Recent updates on progressive familial intrahepatic cholestasis types 1, 2 and 3: Outcome and therapeutic strategies

Table 3 Recent studies describing outcome and complications with biliary diversion surgeries in progressive familial intrahepatic cholestasis

Study	Type of biliary diversion	No of patients	Median follow up	Outcome	Adverse events
Yang et al[54] (2009)	PEBD	14 (11-PFIC)	3.1 yr (2-5.7)	Resolution of pruritus: 50%; Decrease in pruritus: 21%; Decrease in serum bile acids; Improvement in growth; Improved quality of life; No response in 2 patients with advanced fibrosis; 21.4% were listed for LT at mean follow-up 3.2 yr (all had advanced fibrosis pre-PEBD)	3 developed stoma prolapse; Post-op bleed and wound dehiscence in 1 each
Schukfeh et al[55] (2012)	PEBD	24	9.8 yr (1.6-14.3)	Resolution of pruritus with normalization of bile acids in 54%; 37.5% received LT at mean 1.9 yr; All of them had failed PEBD & 78% of them had cirrhosis pre-PEBD	Stomal prolapse in 2; Cholangitis, dyselectrolytemia, GI bleed and intestinal obstruction in 1 each
Wang et al[50] (2017)	PEBD; IE; PIBD	39; 11; 7; (38 PFIC & 20 alagillesyndrome)	24 mopostsurgery	Decrease in severe pruritus-54% in PFIC1 and 30% in PFIC2; Trend towards decreased pruritus after IE and PIBD; PEBD but not IE led to decrease in bilirubin and ALT in PFIC1; 23.7% of PFIC underwent LT post diversion	PEBD: Dehydration/dyselectrolytemia in 4; Stoma prolapse in 3; Intestinal ischemia & bowel obstruction in 1 each; IE; Dyselectrolytemia-2; PIBD: Dyselectrolytemia in 2, intestinal ischemia & intussusception-1 each
Cielecka-Kuszyk et al[47] (2019)	PEBD	4 (all PFIC2)	> 10 yr	Resolved cholestasis in 3; Reversal of fibrosis in 2
Bull et al[48](2018)	PEBD; IE	57; 6		Sustained improvement in pruritus: PFIC1-57%; PFIC2 (D482G/E297G mutations)-76%; PFIC2 other mutations-33%; Improvement in bilirubin and bile acids; Improvement in growth; 27% of PFIC1 & 31% of PFIC2 were listed or received LT (less often in D482G/E297G)	Dehydration/dyselectrolytemia due to high stoma output seen in 6 patients (1 died); Cholangitis in 3; Bile stagnation in 2; Stoma bleed in 1
Van Wessel et al[20] (2020)	PEBD; IE; PIBD	47; 13; 1; (all PFIC2)	8.4 yr (1.6-12)	Relief in pruritus – sustained: 54%; Transient: 17%; None: 29%; Relief in pruritus more common in BSEP1 mutations (66%) vs BSEP2 (36%) & BSEP3 (0%); Decrease in serum bile acids, bilirubin, AST & ALT; A 75% reduction in bile acids or decrease to a level < 102 µmol/L post diversion predicts long term NLS of > 15 yr; Biliary diversion associated with higher NLS: HR 0.51; 95%CI: 0.29-0.91, P = 0.02
Bjørnland et al[49] (2021)	PEBD	33; (25 PFIC)	10 yr (0.6-25.2)	Decrease in bile acids 1 wk post-op predictive of successful drainage; 39% received LT or were listed LT at a median follow up of 10 yr	42% early post op complications; Long term stoma related complications in 55%-20% secondary surgeries
Van Vaisberg et al[51] (2020)	IE	11	5 yr	Significant relief in pruritus: 8 (72.7%); 2/11 (18.2%) progressed to ESLD within a year and were listed for LT	Intussusception in 1; No diarrhoea
Foroutan et al[53] (2020)	PIBD	44	54 mo (10-105)	Significant decrease in jaundice and pruritus	Ascending cholangitis in 19.2%; No difference in cholangitis between standard procedure and PIBD with anti-reflux valve
Chen et al[52](2018)	PIBD	34; (PFIC1-10, PFIC2-14, PFIC3-5)	-	Decreased bilirubin and bile acids; Improved growth; 2 (5.9%) underwent LT at 20 & 39 mo post PIBD	Dyselectrolytemia/dehydration in 2; Relapse of symptoms in 4
Agarwal et al[38] (2016)	PIBD; PEBD	3; 1	2 yr (1-2)	PIBD: Decrease in pruritus score, improved growth & decreased serum bile acids; PEBD: Failed; One with failed PEBD needed LT in 7 yr; Rest all survived with native liver at mean follow up 8 yr	No complications with PIBD
Bull et al[48](2018)	PEBD; IE	57; 6		Sustained improvement in pruritus: PFIC1-57%; PFIC2 (D482G/E297G mutations)-76%; PFIC2 other mutations-33%; Improvement in bilirubin and bile acids; Improvement in growth; 27% of PFIC1 & 31% of PFIC2 were listed or received LT (less often in D482G/E297G)	Dehydration/dyselectrolytemia due to high stoma output seen in 6 patients (1 died); Cholangitis in 3; Bile stagnation in 2; Stoma bleed in 1

PEBD: Partial external biliary diversion; PIBD: Partial internal biliary diversion; PFIC: Progressive Familial Intrahepatic Cholestasis; IE: Ileal Exclusion; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; TBD: Total biliary diversion; LT: Liver transplantation; NLS: Native Liver Survival; BSEP: Bile salt exporter pump; ESLD: End stage liver disease.