Hepatitis C virus infection and bone marrow transplantation: A cohort study with 10-year follow-up

Before the introduction of routine blood donor screening in 1991, marrow tr ansplant recipients were at significant transfusion-associated risk for inf ection with hepatitis C virus (HCV), We followed a cohort of 355 patients u ndergoing transplant in Seattle during 1987 to 1988 to determine (1) the im pact of pretransplant HCV infection on the occurrence and severity of venoc clusive disease (VOD); (2) the impact of HCV infection on liver dysfunction , other than VOD, occurring between 21 and 60 days after transplantation; a nd (3) the natural history of post-transplant HCV liver disease with a 10-y ear follow-up. HCV-RNA status was determined on serum stored before transpl ant and at day 100 post-transplant. Sixty-two (17%) patients were HCV-RNA p ositive before transplant, and 113 (32%) were HCV-RNA positive by day 100 p ost-transplant (or before death), Severe VOD developed in 22 of 46 (48%) ev aluable patients with pretransplant HCV infection and in 150 of 229 (14%) e valuable patients without HCV (P < .0001). In multivariable analysis of ris k factors for developing VOD, pretransplant HCV infection associated with e levated serum aspartate transaminase (AST) levels predicted the development of severe VOD (relative risk, 9.6; P = .0001). The presence of HCV with no rmal AST levels before transplant was not a risk factor for severe VOD, Bet ween 21 and 60 days after transplant, HCV-RNA positive-patients had higher AST levels (median 101 U/L), but similar alkaline phosphatase and total bil irubin levels compared with HCV-negative patients, suggesting that cholesta tic liver disease (particularly graft-versus-host disease [GVHD]) was not r elated to HCV infection, An acute flare of hepatitis (AST >10 times the upp er limit of normal) developed at a mean of 136 +/- 58 days in 31% of HCV-po sitive patients; no patients developed fulminant hepatitis. Between 5 and 1 0 years after transplant, 57% of HCV-positive and 6% of HCV;negative patien ts had mild to moderate elevations of AST (P < .0001), but HCV infection wa s not associated with excess mortality between 3 and 10 years after bone ma rrow transplantation. In summary, HCV infection with elevated AST levels is a significant risk factor for severe VOD after marrow transplant, However, the decision to proceed to transplantation in HCV positive patients must b alance the absolute risk of death from VOD against the risks of the underly ing disease, In long-term survivors, HCV infection is not associated with e xcess mortality over 10 years of follow-up.