Peginterferon alpha-2b plus ribavirin with or without amantadine [correction of amantidine] for the treatment of non-responders to standard interferon and ribavirin.

BACKGROUND: A significant proportion of hepatitis C patients treated with unmodified interferon plus ribavirin fail to respond. The optimal therapy for these patients has not been established yet. The objective of this study was to assess the efficacy and safety of peginterferon plus ribavirin with or without amantidine in such patients. METHODS: In this open-label, prospective controlled trial, a total of 63 patients were randomly divided into groups A and B with a ratio of 1:2. Group A (21 patients) received weekly peginterferon alpha-2b, 1.5 microg/kg concomitantly with ribavirin 1000-1200mg per day. Group B (42 patients) received peginterferon and ribavirin as in group A, plus amantadine [corrected] 200 mg per day. RESULTS: At the completion of treatment, serum levels of hepatitis C virus RNA were undetectable in 14% and 12% of patients in groups A and B, respectively (P=NS). Hepatitis C virus RNA remained undetectable 24 weeks after the end of treatment in one patient (5%) in group A and three patients (7%) in group B (P=NS). Sustained viral clearance was associated with sustained normalization of serum alanine aminotransferase level. Both drug regimens had similar side effect profiles. CONCLUSION: Peginterferon plus ribavirin therapy with or without amantadine [corrected] is associated with a low sustained virological response in patients who failed interferon and ribavirin combination therapy.

Peginterferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4.

BACKGROUND: The hepatitis C virus (HCV) genotype is an important predictive parameter for the success of pegylated interferon plus ribavirin therapy. To date, most published therapeutic trials have enrolled patients infected mainly with HCV genotypes 1, 2, and 3. Data regarding the responsiveness of genotype 4, the predominant type of HCV in the Middle East, are very limited. OBJECTIVE: To assess the efficacy of peginterferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis caused by HCV genotype 4. METHODS: Sixty-six treatment-naive patients infected with HCV genotype 4 were enrolled in this open label, prospective study. Cohort characteristics included the following: 48 M/18 F, mean age 45 +/- 9 years, and mean weight 74 +/- 8 kg. All patients had raised alanine aminotransferase (ALT) and were compensated. The mean pretreatment HCV-RNA level was 4.2 x 10(6) copies/ml (8.4 x 10(5) iu/ml) and median was 2.15 x 10(6) copies/ml. Twenty patients (29%) exhibited cirrhosis or severe fibrosis on pretreatment liver biopsy specimens. Participants were to receive peginterferon alfa-2b, 1.5 mcg/kg/wk plus ribavirin 1,000-1,200 mg/day for 48 wk. Patients were followed up for 24 wk after completing therapy. End of treatment viral response and sustained viral response (SVR) were defined as the absence of HCV-RNA from serum (<100 copies/ml) at 48 wk of treatment and at the end of follow-up, respectively. Data were analyzed on an intention-to-treat basis. RESULTS: End of treatment and sustained virologic response were 77% and 68%, respectively. Among patients with pretreatment HCV-RNA > or =2 x 10(6) SVR was 55% compared with SVR of 86% among patients with HCV-RNA < 2 x 10(6) (p= 0.05). Patients with cirrhosis or severe fibrosis had significantly lower SVR rate compared to those with mild or no fibrosis (29 vs 84%; p < 0.0002). Three patients (4%) discontinued therapy because of severe flu-like symptoms. Four patients developed hypothyroidism. Dose reduction of ribavirin and peginterferon alfa-2b was necessary in 15% and 6% of the patients, respectively. CONCLUSION: Peginterferon alfa-2b in combination with ribavirin is effective in the treatment of HCV genotype 4. The treatment was well tolerated by most of the patients.

Transjugular liver biopsy in patients with end-stage renal disease.

PURPOSE: To assess the efficacy and safety of transjugular liver biopsy (TJLB) in patients with end-stage renal disease (ESRD) who are undergoing hemodialysis treatment. MATERIALS AND METHODS: Forty-six consecutive patients with liver disease who were undergoing hemodialysis were included in this study. An 18-gauge Tru-cut transjugular needle with a 20-mm throw was used to obtain liver tissue. All procedures were performed under fluoroscopic guidance. A single pathologist reviewed the biopsy specimens and assessed the size of fragments, number of portal tracts, and adequacy of the specimens for histologic diagnosis. All complications were recorded. The results were compared with the outcomes of percutaneous liver biopsy carried out at our institution in 32 patients with ESRD. RESULTS: TJLB and percutaneous biopsy techniques yielded adequate specimens for histologic diagnosis in all patients. The mean length of the largest fragments of tissue obtained via the transjugular and percutaneous routes were 16 mm +/- 4 and 14 mm +/- 3, respectively (P = NS). There were no major complications among patients who underwent TJLB. Percutaneous liver biopsy was complicated by hemorrhage in four of 32 patients (12%), three of whom required blood transfusion. CONCLUSION: TJLB is an effective and safe technique to obtain liver tissue in patients with ESRD and is associated with a lower complication rate than percutaneous liver biopsy.

Treatment of chronic hepatitis B with the sequential administration of interferon and lamivudine.

BACKGROUND/AIMS: Interferon monotherapy has been shown to induce a sustained viral response in 30-40% of patients with HbeAg-positive chronic hepatitis B infection. Similarly, lamivudine monotherapy causes HBeAg seroconversion in less than 20% of patients treated for one year. This study aims to assess the efficacy and safety of the sequential administration of interferon alfa-2a plus lamivudine to patients with chronic hepatitis B in comparison to lamivudine monotherapy. METHODOLOGY: Sixty-one patients with HbeAg-positive chronic hepatitis B infection and raised ALT were randomized to receive either interferon Alfa-2a, 4.5 million units daily for 16 weeks plus lamivudine 100 mg daily starting from week 5 and continuing for 48 weeks (Group A, n = 32) or lamivudine monotherapy for 48 weeks (Group B; n = 29). Patients were followed for 48 weeks after completion of therapy. RESULTS: HBeAg seroconversion to anti-HB +ve was observed in 2 (6.2%) patients in Group A. Both patients remained HBeAg negative and HBV-DNA negative throughout the follow-up phase. None of the group B patients seroconverted at the end of therapy or during follow-up (P = NS). All group A patients experienced at least one side effect and as a result, one dropped out. All group B patients completed the study without side effects. CONCLUSIONS: The sequential administration of interferon plus lamivudine was not superior to lamivudine monotherapy for the treatment of chronic hepatitis B and was associated with more side effects.

Interferon-alpha in combination with ribavirin for the treatment of chronic hepatitis C in patients with persistently normal aminotransferase levels.

BACKGROUND AND AIMS: A substantial proportion of patients with chronic hepatitis C virus infection have persistently normal serum transaminase levels. The aim of this study was to assess the efficacy and safety of interferon plus ribavirin combination therapy in this population. METHODS: In this prospective open trial 152 patients with biopsy-proven chronic hepatitis C were enrolled, 32 of whom had persistently normal alanine aminotransferase levels (group A). The remaining 120 patients served as a comparison (group B). Patients were treated for 12 months with 4.5 million units of interferon-alpha(2a) thrice weekly in combination with ribavirin 1,000 or 1,200 mg daily. They were followed up for at least 6 months after therapy. Serum hepatitis C RNA was detected by polymerase chain reaction and quantified by a branched DNA assay. RESULTS: At the end of treatment, 12 (37.5%) and 48 patients (40%) were negative for HCV-RNA in groups A and B, respectively (p = 0.33). After 24 weeks of follow-up, 9 patients (28%) from group A and 36 patients (30%) from group B were still HCV-RNA negative (p = 0.4). Treatment was well tolerated by both groups. There were no alanine transferase elevations among group A patients during therapy. CONCLUSION: Interferon-ribavirin combination therapy was safe and induced a sustained virologic response in a significant proportion of patients with chronic hepatitis C and repeatedly normal serum transaminase levels.