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There is no standard therapy for patients with anti-HBe-positive chronic hepatitis B. The aims of this study were to analyse the efficacy of lamivudine therapy for two years in these patients and to study the sequence variations in the precore and polymerase hepatitis B virus (HBV) regions in relation to therapy. Sixteen patients with chronic anti-HBe-positive hepatitis were treated with lamivudine (100 mg) once daily for 2 years. Levels of alanine aminotransferase (ALT), HBV-DNA and HBsAg were monitored during therapy. The polymerase and precore genes were amplified by polymerase chain reaction and their products were sequenced directly. Thirteen of 16 patients (81%) had a virological and biochemical response after 1 year of therapy and 11 (69%) maintained the complete response after 2 years of lamivudine therapy. Among the three patients without initial virological or biochemical response at year 1, prolonging therapy to 2 years was not associated with an increase in the response. YMDD variants were detected in 19% of cases in the first year and in 44% in the second year: YVDD being the most frequent mutations detected during year 1 and YIDD during year 2 of therapy. YMDD variants were found in 7-27% of cases with complete response depending on the duration of therapy. Our results show that prolonging lamivudine therapy is safe, well tolerated and maintains viral inhibition in anti-HBe-positive patients. However, its efficacy tends to decrease overtime and it is associated with an increase in YMDD variants, even in some cases, of complete response.

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The large number of chronic hepatitis C patients infected by genotype 1 constitutes an important therapeutic challenge because they are the most resistant to combination therapy with interferon alfa and ribavirin. [1][2][3] In these patients, the sustained virologic response to peginterferon and ribavirin for 48 weeks is around 42%. 3,4 It has been shown that one important factor of sustained virologic response (SVR) is rapid hepatitis C virus (HCV)-RNA clearance, ranging from 75% for those patients who cleared the virus at week 12 to only 32% for those who lost HCV RNA at week 24. 3 It has been suggested that extending therapy in patients who cleared HCV RNA between weeks 12 and 24 (i.e., late responders) could increase SVR.We selected 9 patients with chronic hepatitis C who were infected with genotype 1 in treatment with pegylated interferon alfa-2b plus ribavirin who cleared HCV RNA between weeks 12 and 24 for therapy prolonged to 72 weeks. Three were men and 6 were women, with a median age of 41 Ϯ 14.57 years. All patients had elevated alanine aminotransferase levels, positive HCV RNA, and a liver examination showing chronic hepatitis. Patients were treated with a mean dose of 1.0 g/kg of peginterferon alfa-2b once weekly (PEG-INTRON, Schering-Plough, Kenilworth, NJ), plus 800 mg/d of ribavirin (Rebetol, Schering-Plough). HCV RNA was analyzed by using a quantitative, real-time, reverse-transcriptase polymerase chain reaction technique with a lower limit of detection of 100 IU/L. 4 Eight patients completed therapy and 6 months of follow-up. One patient stopped therapy at week 48 because of thyroid alterations. Table 1 shows patient characteristics and changes in HCV-RNA levels from baseline to week 12. In all patients, HCV RNA was positive at week 12 of therapy but undetectable at week 24 and throughout the 72 weeks of therapy. At week 24 of follow-up, 7 patients maintained an SVR and one relapsed (case 3).This study, with a small number of patients, showed that prolonged combination therapy with peginterferon and ribavirin is very useful in late virologic responders because it increases SVR. HCV-RNA determination has an important role not only in the decision to stop therapy but also in better adjusting therapy. 3,[5][6][7] Currently, nonresponders can be detected by a quantitative HCV-RNA test at week 12, showing a decline of less than 2 logs in HCV-RNA concentrations. 3,5 In these patients, combination therapy should be stopped because the probabilities of a sustained response are almost nil. In patients who achieve an early virologic response, the probabilities of achieving an SVR were 80% for those who cleared HCV RNA at week 12 and sooner, and 40% for those who achieved a 2-log reduction in HCV-RNA concentrations but still remained HCV-RNA positive as a recent review of multicenter studies has shown. 5 All of our patients had a 2-log decline but remained HCV-RNA positive at week 12 and, taking into account the previous results, their probabilities of achieving an SVR are lower than those patients who we...