Hepatitis C Virus Spontaneous Clearance: Immunology and Genetic Variance

Abstract

Hepatitis C virus (HCV) infection is one of the most common chronic viral infections in the world. Approximately 80-90% of acutely infected individuals develop persistent infection, which is a major risk for liver cirrhosis and liver cancer. However, a small portion of patients (10-20%) clear the virus. Clinical outcomes of HCV infection are determined by the interplay between the host immune response, and viral and environmental factors. In regulating immune responses, cytokines play an indispensable role that controls the underlying pathogenesis and the resulting outcome of HCV infection. Cytokines themselves are manipulated by polymorphisms in their genes. In fact, the majority of genetic variants that apparently confer a significant risk for chronic HCV infection have been localized in genes involved in cytokine synthesis and the ultimate immune response. So far, treatment strategies for HCV infection have remained controversial. Genotyping of different polymorphisms will aid clinical decision making for both current standard and personalized care. Genotyping can potentially be useful for future integration of other agents, which provides an opportunity for clinicians to personalize treatment regimens for HCV patients. This review summarizes findings of different studies on host immune responses after HCV infection and the association between cytokine gene polymorphisms and the likelihood of HCV clearance.

TNF-alpha 308 SNP Rs3091256 GG Genotype is Strongly Associated with Fibrosis in Patients with Chronic Hepatitis C

“…In a meta-analysis of studies performed at different centers, it has been shown that there is no significant association between TNF-α-308, -238 gene polymorphisms and susceptibility to infection among different HCV subgroups. (30). Besides, the distributions of TNF-α-308, -238 A/G alleles were also not significantly different between the persistent infection group and the spontaneous clearance group.…”

“…Although one study compared ALT levels between SVR patients and non-responders and found no statistically significant difference (10), the other found a statistically significant difference between healthy controls and those with cirrhosis and hepatocellular carcinoma (30), these studies did not include TNF polymorphism. Abbas et al (41) studied HCV genotype 3 and found no association between ALT level and TNF-α-308 polymorphism.…”

Tumour necrosis factor -308 and -238 promoter polymorphisms are predictors of a null virological response in the treatment of Brazilian hepatitis C patients

“…Host immune response as a consequence of genetic background has been shown to play a crucial role in HCV infection pathogenesis and interindividual heterogeneity of disease outcomes (Amini & Poustchi 2012). Cytokine production varies among individuals and these variations are associated with SNPs located in the coding and promoter regions of cytokine genes (Ollier 2004).…”

“…Dai et al (2006) suggested that the TNF polymorphism at position -308 may be a predictor of treatment failure in patients treated with a combination of IFN-α and RBV. However, studies conducted in the United States of America, Ireland and Japan have been unable to identify any association between TNF genetic polymorphisms and histological severity or response to antiviral therapy (Hohler et al 1998, Ollier 2004, Amini & Poustchi 2012). …”

Tumor necrosis factor-α -G308A polymorphism is associated with liver pathological changes in hepatitis C virus patients

“…Multiple factors have been reported to affect the liver disease progression rate[4]. Single nucleotide polymorphisms (SNPs) in the non-coding or coding regions of cytokine genes have been documented to affect their expression and secretion, which can cause chronic inflammation and disease progression[5,6]. …”