Hepatitis C virus to hepatocellular carcinoma

Hepatitis C virus causes acute and chronic hepatitis [1] an can leads to HCC via oxidative stress, insulin resistance (IR), fibrosis, liver cirrhosis and HCV induced steatosis [2]. HCV is a major health problem, almost 350 million individuals are chronically HCV infected [3] and 10% of the Pakistani population is chronically infected with this viral pathogen [4]. Approximately 40-60% of HCV infected individuals leads to chronic liver disease [5], and prevalence of HCV associated HCC is higher in Pakistan as compare to the rest of world [6,7].HCV is an enveloped positive-single stranded RNA virus 9.6 kb in length consisting of (Core, E1, E2 and possibly p7) proteins and nonstructural (NS2, NS3, NS4A, NS4B, NS5A and NS5B) viral proteins [8,9]. HCV Core is known as the inducer of steatosis, oxidative stress and HCC [10]. E1 and E2 are involved in virus attachment with the cells and are considered to be the first viral protein comes in contact with the cells [11]. p7 is possibly concerned with ion channel and virus assembly [12]. HCV has six genotypes and 52 subtypes mainly genotypes in the different region of the world are (1a, b, c, 2a, b, c, 3a, b, 4a, 5a, 6a). Due to absence of proofreading function of the RNA-dependent RNA-polymerase (NS5B), HCV has a high mutation rate and exists as genetically heterogeneous quasispecies in individual patients [13,14]. The genetic diversity is more than 30% in different genotypes and 20% in subtypes. Variations in amino acid sequence of different HCV genotypes cause difference in severity of pathogenesis. Recent studies have shown variable responses for interferon (IFN)-ribavirin combination therapy, oxidative stress/steatosis and insulin resistance due to the amino acid substitutions in the HCV Core region of different HCV genotypes.HCV genotype 3a is mainly prevalent in Pakistan followed by 3b and 1a [15]. Moreover, a strong correlation between chronic HCV infection and HCC in Pakistan associated with genotype 3a has been observ