Patients receiving chemotherapy experience exacerbations of chronic hepatitis B (HBV) or hepatitis C (HCV) viral infections. We examined the pattern of liver disease induced by these infections in 92 children and adolescents with elevated transaminases (median age: 9 years). This included 76 with hematological malignancies (55 ALL, 15 NHL and six Hodgkin's disease) and 16 with thalassemia major. Liver disease was graded: A--occasional hypertransaminemia, B--persistent hypertransaminemia, C--severe hepatitis without encephalopathy, D--fulminant hepatic failure (FHF) and death. Screening included HBsAg, anti-HCV antibody, HBV-DNA and HCV-RNA: 26 had liver biopsies. A total of 60 (79%) patients with malignancies were HBsAg and/or HBV-DNA(+)(genotype D-E) and 47 (62%) were anti-HCV and/or HCV-RNA(+); 33 were coinfected with HBV and HCV. Grade A (n=24) included 16 with HCV and 12 with HBV (six coinfected); 18 with HBV and 11 with HCV (10 coinfected) were graded B (n=22). All grade C (n=25) had HBV with 16 HCV coinfected. FHF and death occurred in five HBV-DNA(+) patients, in four within a month of i.v. methotrexate. Patterns C and D were associated with HBsAg and HBV-DNA (P=0.001 and P<0.001, respectively). In all, 70% of HBV-infected children suffered chemotherapy-associated flares. None of the thalassemics had severe hepatitis exacerbations; 94% had HCV markers with none HBV-DNA(+). One died of progressive cirrhosis.
Conclusions: Children with hematological malignancies have worse liver disease when associated with chronic HBV. FHF occurred in HBsAg/HBV-DNA(+) children following i.v. methotrexate. Early recognition of hepatic dysfunction in HBV carriers is essential in order to reduce incidence of life-threatening complications.