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 transplant recipients were at significant transfusion-associated risk for infection with hepatitis C virus (HCV), We followed a cohort of 355 patients undergoing transplant in Seattle during 1987 to 1988 to determine (1) the impact of pretransplant HCV infection on the occurrence and severity of venocclusive disease (VOD); (2) the impact of HCV infection on liver dysfunction, other than VOD, occurring between 21 and 60 days after transplantation; and (3) the natural history of post-transplant HCV liver disease with a 10-year follow-up. HCV-RNA status was determined on serum stored before transplant and at day 100 post-transplant. Sixty-two (17%) patients were HCV-RNA positive before transplant, and 113 (32%) were HCV-RNA positive by day 100 post-transplant (or before death), Severe VOD developed in 22 of 46 (48%) evaluable patients with pretransplant HCV infection and in 150 of 229 (14%) evaluable patients without HCV (P < .0001). In multivariable analysis of risk factors for developing VOD, pretransplant HCV infection associated with elevated serum aspartate transaminase (AST) levels predicted the development of severe VOD (relative risk, 9.6; P = .0001). The presence of HCV with normal AST levels before transplant was not a risk factor for severe VOD, Between 21 and 60 days after transplant, HCV-RNA positive-patients had higher AST levels (median 101 U/L), but similar alkaline phosphatase and total bilirubin levels compared with HCV-negative patients, suggesting that cholestatic liver disease (particularly graft-versus-host disease [GVHD]) was not related to HCV infection, An acute flare of hepatitis (AST >10 times the upper limit of normal) developed at a mean of 136 +/- 58 days in 31% of HCV-positive patients; no patients developed fulminant hepatitis. Between 5 and 10 years after transplant, 57% of HCV-positive and 6% of HCV;negative patients had mild to moderate elevations of AST (P < .0001), but HCV infection was not associated with excess mortality between 3 and 10 years after bone marrow 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 balance the absolute risk of death from VOD against the risks of the underlying disease, In long-term survivors, HCV infection is not associated with excess mortality over 10 years of follow-up.