Predicting sustained virological response and anaemia in chronic hepatitis C patients treated with peginterferon alfa‐2a (40KD) plus ribavirin

Abstract

AimTo assess the likelihood of a sustained virological response (SVR) vs. the likelihood of anaemia in patients with chronic hepatitis C. MethodsData from 1732 patients treated with peginterferon alfa-2a (40KD) plus ribavirin in two randomized, multinational studies were pooled. Probabilities of SVR and anaemia were modelled using the generalized additive logistic model, with numerous clinical variables considered for entry into the model. Baseline haemoglobin was only considered in the analysis for anaemia. ResultsThe probability of anaemia increased from 6 to 16% as a function of the ribavirin dose kg − 1 (12-16 mg kg − 1 ), whereas the relationship between SVR and ribavirin dose kg − 1 was influenced by hepatitis C virus (HCV) genotype. The probability of an SVR was not influenced by the ribavirin dose kg − 1 in patients with HCV genotype 2 or 3 infection, but increased as a function of ribavirin dose kg − 1 in patients with HCV genotype 1 infection (40-50% increase in probability of SVR for 12-16 mg kg − 1 dose ribavirin increase). The probability of an SVR in patients infected with HCV genotype 1 decreased with increasing HCV RNA level to about 3 million copies ml − 1 , but was relatively independent of increasing HCV RNA level thereafter. In addition, older age, a higher ribavirin apparent oral clearance and cirrhosis had a negative impact on achieving an SVR, but improved with increasing alanine aminotransferase (ALT) quotient. Sex and ribavirin dose kg − 1 were the most important prognostic factors for anaemia, followed by baseline haemoglobin, age, baseline ALT quotient and cirrhosis. ConclusionThis study supports individualizing ribavirin dosages by HCV genotype and body weight, and highlights several clinical variables that influence the likelihood of an SVR compared with anaemia in chronic hepatitis C patients treated with peg interferon alfa-2a (40KD) plus ribavirin.

The role of hepatitis C virus genotyping in evaluating the efficacy of INF-based therapy used in treating hepatitis C infected patients in Libya

“…The SVR in genotype 1 infected patients was the least in both regimens comparable to other genotypes. These results are similar to other studies carried in France on selected multiethnic patients from France, Egypt and other African countries who were treated with Peg INF alfa 2a based regimen [26,39]. In their study the selected patients were French and Egyptian and other African who had HCV genotype 4 infection on Peg INF alfa 2a they found.…”

“…Other studies have shown no differences in the clinical response of patients infected with HCV genotype 2 and 3, when they were treated with PEG INF alfa2a or INF alfa combination therapies [38,39]. The SVR of Peg INF based regimen was higher than INF based Regimen in all genotypes except for genotype 4 because as 11 patient infected with this genotype had ETR of Peg INF miss the follow up and thus excluded for the data analysis.…”

Population Pharmacokinetics and Pharmacodynamics of Ribavirin in Patients with Chronic Hepatitis C Genotype 1 Infection

“…Other studies have reported an association between ribavirin exposure after the first dose, or at steady state, as a predictor of SVR rate (32,33). Loustaud-Ratti et al reported that the probability of SVR increased with an increasing in ribavirin AUC 0-12h and AUC 0 -4h after the first dose at a minimum threshold of 3,014 and 1,755 ng*h/mL, respectively.…”

Safety, Tolerability, and Pharmacokinetics of Ribavirin in Hepatitis C Virus-Infected Patients with Various Degrees of Renal Impairment

“…In addition, patients in these 2 treatment groups had difficulties tolerating their assigned RBV doses, with approximately 75% of patients with severe and one-half of patients with moderate renal impairment requiring RBV dose modification during the first 12 weeks of therapy. Anemia, a common RBV-related adverse event associated with increased RBV exposure (12)(13)(14)21), was the most frequently reported adverse event in patients with moderate and severe renal impairment, reported in 65% and 64% of patients, respectively. Only 20% of patients with moderate and severe renal impairment received their full course of assigned RBV doses for the first 12 weeks.…”

“…RBV exposure has been shown to influence both clinical response and toxicity to therapy (9)(10)(11)(12)(13)(14). Current treatment guidelines recommend RBV doses ranging from 200 to 800 mg/day in patients with moderate to severe kidney disease not undergoing hemodialysis and markedly reduced RBV daily doses in patients on dialysis (5).…”