In natural history studies of hepatitis C virus (HCV) infection, women have a lower risk of disease progression to cirrhosis. Whether gender influences outcomes of HCV in the post-transplant setting is unknown. All patients transplanted for HCV-related liver disease from 2002-2007 at 5 U.S. transplant centers were included. The primary outcome was development of advanced disease, defined as biopsy-proven bridging fibrosis or cirrhosis. Secondary outcomes included death, graft loss, and graft loss with advanced recurrent disease. 1,264 patients were followed for a median of 3.0 years (IQR 1.8-4.7) - 304 (24%) were female.
The cumulative rate of advanced disease at 3-years was 38% for females and 33% for males (p=0.31) but after adjustment for recipient age, donor age, donor anti-HCV positivity, post-transplant HCV treatment, cytomegalovirus infection and center, female gender was an independent predictor of advanced recurrent disease (HR, 1.31; 95%CI, 1.02-1.70; p=0.04). Among women, older donor age and treated acute rejection were the primary predictors of advanced disease. The unadjusted cumulative 3-year rates of patient and graft survival were numerically lower in females than males, 75% vs. 80% and 74% vs. 78%, and in multivariable analyses, female gender was an independent predictor for death (HR, 1.30; 95%CI, 1.01-1.67; p=0.04) and graft loss (HR, 1.31; 95%CI, 1.02-1.67; p=0.03).
CONCLUSION: Female gender represents an under-recognized risk factor for advanced recurrent HCV disease and graft loss. Further studies are needed to determine whether modification of donor factors, immunosuppression, and post-transplant therapeutics can equalize HCV-specific outcomes in women and men.