In natural history studies of hepatitis C virus (HCV) infection, women have a lower risk of disease progression to cirrhosis. Whether female sex influences outcomes of HCV in the posttransplantation setting is unknown. All patients transplanted for HCV-related liver disease from 2002-2007 at five United States transplantation 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. A total of 1,264 patients were followed for a median of 3 years (interquartile range, 1.8-4.7), 304 (24%) of whom were women. The cumulative rate of advanced disease at 3 years was 38% for women and 33% for men (P = 0.31), but after adjustment for recipient age, donor age, donor anti-HCV positivity, posttransplantation HCV treatment, cytomegalovirus infection and center, female sex was an independent predictor of advanced recurrent disease (hazard ratio [HR], 1.31; 95% confidence interval [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 women (75% and 74%, respectively) than men (80% and 78%, respectively), and in multivariable analyses, female sex 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 sex represents an underrecognized risk factor for advanced recurrent HCV disease and graft loss. Further studies are needed to determine whether modification of donor factors, immunosuppression, and posttransplantation therapeutics can equalize HCV-specific outcomes in women and men.
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