A. Guastadisegni

Long-term follow-up of patients with anti-HBe/HBV DNA-positive chronic hepatitis B treated for 12 months with lamivudine

BACKGROUND/AIMS Interferon alpha provides benefit in only a limited number of patients with chronic anti-HBe-positive hepatitis B. The aim of this study was to verify the long-term efficacy of lamivudine treatment of these patients and the incidence of lamivudine-resistant hepatitis B virus mutants. METHODS Fifteen consecutive patients with chronic anti-HBe-positive hepatitis B were treated with lamivudine 100 mg once daily for 52 weeks. Levels of alanine aminotransferase, HBV DNA, hepatitis B surface antigen, and IgM antibodies to hepatitis B core antigen were monitored during therapy and 12-month follow up. The polymerase gene was amplified by polymerase chain reaction and the region coding for YMDD amino acid motif was directly sequenced. RESULTS Only 2/15 patients (13%) had a sustained virological and biochemical response and improved histologically. Eleven out of 15 (74%) showed inhibition of viral replication and normalization of alanine aminotransferase levels during lamivudine treatment but relapsed 1-12 months after terminating therapy. In the two remaining patients (13%), HBV DNA initially became negative but reappeared in the serum after 24 weeks, and in both patients the emergence of YMDD mutants was demonstrated. CONCLUSIONS Our data confirm the antiviral efficacy of lamivudine in anti-HBe-positive patients, but response to a 1-year course was only transient as the majority of patients relapsed after therapy withdrawal. The lack of a sustained effect and the emergence of lamivudine-resistant mutants suggest that therapy for chronic hepatitis B should be based on a combination of several therapeutic agents.

Natural course of acute hepatitis C: a long-term prospective study

BACKGROUND Acute hepatitis C has a high chronicity rate which appears to be significantly reduced by early antiviral treatment. However, it is unclear if all acutely infected patients should be treated, and when. In this prospective study, patients with a well-documented diagnosis of acute hepatitis C were evaluated to define the natural course, the rate of chronicity, and host and virus-related factors which might predict a self-limiting or chronic evolution requiring early antiviral treatment. METHODS From 1995 to 2000, 40 consecutive patients with a community-acquired AHC were enrolled. Liver tests, anti-hepatitis C virus antibodies and hepatitis C virus RNA levels were monitored. Median follow-up was 35 months (range 12-68). RESULTS A total of 24/40 patients had symptomatic disease including 20 with jaundice; 13/40 patients had prompt serum hepatitis C virus RNA clearance and ALT normalisation within 12 weeks; in 12/13 patients this pattern remained unchanged during follow-up. Overall, 27/40 patients remained hepatitis C virus RNA positive with fluctuating ALT levels. Older age and jaundice were predictive of resolution whereas there was no correlation with other host factors, viral genotype or viral load. CONCLUSIONS Our data demonstrate that spontaneous resolution can occur in about 30% of AHC patients. This favourable outcome rarely occurs in patients with anicteric AHC or in those with jaundice but with persistent viremia for more than 12 weeks from onset; early antiviral treatment for these patients may avoid or reduce chronicity.

Lamivudine/interferon combination therapy in anti-HBe positive chronic hepatitis B patients: a controlled pilot study

BACKGROUND/AIMS In this study, lamivudine-interferon (LAM/IFN) combination therapy was compared to LAM monotherapy to verify if the combination treatment might improve efficacy and reduce the emergence of LAM-resistant mutants. METHODS Fifty patients with anti-HBe-positive chronic hepatitis B were treated for 12 months with LAM at 100mg/day (26 pts) or with IFN at 5MU t.i.w.+LAM 100mg/day (24 pts). Serum ALT, HBV DNA and IgM anti-HBc were monitored during treatment and a 6-month follow-up. The polymerase gene was amplified by PCR and the region coding for YMDD motif was directly sequenced. RESULTS All patients normalized ALT and cleared HBV DNA during treatment. The response was maintained until the end of therapy in the LAM/IFN group, while in 5/26 initial responders treated with LAM alone, a virological and biochemical breakthrough was observed after 6-10 months, and selection for YMDD variants resulted. After therapy discontinuation, most patients relapsed; the response rate after 6 months was 17% in the LAM/IFN group and 19% in the LAM group. CONCLUSIONS In anti-HBe-positive chronic hepatitis B, a 12-month course of LAM/IFN combination therapy is as beneficial as LAM monotherapy, however, the combination regimen appeared to prevent or delay the emergence of YMDD variants.

Re‐treatment of patients with anti‐HBe‐positive chronic hepatitis B who relapsed after an initial course of lamivudine

Aim : To evaluate the efficacy of a long‐term course of lamivudine monotherapy in patients with anti‐HBe‐positive chronic hepatitis B who relapsed after the first course of either lamivudine/interferon (n = 16; Group 1) or lamivudine (n = 20; Group 2).

Re-treatment of patients with anti-HBE positive chronic hepatitis B who relapsed after an initial course of lamivudine

AIM To evaluate the efficacy of a long-term course of lamivudine monotherapy in patients with anti-HBe-positive chronic hepatitis B who relapsed after the first course of either lamivudine/interferon (n = 16; Group 1) or lamivudine (n = 20; Group 2). METHODS Biochemical and virological tests were performed every 3 months. At baseline and breakthrough, the region coding for the YMDD amino acid motif was sequenced. RESULTS The length of re-treatment averaged 24 months. The virological response peaked at 6 months (94.4%), and declined to 66.7% and 50% at 12 and 24 months, respectively. The rates of breakthrough were 2.9%, 31.4% and 48.6% at 6, 12 and 24 months, respectively. By the second year, responders amounted to 62.5% and 40% in Groups 1 and 2, respectively (P = 0.10). The 18 responders at month 24 are still on therapy after 25-51 months of treatment: 14 still maintain a response, nine from Group 1 and five from Group 2. CONCLUSIONS Re-treatment with lamivudine can control viral replication. This effect is maintained for the initial 12 months in two-thirds of patients, but afterwards the duration of response lessens due to the development of viral resistance.