Childhood B-Precursor-ALL Presenting as Hepatitis - A Diagnostic and Therapeutic Challenge

Abstract 4331

Liver involvement in childhood acute lymphoblastic leukemia (ALL) at presentation is common with hepatomegaly but severe impairment or hepatitis is rare with only 9 reported cases. The need to start anti-leukemic treatment despite the potential hazard of severe liver failure poses a clinical dilemma. We report a 6 year old girl who presented with jaundice, fever, vomiting and diarrhoea, cytopenia, hyperbilirubinemia of 5.7 mg/dl (direct 5.2), ASAT of 3389, ALAT of 2747 U/L, increased INR to 1.33, but normal ammonia. An acute common-ALL was diagnosed and serology, PCR-studies and cultures were negative for viruses causing hepatitis. Liver biopsy revealed diffuse hepatic blast infiltration, piecemeal necrosis and hepatocellular cholestasis without signs of infectious hepatitis. We treated the patient according to the ALL-BFM-2000-protocol without dose reductions and on day 8, hyperbilirubinemia had completely normalized and liver enzymes had significantly decreased. Further therapy was uneventful and the patient is alive and well 12 month after diagnosis, without any signs of hepatic dysfunction. Reviewing the literature on children with ALL presenting with hepatitis revealed 9 patients with a mean age of 8.8 years (range 4 to 15), female to male ratio of 2.0 and precursor B-cell immunophenotype in 8/9 patients. Patients had a mean bilirubin of 8.7 mg/dl (range 2 – 16.5), 3 had highly elevated transaminases above 2000 U/L, and two of them died initially. Another patient with moderately increased liver enzymes but hepatic encephalopathy needed transient hemofiltration, but survived. In none of the reported cases a viral organism has been identified and abnormal liver function normalized during chemotherapy in most of the patients. This indicates, that leukemia rather than infection was responsible for hepatitis. In conclusion, severe hepatitis in children with ALL is rare, seems to affect the older girl, and highly elevated liver enzymes are associated with early death. After infective organisms have been excluded, instant start of an effective induction therapy is required, even despite severe hepatitis, most probably caused by blast infiltration.