RARE DISEASE
Benign recurrent intrahepatic cholestasis type 1
Benign recurrent intrahepatic cholestasis type 1
Benign recurrent intrahepatic cholestasis type 1
Synonyms: BRIC type 1, BRIC1
Synonyms: BRIC type 1, BRIC1
Synonyms: BRIC type 1, BRIC1
Drug discovery
32
papers
On emerging therapies
Overview
Benign recurrent intrahepatic cholestasis type 1 (BRIC1) is a rare autosomal recessive disorder caused by ATP8B1 gene mutations, leading to impaired phospholipid transport and bile acid accumulation. It manifests as recurrent, self-limiting episodes of pruritus, jaundice, and cholestasis with normal/low GGT levels. Episodes last weeks to months, separated by asymptomatic intervals lasting months to years. While classically non-progressive, rare cases evolve into progressive liver disease (PFIC1) [1][4][14][16]. Diagnosis relies on genetic testing and exclusion of secondary cholestasis [2][17].
Burden
Recurrent episodes cause severe pruritus, fatigue, and malnutrition, significantly impacting quality of life [7][16].
~5–10% progress to chronic cholestasis or cirrhosis, requiring liver transplantation [1][14].
Frequent hospitalizations and psychological stress due to unpredictable flares [4][8][14].
Therapies
Categories: rare genetic diseases, rare hepatic diseases, rare inborn errors of metabolism, rare transplant-related disorders
Research Papers
32 drug discovery papers about Benign recurrent intrahepatic cholestasis type 1, with 1 first-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
32 drug discovery papers about Benign recurrent intrahepatic cholestasis type 1, with 1 first-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-06-17 | Use of genetic analysis in adult cholestatic liver disease: lessons from progressive paediatric syndromes and cohort studies
The increasing availability and decreasing costs of DNA sequencing have resulted in the re-grouping of rare, severe paediatric cases of progressive familial intrahepatic cholestasis (PFIC) with more frequent, later-onset cases of cholestasis (eg, intrahepatic cholestasis of pregnancy, benign recurrent intrahepatic cholestasis, low phospholipid-associated cholelithiasis) under the umbrella of genetic cholestasis. The common denominator is the presence of functional variants in the PFIC-associated genes, predominantly in ABCB4 , ABCB11 and ATP8B1 , which cause PFIC types 1–3. Several other congenital diseases such as Alagille syndrome and alpha1-antitrypsin deficiency comprise cholestatic pruritus as frequent symptoms. With the availability of intestinal bile acid transporter inhibitors (IBATi) as new and efficacious therapeutics for pruritus, the most debilitating symptom of PFIC, it is essential to envision their usefulness for patients with later-onset cholestatic liver disease suffering from pruritus. In this review, we summarise published studies on the genetic makeup of patients with paediatric, juvenile and adult-onset cholestasis, and discuss their findings with respect to genotype-specific treatment with IBATi, ursodeoxycholic acid, or alternative drugs. The aim is to provide an overview of the genetic variants likely to be encountered in future sequencing investigations of patients with cholestatic liver diseases, and how to translate this genetic information into personalised treatment recommendations.
2026-06-02 | Recurrent pruritus, jaundice, and pancreatitis in an adult due to a rare etiology: A case report
BACKGROUND Benign recurrent intrahepatic cholestasis type 1 (BRIC1) is an autosomal recessive disorder linked to mutations in ATP8B1 . We report a case of BRIC1 with the unusual combination of recurrent pancreatitis and hearing loss, features that extend beyond the classic hepatic phenotype. CASE SUMMARY An adult male with recurrent jaundice, pruritus, and pancreatitis from 2019 to 2025 underwent laboratory and imaging studies, liver biopsy, and genetic sequencing. Histology confirmed intrahepatic cholestasis. An ATP8B1 minigene plasmid was constructed to assess splicing effects in vitro . Sequencing identified compound heterozygous ATP8B1 variants: c.1214_1215delAT (p.Y405Cfs*24) and c.3015G>A (p.Q1005Q). Functional studies provided the evidence for reclassifying the c.3015G>A variant from uncertain significance to likely pathogenic (LP) in BRIC1. In addition, the patient appeared to show a favorable response to glucocorticoids therapy. CONCLUSION An adult with BRIC1 and relatively rare extrahepatic phenotype had functional evidence for the LP of a novel ATP8B1 variant.
2026-04-07 | Benign Recurrent Intrahepatic Cholestasis: A Rare Diagnostic Challenge
Benign Recurrent Intrahepatic Cholestasis (BRIC) is a rare liver disorder that occurs sporadically or via autosomal recessive inheritance. It is characterised by recurrent episodes of cholestasis with pruritus and jaundice in the absence of chronic liver disease. It typically first presents in childhood or adolescence; however, adult-onset forms may occur and can be difficult to diagnose. The present case report involves a 23-year-old male who presented with recurrent episodes of jaundice, pruritus and pale stools. A thorough evaluation, including autoimmune, infectious and metabolic workup, was negative. Imaging studies showed no evidence of extrahepatic biliary obstruction, and liver biopsy indicated a cholestatic pattern consistent with intrahepatic cholestasis. Whole-exome sequencing, a form of genetic testing, identified a mutation in the ATP8B1 gene, confirming the diagnosis of BRIC. Whole-exome sequencing revealed a pathogenic mutation in ATP8B1, which encodes the Familial Intrahepatic Cholestasis 1 (FIC1) protein responsible for bile salt homeostasis. Mutations in ATP8B1 are associated with BRIC type 1 and are essential to confirm the diagnosis, particularly in atypical or late-onset presentations. The patient was managed conservatively, with resolution of symptoms, and experienced no further attacks during follow-up. The present case illustrates the need to consider BRIC in the differential diagnosis of recurrent cholestatic jaundice in young adults when other common aetiologies have been excluded. Timely recognition allows appropriate supportive management and reduces the burden of unnecessary investigations.
2025-10-14 | Enigmatic functions of ATP8B1: cholestasis, inflammation, phosphoinositide flipping, and cellular homeostasis.
Mutations in ATP8B1 cause a spectrum of cholestatic liver disease, ranging from Progressive-Familial-Intrahepatic-Cholestasis type-1 (PFIC1) to Benign-Recurrent-Intrahepatic-Cholestasis type-1 (BRIC1). Manifestations of PFIC1 include severe pruritus, jaundice, and liver damage. Extrahepatic features sometimes observed in PFIC1 include sensorineural hearing loss, diarrhea, pancreatitis, and short stature. ATP8B1 was shown to translocate phospholipids across the plasma membrane; however, expression of ATP8B1 in many tissues and the range of pathological manifestations in ATP8B1 deficiency suggest diverse physiological functions of ATP8B1, and pleiotropic mechanisms regulating its activity. Recent studies suggest that phosphoinositides, including PIP2 and PIP3, can function as regulators, substrates, and binding partners of ATP8B1. New research shows that ATP8B1 modulates host immune system by regulating cleavage of pyroptotic-executioner Gasdermin D (GSDMD), and inflammation-resolution pathways such as phagocytosis/efferocytosis. Further mechanistic insights can accelerate development of new therapies for restoring membrane integrity, reducing inflammasome activity, and correcting metabolic imbalances caused by ATP8B1 dysfunction.
2025-10-05 | Odevixibat after liver transplant in patients with progressive familial intrahepatic cholestasis type 1: A case series.
Patients with progressive familial intrahepatic cholestasis type 1 (PFIC1) who have undergone liver transplantation (LT) may have unmet needs and impacts on daily life due to post-LT complications, including diarrhea and hepatic steatosis. Here, we describe the effects of the ileal bile acid transporter inhibitor odevixibat on diarrhea and hepatic steatosis in a cohort of patients with PFIC1 post-LT. Treating physicians from six centers retrospectively collected data through July 2023 on patients with PFIC1 who received odevixibat post-LT. Data collected included demographics, medical history, and symptom presentation, characteristics of diarrhea, and liver imaging and/or histopathology. Overall, nine male patients with PFIC1 (seven aged <18 years at initial completion of the case report form) were included. In most patients, the primary indication for odevixibat treatment was diarrhea and/or steatosis post-LT. Odevixibat was initiated at a daily dose of 30-120 µg/kg (median exposure: 13 months). All patients had post-LT diarrhea, which was generally associated with negative impacts on daily life (e.g., ability to attend school, needing to wear diapers due to fecal urgency). After odevixibat initiation, most patients had improved diarrhea and positive impacts on daily life. Among five patients with post-LT steatosis and data available before and after odevixibat initiation, steatosis appeared to improve in three and did not change in two. Overall, the majority of patients with PFIC1 post-LT complications in this case series experienced improvements in diarrhea and daily activities with odevixibat. Treatment with odevixibat following LT also appeared to reduce steatosis in some patients. Further studies, particularly those with a prospective design, are needed to confirm these findings.
small molecules
2026-06-17 | Use of genetic analysis in adult cholestatic liver disease: lessons from progressive paediatric syndromes and cohort studies
The increasing availability and decreasing costs of DNA sequencing have resulted in the re-grouping of rare, severe paediatric cases of progressive familial intrahepatic cholestasis (PFIC) with more frequent, later-onset cases of cholestasis (eg, intrahepatic cholestasis of pregnancy, benign recurrent intrahepatic cholestasis, low phospholipid-associated cholelithiasis) under the umbrella of genetic cholestasis. The common denominator is the presence of functional variants in the PFIC-associated genes, predominantly in ABCB4 , ABCB11 and ATP8B1 , which cause PFIC types 1–3. Several other congenital diseases such as Alagille syndrome and alpha1-antitrypsin deficiency comprise cholestatic pruritus as frequent symptoms. With the availability of intestinal bile acid transporter inhibitors (IBATi) as new and efficacious therapeutics for pruritus, the most debilitating symptom of PFIC, it is essential to envision their usefulness for patients with later-onset cholestatic liver disease suffering from pruritus. In this review, we summarise published studies on the genetic makeup of patients with paediatric, juvenile and adult-onset cholestasis, and discuss their findings with respect to genotype-specific treatment with IBATi, ursodeoxycholic acid, or alternative drugs. The aim is to provide an overview of the genetic variants likely to be encountered in future sequencing investigations of patients with cholestatic liver diseases, and how to translate this genetic information into personalised treatment recommendations.
2026-06-02 | Recurrent pruritus, jaundice, and pancreatitis in an adult due to a rare etiology: A case report
BACKGROUND Benign recurrent intrahepatic cholestasis type 1 (BRIC1) is an autosomal recessive disorder linked to mutations in ATP8B1 . We report a case of BRIC1 with the unusual combination of recurrent pancreatitis and hearing loss, features that extend beyond the classic hepatic phenotype. CASE SUMMARY An adult male with recurrent jaundice, pruritus, and pancreatitis from 2019 to 2025 underwent laboratory and imaging studies, liver biopsy, and genetic sequencing. Histology confirmed intrahepatic cholestasis. An ATP8B1 minigene plasmid was constructed to assess splicing effects in vitro . Sequencing identified compound heterozygous ATP8B1 variants: c.1214_1215delAT (p.Y405Cfs*24) and c.3015G>A (p.Q1005Q). Functional studies provided the evidence for reclassifying the c.3015G>A variant from uncertain significance to likely pathogenic (LP) in BRIC1. In addition, the patient appeared to show a favorable response to glucocorticoids therapy. CONCLUSION An adult with BRIC1 and relatively rare extrahepatic phenotype had functional evidence for the LP of a novel ATP8B1 variant.
2026-04-07 | Benign Recurrent Intrahepatic Cholestasis: A Rare Diagnostic Challenge
Benign Recurrent Intrahepatic Cholestasis (BRIC) is a rare liver disorder that occurs sporadically or via autosomal recessive inheritance. It is characterised by recurrent episodes of cholestasis with pruritus and jaundice in the absence of chronic liver disease. It typically first presents in childhood or adolescence; however, adult-onset forms may occur and can be difficult to diagnose. The present case report involves a 23-year-old male who presented with recurrent episodes of jaundice, pruritus and pale stools. A thorough evaluation, including autoimmune, infectious and metabolic workup, was negative. Imaging studies showed no evidence of extrahepatic biliary obstruction, and liver biopsy indicated a cholestatic pattern consistent with intrahepatic cholestasis. Whole-exome sequencing, a form of genetic testing, identified a mutation in the ATP8B1 gene, confirming the diagnosis of BRIC. Whole-exome sequencing revealed a pathogenic mutation in ATP8B1, which encodes the Familial Intrahepatic Cholestasis 1 (FIC1) protein responsible for bile salt homeostasis. Mutations in ATP8B1 are associated with BRIC type 1 and are essential to confirm the diagnosis, particularly in atypical or late-onset presentations. The patient was managed conservatively, with resolution of symptoms, and experienced no further attacks during follow-up. The present case illustrates the need to consider BRIC in the differential diagnosis of recurrent cholestatic jaundice in young adults when other common aetiologies have been excluded. Timely recognition allows appropriate supportive management and reduces the burden of unnecessary investigations.
2025-10-14 | Enigmatic functions of ATP8B1: cholestasis, inflammation, phosphoinositide flipping, and cellular homeostasis.
Mutations in ATP8B1 cause a spectrum of cholestatic liver disease, ranging from Progressive-Familial-Intrahepatic-Cholestasis type-1 (PFIC1) to Benign-Recurrent-Intrahepatic-Cholestasis type-1 (BRIC1). Manifestations of PFIC1 include severe pruritus, jaundice, and liver damage. Extrahepatic features sometimes observed in PFIC1 include sensorineural hearing loss, diarrhea, pancreatitis, and short stature. ATP8B1 was shown to translocate phospholipids across the plasma membrane; however, expression of ATP8B1 in many tissues and the range of pathological manifestations in ATP8B1 deficiency suggest diverse physiological functions of ATP8B1, and pleiotropic mechanisms regulating its activity. Recent studies suggest that phosphoinositides, including PIP2 and PIP3, can function as regulators, substrates, and binding partners of ATP8B1. New research shows that ATP8B1 modulates host immune system by regulating cleavage of pyroptotic-executioner Gasdermin D (GSDMD), and inflammation-resolution pathways such as phagocytosis/efferocytosis. Further mechanistic insights can accelerate development of new therapies for restoring membrane integrity, reducing inflammasome activity, and correcting metabolic imbalances caused by ATP8B1 dysfunction.
2025-10-05 | Odevixibat after liver transplant in patients with progressive familial intrahepatic cholestasis type 1: A case series.
Patients with progressive familial intrahepatic cholestasis type 1 (PFIC1) who have undergone liver transplantation (LT) may have unmet needs and impacts on daily life due to post-LT complications, including diarrhea and hepatic steatosis. Here, we describe the effects of the ileal bile acid transporter inhibitor odevixibat on diarrhea and hepatic steatosis in a cohort of patients with PFIC1 post-LT. Treating physicians from six centers retrospectively collected data through July 2023 on patients with PFIC1 who received odevixibat post-LT. Data collected included demographics, medical history, and symptom presentation, characteristics of diarrhea, and liver imaging and/or histopathology. Overall, nine male patients with PFIC1 (seven aged <18 years at initial completion of the case report form) were included. In most patients, the primary indication for odevixibat treatment was diarrhea and/or steatosis post-LT. Odevixibat was initiated at a daily dose of 30-120 µg/kg (median exposure: 13 months). All patients had post-LT diarrhea, which was generally associated with negative impacts on daily life (e.g., ability to attend school, needing to wear diapers due to fecal urgency). After odevixibat initiation, most patients had improved diarrhea and positive impacts on daily life. Among five patients with post-LT steatosis and data available before and after odevixibat initiation, steatosis appeared to improve in three and did not change in two. Overall, the majority of patients with PFIC1 post-LT complications in this case series experienced improvements in diarrhea and daily activities with odevixibat. Treatment with odevixibat following LT also appeared to reduce steatosis in some patients. Further studies, particularly those with a prospective design, are needed to confirm these findings.
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