Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B.

OBJECTIVE: Treatment with peginterferon α-2a (PegIFN) for 48 weeks is the standard of care for selected HBeAg-negative patients chronically infected with hepatitis B virus (HBV), but with limited treatment efficacy. A study was undertaken to investigate whether treatment extension to 96 weeks improves the outcome in this patient population. METHODS: 128 HBeAg-negative patients (120 genotype D) were randomised to weekly 180 µg PegIFN for 48 weeks (group A, n=51), 180 µg PegIFN for 48 weeks followed by 135 µg weekly for an additional 48 weeks (group B, n=52) or 180 µg PegIFN plus lamivudine (100 mg/day) for 48 weeks then 135 µg PegIFN for 48 weeks (group C, n=25). Endpoints were alanine aminotransferase normalisation plus HBV DNA <3400 IU/ml (primary), HBV DNA <2000 IU/ml and HBsAg clearance at 48 weeks after treatment. RESULTS: Forty-eight weeks after treatment, six patients in group A and 13 in group B achieved alanine aminotransferase normalisation plus HBV DNA <3400 IU/ml (11.8% vs 25.0%, p=0.08), 6 vs 15 patients had HBV DNA <2000 IU/ml (11.8% vs 28.8%, p=0.03), 0 vs 3 achieved HBsAg clearance (0% vs 5.8%, p=0.24) and 0 vs 5 had HBsAg <10 IU/ml (0% vs 9.6%, p=0.06). While extended PegIFN treatment was the strongest independent predictor of response, the combination with lamivudine did not improve responses. Discontinuation rates were similar among the groups (19.6%, 23.1%, 32.0%, p=0.81) and were mostly due to PegIFN-related adverse events. CONCLUSIONS: In HBeAg-negative genotype D patients with chronic hepatitis B, PegIFN treatment for 96 weeks was well tolerated and the post-treatment virological response improved significantly compared with 48 weeks of treatment. TRIAL REGISTRATION NUMBER: http://ClinicalTrials.gov registration number: NCT01095835.

Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus infection.

BACKGROUND & AIMS: Patients with chronic hepatitis C virus (HCV) infection are frequently treated with a combination of pegylated interferon (peginterferon) and ribavirin. This study compared the efficacy and safety of peginterferon alfa-2a and peginterferon alfa-2b, each in combination with ribavirin. METHODS: A total of 320 consecutive, treatment-naive, HCV RNA-positive patients with chronic hepatitis were randomly assigned to once-weekly peginterferon alfa-2a (180 microg, group A) or peginterferon alfa-2b (1.5 microg/kg, group B) plus ribavirin 1000 mg/day (body weight <75 kg) or 1200 mg/day (body weight >or=75 kg) for 48 weeks (genotype 1 or 4) or 24 weeks (genotype 2 or 3). The primary end point was sustained virological response (SVR) by intention-to-treat. RESULTS: More patients in group A than group B achieved an SVR (110/160 [68.8%] vs 87/160 [54.4%]; P = .008). Higher SVR rates were obtained in group A than group B among patients with genotype 1/4 (51/93 [54.8%] vs 37/93 [39.8%]; P = .04), with genotype 2/3 (59/67 [88.1%] vs 50/67 [74.6%]; P = .046), without cirrhosis (96/127 [75.6%] vs 75/134 [55.9%]; P = .005), and with baseline levels HCV RNA >500,000 IU/mL (58/84 [69%] vs 43/93 [46.2%]; P = .002). SVR rates in groups A and B were not statistically different among patients with baseline HCV RNA

Three cases of severe acute hepatitis after parenteral administration of amiodarone: the active ingredient is not the only agent responsible for hepatotoxicity.

Amiodarone is one of the most effective antiarrhythmic drugs available and is widely prescribed despite several potentially life-threatening side-effects. Hepatotoxicity is the most frequent one during long-term oral therapy: occasionally acute hepatitis necessitates the suspension of treatment but monitoring of a transient increase in serum aminotransferases is usually sufficient; the clinical-morphological pictures of liver cirrhosis have also been reported. Fulminant hepatitis soon after a parenteral load of the drug is far less well described in the literature. Most published cases were reversible after the suspension of treatment. A negative challenge after oral amiodarone exposure suggested that polysorbate 80, a solvent added to the intravenous infusion and already implied in the pathogenesis of a similar syndrome observed in infants, is a more likely cause of this complication. The occurrence of acute hepatitis complicating parenteral amiodarone treatment does not preclude subsequent oral use of the drug: an evidence-based therapeutic behavior now definitively consolidated. Because of the rarity of this diagnosis, we report 3 cases of short-term hepatotoxicity secondary to amiodarone treatment for supraventricular tachyarrhythmias: in 2 male patients with dilated cardiomyopathy and in a female with liver disease. The diagnosis was presumptive and based on a thorough drug history, the temporal relationship, the time-course of liver dysfunction, the exclusion of other causes and on the rapid improvement observed after parenteral amiodarone withdrawal in 2 cases; in no case could we find any other explanation for the liver damage. Since amiodarone is sometimes still an irreplaceable antiarrhythmic drug, we raise the question of whether careful and continuous vigilance should be mandatory in patients receiving the drug or whether it is possible to introduce a pharmaceutical preparation not containing the vehicle that induces acute liver toxicity.

Sustained virological response to antiviral therapy reduces mortality in HCV reinfection after liver transplantation.

BACKGROUND/AIMS: HCV infection recurs almost in all HCV-positive patients receiving liver transplantation and carries a poor prognosis. Aim of this study was to analyze efficacy and effect on survival of antiviral therapy in this clinical setting. METHODS: Pegylated-interferon alpha-2b and ribavirin were administered at a dose of 1 microg/kg of bwt weekly and 600-800 mg/day. Planned duration of treatment was 24 or 48 weeks according to HCV genotype. Patients who failed to respond at week 24 were considered as non-responders. RESULTS: 61 patients were enrolled. According to intention-to-treat analysis, 44 (72%) patients were considered as treatment failure (31 non-responders, 4 relapsers, 9 dropout). Sustained virological response was achieved in 17 cases (28%). Genotype 2, higher doses of antivirals and absence of histological cirrhosis were predictors of sustained virological response. In the follow up, patients with sustained virological response had a significantly lower mortality compared to patients with treatment failure (chi2=6.9; P<0.01). CONCLUSIONS: Response rate to antiviral therapy in HCV reinfection after liver transplantation is higher if a full dose of antiviral drugs is administered and if treatment starts before histological cirrhosis has developed. Sustained virological response improves patient survival.