Efficacy and safety of combination therapy with pegylated interferon and ribavirin in aged patients with chronic hepatitis C

Background & Aims: Combination therapy with pegylated interferon (PEGIFN) and ribavirin has significantly improved virus eradication rate in patients affected by HCV-related chronic hepatitis (C-HC). However, only few data are available with respect to efficacy and safety of this therapy in aged patients. This study aimed at investigating efficacy and tolerability of combination therapy in aged patients with CH-C. Methods: 473 patients [319 (67.4%) naive, 195 (41,2% female) with CH-C (genotype 1, n=266; genotype 2, n=112, genotype 3, n=72, genotype 4, n=23), of whom 68 (14.4%) over 65 years old (mean age 69\ub12 years), were treated with Peg-IFN (alpha-2a or alpha-2b) plus ribavirin according to international guidelines from January 2007 to July 2011. These patients were assessed for sustained viral response (SVR) rate and for all known main predictors of SVR in CH-C. Results: The overall SVR rate resulted similar in both age groups [270/405 (66.6%) in subjects <65 years vs. 41/68 (60.3%) in subjects 6565 years, respectively, p=0.334)]. Overall, therapy discontinuance rate was low, with no significant difference between patients over or under age 65 (4.4% vs. 4.9%, respectively), the most common reason for discontinuance being anemia in both groups.For patients over 65, at multivariate analysis, non-na\uefve status, EVR and use of hematological growth factors were independent predictors of SVR. Factors independently related to EVR at multivariate analysis were non-naive, staging, genotype 2-3 vs. genotype1-4 and use of hematological growth factors Conclusions: Aged patients can be candidates for Peg-IFN plus ribavirin therapy. The appropriate use of hematological factors in these patients may be useful to achieve a significant reduction in the rate of therapy discontinuation due to hematological side-effects. The response-guided therapy may be applied in predicting therapy efficacy in this patient grou

Serum ferritin as a predictor of treatment outcome in patients with chronic hepatitis C

OBJECTIVES: Antiviral treatment in chronic hepatitis C (CHC) involves ribavirin, a hemolytic agent. We planned a prospective study to evaluate whether drug-induced iron perturbation is clinically relevant as it relates to therapeutic outcome. METHODS: Iron variables were sequentially assessed in 206 CHC patients undergoing antiviral therapy and were correlated with pretreatment iron status and histology, hemolysis, and therapeutic outcome. RESULTS: At week 1 of therapy, serum iron (SI), transferrin saturation (TS), and serum ferritin (SF) increased markedly in all patients. All iron parameters correlated with hemolysis up to week 4; this correlation was lost for SF at later time points. SF rise during treatment was inversely related to baseline SF and iron deposits in hepatic mesenchymal/Kupffer cells. Both baseline SF and mesenchymal iron significantly correlated with fibrosis at multivariate analysis (P=0.015 and 0.008, respectively). Interestingly, baseline SF, despite good specificity (89%), had low sensitivity in predicting siderosis (25%). During therapy, SI, TS, and hemolysis parameters did not correlate with sustained virological response (SVR), whereas SF rise became an independent predictor of therapeutic response: a 2.5-fold increase of SF at week 12 associated with higher likelihood of SVR (odds ratio 1.91, P=0.032). Accordingly, lack of mesenchymal iron deposits at the baseline biopsy correlated with SVR (odds ratio 3.02, P=0.043). CONCLUSIONS: In CHC, SF is a useful marker for assessing disease duration and progression before starting treatment and for predicting therapeutic response while on therapy. SF rise during antiviral therapy is largely independent of hemolysis and likely indicates activation of macrophages in response to antivirals. © 2009 by the American College of Gastroenterology