Executive Summary : | Hepatitis C virus (HCV) is a global public health issue with 58 million people infected worldwide. High chronicity rates and progressive liver diseases, such as fibrosis, cirrhosis, and hepatocellular carcinoma, are associated with HCV infection. The HCV genome, which is approximately 9.6 kb, codes for its own RNA dependent RNA polymerase Ns5B, which aids in viral replication. Due to the lack of proofreading activity of the Ns5B polymerase, the HCV genome is highly genetically diverse. HCV is classified into eight genotypes, with genotype 1 being the most prevalent worldwide. Recent studies have shown that HCV genotypes have differential impacts on liver disease progression, with genotype 1, particularly subtype 1b, having a greater chance of developing cirrhosis. To treat chronic infection, different combinations of direct-acting antivirals (DAAs) targeting non-structural regions of viral genomes, such as Ns3/Ns4, Ns5A, and Ns5B, provide 95% sustained virological response (sVR) in many cases except genotype 3. However, resistance-associated substitutions (RAss) in these regions have been reported to be associated with therapeutic failure. The most common RAss associated with genotype 3 and genotype 4 are Y93H and L30R, which are associated with lower sVR rates in patients. In India, HCV genotype 3 is the most predominant (63.85%), followed by genotype 1 (25.72%), genotype 2 (0.002%), genotype 4 (7.5%), and genotype 6 (2.7%). Further comparative studies between HCV genotypes, especially genotype 1 and 3, are lacking in the Indian population. This study aims to evaluate the distinctive roles of different HCV genotypes in India, aiming to develop better therapeutic approaches for all genotypes prevalent in the country. |