The Impact of Host Factors on Management of Hepatitis C Virus

Hepatitis C virus (HCV) was identified in 1989 as an enveloped virus with a 9.6-kb single-stranded RNA genome and a member of the Flaviridae family, genus Hepacivirus. It is characterized by a high spontaneous mutation rate with an estimated frequency of 1.4–1.9 × 103 mutations per nucleotide per year (1, 2). As a result, HCV exists as a heterogeneous group of viruses, sharing approximately 70% homology. On the basis of nucleotide sequence homology, HCV has been classified into no fewer than 6 major genotypes and a series of subtypes (3). HCV is among the leading causes of chronic liver disease worldwide and affects approximately 170 million people (4). The severity of the disease that is associated with HCV infection varies from asymptomatic, chronic infection to cirrhosis and hepatocellular carcinoma (5, 6). Combination therapy with pegylated interferon alpha and ribavirin (Peg-IFN-α/RBV) for 24–48 weeks is the current standard of care in CHC patients (7). Unfortunately, more than 40% of patients with chronic HCV infection will fail to control viral replication with therapy (nonresponders) or will experience a relapse when therapy is stopped (relapsers); in addition, it is physically and economically demanding. Thus, it is crucial to understand the mechanisms of nonresponse to overcome it and identify factors that can help predict the chances of a patient responding to the treatment. The molecular mechanisms that underlie the failure of standard therapy are not well understood, but evidence indicates that both viral and host factors are involved. The focus of interest of this review is to present the host factors that are associated with response to the current treatment against HCV. Several host factors are implicated in modulating the effectiveness of interferon therapy for the treatment of HCV infection (8). Likely, these host factors play an equally important role in modulating the efficacy of interferon therapy. Therefore, an understanding of how these factors influence interferon therapy may identify therapeutic targets to improve the efficacy of interferon therapy (9). Host factors that are responsible for responsiveness to HCV therapy with Peg-IFN-α/RBV include host genetic factors, age, ethnicity, gender, cirrhosis, weight (BMI), steatosis, insulin resistance (IR), and type 2 diabetes mellitus (T2DM). Hepat Mon. 2012;12(4):235-241. DOI: 10.5812/hepatmon.709