Predictors of Liver Disease Outcomes in Individuals with Hemophilia and HCV Infection

• In HCV+ hemophilic men, major risk factors for ESLD are platelets<100,000 and HIV infection.

• Despite antiviral therapy, ESLD is the major predictor of HCC and cause of death in this group.

Hemophilia is an X-linked congenital bleeding disorder characterized by spontaneous and traumatic bleeding. Factor replacement is life-saving but complicated by the sequelae of chronic hepatitis C (HCV) infection acquired decades ago. While antiviral therapy clears HCV and reduces end-stage liver disease (ESLD), it may not reverse cirrhosis or prevent hepatocellular carcinoma (HCC). This was a retrospective cohort study of 121 hemophilic men with HCV infection cared for at the Hemophilia Center of Western PA, to determine incidence and predictors of ESLD and HCC. ESLD and HCC predictors were analyzed by Fisher's exact test. HCV-associated outcomes were evaluated by Kaplan-Meier time-to-event analyses and Cox proportional hazards regression. At a mean 54 years (36-80 yr) duration of HCV, ESLD occurred in 24 (19.8%), 0.365 per 100 person-years (py); and HCC in 7 (5.8%), 0.106 per 100 py. All 46 (38.0%) alive when HCV antiviral therapy became available, received it. Overall, 31 (25.6%) were HIV-positive. The leading causes of death were ESLD in 11 (32.3%), bleeding in 9 (26.5%), and HCC in 6 (17.6%). Major risk factors for ESLD included platelets<100,000/uL, OR=6.009, p=0.012, and HIV infection, OR=3.883, p=0.001. The major predictors of HCC were ESLD, OR=11.476, p=0.003, and platelets<100,000/uL, OR=6.159, p=0.014. No antiviral-treated subject developed ESLD, p=0.001. In hemophilic men, the sequelae of chronic HCV infection are significant. The major risk factors for ESLD are platelets<100,000/uL and HIV infection. Despite antiviral therapy, ESLD is the most significant predictor of HCC, and ESLD is the leading cause of death.