Liver abnormalities are frequent and persistent in patients with Fanconi anemia.

Liver disease has not been well-described in patients with Fanconi anemia (FA). Chronic hepatobiliary disease in patients with FA has been attributed variously to the consequences of androgen therapy, acute and late toxicities from hematopoietic stem cell transplant and hepatic tumors. Improvements in outcomes of transplant mean that more individuals with FA are reaching adulthood and new features of the FA phenotype are being discovered. We performed a retrospective review of liver function in a cohort of 97 FA patients followed for at least 10 years at a single center. We identified a high frequency of transaminitis without elevation of bilirubin and with no evidence of structural abnormality, in patients with FA. Transaminitis was persistent in many cases, sometimes lasting more than a decade without clinical manifestations. Transaminitis was found in patients who had and had not received transplant but was more frequent in transplant recipients. Exposure to total body irradiation increased risk, while treatment with anabolic steroids did not. Review of limited numbers of liver biopsies and autopsy material showed a cholestatic pattern of liver injury, with progressive fibrosis, in the majority of patients. Occurrence in untransplanted as well as transplanted cases argues against a potential diagnosis of atypical liver graft versus host disease. Limited data regarding therapy suggested no benefit from treatment with steroids or other immune suppressive medications. Our data show that liver disease is common in patients with FA, and as most children with FA now reach adulthood we are starting to see end-stage liver disease.