Non transplant treatment experience with familial cholestasis type II

Objectives: To evaluate non-transplant treatment modalities for familial cholestasis type II (PFIC-II). Methods: Retrospective analysis of our non-transplanted PFIC-II patients. Results: n=11, mean age of presentation 30.8 months, males 5/11, family history of PFIC in 3/11. Presenting symptoms were pruritus and increased liver enzymes (AST/ALT) in 9/11. Bile salt exporter pump (BSEP) seen on canalicular surface in 3/9 on immune-chemistry. Heterozygous mutations seen in 10/11 of which 9/10 were compound heterozygote. 1/11 had a homozygous mutation. Mean bile acid level on diagnosis was 329.81µMol/l. Treatment modalities were ursochol, ursochol followed by biliary diversion (BD) and ursochol followed by 4-phenybutyrate (4-PBA). 7/11 received only ursochol, mean duration of follow up is 93 months. Bile acid levels monitored in 6/7 and normalized in 23.25 months (mean) in 4/6. 1/6 shows sustained decreasing trend but not normalized and 1/6 showed a transient decrease. AST, ALT were increased in 4/7 before treatment and became normal in 32.3 months. Follow up biopsy was done in 4/7, fibrosis remained stable in 1/4 at F1 after 215 months of treatment, increase from F1 to F2 was seen in 2/4 in 84 months and increase from F1-F4 in 205 months was seen in ¼. 3/11 received ursochol followed by BD. No intergroup variation seen from the group who received only ursochol in genetic mutation frequency, zygosity, bile acid levels or AST, ALT levels. The age of presentation was lower – 2, 6 and 48 months. Mean duration of follow up is 153 months. The indication for BD was increasing pruritus and bile acid levels after a transient decrease with ursochol. After BD pruritus grade decreased from 4 to 1 in 2/3 and from 3 to 1 in 1/3.Mean duration of ursochol therapy was 111.3 months and the upswing of bile acids was seen after mean of 89.6 months of therapy. After BD 2/3 have normalized bile acid levels in mean 21.5 mo (15 and 28 mo) and continue to be normal. In the 3rd after 22 months of BD the bile acid level is 40.8 (614 pre-BD) and shows sustained decreasing trend. 1/11 received ursochol followed by 4-PBA. His presenting symptom was pruritus and increased liver enzymes. Homozygous mutation is present. Duration of UDCA therapy was 12 months and increase in pruritus from grade 2 to 4, increase in bile acids and non normalization of AST/ALT was observed. Subsequently 4PBA therapy for 1 month produced a decrease in pruritus from grade 4 to grade 1 and bile acids decrease from 462 to 399, AST/ALT also decreased though not normalized. Conclusion: Non transplant modalities in patients with heterozygote mutations shows a good response and transplant can be postponed if not avoided. The patients who do not normalize or show a transient response in their bile acid, liver enzyme levels with ursochol therapy benefit from a BD in achieving sustained clinical and biochemical response. 4-PBA as a chaperone therapy seems to show promising result but long term evaluation is pending.