Article

Indications and limitations for aged patients with chronic hepatitis C in pegylated interferon alfa-2b plus ribavirin combination therapy

Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Journal of Hepatology (Impact Factor: 11.34). 12/2010; 54(4):604-11. DOI: 10.1016/j.jhep.2010.07.043
Source: PubMed

ABSTRACT

This study investigated the efficacy and adverse effects of pegylated interferon (Peg-IFN) plus ribavirin therapy in aged patients with chronic hepatitis C (CH-C).
A total of 1040 naïve patients with CH-C (genotype 1, n=759; genotype 2, n=281), of whom 240 (23%) over 65 years old (y.o.), were treated with Peg-IFN alfa-2b plus ribavirin and assessed after being classified into five categories, according to age.
The discontinuance rate was higher for patients over 70 y.o. (36%), the most common reason being anemia. In the presence of genotype 1, the SVR rate was similar (42-46%) among patients under 65 y.o. and declined (26-29%) among patients over 65 y.o. For patients over 65 y.o., being male (Odds ratio, OR, 3.5, p=0.035) and EVR (OR, 83.3, p<0.001) were significant factors for SVR, in multivariate analysis. The Peg-IFN dose was related to EVR, and when EVR was attained, 76-86% of patients over 65 y.o. achieved SVR. SVR was not achieved (0/35, 0/38, respectively) if a 1-log decrease and a 2-log decrease were not attained at week 4 and week 8, respectively. In the presence of genotype 2, the SVR rate was similar (70-71%) among patients under 70 y.o. and declined among patients over 70 y.o. (43%).
Aged patients up to 65 y.o. with genotype 1 and 70 y.o. with genotype 2 can be candidates for Peg-IFN plus ribavirin therapy. The response-guided therapy can be applied for aged patients with genotype 1.

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    • "The current standard of care (SoC) for HCV infection consists of a combined therapy of injectable pegylated interferon alfa (pegIFNa ) and ribavirin administered for 24e48 weeks depending on the HCV genotype [13] [14]. However, this therapy has many limitations, being long, expensive, toxic, and only effective in around 50% of the patients for the most common genotype [15] [16]. Moreover, SoC therapy is not suitable for people suffering from severe HCV related cirrhosis, undergone organ transplant, children of <3 years and specific contraindication to the medication [17]. "
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    • "The viral factors include virus titer, genotype, amino acid substitution at position 70 of the core protein (Core 70) and mutations in the interferon sensitivity-determining region (ISDR) in the HCV NS5A region [23–27]. The host factors include age, sex, the degree of liver fibrosis, and a single nucleotide polymorphism (SNP) close to the IL-28B gene [28–33]. "
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    ABSTRACT: Background We conducted a multicenter randomized clinical trial to determine the optimal treatment strategy against chronic hepatitis C virus (HCV) with genotype 1b and a high viral load (G1b/high). Methods The study subjects included 153 patients with G1b/high. Patients were initially treated with PEG-IFNα-2a alone and then randomly assigned to receive different treatment regimens. Ribavirin (RBV) was administered to all patients with HCV RNA at week 4. Patients negative for HCV RNA at week 4 were randomly assigned to receive PEG-IFNα-2a (group A) or PEG-IFNα-2a/RBV (group B). Patients who showed HCV RNA at week 4 but were negative at week 12 were randomly assigned to receive weekly PEG-IFNα-2a (group C) or biweekly therapy (group D). Patients who showed HCV RNA at week 12 but were negative at week 24 were randomly assigned to receive PEG-IFNα-2a/RBV (group E) or PEG-IFNα-2a/RBV/fluvastatin (group F). Results Overall, the rate of sustained virological response (SVR) was 46 % (70/153). The total SVR rate in the group (A, D, and F) of response-guided therapy was significantly higher than that in the group (B, C, and E) of conventional therapy [70 % (38/54) versus 52 % (32/61), p = 0.049]. Although IL28-B polymorphism and Core 70 mutation were significantly associated with efficacy, patients with rapid virological response (RVR) and complete early virological response (cEVR) achieved high SVR rates regardless of their status of IL-28B polymorphism and Core 70 mutation. Conclusion In addition to knowing the IL-28B polymorphism and Core 70 mutation status, understanding the likelihood of virological response during treatment is critical in determining the appropriate treatment strategy.
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    • "The SVR rate and the discontinuation rate of patients aged ≥ 65 years in the present study are better than those of previous studies [20-24]. Oze et al. reported that the Peg-IFN dose affects the virologic response [25], and Hiramatsu et al. reported that ribavirin dose reduction increases the relapse rate [26]. "
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