Boceprevir and telaprevir for chronic genotype 1 hepatitis C virus infection. A systematic review and meta-analysis.

BACKGROUND: Treatment of hepatitis C virus (HCV) infection with newer direct-acting antivirals is unrealistic in some countries because of the lack of availability. AIM: Assess benefits and harms of boceprevir (BOC) and telaprevir (TLV) in treatment of genotype 1 HCV infection, and identifying subgroups with most benefit. MATERIAL AND METHODS: Search from 2009-2013 in PubMed, EMBASE, and "gray literature" of published and unpublished randomized trials reporting sustained viral response (SVR) or adverse events (AE) with BOC or TLV + pegylated interferon and ribavirin (PR) in HCV-infected patients; cohorts or case reports for comparison protease inhibitors (PI), evaluation of predictors of SVR, and resistant variants. Cochrane guidelines were applied. Comparisons between PI + PR vs. PR were performed. Main outcomes were expressed as risk-ratios with 95% CIs. Meta-regression and trial sequential analysis were performed. RESULTS: 33 studies (10,525 patients) were analyzed. SVR was higher for PI + PR (RR, 2.05; 95% CI 1.70-2.48). In meta-regression, previously treated patients exhibited greater benefit from PI + PR (RR, 3.47; 95% CI, 2.78-4.33). AE were higher with PI + PR (RR, 1.01; 95% CI, 1-1.03; NNH 77.59), also the discontinuation rate (RR, 1.69; 95% CI, 1.36-2.10, NNH, 18). Predictors of SVR were IL-28 TT, nonblack race, low viral load, age, no cirrhosis, statin use, undetectable viral load at the first anemia episode and at week 2 of treatment, and low IL-6 levels. In conclusion SVR was higher in patients treated with PIs, patients previously exposed to PR showed superior response rates. Specific predictors will determine the best candidates for treatments that will offer real-life therapeutic alternatives.

An update on the management of hepatitis C: guidelines for protease inhibitor-based triple therapy from the Latin American Association for the Study of the Liver.

Hepatitis C is a common cause of end-stage liver disease, and the main indication for liver transplantation in Latin America. Treatment of hepatitis C infected patients improves important long-term outcomes as mortality. Sustained viral response is reached in near 50% of patients with the previous management based in pegylated interferon and ribavirin. Recently new drugs were available increasing sustained viral response significantly, changing the standard of care to triple therapy. This guidelines provides a framework for practitioner in Latin America, to the management of patients with hepatitis C chronic infection. 

Efficacy of triple therapy with thymalfasin, peginterferon alpha-2a, and ribavirin for the treatment of hispanic chronic HCV nonresponders.

BACKGROUND/AIMS: Thymalfasin has shown efficacy in the treatment of chronic HCV infection. The aim of this study was to evaluate the efficacy and tolerability of triple therapy with thymalfasin, peginterferon alpha-2a (PEG-IFN alpha-2a), and ribavirin in Hispanic patients with chronic viral hepatitis C who were nonresponders to prior treatment with interferon alfa (IFN-alpha)/ribavirin. METHODS: In this open-label study, 40 subjects received thymalfasin (1.6 mg twice a week), PEG-IFN alpha-2a (180 microg once a week), and ribavirin (800-1,000 mg/day) for 48 weeks. All patients had positive HCV RNA by PCR analysis, abnormal levels of ALT, compensated hepatic disease, and liver biopsy with chronic damage. RESULTS: Viral response was observed in 52.5% patients at week 12 and 50% at week 24. Of the per protocol group, 52.6% showed an end-of-treatment response at week 48 and 21.1% achieved an SVR at week 72. Among genotype 1 patients, 23.5% achieved an SVR at week 72. A reduction of the dose of PEG IFN alpha-2a and ribavirin was required. Thymalfasin was well tolerated without dose reduction. CONCLUSION: Triple therapy with thymalfasin, PEG IFN alpha-2a, and ribavirin is an effective treatment option for difficult-to-treat HCV patients who are refractory to prior conventional treatment, with adequate tolerability.

IFN-stimulated gene expression is a useful potential molecular marker of response to antiviral treatment with Peg-IFNα 2b and ribavirin in patients with hepatitis C virus genotype 1.

BACKGROUND AND AIMS: We undertook this study to determine the baseline gene expression of IFI27, IFIT1, IFI6, ISG15, IRF-1, IRF-3, OAS-2 and CXCL10 and its usefulness as molecular markers of response to antiviral treatment with peg-IFNα 2b/RBV in patients with hepatitis C virus genotype 1 (HCV-1). METHODS: Gene expression was analyzed by RT-PCR in baseline liver biopsies from 42 HCV-1 patients who were treated with Peg-IFNα 2b/RBV for 48 weeks. In addition, we investigated gene expression of these genes in a second liver biopsy obtained 24 weeks post-treatment in sustained viral response (SVR) and relapser patients. RESULTS: Thirteen patients achieved SVR, four were relapsers, four patients with viral response (VR) discontinued the following for 24 weeks post-treatment and 21 patients did not respond to antiviral therapy (NR). All patients with HCV-1 showed gene overexpression in baseline liver tissue, but only IFI27, IFIT1, IFI6, ISG15, and CXCL10 showed differential gene expression, which is inversely related to the response to antiviral therapy. Thus, liver tissue of NR patients showed upregulation of these genes, whereas patients with SVR gene expression level was significantly lower. Furthermore, 24 weeks afterwards treatment, SVR patients showed a significant downregulation of such genes, which was consistent with the RNA-HCV suppression. ISGs (IFI27, IFIT1, IFI6) and chemokine CXCL10 showed the best positive and negative predictive values on SVR to IFN/RBV therapy (range: 70.8-75% and 71.43-82.35%), respectively. CONCLUSIONS: IFI27, IFIT1, IFI6, ISG15, and CXCL10 genes are potential biological markers useful for predicting response to Peg-IFNα 2b/RBV therapy in HCV-1 patients.