Identifying ChLD

All images are actor portrayals.

A circle window showing a liver with spilling bile surrounded by 3 glowing red gauges on the stomach of a young boy wearing blue sweater

For illustrative purposes only.
Does not reflect a liver with ChLD.


Recognizing the signals of cholestatic liver 
diseases (ChLD) early is key to addressing its 
impact on patients

ChLD can be identified by several common signals associated with disease progression

Elevated serum bile acid

  • High sBA may be a surrogate biomarker for native liver survival in PFIC 1 and PFIC 2.1,2*
  • In ALGS, sBA levels are not always evaluated routinely; however, total bilirubin, ALT, AST, APRI, and CB have been identified as additional prognostic markers for native liver survival.3
  • *Based on retrospective analyses of 130 PFIC 1 and 264 PFIC 2 patients from the NAPPED consortium.

Cholestatic pruritus, or itch

Cholestatic pruritus may lead to life-altering symptoms, such as cutaneous mutilation, difficulty sleeping, and impaired school performance.4,5

Failure to thrive

When a child with ChLD has a height and weight that are significantly below that of other children of similar age and sex, they may be diagnosed with failure to thrive.4,6-9

Malabsorption, malnutrition, and FSV deficiency are likely the main causes of these growth impairments in PFIC and ALGS.4,6-9

A circle window showing a liver with spilling bile, punctured by a rusty pole, and surrounded by glowing red gauges with steam billowing A circle window showing a liver with spilling bile, punctured by a rusty pole, and surrounded by glowing red gauges with steam billowing

For illustrative purposes only. Does not reflect a liver with ChLD.

Other indicators of ChLD include jaundice and discolored stools

Jaundice occurs when bilirubin, a biliary pigment, accumulates in tissues like the skin, eyes, and mucus membranes. In ChLD, this happens due to improper elimination of biliary substances in the liver.8,10

Excretory symptoms are also common, including dark urine and pale, discolored, or acholic stools.11

These manifestations lead to an array of physical symptoms and emotional distress, severely impacting quality of life of both patients and caregivers4,7,10,12-15

A glowing gauge with indicator needle in the red connected to a pipe on its right side and has steam billowing out of its left

sBA is one possible indicator of ChLD – and may play a role in pruritus

sBA levels in types of ChLD

Laboratory findings show patients with PFIC and ALGS may present with elevated levels of sBA4,8,9,16
A linear gauge that transitions from green to red and normal to high to very high. PFIC and ALGS arrows point to high and very high PFIC-ALGS-Mobile

Elevated sBA may be linked to 
pruritus, a signature symptom in PFIC and  ALGS.8,9,16-18

sBA and pruritus

Hypothesized pathogenesis of pruritus

There are numerous possible pruritogens involved in pruritus, including bile acids, endogenous opioids, and steroid metabolites. While the exact causes of cholestatic pruritus are unclear, one hypothesis is a causative relationship between bile acids and pruritus through multiple pathways.19

Icon of a liver that has bile acid spilling out of it

Cholestatic Liver

Bile acids in the liver build up, then spill over into the bloodstream12

Icon of a microscopic view of the layers of the skin


Nerve ends under the skin are stimulated19

Icon of a brain


Nerves send itch signals to the spinal cord and brain19

Icon of a person who is covered in marks, scratching their stomach and arm


Increased pruritic response19

It is important to know that severity of pruritus differs from patient to patient and may not always directly correlate with their sBA levels.10,17,20

Pruritus is a classic warning sign of ChLD that may warrant serious and prompt attention12,21

A glowing gauge with indicator needle in the red connected to a pipe on its right side and has steam billowing out of its left

ALT=alanine aminotransferase; APRI=aspartate aminotransferase to platelet ratio index; AST=aspartate aminotransferase; CB=conjugated bilirubin; ChLD=cholestatic liver diseases.

References: 1. van Wessel DBE, Thompson RJ, Gonzales E, et al. Impact of genotype, serum bile acids, and surgical biliary diversion on native liver survival in FIC1 deficiency. Hepatology. 2021;74(2):892-906. 2. van Wessel DBE, Thompson RJ, Gonzales E, et al. Genotype correlates with the natural history of severe bile salt export pump deficiency. J Hepatol. 2020;73(1):84-93. 3. Vandriel SM, Li L-T, She H, et al. Natural history of liver disease in a large international cohort of children with Alagille syndrome: results from the GALA study. Hepatology. 2023;77(2):512-529. 4. Srivastava A. Progressive familial intrahepatic cholestasis. J Clin Exp Hepatol. 2014;4(1):25-36. 5. Kamath BM, Abetz-Webb L, Kennedy C, et al. Development of a novel tool to assess the impact of itching in pediatric cholestasis. Patient. 2017;11:69-82. 6. Pawlikowska L, Strautnieks S, Jankowska I, et al. Differences in presentation and progression between severe FIC1 and BSEP deficiencies. J Hepatol. 2010;53(1):170-178. 7. Kamath BM, Baker A, Houwen R, Todorova L, Kerkar N. Systematic review: the epidemiology, natural history, and burden of Alagille syndrome. J Pediatr Gastroenterol Nutr. 2018;67(2):148-156. 8. Krantz ID, Piccoli DA, Spinner NB. Alagille syndrome. J Med Genet. 1997;34(2):152-157. 9. Turnpenny PD, Ellard S. Alagille syndrome: pathogenesis, diagnosis, and management. Eur J Hum Genet. 2012;20(3):251-257. 10. Gunaydin M, Bozkurter Cil AT. Progressive familial intrahepatic cholestasis: diagnosis, management, and treatment. Hepat Med. 2018;10:95-104. 11. Hilscher MB, Kamath PS, Eaton JE. Cholestatic liver diseases: a primer for generalists and subspecialists. Mayo Clin Proc. 2020;95(10):2263-2279. 12. Kamath BM, Stein P, Houwen RHJ, Verkade HJ. Potential of ileal bile acid transporter inhibition as a therapeutic target in Alagille syndrome and progressive familial intrahepatic cholestasis. Liver Int. 2020;40(8):1812-1822. 13. Mighiu C, O’Hara S, Ferri Grazzi E, et al. Impact of progressive familial intrahepatic cholestasis on caregivers: caregiver-reported outcomes from the multinational PICTURE study. Orphanet J Rare Dis. 2022;17(1):1-9. 14. Elisofon SA, Emerick KM, Sinacore JM, Alonso EM. Health status of patients with Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010;51(6):759-765. 15. Quadrado L, Mogul DB, Gurevich A, et al. Caregiver burden associated with caring for a child with Alagille syndrome: a multi-national, quantitative analysis. Presented at: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Annual Meeting; October 12-15, 2022; Orlando, FL, USA. 16. Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis. 2009;4:1. 17. Ibrahim SH, Kamath BM, Loomes KM, Karpen SJ. Cholestatic liver diseases of genetic etiology: advances and controversies. Hepatology. 2022;75(6):1627-1646. 18. Mehl A, Bohorquex H, Serrano M-S, Galliano G, Reichman TW. Liver transplantation and the management of progressive familial intrahepatic cholestasis in children. World J Transplant. 2016;6(2):278-290. 19. Imam MH, Gossard AA, Sinakos E, Lindor KD. Pathogenesis and management of pruritus in cholestatic liver disease. J Gastroenterol Hepatol. 2012;27(7):1150-1158. 20. Ayoub MD, Kamath BM. Alagille syndrome: diagnostic challenges and advances in management. Diagnostics (Basel). 2020;10(11):1-18. 21. Tessitore M, Sorrentino E, Schiano Di Cola G, Colucci A, Vajro P, Mandato C. Malnutrition in pediatric chronic cholestatic disease: an up-to-date overview. Nutrients. 2021;13(8):1-23.