Blood Journal
Leading the way in experimental and clinical research in hematology

A silent epidemic in survivors of hematopoietic cell transplantation

  1. George B. McDonald
  1. Fred Hutchinson Cancer Research Center; and University of Washington School of Medicine

The field of hematopoietic cell transplantation is now 35 years old, and many complications seen in the early days have been consigned to the historic record. One complication, however, was never anticipated. Cirrhosis caused by chronic hepatitis C infection has a cumulative frequency in transplantation survivors of 2% to 4% after 20 years. Chronic hepatitis C and progression to cirrhosis are usually clinically silent until falling platelet counts, jaundice, bleeding varices, and fluid accumulation herald endstage liver disease.

The study by Peffault de Latour and colleagues (page 1618) provides important insights into this problem by careful follow-up of 96 hepatitis C virus (HCV)–infected survivors for up to 28 years. The cumulative incidence of cirrhosis was 24% at 20 years after transplantation, a remarkably high figure in comparison to the progression of HCV infection in nontransplantation patients. While genotype 3 and the presence of extrahepatic manifestations of HCV infection were related to development of cirrhosis, the hazard ratios were less than 2 for both factors. Other studies have shown that progression of HCV to cirrhosis is HLA restricted, that is, not a matter of bad luck but of biologic determinism. Why progression to cirrhosis should be so rapid in one fourth of this cohort of transplantation survivors is not clear from the data, but as the authors point out, a similar situation obtains in other patients with depressed T-cell immunity, for example, after renal transplantations and with HIV infection. Although immunity after transplantation often returns to normal after one year, during that year there is opportunity for unfettered viral replication and infection of more hepatocytes than would ever occur naturally.

As many as 35% of survivors from transplantation surgeries before 1992 may be infected with HCV. All survivors, particularly those from transplantation surgeries before 1992, must be tested for anti-HCV and staged by biopsy for extent of liver disease if infected. This is easier said than done. Some people are lost to follow-up. Others do not want their history of transplantation known to anyone. Some are uninsured and cannot bear the costs of liver biopsy and lengthy therapy. In the absence of a contraindication to therapy with interferon-α (IFNα) and ribavirin, all patients who have evidence of progressive liver disease on a biopsy should be treated, albeit with limited expectations, as the clearance of HCV following pegylated IFNα and ribavirin therapy is achieved only half of the time. One note of caution about using IFNα in transplantation survivors: our experience has been that platelet and granulocyte counts in some transplantation survivors may be very sensitive to IFNα. Use of ribavirin and pegylated IFNα as initial treatment poses the risk of profound depression of blood counts because of the long half-life of pegylated IFNα. It may be safer to initiate therapy with ribavirin and IFNα daily or 3 times a week until patient tolerance is demonstrated. Better, less toxic therapy for HCV infection is urgently needed. The first step toward preventing the development of cirrhosis, however, is to emulate the practice of the Paris group by tracking all transplantation survivors and determining who is infected by HCV.