High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C

Abstract

Improved treatment regimens for patients with chronic hepatitis C, genotype 1 and high viral load are needed. Increasing the dose of ribavirin has increased the response rate, but experience with doses of more than 1,200 mg/day is limited. The aim of this study was to investigate the safety and tolerance to treatment with a high and individualized dose of ribavirin in combination with peginterferon. Ten patients with chronic hepatitis C, genotype 1 and high viral load were treated with peginterferon alfa-2a and ribavirin for 48 weeks in a prospective trial. The initial ribavirin dose was individualized and calculated from a pharmacokinetic formula based mainly on renal function. Ribavirin plasma concentrations were monitored, and the dose was adjusted to reach the target concentration. Hemoglobin was monitored, and patients were treated with erythropoietin and blood transfusions when indicated. After dose adjustments, the mean dose of ribavirin was 2,540 mg/day (range, 1,600-3,600) at week 24. The main side effect was anemia, which was controlled with erythropoietin. Two patients required blood transfusions. One patient was withdrawn at week 24 because of a lack of viral response, and one patient at week 39 because of side effects, primarily interferon associated. A lthough improvements have been made in the antiviral therapy of chronic hepatitis C virus (HCV), patients with genotype 1 infection with a high level of HCV RNA still pose a therapeutic challenge. The standard combination treatment with 12 months of peginterferon combined with ribavirin results in a sustained virological response rate of approximately 40% for this subset of patients. [1][2][3]

Epoetin alpha improves the response to antiviral treatment in HCV-related chronic hepatitis

“…Therefore, only in group 1 treated with Epoetin Alpha was the "80/80/80 rule" respected, i.e. administration of at least 80% of the dose of peg-IFN and RBV for at least 80% of the time of treatment [42].…”

“…In patients with CHC it is extremely important to ensure complete adherence to therapy with peg-IFN and RBV in order to achieve therapeutic success (greater percentage of SVR). Indeed, early interruption of therapy or reduction of peg-IFN or RBV dose because of side effects, leads to a significant decrease in SVR [21,[41][42][43].…”

“…This rule, which means taking 80% of the dose of peg-IFN and RBV for at least 80% of the duration of therapy, yields a greater SVR [41][42][43][44][45].…”

Host-Based Ribavirin Resistance Influences Hepatitis C Virus Replication and Treatment Response

“…Infections were conducted using 15 M RBV, to mimic an achievable plasma concentration in patients, as well as 50 M (Fig. 4B) (14,31). No titer reductions were observed at either concentration, indicating that reduced cell health from RBV exposure may have inhibited HCV replication at high RBV concentrations.…”

Pushing the treatment envelope for chronic hepatitis C?is more necessarily better?

“…6 They conducted a small pilot study in which they treated 10 patients with standard doses of peginterferon alfa-2a and individualized the daily dose of ribavirin to achieve a target ribavirin concentration in serum of 15 mol/mL. The primary goal was to evaluate the safety of using higher doses of ribavirin in patients with genotype 1 and high viral load (the difficult-to-treat patient profile).…”