Outcomes of Surgical Management of Familial Intrahepatic Cholestasis 1 and 2

Summary:

The goal of this study is to assess the outcomes of partial external biliary diversion (PEBD), ileal exclusion (IE), and liver transplant (LTX). The authors analyzed data from 102 patients who underwent one or more of these three procedures. In this cohort 42 patients had FIC1 deficiency (PFIC1) and 60 had Bile Salt Pump Export Protein (BSEP) deficiencies (PFIC2). The BSEP group was further split into two groups because other research has indicated that some mutations may result in more severe illness. More specifically, while some mutations may totally eliminate BSEP function, it is possible that two common mutations (D482G and E297G) may result in partial function of the BSEP protein, and less severe disease. This latter group was called “BSEP-common”, and the potentially more severe group “BSEP-other”.

            The authors of this paper looked at a number of different outcomes such as the effect on pruritis (itch), growth, progression to liver cirrhosis after PEBD, and liver function after transplant.

The effect of PEBD on pruritis showed sustained improvement in 57% of the FIC1 group, and 76% in the BSEP group with either the D482G or E297G mutation. However, in the BSEP group with other mutations the improvement percentage was only 33%.

More patients in the BSEP-other group progressed to cirrhosis compared to FIC1 patients and were listed for or underwent liver transplant. Outcomes after transplant showed that BSEP patients in general fared better than FIC1 patients. This is most likely due to the fact that the FIC1 protein not only plays an important role in the liver, but also in for instance the small and large intestine. Specifically, fatty liver (steatosis) was found in 19 out of 21 FIC1 patients with available data, but only in 2 out of 31 BSEP patients. In addition, diarrhea was reported in 81% of the FIC1 group vs. 7% in the BSEP group, and 8 FIC1 patients had pancreas problems vs. none in the BSEP group.

The general line of results indicated that the BSEP-common group (mutations in D482G and E297G) had more positive outcomes. This is consistent with the idea that these specific mutations still allow for partial functioning of the BSEP protein whereas other mutations may completely eliminate BSEP functioning. This study also supported the idea that FIC1 deficiency is a multi-system disease. This result indicates that liver transplant alone might not alleviate all symptoms in FIC1 patients, and should possibly be combined with PEBD to avoid fatty liver (steatosis).

Keywords:

FIC1 deficiency, BSEP deficiency, D482G, E297G, PEBD, transplant

Citation:

Bull et al. Outcomes of Surgical Management of Familial Intrahepatic Cholestasis Type 1 and 2. Hepatology Communications, 2(5), 515-528. 2018

Summary:

This article focusses on the potential reoccurrence of symptoms after liver transplant in PFIC 2 patients. PFIC 2 is caused by mutations in the bile salt export pump (BSEP), leading BSEP to function poorly or not at all (BSEP deficiency). This in turns leads to build up of bile salts in the liver (cholestasis). Depending on severity, liver transplant is often the only working treatment option. However, some PFIC 2 patients seem to develop BSEP deficiency again after liver transplant.

The researchers investigated the potential causes in 9 patients who had undergone liver transplantation previously, and showed that some of these patients had developed antibodies that inhibit BSEP between 3 and 108 months post-transplant. This is called antibody induced BSEP deficiency, AIBD, and it seems to occur in severely affected patients who have complete BSEP deficiency before transplant.

Keywords:

PFIC 2 Post-transplant, BSEP deficiency, AIBD

Citation:

Stindt et al. Bile Salt Export Pump-Reactive Antibodies Form a Polyclonal, Multi-Inhibitory Response in Antibody Induced Bile Salt Export Pump Deficiency. Journal: Hepatology, Vol. 63, No. 2 Year: 2016.