Chronic Hepatitis B Virus Infection Acquired Under Cytostatic Treatment in Childhood — Clinical, Virological and Immunological Long‐Term Follow‐Up

Oncology patients receiving cytostatic therapy used to be at high risk of HBV infection when HBV screening measures were less reliable. Infections acquired under these conditions often persist, like those acquired perinatally or during early infancy. We studied the long-term clinical outcomes, viral characteristics, and virus-specific T-cell immunity of chronic HBV infection acquired during chemotherapy. We examined 16 chronically HBV-infected former paediatric oncology patients who were infected during cytostatic treatment in the 1980s. Patients underwent physical examination, laboratory liver function testing, non-invasive measurement of liver stiffness, and determination of HBV serology and DNA levels. If the material was sufficient, HBV sub-genotype, drug resistance and immune escape mutations, and mutations associated with HBeAg negativity were analysed. The frequency of HBV core-specific CD8+ T cells was measured after in vitro antigen-specific expansion. All but one patient were chronically infected with detectable HBsAg but were HBeAg-negative, mostly with low viraemia. Four patients were under ongoing effective antiviral therapy, and four required treatment initiation due to high viraemia or advanced liver disease. Hepatic effects were predominantly observed in highly viraemic patients. No drug resistance or immune escape mutations were observed. In two highly viraemic patients, basal core promoter and precore region mutations reducing HBeAg expression were identified. HBV core-specific CD8+ T cells were detected in all patients, but their frequency was low. In conclusion, more than 30 years after primary HBV infection was acquired during chemotherapy, the course of infection still resembles that of perinatally acquired infections.