Ultrastructural changes and mitochondrial DNA content in the hepatocytes of individuals co-infected with HIV and Hepatitis C virus following HCV combination therapy

• Main Author: Hiebert, Hayley
• Language: English
• Published: University of British Columbia 2013
• Online Access: http://hdl.handle.net/2429/44238

Background and objectives: Hepatitis C Virus (HCV) affects approximately 170 million people worldwide. Some estimates suggest up to 30% of these individuals are also infected with Human Immunodeficiency Virus (HIV). In Vancouver, British Columbia, the percent of HIV/HCV co-infected individuals is even greater, approaching 50% of those infected with HIV. Since the advent of highly active anti-retroviral therapy (HAART), the leading cause of death for HIV positive individuals is end stage liver disease often associated with chronic HCV infection. Previous work by our laboratory did not provide evidence of significant hepatocellular or mitochondrial toxicity associated with HAART treatment. Since it is suggested that drugs used in both HAART and HCV combination therapy may be toxic to the liver, the concurrent use of these treatments in co-infected individuals may be associated with increased hepatocellular and mitochondrial toxicity. The objective of this study was to determine the ultrastructural and mitochondrial DNA content changes that occur in liver hepatocytes in response to HCV combination therapy in co-infected individuals. Hypothesis: HCV combination therapy is associated with ultrastructural hepatocellular changes consistent with either damage or tissue repair in HIV and HCV co-infected patients. Methods: Liver biopsies were taken from co-infected patients before and after receiving HCV combination therapy. One biopsy was used for pathology assessment, the other was divided for nucleic acid assays and transmission electron microscopy (TEM). TEM samples were then examined for ultrastructural changes in hepatocytes following HCV combination therapy. Results: Biopsies from 11 subjects were collected. Of the subjects examined, liver pathology improved significantly following HCV combination therapy while no differences were observed in the mtDNA to nDNA ratio before and after treatment. Ultrastructural analysis of hepatocytes revealed a significant decrease in lipid content following HCV combination therapy. Conclusions: Overall, these results suggest that HCV combination therapy is beneficial to liver health and lessens liver pathology in HIV/HCV co-infected patients featuring a reduction in lipid content or steatosis. Future studies involving greater sample size are required to determine additional effects of HCV combination therapy on co-infected individuals.