Drug Resistance in Hepatitis C Virus: Future Prospects and Strategies to Combat It.

Induction of highly pathogenic hepatitis C virus (HCV) causes chronic hepatitis round the world. This virus is easily prone to developing resistance against antiviral drugs because of two viral polymerases that do not possess the proofreading and overlapping reading frame abilities. There is more than one explanation for how this virus builds up resistance against antiviral drug treatments. Assays are now available to detect HCV-resistant variants, based on phenotypic and genotypic assays, and next generation sequencing. But these assays are of a little value at baseline, because they are not influential enough for making therapeutic decisions in HCV patients. Moreover, HCV monitoring is now an essential part of clinical practice. Special patients, such as those with thalassemia, renal transplant due to renal failure, and the patients undergoing hemodialysis, are at higher risk for acquiring this infection. Management of HCV infection in these patient groups is complicated by multiple side effects, including flu-like symptoms, neutropenia, fever, and neuropsychiatric disorders, thus limiting the use of ribavirin and coexisting iron overload. In HCV patients suffering from depression, the treatment may be discontinued because of some defects in neurochemical pathways caused by interferon, which can enhance the level of depression in these patients. In addition, obesity has been found to be a marker of failure of HCV treatment. There will be many resistance tolerant HCV treatment options available in the near future.

HCV-induced regulatory alterations of IL-1ß, IL-6, TNF-α, and IFN-ϒ operative, leading liver en-route to non-alcoholic steatohepatitis.

Over the course of time, Hepatitis C has become a universal health menace. Its deleterious effects on human liver encompass a lot of physiological, genetic as well as epigenetic alterations. Fatty liver (Hepatic steatosis) is an inflammation having multifactorial ancestries; one of them is HCV (steatohepatitis). HCV boosts several cellular pathways involving up-regulation of a number of cytokines. Current study reviews the regulation of some selective key cytokines during HCV infection, to help generate an improved understanding of their role. These cytokines, IL-1ß, IL-6, TNF-α, and IFN-ϒ, are inflammatory markers of the body. These particular markers along with others help hepatocytes against viral infestation. However, recently, their association has been found in degradation of liver on the trail heading to non-alcoholic steatohepatitis (NASH). Consequently, the disturbance in their equilibrium has been repeatedly reported during HCV infection. Quite a number of findings are affirming their up-regulation. Although these cell markers are stimulated by hepatocytes as their standard protection mechanism, but modern studies have testified the paradoxical nature of this defense line. Nevertheless, direct molecular or epigenetic research is needed to question the actual molecular progressions and directions commanding liver to steatosis, cirrhosis, or eventually HCC (Hepatocellular Carcinoma).

Role of circulatory microRNAs in the pathogenesis of hepatitis C virus.

Hepatitis C virus (HCV) is associated with one of the major health problem in world that ultimate results in the liver cirrhosis and leads to carcinoma of hepatocellular components round the world. More than 185 million people were found to be infected with HCV. MicroRNAs are small oligonucleotide RNA having 18-22 nucleotides. Circulating mi-RNAs regulate the replication of HCV and HCV-induced liver fibrosis and HCC. By comparing the expression profiles of mi-RNAs of normal individuals with HCV infected patients, aberrant changes in expression of different mi-RNAs have been observed so it can be predicted that these mi-RNAs are associated with and play a central role in the hepatitis C infection and diseases associated with it. This review demonstrates the major role of circulatory microRNAs in the HCV and HCV associated ailments.