Chronic hepatitis C in children cured of leukemia: Which management and therapy?

Abstract

Background: Hepatitis C virus (HCV) is the major etiological agent of post-transfusion hepatitis. In patients cured of pediatric malignancy, chronic hepatitis C tends to run an indolent course. In contrast with these findings, cirrhosis in a cohort HCV infected cancer survivors was reported. So, we decided to evaluate the course of HCV infection and response to treatment in a cohort of children infected with HCV and cured of leukemia. Patients and methods: All children with a diagnosis of HCV infection and history of leukemia, referred to our Department of Pediatrics, were retrospectively evaluated for long-term course of HCV infection, antiviral therapy and response to treatment with pegylated-IFN alfa 2b plus ribavirin. Results: Among 185 consecutive children with diagnosis of HCV infection, 19 (12 males) had history of leukaemia (age range at diagnosis 9–15 years). All of them had received blood transfusion during cytostatic therapy. Eighteen of 19 (95%) patients presented a favourable clinical course, with sustained remission of malignant disease and presence of a mild symptom-free liver disease. After a median period of 7 years (range 2–10), a sustained virological response was observed in 6 patients treated with pegylated-IFN and ribavirin. Twelve patients remained untreated and 7 of them cleared viremia. These patients did not change their biochemical and virological status during the entire period of observation. Only a patient showed a very severe course of HCV infection requiring orthotopic liver trasplantation. This patient, at the age of 12 years, was diagnosed as affected by pre-B LLA and treated according to the National AIEOP Protocol, with remission of malignancy. Nine months later he developed a progressive liver disease. On the basis of virological markers (HCV-RNA serum levels: 3 × 106 copies/ml, genotype 1b), HCV infection was diagnosed. Liver biopsy showed chronic hepatitis. After 11 months from diagnosis of HCV infection and one month after chemotherapy discontinuation, the patient showed liver failure with jaundice, portal hypertension and hypersplenism. Liver biopsy showed HAI 9/18, stage 6, advanced cirrhosis. Treatment with ribavirin and peg-IFN-2a was started. HCV-RNA serum levels declined but the treatment was discontinued because of severe bone marrow toxicity and progressive liver failure. At the age of 15 years, the patient received a liver transplant. After this procedure, the patient showed a favourable course with absence of clinical signs of liver disease. In contrast with this favourable picture, the patient showed persistence of viremia. No predictive factor of this unfavourable outcome was identified. Conclusions: Chronic hepatitis C is usually characterized by an asymptomatic course in children cured of leukaemia. In the subset of treated patients, combination therapy with peg-IFN and ribavirin is generally associated with a favourable outcome. Nevertheless, a severe liver disease may occur in sporadic cases.