July 27, 2010

Genetic Diversity of Hepatitis C Virus Predicts Recurrent Disease after Liver Transplantation

SUMMARY: The genetic diversity of the hepatitis C virus (HCV) predicts recurrent disease after liver transplantation among patients with end-stage hepatitis C disease, according to a recent article published in Virology authored by researchers at the University of Washington in Seattle, WA. Their discovery could lead to more beneficial decisions regarding the use of antiviral therapy in HCV patients after transplantation.
 
Chronic hepatitis C is one of the leading causes of liver transplantation, and recurrent hepatitis is almost universal post transplant. For this reason, the ability to predict which HCV patients undergoing transplantation will develop recurrent disease would significantly benefit decisions regarding the use of antiviral therapy.

In an article published in the July 5, 2010 issue of Virology, researchers at the University of Washington in Seattle, WA show that the genetic diversity of the hepatitis C virus predicts recurrent disease after liver transplantation.

Approximately 20% of patients receiving liver transplants for end-stage hepatitis C rapidly develop severe hepatitis C disease within the first 24 months after transplant. In contrast, approximately 50% of HCV genotype-matched cases have completely asymptomatic post-transplant infections.

In the current study, hepatitis C virus (HCV) variants were evaluated in 56 genotype-1-infected subjects with end-stage hepatitis C disease at the time before and 12 months after liver transplant, and post-transplant outcome was followed with serial liver biopsies.

Results 
  • In 15 cases, pre-transplant HCV genetic diversity was studied in detail in liver (n=15), serum (n=15), peripheral blood mononuclear cells (n=13), and perihepatic lymph nodes (n=10).
  • Pre-transplant HCV genetic diversity predicted the histological outcome of recurrent hepatitis C disease after transplant.
  • Mild disease recurrence after transplant was significantly associated with higher genetic diversity and greater diversity changes between the pre- and post-transplant time points (p=0.004).
  • Pre-transplant genetic differences between serum and liver were related to a higher likelihood of development of mild recurrent disease after transplant (p=0.039).
In summary, the authors wrote, "Our data suggest that HCV genetics at the pre-transplant stage predicts hepatitis disease severity in transplanted allograft." They also noted, "Viral predictors of poor outcome include low genetic diversity in circulation and decreased genetic differences between serum and tissue specimens."
 
Finally, they stated, "Longitudinal studies are still going on in our laboratory to further define the HCV pathogenic mechanism that determines the outcome of hepatitis C disease after transplant."
 
Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA; Department of Pathology, University of Washington Medical Center, Seattle, WA; Department of Surgery, University of Washington Medical Center, Seattle, WA; and Department of Medicine, University of Washington Medical Center, Seattle, WA.
 
Reference
 
H Li, DG Sullivan, N Feuerborn, and others. Genetic Diversity of Hepatitis C Virus Predicts Recurrent Disease after Liver Transplantation. Virology 402(2): 248-255. July 5, 2010.
 

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