Related Experiment Videos
Hepatitis C virus infection and bone marrow transplantation: a cohort study with 10-year follow-up
S I Strasser1, D Myerson, C L Spurgeon
1Department 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.
Insights
Hepatitis C virus (HCV) infection significantly increases the risk of severe veno-occlusive disease (VOD) after bone marrow transplant, especially with elevated liver enzymes. Long-term, HCV does not increase mortality but can cause persistent liver enzyme elevations.
Area of Science:
- Hepatology
- Transplantation Immunology
- Infectious Diseases
Background:
- Routine blood donor screening for hepatitis C virus (HCV) began in 1991.
- Marrow transplant recipients faced significant transfusion-associated risk of HCV infection before 1991.
- Pre-transplant HCV infection status impacts post-transplant outcomes.
Purpose of the Study:
- To determine the impact of pre-transplant HCV infection on veno-occlusive disease (VOD) occurrence and severity.
- To assess HCV infection's effect on liver dysfunction (excluding VOD) between 21 and 60 days post-transplant.
- To investigate the 10-year natural history of post-transplant HCV liver disease.
Main Methods:
- Followed a cohort of 355 marrow transplant patients from 1987-1988.
- Determined HCV-RNA status on stored serum samples (pre-transplant and day 100 post-transplant).
- Analyzed risk factors for severe VOD and liver dysfunction using multivariable analysis.
Main Results:
- Pre-transplant HCV infection, particularly with elevated AST, was a significant predictor of severe VOD (RR 9.6, P=.0001).
- HCV-positive patients showed higher AST levels post-transplant but similar bilirubin and alkaline phosphatase, suggesting no link to cholestatic liver disease or GVHD.
- HCV-positive patients had a higher incidence of hepatitis flares (31%) and persistent mild-moderate AST elevations (57% at 5-10 years), but no increased long-term mortality.
Conclusions:
- Pre-transplant HCV infection with elevated AST is a major risk factor for severe VOD post-marrow transplant.
- The decision to transplant HCV-positive patients requires balancing VOD risk against underlying disease risks.
- In long-term survivors, HCV infection does not appear to increase mortality after bone marrow transplantation.
Abstract:
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.