Impact of genotype on childhood bile salt export pump deficiency in Indian Progressive Familial Intrahepatic Cholestasis registry

BACKGROUND: A mutation in the ABCB11 gene causes the bile salt export pump (BSEP) deficiency. We aimed to study the genotype-phenotype correlation and the native liver survival (NLS) of BSEP deficiency among Indian children. METHODS: The data were retrieved from the Indian Progressive Familial intrahepatic Cholestasis (PFIC) registry. RESULTS: Among those enrolled in the registry, BSEP deficiency was the commonest (138/447, 30.9%) disorder. Among the 116 biallelic mutations, BSEP India1 (biallelic missense mutations) were present in 55 (47.4%) cases, whereas BSEP India2 (protein truncating mutation in at least one allele) in 17 (14.6%) cases, and BSEP India3 (biallelic protein truncating mutations) was seen in 44 (39.7%) cases, respectively. Of the 110 cases who presented with jaundice, in 36 (32.7%) cases jaundice resolved on urosdeoxycholic acid. Of the total, 91 with pruritus, grade 3 and 4 of pruritus was present in 54 (59.3%) cases, 43 (47.25%) cases did not resolve on medical management. On analysis of variance, median values of serum albumin (F-statistics 4.75, p = 0.011) were significantly lower in BSEP India3 versus BSEP India1 within the group. Risk predictive factors at baseline for death and LT were BSEP India3 (adjusted odds ratio [OR] 6.1, 95% confidence interval [CI] 1.9-19.3, p = 0.002) and grade 3 and 4 of pruritus (adjusted OR 5.9, 95% CI 2-17.1, p < 0.001). Kaplan-Meier survival analysis showed that non-resolution of jaundice, higher grade of pruritus and BSEP India3 was associated with significantly shorter duration of NLS. There were 49 likely novel mutations in various combinations and 2 PTMs (c.2115C>A [p.Tyr705Ter] and c.3659_3660del [p.Ser1220Ter]) as part of BSEP India3 genotype, were shown to be associated with death and liver transplantation (LT) in this Indian cohort. CONCLUSION: BSEP deficiency/ABCB11 mutation was the commonest PFIC seen in the registry. Risk predictive factors at baseline for death and LT were BSEP India3 and grades 3 and 4 of pruritus. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05704517 (retrospective study).

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Journal
Journal of Pediatric Gastroenterology and Nutrition
Published
2026-10-26
DOI
https://doi.org/10.1002/jpn3.70610
Primary Topic
Pediatric Hepatobiliary Diseases and Treatments
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article
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article

Impact of genotype on childhood bile salt export pump deficiency in Indian Progressive Familial Intrahepatic Cholestasis registry

John Matthai, Parijat Ram Tripathi, Arjun Maria, Smita Malhotra et al.
Journal of Pediatric Gastroenterology and Nutrition
Pediatric Hepatobiliary Diseases and Treatments
article

Impact of genotype on childhood bile salt export pump deficiency in Indian Progressive Familial Intrahepatic Cholestasis registry

John Matthai, Parijat Ram Tripathi, Arjun Maria, Smita Malhotra, A. Ashritha, Seema Alam, Bikrant Bihari Lal, Aathira Ravindranath, Zahabiya Nalwalla, Anuradha Rai, Nishant Wadhwa, Anupam Sibal, Arya Suchismita, Aabha S. Nagral, Ashish Bavdekar, Piyush Upadhyay, Rajeev Khanna, Karunesh Kumar, Vipul Gautam, Yogesh Waikar, Vikram Kumar, Vaibhav Shah, Viswanathan M. Sivaramakrishnan, Vikrant Sood, Maya Peethambaran, K. P. Srikanth, Ira Shah, Nowneet Kumar Bhat, Lalit Verma, Dulasi Durga, Sanjeev Kumar Verma, Pandey Snehavardhan, Somashekara Hosaagrahara Ramakrishna, Nirmala Dheivamani, Aashay Shah, Subhash Gupta, Aniket Deshmukh
article en

Abstract

BACKGROUND: A mutation in the ABCB11 gene causes the bile salt export pump (BSEP) deficiency. We aimed to study the genotype-phenotype correlation and the native liver survival (NLS) of BSEP deficiency among Indian children. METHODS: The data were retrieved from the Indian Progressive Familial intrahepatic Cholestasis (PFIC) registry. RESULTS: Among those enrolled in the registry, BSEP deficiency was the commonest (138/447, 30.9%) disorder. Among the 116 biallelic mutations, BSEP India1 (biallelic missense mutations) were present in 55 (47.4%) cases, whereas BSEP India2 (protein truncating mutation in at least one allele) in 17 (14.6%) cases, and BSEP India3 (biallelic protein truncating mutations) was seen in 44 (39.7%) cases, respectively. Of the 110 cases who presented with jaundice, in 36 (32.7%) cases jaundice resolved on urosdeoxycholic acid. Of the total, 91 with pruritus, grade 3 and 4 of pruritus was present in 54 (59.3%) cases, 43 (47.25%) cases did not resolve on medical management. On analysis of variance, median values of serum albumin (F-statistics 4.75, p = 0.011) were significantly lower in BSEP India3 versus BSEP India1 within the group. Risk predictive factors at baseline for death and LT were BSEP India3 (adjusted odds ratio [OR] 6.1, 95% confidence interval [CI] 1.9-19.3, p = 0.002) and grade 3 and 4 of pruritus (adjusted OR 5.9, 95% CI 2-17.1, p < 0.001). Kaplan-Meier survival analysis showed that non-resolution of jaundice, higher grade of pruritus and BSEP India3 was associated with significantly shorter duration of NLS. There were 49 likely novel mutations in various combinations and 2 PTMs (c.2115C>A [p.Tyr705Ter] and c.3659_3660del [p.Ser1220Ter]) as part of BSEP India3 genotype, were shown to be associated with death and liver transplantation (LT) in this Indian cohort. CONCLUSION: BSEP deficiency/ABCB11 mutation was the commonest PFIC seen in the registry. Risk predictive factors at baseline for death and LT were BSEP India3 and grades 3 and 4 of pruritus. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05704517 (retrospective study).

Journal of Pediatric Gastroenterology and Nutrition
Indraprastha Apollo Hospitals (IN), Apollo Hospitals (IN), Indira Gandhi Institute of Medical Sciences (IN), Lakeshore Hospital (IN), Apollo Gleneagles Hospitals (IN), Gleneagles Hospital (SG), Jaslok Hospital (IN), Max Super Speciality Hospital (IN), King George's Medical University (IN), Bai Jerbai Wadia Hospital for Children (IN), Sir Ganga Ram Hospital (IN), Institute of Liver and Biliary Sciences (IN), Dr. Ram Manohar Lohia Institute of Medical Sciences (IN), Institute of Child Health (IN), Aster Medcity (IN), Chacha Nehru Bal Chikitsalaya (IN), Apollo Hospitals (IN), Sahyadri Hospital (IN), Manipal Hospital (IN), All India Institute of Medical Sciences Rishikesh (IN)
Openalex Percentile: Top 10%
Pediatric Hepatobiliary Diseases and Treatments
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