Effect of intrahepatic hepatitis C virus internal ribosomal entry site activity on the outcome of infection
Abstract number: 1733_1387
Motazakker M., McCruden E., Preikschat P., Elliott J., Smith C., Oien K., Spence E., Elliott R., Mills P.
Introduction: The course of chronic hepatitis C virus (HCV) infection is variable and unexplained. Hepatic steatosis has been linked to the progression of fibrosis in HCV and is known to be more common in genotype (gt) 3 infected patients. This study explores variation in intrahepatic HCV internal ribosomal entry site (IRES) nucleotide sequences and outcome of infection.
Method: The translation efficiencies of eight gt 1a and eight gt 3a 5UTR sequences derived from 16 liver biopsies were measured in cell culture using a dual luciferase reporter system. The values obtained were then compared to the liver biopsy scores for steatosis and for inflammation and fibrosis (Ishak system) score and serum viral load.
Results: The steatosis scores correlated positively with the presence of gt 3a (Mann-Whitney test, p = 0.008), increasing viral load (correlation coefficient (r) = 0.49, p= 0.02) and fibrosis stage (r = 0.47, p= 0.03). The IRES activity did not correlate with severity of steatosis (r = -0.3, p = 0.1), inflammation grade (r = 0.09, p = 0.6), stage of fibrosis (r = 0.1, p = 0.5) or with serum HCV RNA levels (r = -0.11, p = 0.6).
Conclusion: The previously reported association of steatosis with genotype 3, viral load and stage of fibrosis is confirmed. No correlation was seen between IRES activity and these parameters. The efficiency with which the IRES directs translation of the polyprotein appears not to be the limiting factor governing the rate of replication of HCV and pathological features seen in the liver
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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