Subclinical biliary strictures as a cause of long term allograft dysfunction in children who underwent liver transplantation

We aimed to evaluate the role of liver biopsy to predict subclinical biliary strictures (BS), and assess the impact of BS on long-term allograft dysfunction following liver transplantation in children (LT). We reviewed all liver biopsies performed from 2012-2018. Percutaneous trans-hepatic cholangiography (PTC) was performed in patients presenting cholangiolar proliferation on cytokeratin-7 stained sections. We performed 271 biopsies in 161 children (86% with a left lateral segment); 44/161 (27%) presented with diffuse or multifocal cholangiolar proliferation. Among them, a tight BS was confirmed in 38/44 (86%, 24% of total) and it was managed by balloon dilatation. Cholangiolar proliferation showed a positive predictive value (PPV) for BS of 86.4%. Levels of alkaline phosphatase >325 IU/l predicted BS (p=0.007). Dilatation of intra-hepatic bile ducts on ultrasound was found only in 44% of patients with BS. Following a median follow up of 9.2 years, only 15/38 (39%) patients resolved the BS. In conclusion subclinical BS is very common and probably underdiagnosed in these patients. Histological evidence of cholangiolar proliferation detectable by cytokeratin-7 immunostain should be preferred to liver function tests and ultrasound to suspect BS. BS in this setting should be regarded as a main cause of long-term allograft dysfunction.