Long-term follow-up in children with progressive familial intrahepatic cholestasis type 2 after partial external biliary diversion with focus on histopathological features

Progressive familial intrahepatic cholestasis (PFIC) comprises a group of rare cholestatic liver disorders of childhood that could lead to liver cirrhosis. Nowadays, the partial biliary diversion procedure is still a therapeutic option in non-cirrhotic children with PFIC1 or PFIC2 after an ineffective ursodeoxycholic acid (UDCA) therapy. However, the relevant disadvantage of the partial external biliary diversion (PEBD) is that adolescent patients could not accept a permanent stoma. In some of them, despite of good clinical and biochemical results of this procedure, the ileal exclusion (IE) procedure had to be performed many years after PEBD.

Our aims were to find the most characteristic early microscopic features of the disease as well as to compare changes in the liver biopsy specimens at the time of diagnosis and long-time (more than 10 years) after a surgical procedure.

We examined retrospectively 8 liver biopsies from 4 PFIC2 patients comparing the results from the first biopsies done at the time of PFIC diagnosis and the second ones, done many years after PEBD.

The characteristic lobular rosette formations of hepatocytes were found in all patients at the time of diagnosis. Cholestasis was observed in each patient, but only in two of them, centrally located bile plugs were found. The majority of hepatocytes showed degenerative changes from mild to severe degree. In the follow-up biopsies, cholestasis completely disappeared in 3 patients and decreased significantly in 1 other patient. Based on Batts and Ludwig fibrosis scoring system, the liver fibrosis had resolved in two out of three patients.

The formation of lobular rosettes with centrally located bile plugs and degenerative changes of hepatocytes seem to be the most characteristic microscopic features in early liver biopsies in PFIC2 patients. Partial external biliary diversion significantly improved the clinical, anthropological, biochemical as well histological outcome of the patients.