Viral Clearance and Disease Progression in Siblings with Hepatitis C

By Liz Highleyman

Research increasingly shows that genetic variations influence hepatitis C disease progression and response to treatment.

One of the best ways to study the role of genetic factors is to compare treatment responses in close relatives versus unrelated individuals. Hemophilia is a hereditary disease that often affects multiple siblings in a family. Before the hepatitis C virus (HCV) was identified and a blood screening test developed, many hemophiliacs became infected with HCV through transfusions of blood factors required to treat the disease.

In the September 2006 issue of Gastroenterology, researchers from the University of North Carolina at Chapel Hill reported data from a study of spontaneous and treatment-related HCV clearance and liver disease progression in 257 sibling pairs in which both members had evidence of HCV infection.

Many hemophiliacs were also infected with HIV through blood product transfusions, but the researchers only analyzed HIV negative (not coinfected) individuals. The authors compared the concordance (matching) of hepatitis C disease characteristics within sibling pairs to that which would be expected between randomly paired unrelated individuals with hemophilia.

Results

Concordance for spontaneous HCV clearance was 2-fold higher in siblings compared with randomly paired subjects (8.8% vs 4.3%, respectively; P = 0.04).

Concordance for treatment-induced HCV clearance among sibling pairs was more than twice that of randomly paired hemophiliacs (31.3% vs 13.3%, respectively), though this difference was not statistically significant.

Heritability estimates for spontaneous and treatment-induced viral clearance were 0.24 +/- 0.14 (P = 0.04) and 0.43 +/- 0.42 (P = 0.10), respectively.

The sibling relative risks for spontaneous and treatment-induced viral clearance were 1.6 and 1.7, respectively.

Concordance for advanced liver disease was higher among siblings than among unrelated individuals (4.0% vs 2.3%, respectively), but this difference did not reach statistical significance.

The heritability estimate for advanced liver disease was 0.29 +/- 0.13 (P = 0.02).

Conclusion

In conclusion, the authors wrote, "Concordance rates and heritability estimates for spontaneous and treatment-related viral clearance indicate that genetic factors have a modest influence on the outcome of hepatitis C, although shared environmental factors cannot be excluded." They added, however, that, "Investigations to map candidate disease-susceptibility genes associated with these characteristics must be approached with caution."

9/15/06

Reference
M W Fried, B L Kroner, L R Preiss, and others. Hemophilic siblings with chronic hepatitis C: familial aggregation of spontaneous and treatment-related viral clearance. Gastroenterology 131(3): 757-764. September 2006.