Long term survival in persons with hemophilia and chronic hepatitis C: 40 year outcomes of a large single center cohort

Abstract

We studied the course of chronic HCV infections in a cohort of 222 persons with hemophilia (PWH) and von Willebrand disease followed at our center since 1973. Twenty two (10%) developed end stage liver disease (ESLD). Forty years after HCV infection, cumulative incidence of ESLD was 12.3% and overall survival was 45.5%. Those who were infected with HCV only (n=100) had a survival of 75.2%, while those infected with HIV (n=122) had a survival of 24% (P<.001). Survivals were significantly longer for those infected with HCV at younger age (< 15 years) compared to those infected over age 30 years (P=0.014). Cause specific deaths for ESLD and bleeding were 8.8% and 8.3% respectively. For HIV negative subjects, the annual hazard of death from ESLD and bleeding was near zero for the first 10 years, and then rose slowly over the next 20 years to 0.4/100py for ESLD and 0.2/100py for bleeding. Sixty subjects completed 79 treatment episodes. Sustained viral response rates increased from 7/21 (33%) between 1990-2001, to 17/29 (58%) between 2002-2011, and to 27/29 (93%), since 2012 with the advent of the directly acting antiviral agents. These results confirm the very slow ESLD progression rate in HIV negative PWH. However, the risk of death from both ESLD and bleeding increases steadily with longer duration of HCV infection. More aggressive surveillance to detect those with early fibrosis is needed now that curative treatment is possible in >95% of individuals.

Progression of hepatitis C in the haemophiliac population in Ireland, after 30 years of infection in the pre‐DAA treatment era

“…Including this subset of patients would increase all‐cause mortality from 44% to 70% in HIV positive patients. This is similar to the mortality rate of 76% reported in a similar long‐term study of 122 HIV/HCV co‐infected haemophiliacs in Pennsylvania .…”

“…Similar outcomes were observed in a cohort of 222 people who attended a haemophilia centre in Pennsylvania. After 28 years of infection, only 10% of this cohort had developed end‐stage liver disease . This is much lower than in the Irish haemophilia group, but the duration of follow‐up was shorter, particularly for HIV positive patients.…”

Prevalence and risk factors associated with hepatitis C among Brazilian male patients with haemophilia: A long‐term follow‐up

“…This finding showed that hepatitis C remains a critical problem for patients with haemophilia in Brazil. Several other authors also demonstrated the HCV impact in the mortality of patients with haemophilia …”

“…Several other authors also demonstrated the HCV impact in the mortality of patients with haemophilia. 6,7,15,34 Currently, we are experiencing a truly innovation in the treatment of HCV infection with the new direct-acting antivirals (DAAs).…”

The elevated prevalence of risk factors for chronic liver disease among ageing people with hemophilia and implications for treatment

“…Studies of PWH have shown that HIV-HCV coinfection leads to accelerated HCV infection, and in 10% to 35% of the cases, ultimately ESLD. [ 5 – 10 ] Longer duration of HCV infection, alcohol abuse, HIV coinfection, older age at infection, and presence of HCV genotype 1 have been identified as risk factors for rapid progression to ESLD. [ 8 ] The introduction of highly active antiretroviral therapy (HAART) in the mid-1990s has diminished the mortality due to HIV-AIDS (acquired immunodeficiency syndrome).…”