Liver & intrahepatic bile ducts

Developmental anomalies / cysts

Benign recurrent intrahepatic cholestasis

Editorial Board Member: Naziheh Assarzadegan, M.D.
Deputy Editor-in-Chief: Aaron R. Huber, D.O.
Zaid Mahdi, M.D., Ph.D.

Last author update: 27 July 2023
Last staff update: 27 July 2023

Copyright: 2019-2023,, Inc.

PubMed Search: Benign recurrent intrahepatic cholestasis liver

Zaid Mahdi, M.D., Ph.D.
Page views in 2023 to date: 410
Cite this page: Mahdi Z. Benign recurrent intrahepatic cholestasis. website. Accessed September 21st, 2023.
Definition / general
  • Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive disease of hepatocanalicular protein transporters characterized by recurrent episodes of jaundice and pruritis that resolve spontaneously without subsequent liver damage
  • Considered to be a known clinical entity in the spectrum of primary familial intrahepatic cholestasis (PFIC)
  • First described by Summerskill and Walshe in 1959 (Z Gastroenterol 1998;36:379)
Essential features
  • Cholestasis during attacks but no histologic progression to fibrosis
  • Autosomal recessive disease
  • Subclassified into 2 types (BRIC1 and BRIC2), which are caused by mutations of ATP8B1 and ABCB11 genes, respectively (the same genes that are mutated in progressive familial intrahepatic cholestasis [PFIC]) (Case Rep Gastroenterol 2022;16:110)
  • BRIC and its subtypes can be considered as a mild form of the more severe progressive familial intrahepatic cholestasis (PFIC)
  • Mainly affects patients in early life or before their twenties (World J Hepatol 2020;12:64)
  • Diagnosis is based on clinical suspicion after excluding other causes of cholestasis and can be confirmed by genetic testing
  • Formerly known as Summerskill-Walshe-Tygstrup syndrome
  • Benign recurrent intrahepatic cholestasis (BRIC)
ICD coding
  • ICD-10: K83 - other diseases of biliary tract
  • ICD-11: 5C58.04 - benign recurrent intrahepatic cholestasis
  • Incidence is ~1 in 50,000 - 100,000 people worldwide (J Clin Exp Hepatol 2014;4:25)
  • Age at diagnosis is typically ≤ 20 years of age
  • M = F
  • Genetic mutation: autosomal recessive inheritance (see Etiology)
  • Liver
  • Autosomal recessive disorder is associated with mutation of ATP8B1 and ABCB11 genes
  • Nonsense and missense mutations in those genes will lead to partial protein expression for bile canalicular protein transport (complete deletion of protein expression will show a severe form of cholestasis, which is known as primary familial intrahepatic cholestasis [types 1 and 2]) (Hepatology 2009;50:1597)
  • Defective ATP8B1 gene is located on chromosome 18 and encodes F1C1, which causes impaired bile salt excretion, while defective ABCB11 gene is located on chromosome 2, which causes impaired functioning of the canalicular pump, leading to cholestasis
Clinical features
  • Patients will experience spontaneous resolution within a few weeks to some months
  • Presents without liver parenchymal involvement toward chronic liver disease
  • Episodes are precipitated by stress, infections, medications or oral contraceptives and pregnancy (Front Med (Lausanne) 2022;9:897108)
  • Clinical picture and history after excluding other forms of cholestasis
  • Genetic testing can be confirmatory
  • Luketic and Shiffman diagnostic criteria includes (J Clin Diagn Res 2016;10:OD01)
    • At least 2 episodes of jaundice with free interval of months to years
    • Laboratory investigations suggestive of intrahepatic cholestasis
    • Cholestasis induced severe pruritus
    • Cholangiography showing normal intra and extrahepatic bile ducts
    • Liver histology suggests cholestasis with no advanced fibrosis
    • Absence of other causes of cholestasis
  • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are usually normal
  • Mildly elevated bilirubin concentrations
  • Mildly elevated gamma glutamyl transferase (GGT) values
Radiology description
  • Unremarkable biliary tree by cholangiography
Prognostic factors
  • Favorable; prognosis is good and does not usually lead to fibrosis
Case reports
Microscopic (histologic) description
  • Canalicular and intracellular cholestasis with associated hepatocyte rosettes
  • No associated inflammation, bile duct loss or marked ductular reaction
  • No advanced fibrosis
  • Reference: Case Rep Gastrointest Med 2020;2020:2894293
Microscopic (histologic) images

Contributed by Pierre Russo, M.D.
Mild cholestasis

Mild cholestasis

Mild cholestasis (canalicular and intracytoplasmic)

Mild cholestasis (canalicular and intracytoplasmic)

Molecular / cytogenetics description
  • Mutation in ATP8B1 gene that is located on chromosome 18 and encodes F1C1, which causes impaired bile salt excretion due to partial protein expression
  • Mutation in ABCB11 gene is located on chromosome 2, which causes impaired functioning of the canalicular pump, leading to cholestasis
  • Rare cases have been associated with TJP2 gene mutation (JPGN Rep 2021;2:e087)
Sample pathology report
  • Liver, biopsy:
    • Liver parenchyma with mild cholestasis (canalicular and intracellular); no fibrosis (see comment)
    • Comment: The patient's history of recurrent attacks of jaundice and pruritis are noted. Sections show liver core biopsies with bland cholestasis (both canalicular and intracytoplasmic). No associated inflammation, bile ductular reaction or bile duct loss is seen. No fibrosis is seen.
Differential diagnosis
Board review style question #1
What statement is true regarding benign recurrent intrahepatic cholestasis (BRIC)?

  1. Biliary tree usually shows severe strictures by radiology
  2. Frameshift mutation or deletion in ATP8B1 gene or ABCB11 genes
  3. Liver parenchyma with cirrhosis
  4. Normal serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
  5. Usually associated with cystic fibrosis
Board review style answer #1
D. Normal serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Serum ALT and AST are usually normal in cases of BRIC. Answers A and C are incorrect because BRIC is not usually associated with advanced liver disease / cirrhosis or abnormal biliary tree by imaging. Answer B is incorrect because the mutated genes show missense mutations and not frameshift mutations. Answer E is incorrect because BRIC is not usually associated with cystic fibrosis.

Comment Here

Reference: Benign recurrent intrahepatic cholestasis
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