Pegylated IFN-alpha 2b added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B.

AIM: To investigate the role of pegylated-interferon (IFN) alpha-2b in the management of patients with lamivudine-resistant chronic hepatitis B. METHODS: Twenty consecutive anti-HBe positive patients were treated with pegylated IFN alpha-2b (100 mug sc once weekly) for 12 mo. There was no interruption in lamivudine therapy. Hematology, liver biochemistry, serum HBV DNA levels were detected by PCR, and vital signs were also assessed. Liver histology was assessed in some patients at entry and at wk 52 for comparison. RESULTS: Nine patients (45%) had a partial virological end-treatment response; seven patients (35%) showed complete virological end-treatment response. Eight patients (40%) showed biochemical end-treatment response. There was a trend for higher virological response rates in patients who had previously responded to IFN and relapsed compared to IFN non-responders (four out of seven patients vs none out of six patients, respectively; P=0.1). Patients without virological end-treatment response showed significant worsening of fibrosis [median score 2 (range, 1 to 3) vs median score 3 (range, 1 to 4)], in the first and second biopsy respectively (P=0.014), whereas necroinflammatory activity was not significantly affected. Patients with complete or partial virological end-treatment response did not show any significant changes in histological findings, possibly due to the small number of patients with paired biopsies (n=5). Nevertheless, after 12 mo of follow-up, only one patient (5%) showed sustained virological response and only 2 patients (10%) showed sustained biochemical response. Two patients (10%) discontinued pegylated IFN both after 6 mo of treatment due to flu-like symptoms. CONCLUSION: Pegylated IFNalpha-2b, when added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B, induces sustained responses only in a small minority of cases.

Thyroid dysfunction and long-term outcome during and after interferon-alpha therapy in patients with chronic hepatitis C.

INTRODUCTION: Thyroid dysfunction (TD) is a well-established adverse effect in chronic hepatitis C virus (HCV)-infected patients, treated with interferon-alpha (IFN-α), with or without ribavirin. However, the long-term outcome is not well-studied. The purpose of this study was to estimate the prevalence and long-term outcome of TD after HCV-therapy. MATERIALS AND METHODS: Retrospective analysis of 109 HCV-treated patients (for 6 to 12 months, according to HCV genotype), for the period 1996 to 2008. Thyroid function tests were performed every 3 months during therapy and after discontinuation (3 months to 12 years). Routine laboratory tests and virological assessment were performed according to generally accepted practice. RESULTS: TD was observed in 26 patients (23.85%). The positive and negative predictive value for thyroid autoantibodies (ATA) was 80% and 72.7%, respectively. Relative risk for those with positive ATA was 2.9 (95% CI: 1.6 to 5.3, P = 0.014). The median duration of TD was 12.0 months (min: 3; max: 132). The median follow-up period for the patients with TD was 25.5 months (min: 12; max: 144). Finally, 15 patients developed permanent TD (57.69%), compared to 11 with temporary TD (42.31%). Sex is a risk factor for TD, as there were more females than males affected (P = 0.011). Genotype, viral load, time of HCV-exposure prior to therapy, and virological response did not differ between patients with and without TD. CONCLUSION: TD among HCV-treated patients was more frequent than usually reported, with >50% developing permanent TD. ATA status may play a role in estimating the risk of subsequent TD. Women appear to be more vulnerable to TD than men.

Lamivudine/pegylated interferon alfa-2b sequential combination therapy compared with lamivudine monotherapy in HBeAg-negative chronic hepatitis B.

BACKGROUND AND AIM: Monotherapy has been proven insufficient in achieving sustained control of chronic hepatitis B. We aimed to assess the efficacy of combined sequential administration of lamivudine and pegylated interferon alfa-2b in patients with hepatitis Be antigen (HBeAg)-negative chronic hepatitis B. METHODS: Eighteen patients were given sequential combination treatment starting with 3 months of lamivudine monotherapy followed by 9 months of pegylated interferon alfa-2b (after a 3-month period of concomitant administration of the two drugs) and 24 patients received lamivudine monotherapy. RESULTS: At the end of treatment, 88.9% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy had hepatitis B virus (HBV) DNA levels below 400 copies/mL (P = not significant). At the end of treatment, 72.2% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy achieved alanine aminotransferase normalization (P = not significant). After 12 months of follow up, 33.3% of the patients who received sequential combination treatment and 16.7% of those who received lamivudine monotherapy had HBV-DNA levels below 400 copies/mL (P = 0.4). After 12 months of follow up, 72.2% of the patients who received sequential combination treatment and 25.0% of those who received lamivudine monotherapy had normal alanine aminotransferase levels (P < 0.01). Twenty-five percent of the patients in the lamivudine monotherapy group had virological breakthrough compared to none in the sequential combination treatment group (P = 0.06). CONCLUSIONS: Sequential combination treatment is able to improve sustained biochemical response rates and prevent the emergence of lamivudine-resistant mutants in patients with HBeAg-negative chronic hepatitis B.

Effect of lamivudine treatment in patients with decompensated cirrhosis due to anti-HBe positive/HBeAg-negative chronic hepatitis B.

Lamivudine has been shown to improve liver function and reduce the need for liver transplantation (LT) in patients with decompensated HBeAg-positive cirrhosis. Nevertheless, there is only limited experience with lamivudine in patients with anti-HBe-positive/HBeAg-negative cirrhosis. The primary aim of this study was to determine whether lamivudine treatment improves liver function and subsequently pre-LT survival or delays or obviates the need for LT in patients with anti-HBe-positive/HBeAg-negative cirrhosis. Between July 1998 and June 2003, 20 consecutive patients awaiting LT were enrolled in the study. All patients showed active viral replication and were treated with lamivudine 100 mg daily. Significant clinical improvement, defined as a decrease in the Child-Pugh-Turcotte score by >or=2 points, was observed in 11 (55%) patients. The median change in the Child-Pugh-Turcotte score was -2 (range -5 to +2). The median time required to achieve a 2-point or greater reduction in Child-Pugh-Turcotte score was 6 months (range 3-12 months). In nine patients (45%), the Child-Pugh-Turcotte score decreased to

Interferon/long-term lamivudine combination therapy in anti-HBe positive chronic hepatitis B patients.

BACKGROUND: Monotherapy with a single antiviral agent is insufficient in controlling hepatitis B virus infection in the majority of patients with anti-HBe positive chronic hepatitis B. Interferon/long-term lamivudine combination therapy was evaluated to determine if this strategy would improve treatment efficacy and reduce the emergence of lamivudine resistance. METHODS: In total, 36 consecutive anti-HBe positive patients were treated with interferon (3 MU subcutaneously three times weekly) and lamivudine (100 mg orally once a day) for 12 months. After completion of the combined treatment, all patients continued to receive lamivudine monotherapy indefinitely. RESULTS: Overall, 35 patients (97%) showed virological response at 12 months. Four patients (11%) cleared HBsAg and developed anti-HBs. During the follow-up time, after the discontinuation of interferon, of 30 +/- 12 months (range: 7-57 months), 13 patients (36%) exhibited breakthrough infection. The cumulative rates of breakthrough infection at the end of 1, 2, 3 and 4 years of treatment were 0%, 14%, 32%, and 59%, respectively. CONCLUSIONS: Combination therapy appears to be effective and may also delay the selection of lamivudine-resistant variants. However, controlled trials are definitely warranted to clarify the potential benefits of combination antiviral treatment over monotherapy.