Hepatitis C: viral and host factors associated with non-response to pegylated interferon plus ribavirin

Abstract

Treatment for chronic hepatitis C virus (HCV) infection has evolved considerably in the last years. The standard of care (SOC) for HCV infection consists in the combination of pegylated interferon (PEG-IFN) plus ribavirin. However, it only induces a sustained virological response (SVR) in half of genotype 1-infected patients. Several viral and host factors have been associated with non-response: steatosis, obesity, insulin resistance, age, male sex, ethnicity and genotypes. Many studies have demonstrated that in non-responders, some interferon-stimulated genes were upregulated before treatment. Those findings associated to clinical, biochemical and histological data may help detect responders before starting any treatment. This is a very important issue because the standard treatment is physically and economically demanding. The future of HCV treatment would probably consist in the addition of specifically targeted antiviral therapy for HCV such as protease and/or polymerase inhibitors to the SOC. In genotype 1 patients, very promising results have been reported when the protease inhibitor telaprevir or boceprevir is added to the SOC. It increases the SVR rates from approximately 50% (PEG-IFN plus ribavirin) to 70% (for patients treated with a combination of PEG-IFN plus ribavirin plus telaprevir). Different elements are associated with non-response: (i) viral factors, (ii) host factors and (iii) molecular mechanisms induced by HCV proteins to inhibit the IFN signalling pathway. The goal of this review is to present the mechanisms of non-response, to overcome it and to identify factors that can help to predict the response to anti-HCV therapy.

Soluble inflammatory markers as predictors of virological response in patients with chronic hepatitis C virus infection treated with interferon-α plus ribavirin

“…SVRs [i.e., negative HCV qualitative polymerase chain reaction (PCR) 24 weeks after the end of treatment] are observed in approximately half of the treated patients and many factors, such as age, genotype, viral load and body weight, are related to treatment outcome (Manns et al 2001, Asselah et al 2010. The outcome of HCV treatment seems also to depend on the ability of host cellular immune responses to control viral replication.…”

Efficacy of Treatment With Pegylated Interferon and Ribavirin in Patients With Chronic HCV Infection “Under Real Life“ Conditions

“…Patients infected with "easy-to-treat" genotypes 2 and 3 respond much better than those with "difficult-to-treat" genotypes 1 and 4. HCV genotype, pretreatment viral load, ethnicity, gender, presence of cirrhosis or advanced fibrosis, obesity, steatosis, insulin resistance, elevated γGT and other are significantly associated with the outcome of Peg-IFN plus RBV combination therapy [32,[34][35][36][37][38]. Furthermore, those with low pretreatment viral load respond much better than those with high pretreatment viral load.…”

Pharmacogenomic Testing in the Era of Patient-Tailored HCV Treatment

“…It has been noticed that many clinical factors, including pharmacogenetics, could influence the treatment response rate [9]. Both virological factors (such as HCV genotype, quasispecies diversity, and baseline viremia) and host factors (age, gender, race-ethnicity, fibrosis stage, obesity, hepatic steatosis, low-density lipoprotein cholesterol, insulin resistance, and genetic variances) played an important role in predicting the natural course of hepatitis C and IFN response to therapy [7,[55][56][57]. Pharmacogenetic testing could play very important role in optimizing HCV therapy by identifying variations in response to treatment, considering ethnic variations in response to therapy, enlightening the molecular mechanism of current and future therapies, and advancement of innovative genetic tools that will enable physicians to individualize drug therapy, adjust dosages, and reduce the possibility of adverse drug reactions and therapeutic costs ( Table 1) [54,58].…”