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

[Guest guest]

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