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Abstract
Chronic hepatitis C affects more than 170 million people worldwide and is one of the most common infectious diseases on earth. If untreated, it can lead to progressive liver injury, cirrhosis, liver failure and hepatocellular carcinoma. While curative antiviral therapy is currently available, it is far from 100% effective. The broad aim of this thesis is to examine factors influencing treatment response and liver injury in chronic hepatitis C virus.
The first two studies examine treatment responses in ethnic groups where chronic hepatitis C is prevalent. A case-control study was conducted to compare the treatment responses between Arabic patients infected with genotype 4 with Caucasians infected with genotype 1 who were treated with interferon and ribavirin combination antiviral therapy, and found a superior sustained virological response rate of 64.0% , compared to that of 32.3% of genotype 1 infected patients, independent of other factors. Another retrospective case control study found Asians infected with chronic hepatitis C genotype 1 also had better sustained virological response rate of 73%, as compared to that of 36% of Caucasians infected with genotype 1. Findings of these two studies challenges the current clinical practice of extrapolating data from clinical trials originating from genotype 1 infected Caucasians, and treating different ethnic groups with same regimen, and prompted further research into treatment of different patient groups.
The third study examined the role of two adipocytokines, namely adiponectin and retinal binding protein 4 in the pathogenesis of chronic hepatitis C by examining their serum levels and their expression at the genetic level in the liver, and contrasted that with non-alcoholic fatty liver disease. The study found that the relationship between insulin resistance and liver injury in chronic hepatitis C is probably independent from the effects of retinal binding protein 4. In addition, this study found the complex role of retinal binding protein 4 in non-alcoholic fatty liver disease, and prompted further research into identifying the pathways of adipocytokines in pathogenesis of chronic hepatitis C and non-alcoholic fatty liver disease.