96 consecutive chronic hepatitis C patients (53, genotype 2 and 43, genotype 3) without cirrhosis who were not obese and who achieved a RVR to therapy with peg-IFN-α-2a and ribavirin were enrolled. Fibrosis, steatosis, homeostatic model assessment-insulin resistance and HCV RNA were predefined variables to be evaluated in relapse. An intention-to-treat analysis was performed. SVR rates were 98% and 84% for genotype 2 and 3, respectively. Analysis of genotype 3 patients who had relapse showed a negative correlation with steatosis (P < 0.0001) and HCV RNA (P < 0.015). Multivariate analysis showed that steatosis was the independent predictor of relapse (OR, 0.988; 95% CI, 0.981-0.993; P < 0.001). Genotype 3 patients with steatosis had a relapse rate of 36.4% and 15.8% in those with high and low viral load, respectively, whereas there was no relapse in those without steatosis. In conclusion, a 12-week course of therapy is sufficient for patients without cirrhosis, not obese and infected with HCV genotype 2 achieve a RVR. This is not the case for genotype 3. Steatosis is the independent predictor of relapse. New therapeutic strategies are necessary for this subgroup of HCV genotype 3.

Clinical reactivation during lamivudine treatment correlates with mutations in the precore/core promoter and polymerase regions of hepatitis B virus in patients with anti-hepatitis B e-positive chronic hepatitis.

BACKGROUND: Drug-resistant mutants may emerge in patients with chronic hepatitis B receiving lamivudine therapy. AIM: To evaluate whether different viral mutational patterns may be associated with clinical reactivation during lamivudine treatment in patients with chronic B hepatitis. METHODS: Eight anti-hepatitis B e-positive patients with (group A) and 14 patients without clinical exacerbation (five anti-hepatitis B e-positive, group B1; nine hepatitis B e antigen-positive, group B2) during lamivudine treatment were investigated. RESULTS: 'Polymerase region': M204V/I variants were found in all group A patients, but in none of group B1 (P=0.0007) and in four of nine of group B2 (44%; P=0.02) patients. The L180M substitution was detected in four of eight (50%) of group A and in none of groups B1 and B2. 'Core promoter': the double basic core promoter (A1762T/G1764A) variant was detected in seven of eight (87%) of group A and in one of five (20%; P=0.03) of group B1 and one of nine (11%; P=0.002) of group B2 patients. 'Precore': the G1896A stop codon mutation was present in seven of eight (87%) of group A and in zero of five (P=0.004) of group B1 and one of nine (11%; P=0.002) of group B2. CONCLUSIONS: Different mutational patterns were observed in the lamivudine-treated patients with and without exacerbation. There was an association of the basic core promoter and stop codon mutations with lamivudine resistance in patients with disease exacerbation.