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Navigating Cholestasis Logo

This website is intended for U.S. healthcare professionals only.

Navigating Cholestasis logo

Understanding Rare Cholestatic Liver Diseases

Causes and Symptoms of Liver Cholestasis and Rare Cholestatic Liver Disease

Liver cholestasis refers to impaired bile formation and/or flow that leads to the build-up of bile acids and other biliary components in the liver. This accumulation can cause inflammation, fibrosis, and progressive damage to the liver. Cholestasis is characteristic of a group of disorders known as rare cholestatic liver diseases, such as Alagille syndrome, biliary atresia, primary biliary cholangitis, primary sclerosing cholangitis, and progressive familial intrahepatic cholestasis. Common overlapping signs and symptoms observed in these conditions include fatigue, pruritus, and jaundice, all of which result from cholestatic liver damage.1–5

Impact on Patients and Caregivers

Rare cholestatic liver diseases can affect both children and adults. The symptoms of cholestasis can significantly reduce a patient’s quality of life, impacting physical, mental, and social well-being. The burden of these conditions extends beyond the patients themselves, affecting families and caregivers who often experience substantial challenges in their personal and professional lives due to the demands of ongoing care and emotional strain.6–11

Disease Areas

Biliary Atresia (BA)

BA is a rare condition affecting infants where the bile ducts become blocked shortly after birth, preventing bile from flowing into the intestine. This build-up of bile in the liver causes progressive damage, leading to inflammation, fibrosis, and eventually cirrhosis, as well as other symptoms such as pruritus and fatigue.5,12

Liver Cholestasis

Liver cholestasis refers to impaired bile formation and/or flow that leads to the build-up of bile acids and other biliary components in the liver, and it can have numerous underlying causes. This accumulation can cause inflammation, fibrosis, and progressive damage to the liver.1–3

Primary Biliary Cholangitis (PBC)

PBC is a rare, progressive autoimmune liver disease that primarily affects women aged 40 to 80. It is characterized by the build-up of bile caused by immune cell-mediated destruction of the bile ducts. This impairs bile flow and can lead to liver fibrosis, cirrhosis, and eventually end-stage liver disease if not effectively treated.13–15

Progressive Familial Intrahepatic Cholestasis (PFIC)

PFIC is a group of rare, inherited liver disorders caused by genetic variations that impair the liver’s ability to properly drain bile, leading to a build-up of bile acids in the liver. Although PFIC can occasionally present in adulthood, it most commonly appears in the early childhood and tends to be more aggressive in pediatric cases. As the disease progresses, it can lead to a range of hepatic complications, including inflammation, fibrosis, cirrhosis, and end-stage liver disease.16,17

Primary Sclerosing Cholangitis (PSC)

PSC is a rare, immune-mediated liver disease characterized by inflammation and fibrosis of the bile ducts. This process leads to the narrowing and hardening of the bile ducts, resulting in impaired bile drainage and a subsequent build-up of bile acids within the liver. Individuals with PSC may initially experience symptoms such as pruritus and fatigue. As the disease progresses, it can lead to complications including cirrhosis, portal hypertension, and liver failure.18,19

Alagille Syndrome (ALGS)

ALGS is a rare genetic condition that primarily affects babies and infants and presents with a wide range of multi-organ symptoms. Individuals with ALGS have fewer bile ducts than unaffected individuals, which results in a build-up of bile acids in the liver. This condition may also involve distinctive facial features, as well as abnormalities of the heart, kidneys, skeleton, and eyes.4

Disease Areas

Alagille Syndrome (ALGS)

ALGS is a rare genetic condition that primarily affects babies and infants and presents with a wide range of multi-organ symptoms. Individuals with ALGS have fewer bile ducts than unaffected individuals, which results in a build-up of bile acids in the liver. This condition may also involve distinctive facial features, as well as abnormalities of the heart, kidneys, skeleton, and eyes.4

Biliary Atresia (BA)

BA is a rare condition affecting infants where the bile ducts become blocked shortly after birth, preventing bile from flowing into the intestine. This build-up of bile in the liver causes progressive damage, leading to inflammation, fibrosis, and eventually cirrhosis, as well as other symptoms such as pruritus and fatigue.5,12

Liver Cholestasis

Liver cholestasis refers to impaired bile formation and/or flow that leads to the build-up of bile acids and other biliary components in the liver, and it can have numerous underlying causes. This accumulation can cause inflammation, fibrosis, and progressive damage to the liver.1–3

Primary Biliary Cholangitis (PBC)

PBC is a rare, progressive autoimmune liver disease that primarily affects women aged 40 to 80. It is characterized by the build-up of bile caused by immune cell-mediated destruction of the bile ducts. This impairs bile flow and can lead to liver fibrosis, cirrhosis, and eventually end-stage liver disease if not effectively treated.13–15

Progressive Familial Intrahepatic Cholestasis (PFIC)

PFIC is a group of rare, inherited liver disorders caused by genetic variations that impair the liver’s ability to properly drain bile, leading to a build-up of bile acids in the liver. Although PFIC can occasionally present in adulthood, it most commonly appears in the early childhood and tends to be more aggressive in pediatric cases. As the disease progresses, it can lead to a range of hepatic complications, including inflammation, fibrosis, cirrhosis, and end-stage liver disease.16,17

Primary Sclerosing Cholangitis (PSC)

PSC is a rare, immune-mediated liver disease characterized by inflammation and fibrosis of the bile ducts. This process leads to the narrowing and hardening of the bile ducts, resulting in impaired bile drainage and a subsequent build-up of bile acids within the liver. Individuals with PSC may initially experience symptoms such as pruritus and fatigue. As the disease progresses, it can lead to complications including cirrhosis, portal hypertension, and liver failure.18,19

References

1. Li T, Apte A. Adv Pharmacol 2015;74:263–302. 2. European Association for the Study of the Liver. Journal of Hepatology 2009;51:237–267. 3. Hasegawa S et al. Drugs 2021;81:1181–1192. 4. Turnpenny PD, Ellard S. Eur J Hum Genet 2012;20:251–257. 5. Karpen SJ et al. Hepatol Int 2020;14:677–689. 6. Naghashi S et al. Iran J Pediatr 2019;29:e83559. 7. Elisofon SA et al. J Pediatr Gastroenterol Nutr 2010;51:759–765. 8. Baker A et al. Clin Res Hepatol Gastroenterol 2019;43:20–36. 9. Srivastava A. J Clin Exp Hepatol 2014;4:25–36. 10. Rodijk LH et al. J Pediatr Surg 2021. 11. Mighiu C et al. Orphanet J Rare Dis 2022;17:32. 12. Davenport M. Children 2025;12:95. 13. Jones D et al. Clin Exp Immunol 1997;107:562–568. 14. Lleo A et al. Hepatology 2009;49:871–879. 15. Lleo A et al. Hepatology 2010;52:987–998. 16. Goldberg A, Mack CL. Clin Liver Dis (Hoboken) 2020;15:105–109. 17. Bull LN, Thompson RJ. Clin Liver Dis 2018;22:657–669. 18. Dyson JK et al. The Lancet 2018;391:2547–2559. 19. Chapman RW. Clin Liver Dis (Hoboken) 2017;9:107–110.