Viral hepatitis as a complication of haemophilia treatment
Post transfusion hepatitis is seen in all haemophiliacs treated with non-virus inactivated (NVI) concentrates. First generation anti-HCV ELISA produced false negative results in 10/78, with four individuals ELISA negative, HCV RNA positive. Using second generation assays incorporating c22, C1-4 and c33c peptides, HCV infection was demonstrated in all recipients of NVI concentrates and 0/7 PUPS treated with heat treated concentrates. Phylogenetic analysis of HCV sequences outlined the demographic of HCV infection in Edinburgh and suggested that recent post-transfusion HCV infection is due to transmission of virus from the drug using community. HCV sequences were detected in 10/10 NVI commercial concentrates, but in 0/5 virus inactivated and 0/14 batches of NVI volunteer donor concentrates. None of 43 batches of commercial or volunteer donor concentrate, either NVI or virus inactivated had detectable HBV DNA. 28 batches of high purity, solvent detergent treated and 17 batches of intermediate purity SNBTS were negative for HAV RNA. No HAV seroconversions were seen in 29 susceptible recipients of these concentrates. Longitudinal studies of HBV and HCV infection demonstrate that HIV-positive haemophiliacs are more likely to lose seroreactivity to both viruses although antibody responses also declined in HIV-negative individuals. Loss of anti-HBs was accompanied by reactivation of HBV DNA in 1/9 individuals with advanced HIV infection. Change in HCV genotype was more common in HIV-positive (70%) than in HIV-negative (22%) individuals (p<0.02), with tendency to change to type 1. Virus load increased with time in both groups, level of viraemia did not correlate with ALT levels or clinical disease severity. Massive variations in viraemia were observed over short intervals, suggesting that studies of virus load need to be interpreted with caution.