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.
Strasser
S I
SI
Department of Gastroenterology/Hepatology, Clinical Statistics and Long-Term Follow-Up Programs of the Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, WA, USA.
Myerson
D
D
Spurgeon
C L
CL
Sullivan
K M
KM
Storer
B
B
Schoch
H G
HG
Kim
S
S
Flowers
M E
ME
McDonald
G B
GB
D000328:Adult; D016026:Bone Marrow Transplantation; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006526:Hepatitis C / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D015994:Incidence; D008111:Liver Function Tests; D008297:Male; D011183:Postoperative Complications / Q000453:epidemiology*; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors
D012367:RNA, Viral