Hepatitis C Virus Infection and Bone Marrow Transplantation: A Cohort Study With 10–Year Follow–Up

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 F .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 G10 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 F .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. (HEPATOLOGY 1999;29:1893-1899.)

Long-term outcome after allo-SCT: close follow-up on a large cohort treated with myeloablative regimens

“…33 Strasser et al 34 found that cirrhosis after HSCT was mainly attributed to hepatitis C. In another study from the same group on long-term survivors, with over 10 years follow-up, HCV infection was not associated with excess mortality. 35 Most patients have adequate immune reconstitution by 1 year after transplant, but patients with cGVHD remain immunoincompetent and are at higher risk of infections. Two years and more post HSCT, Varicella zoster virus (VZV) infection was still an active issue occurring in 16.5% of long-term survivors.…”

Hepatitis C virus in long-term bone marrow transplant survivors

“…With recovery of cellular immunity after transplantation, severe hepatitis and fulminant liver failure may occur. 4 In the long term, affected patients may develop an accelerated course of chronic liver disease leading to cirrhosis and to hepatocellular carcinoma (HCC) more rapidly than virus carriers who have not had a BMT. 4 Projections about these risks have been based on case reports and studies of patients with a survival rate of about 10 years, some of them significantly differing in regard to the importance of the HCV in the post-BMT.…”

“…4 In the long term, affected patients may develop an accelerated course of chronic liver disease leading to cirrhosis and to hepatocellular carcinoma (HCC) more rapidly than virus carriers who have not had a BMT. 4 Projections about these risks have been based on case reports and studies of patients with a survival rate of about 10 years, some of them significantly differing in regard to the importance of the HCV in the post-BMT. [4][5][6][7] Today, with a worldwide BMT history of more than 30 years, hepatitis C in longterm survivors requires special attention.…”

Aggressive hepatocellular carcinoma complicating pregnancy after autologous bone marrow transplantation for non-Hodgkin's lymphoma

“…11 Chemotherapy and immunosuppression both facilitate viral replication and HBV-related liver diseases. 12 Hepatic GVHD, drug toxicity and veno-occlusive disease cause further direct liver damage, 13,14 and accelerated cirrhosis and HCC in hepatitis C carriers have been reported. 15 In HBV carriers, the incidence of significant viral reactivation ranges from 15% for autologous BMT to 85% for allogeneic BMT between HBV positive donor-recipient pairs.…”