Safety and efficacy of ledipasvir/sofosbuvir with or without ribavirin in hepatitis C genotype 1 patients including those with decompensated cirrhosis who failed prior treatment with simeprevir/sofosbuvir.

BACKGROUND: Combination therapy of simeprevir (SIM)/sofosbuvir (SOF) is an approved treatment for hepatitis C genotype (gen) 1 with overall SVR12 rate of 85%-95%. The single tablet fixed-dose combination of ledipasvir (LDV)/SOF is also approved for gen 1 with sustained virologic response at 12 weeks (SVR12) rates ≥95%. No data are available on the efficacy of retreatment with LDV/SOF in patients who failed initial treatment with SIM/SOF. AIM: To evaluate the efficacy of retreatment with LDV/SOF ± ribavirin (RBV) in gen 1 patients who had previously failed treatment with SIM/SOF. METHODS: Data from a combined treatment cohort of 2 hepatology centres, which included patients previously treated with SIM/SOF ± RBV for 12 weeks but failed to achieve SVR and then underwent retreatment with LDV/SOF ± RBV, were analysed (n = 30). LDV/SOF ± RBV was administered for 12-24 weeks based on the discretion of the treating hepatologist. RESULTS: Of the 30 patients, 23 (77%) were male, 77% were Caucasian and 26 (87%) were gen 1a. 26 (86%) had cirrhosis, of which 16 (62%) had decompensated, Child's class B or C cirrhosis. Three patients were liver transplant recipients with recurrent hepatitis C. Overall, 27/30 (90%) achieved SVR. Treatment was well tolerated with 37% reporting no adverse events. The most common adverse events were fatigue, headache, insomnia and nausea. Two patients with Child's B cirrhosis required hospitalization during treatment for variceal haemorrhage and abdominal pain respectively. However, no treatment discontinuations or deaths occurred. CONCLUSION: Single tablet fixed-dose combination LDV/SOF ± RBV is efficacious and well tolerated in patients who previously failed treatment with SIM/SOF, including those with decompensated cirrhosis and recurrent hepatitis C following liver transplantation.

Low- and standard-dose peginterferon alfa-2a for chronic hepatitis C, genotype 2 or 3: efficacy, tolerability, viral kinetics and cytokine response.

BACKGROUND: Chronic infection with hepatitis C, genotype 2/3, responds better than other genotypes to peginterferon and ribavirin treatment. We hypothesized that a lower dose of peginterferon would be as effective, but less toxic than standard doses. AIM: To test the hypothesis that a lower dose of peginterferon would be as effective as, but less toxic than, standard doses. METHODS: A total of 30 patients were treated with low-dose peginterferon alfa-2a (90 microg/week) and 27 patients with standard doses (180 microg/week) for 24 weeks in combination with 800 mg/day of ribavirin. Patients who failed treatment were offered 48 weeks of standard-dose treatment. Viral and serum inducible protein 10 (IP-10) levels were measured and early viral kinetic parameters were calculated. RESULTS: Sustained virological response was achieved in 68% of the low-dose and 87% of the standard-dose patients (per protocol, P = 0.79 for non-inferiority). Re-treatment was successful in all patients who tolerated full dose and duration. The standard-dose group had greater first-phase declines of viral levels and faster time to negativity. The second-phase slope was not dose-dependent. IP-10 induction was significantly greater with the standard dose. Although fatigue and general feeling during treatment were worse for standard dose, haematological toxicity and depression did not differ between groups. CONCLUSION: A lower dose of peginterferon is associated with some symptomatic benefit, but the response is not equivalent to standard dosing.

Hepatitis C: a clinical review.

Hepatitis C is a major cause of chronic liver disease. It has been recognized as a global health problem because of the progression to cirrhosis and hepatocellular cancer. Chronic hepatitis C is usually asymptomatic but can cause considerable liver damage before its recognition. This review discusses the natural history, clinical features, diagnosis, therapy, treatment responses and the side effects associated with the treatment of hepatitis C.