An insight into the diagnosis and pathogenesis of hepatitis C virus infection

This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus(HCV)infection over the last few decades.The information based on published literature provides an update on these two aspects of HCV.HCV infection,previously called blood transmitted non-A,non-B infection,is prevalent globally and poses a serious public health problem worldwide.The diagnosis of HCV infection has evolved from serodetection of non-specific and low avidity anti-HCV antibodies to detection of viral nucleic acid in serum using the polymerase chain reaction(PCR)technique.Current PCR assays detect viral nucleic acid with high accuracy and the exact copy number of viral particles.Moreover,multiplex assays using real-time PCR are available for identification of HCV-genotypes and their isotypes.In contrast to previous methods,the newly developed assays are not only fast and eco-nomic,but also resolve the problem of the window period as well as differentiate present from past infection.HCV is a non-cytopathic virus,thus,its pathogenesis is regulated by host immunity and metabolic changes including oxidative stress,insulin resistance and hepatic steatosis.Both innate and adaptive immunity play an important role in HCV pathogenesis.Cytotoxic lymphocytes demonstrate crucial activity during viral eradication or viral persistence and are influenced by viral proteins,HCV-quasispecies and several metabolic factors regulating liver metabolism.HCV pathogenesis is a very complex phenomenon and requires further study to determine the other factors involved.

Molecular basis of hepatocellular carcinoma induced by hepatitis C virus infection

Present study outlines a comprehensive view of published information about the underlying mechanisms operational for progression of chronic hepatitis C virus(HCV) infection to development of hepatocellular carcinoma(HCC). These reports are based on the results of animal experiments and human based studies. Although, the exact delineated mechanism is not yet established, there are evidences available to emphasize the involvement of HCV induced chronic inflammation, oxidative stress, insulin resistance, endoplasmic reticulum stress, hepato steatosis and liver fibrosis in the progression of HCV chronic disease to HCC. Persistent infection with replicating HCV not only initiates several liver alterations but also creates an environment for development of liver cancer. Various studies have reported that HCV acts both directly as well as indirectly in promoting this process. Whereas HCV related proteins, like HCV core, E1, E2, NS3 and NS5A, modulate signal pathways dysregulating cell cycle and cell metabolism, the chronic infection produces similar changes in an indirect way. HCV is an RNA virus and does not integrate with host genome and therefore, HCV induced hepatocarcinogenesis pursues a totally different mechanism causing imbalance between suppressors and proto-oncogenes and genomic integrity. However, the exact mechanism of HCC inducement still needs a full understanding of various steps involved in this process.

Torque teno virus:Its prevalence and isotypes in North India

AIM: To investigate the prevalence and genotype dis-tribution of Torque teno virus (TTV) in patients with different liver diseases and chronic renal failure treated at a referral hospital in North India. METHODS: Whereas prevalence of TTV was based on amplification of conserved region of ORF2 of TTV genome,the genotyping of TTV was carried out using restriction fragment length polymorphism (RFLP) procedure on the N22 region of ORF1. RESULTS: TTV-DNA was detected in 137 of 513 (26.7%) patients with liver diseases and 38 of 65 (58.5%) patients with chronic renal failure. TTV was also detected in 27% of healthy controls. The sequence analysis of the PCR product from 10 randomly selected cases failed to show a significant sequence divergence when compared with that of the TRM1 isolate of TTV genotype 1. The results of genotyping in 55 randomly selected patients showed the presence of genotype 1 (G1) in 53 (96.4%) and genotype 2 (G2) in 2 cases (3.6%),respectively. Other genotypes were not identified in this patient subgroup,suggesting that G1 is predominant in this area. The results of genotyping by RFLP were also supported by phylogenetic tree analysis,where G1 was found to be the major genotype. CONCLUSION: These results indicate that TTV is moderately present in Indian patients,with G1 to be the major genotype in North India. The pathogenicity and etiological role of TTV in different diseases is still a question mark and warrant further studies.