Correspondence

Acute Vanishing Bile Duct Syndrome after Interferon Therapy for Recurrent HCV Infection in Liver-Transplant Recipients

N Engl J Med 1994; 330:1160-1161April 21, 1994

Article

To the Editor:

Interferon alfa therapy has been recently proposed1 to treat patients with recurrent hepatitis C virus (HCV) infection following liver transplantation2,3. We report on two patients in whom we believe that interferon alfa therapy (interferon alfa-2b, Schering-Plough) may have triggered acute vanishing bile duct syndrome. Among 28 patients who received liver transplants for cirrhosis due to HCV between 1987 and 1992, serologic (enzyme-linked immunosorbent and recombinant immunoblotting assays), viral (polymerase chain reaction), and histologic evidence of recurrent HCV infection was demonstrated in 21. Interferon alfa therapy (3 million units three times weekly) was instituted in five patients with severe histologic features (Knodell score, ≥ 9).

A 40-year-old man received a liver transplant in 1987, and his condition remained stable until 1991. HCV reinfection was documented shortly thereafter. Liver biopsy revealed severe chronic hepatitis (Knodell score, 11), for which interferon alfa therapy was instituted. Acute rejection was diagnosed one month later and was unresponsive to corticosteroids (Patient 1, Figure 1Figure 1Results of Serial Liver-Function Tests in Patients 1 and 2.). A second liver biopsy was performed because of a further decline in liver function and showed severe portal tract inflammation and loss of bile ducts. Therapy with interferon alfa was stopped, and the patient underwent transplantation again three months later.

A 46-year-old woman (Patient 2, Figure 1) underwent liver transplantation in 1989. Recurrent HCV infection (Knodell score, 10) was diagnosed one year later. Two months after interferon alfa therapy was begun there was further deterioration in liver function (Figure 1). Liver biopsy demonstrated severe, acute rejection with portal tract inflammation, centrizonal necrosis, and severe loss of bile ducts. The patient died three months later, despite the discontinuation of interferon alfa and antirejection therapy. In both patients, pathological examination of the liver (after retransplantation or at autopsy) confirmed the diagnosis of acute vanishing bile duct syndrome with perivenular necrosis, lack of recognizable small bile ducts, and foam-cell arteritis of hilar vessels.

An increased risk of severe rejection has been reported in renal-transplant recipients treated with interferon alfa4. The occurrence of this complication after liver transplantation might be attributed to the induction of the expression of HLA class I antigens on liver cells by interferon alfa5. In our patients, interferon alfa therapy was begun late after transplantation -- after the dose of cyclosporine had been gradually reduced to maintain levels in the lower therapeutic range. It is noteworthy that both patients had an episode of acute rejection during interferon alfa therapy despite continuation of the same immunosuppressive regimen. This strongly suggests that interferon alfa therapy should be instituted very cautiously in liver-transplant recipients, with close monitoring of immunosuppression.

Bertrand Dousset, M.D.
Filomena Conti, M.D.
Didier Houssin, M.D.
Yvon Calmus, M.D.
Hopital Cochin, 75014 Paris, France

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