Human Genetic Variation May Protect Against HCV-related Liver Disease Progression

Over years or decades, chronic hepatitis C virus (HCV) infection can lead to advanced liver disease, including cirrhosis, hepatocellular carcinoma, and end-stage liver failure. However, more than half of patients do not develop severe liver disease, and the factors that influence outcomes are not well understood.

In a report published in the December 2007 issue of Hepatology, researchers from Los Alamos National Laboratory noted as background that previous studies have shown statistical associations between human leukocyte antigen (HLA) heterozygosity (presence of 2 different alleles, or genetic variants) and favorable outcomes of infection with hepatitis B virus (HBV) or HIV -- a phenomenon known as “heterozygote advantage.”

In the present study, the authors investigated whether HLA zygosity is associated with outcomes of HCV infection. They used data from the United States Organ Procurement and Transplantation Network database of 52,435 liver transplant recipients from 1995 through 2005. Of these, 30,397 were excluded for lack of HLA data, re-transplantation, known HIV-HCV coinfection, or insufficient information regarding HBV coinfection.

Results

• There was a significantly lower proportions of HLA-DRB1 heterozygosity among HCV-infected compared with uninfected individuals.

• These differences were more pronounced with alleles represented as functional supertypes than as low-resolution genotypes.

• No significant associations were observed between zygosity and HCV infection other HLA locations.

Conclusion

“These findings constitute evidence for an advantage among carriers of different supertype HLA-DRB1 alleles against HCV infection progression to end-stage liver disease in a large-scale, long-term study population,” the authors concluded.

They added that, “Considering HLA polymorphism in terms of supertype diversity is recommended in strategies to design association studies for robust results across populations and in trials to improve treatment options for patients with chronic viral infection.”

Finally, they wrote, “Access to de-identified clinical information relating genetic variation to viral infection improves understanding of variation in infection outcomes and might help to personalize medicine with treatment options informed in part by human genetic variation.”

01/04/08

Reference
P Hraber, C Kuiken, and K Yusim. Evidence for human leukocyte antigen heterozygote advantage against hepatitis C virus infection. Hepatology 46(6): 1713-1721. December 2007.