A 32-Year-Old Man with Hepatitis C Who Developed Progressive Liver Failure after a Bone Marrow Transplant

A 32-year-old white man with a history of stage IV nonHodgkin's lymphoma was referred to our institution for allogeneic bone marrow transplant (BMT). He had been subjected to chemotherapy 2 years earlier and had initially responded to therapy, but when the lymphoma recurred 1 year later, bone marrow transplantation was considered. During the process of evaluation for BMT, the patient was found to be sero-positive for anti-HCV and for HCV RNA. The presumed source of infection was injection drug use, approximately 15 years previously. He had no prior history of hepatitis or jaundice, and had never been told about having abnormal liver tests. The patient smoked half a pack of cigarettes a day and drank alcohol occasionally. He had no family history of liver disease. On physical examination prior to the BMT, there were no signs of chronic liver disease. Laboratory tests at that time showed alanine aminotransferase (ALT) 19 U/L, aspartate amino transferase (AST) 16 U/L, bilirubin 0.9 mg/dL and albumin 4.0 g/dL. A liver biopsy was performed prior to the BMT and showed mild necroinflammatory activity, grade 2, and no significant portal fibrosis, stage 1 (Fig. [1]A, B).

Pre-transplant treatment with cyclophosphamide and total body radiation was initiated and, 1week later, stem cell infusion was performed (day 0). The patient was started on immunosuppression with cyclosporin; antimicrobial prophylaxis with ciprofloxacin, fluconazole, and valacyclovir also was initiated. Over the next several days he was treated supportively and transfused as necessary for thrombocytopenia. Seven days after the transplant he developed fever; an antibiotic regimen of ceftazidime and vancomycin was started. Blood culture results were positive for Streptococcus mitis. On day 8 his total serum bilirubin, AST, and ALT were slightly elevated, and over the next few days these liver tests progressed with a sharp rise in serum AST and ALT levels; bilirubin increased (Fig. [2]), serum creatinine also increased to 4.5 mg/dL and alkaline phosphatase levels became twice the upper limit of normal. The clinical examination was notable for hepatomegaly and ascites. A Doppler ultrasound and computed tomography (CT) scan of the abdomen on days 9 and 10 showed moderate ascites and hepatosplenomegaly, with normal flow in the hepatic veins. A diagnostic procedure was performed.

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