Korean J Gastroenterol.  2020 May;75(5):246-256. 10.4166/kjg.2020.75.5.246.

Novel Insights of Primary Sclerosing Cholangitis and Primary Biliary Cholangitis

Affiliations
  • 1Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea

Abstract

Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are immune-mediated chronic liver diseases. PSC is a rare disorder characterized by multi-focal bile duct strictures and progressive liver diseases that ultimately results in the need for liver transplantation in most patients. Imaging studies, such as MRCP, have an essential role in the diagnosis of most cases of PSC. PSC is usually accompanied by inflammatory bowel disease, and there is a high risk of cholangiocarcinoma and colorectal cancer in PSC. No medical therapies have been proven to delay the progression of PSC. Endoscopic intervention for tissue diagnosis or biliary drainage is frequently required in cases of PSC with a dominant stricture, acute cholangitis, or clinically suspected cholangiocarcinoma. PBC is a chronic inflammatory autoimmune cholestatic liver disease, which, when untreated, will culminate in end-stage biliary cirrhosis requiring liver transplantation. A diagnosis is usually based on the presence of serum liver tests indicative of cholestatic hepatitis in association with circulating antimitochondrial antibodies. Patient presentation and course can be diverse in PBC, and risk stratification is important for ensuring that all patients receive a personalized approach to their care. Medical therapy using ursodeoxycholic acid or obeticholic acid has an important role in reducing the progression to end-stage liver disease in PBC.

Keyword

Primary sclerosing cholangitis; Primary biliary cholangitis; Cholangiocarcinoma; Ursodeoxycholic acid; Liver transplantation

Figure

  • Fig. 1 Algorithm of clinical, biochemical, and technical diagnostic measures in chronic cholestasis. In patients with cholestasis, a structured approach is recommended to reach a safe and secure diagnosis, facilitating prompt interventions where appropriate. ALP, alkaline phosphatase; GGT, gamma-glutamyltranspeptidase; HBsAg, hepatitis B surface antigen; anti-HCV, antibody to hepatitis C virus; US, ultrasonography; DILI, drug-induced liver injury; PSC, primary sclerosing cholangitis; SC, sclerosing cholangitis; PBC, primary biliary cholangitis; AMA, anti-mitochondrial antibody; ANA, anti-nuclear antibody; MRCP, magnetic resonance cholangiopancreatography; EUS, endoscopic ultraeonography; PFIC1-3, progressive familial intrahepatic cholestasis, type 1-3; BRIC, benign recurrent intrahepatic cholestasis; PHSF, persistent hepatocellular secretory failure; ICP, intrahepatic cholestasis of pregnancy.

  • Fig. 2 Algorithm for the investigation of possible cholangiocarcinoma in patients with primary sclerosing cholangitis. CA19-9, carbohydrate antigen 19-9; CCA, cholangiocarcinoma; PSC, primary sclerosing cholangitis; ERCP, endoscopic retrograde cholangiopancreatography, MRI, magnetic resonance imaging; MRCP, magnetic resonance cholangiopancreatography; IgG4, immunoglobulin G4; CT, computed tomography; HPB MDM, hepato-pancreato-biliary multidisciplinary meeting.

  • Fig. 3 EASL clinical guideline in a primary biliary cholangitis consensus-management flow chart. In patients with primary biliary cholangitis, a structured approach to their life-long care is important and recommended. EASL, European Association for the Study of the Liver; UDCA, ursodeoxycholic acid; AIH, autoimmune hepatitis; ALP, alkaline phosphatase; AST, aspartate aminotransferase.


Reference

1. European Association for the Study of the Liver. 2017; EASL clinical practice guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 67:145–172. DOI: 10.1016/j.jhep.2017.03.022. PMID: 28427765.
2. Tanaka A. 2019; IgG4-related sclerosing cholangitis and primary sclerosing cholangitis. Gut Liver. 13:300–307. DOI: 10.5009/gnl18085. PMID: 30205418. PMCID: PMC6529173.
Article
3. Lazaridis KN, LaRusso NF. 2016; Primary sclerosing cholangitis. N Engl J Med. 375:1161–1170. DOI: 10.1056/NEJMra1506330. PMID: 27653566. PMCID: PMC5553912.
Article
4. Chapman MH, Thorburn D, Hirschfield GM, et al. 2019; British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut. 68:1356–1378. DOI: 10.1136/gutjnl-2018-317993. PMID: 31154395. PMCID: PMC6691863.
Article
5. Karlsen TH, Folseraas T, Thorburn D, Vesterhus M. 2017; Primary sclerosing cholangitis - a comprehensive review. J Hepatol. 67:1298–1323. DOI: 10.1016/j.jhep.2017.07.022. PMID: 28802875.
Article
6. Bergquist A, Montgomery SM, Bahmanyar S, et al. 2008; Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis. Clin Gastroenterol Hepatol. 6:939–943. DOI: 10.1016/j.cgh.2008.03.016. PMID: 18674735.
Article
7. Lammert C, Juran BD, Schlicht E, et al. 2014; Reduced coffee consumption among individuals with primary sclerosing cholangitis but not primary biliary cirrhosis. Clin Gastroenterol Hepatol. 12:1562–1568. DOI: 10.1016/j.cgh.2013.12.036. PMID: 24440215. PMCID: PMC4101072.
Article
8. Eaton JE, Juran BD, Atkinson EJ, et al. 2015; A comprehensive assessment of environmental exposures among 1000 North American patients with primary sclerosing cholangitis, with and without inflammatory bowel disease. Aliment Pharmacol Ther. 41:980–990. DOI: 10.1111/apt.13154. PMID: 25783671. PMCID: PMC4402146.
Article
9. Isayama H, Tazuma S, Kokudo N, et al. 2018; Clinical guidelines for primary sclerosing cholangitis 2017. J Gastroenterol. 53:1006–1034. DOI: 10.1007/s00535-018-1484-9. PMID: 29951926.
Article
10. Vlăduţ C, Ciocîrlan M, Bilous D, et al. 2020; An overview on primary sclerosing cholangitis. J Clin Med. 9:E754. DOI: 10.3390/jcm9030754. PMID: 32168787. PMCID: PMC7141307.
Article
11. Angulo P, Peter JB, Gershwin ME, et al. 2000; Serum autoantibodies in patients with primary sclerosing cholangitis. J Hepatol. 32:182–187. DOI: 10.1016/S0168-8278(00)80061-6.
Article
12. Boonstra K, Weersma RK, van Erpecum KJ, et al. 2013; Populationbased epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis. Hepatology. 58:2045–2055. DOI: 10.1002/hep.26565. PMID: 23775876.
Article
13. Tanaka A, Tazuma S, Nakazawa T, et al. 2017; No negative impact of serum IgG4 levels on clinical outcome in 435 patients with primary sclerosing cholangitis from Japan. J Hepatobiliary Pancreat Sci. 24:217–225. DOI: 10.1002/jhbp.432. PMID: 28103424.
Article
14. Tischendorf JJ, Hecker H, Krüger M, Manns MP, Meier PN. 2007; Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: a single center study. Am J Gastroenterol. 102:107–114. DOI: 10.1111/j.1572-0241.2006.00872.x. PMID: 17037993.
Article
15. Mertz A, Nguyen NA, Katsanos KH, Kwok RM. 2019; Primary sclerosing cholangitis and inflammatory bowel disease comorbidity: an update of the evidence. Ann Gastroenterol. 32:124–133. DOI: 10.20524/aog.2019.0344. PMID: 30837784. PMCID: PMC6394256.
Article
16. Boonstra K, van Erpecum KJ, van Nieuwkerk KM, et al. 2012; Primary sclerosing cholangitis is associated with a distinct phenotype of inflammatory bowel disease. Inflamm Bowel Dis. 18:2270–2276. DOI: 10.1002/ibd.22938. PMID: 22407885.
Article
17. Lewis JT, Talwalkar JA, Rosen CB, Smyrk TC, Abraham SC. 2007; Prevalence and risk factors for gallbladder neoplasia in patients with primary sclerosing cholangitis: evidence for a metaplasiadysplasia-carcinoma sequence. Am J Surg Pathol. 31:907–913. DOI: 10.1097/01.pas.0000213435.99492.8a. PMID: 17527079.
Article
18. Chapman R, Fevery J, Kalloo A, et al. 2010; Diagnosis and management of primary sclerosing cholangitis. Hepatology. 51:660–678. DOI: 10.1002/hep.23294. PMID: 20101749.
Article
19. Lindor KD, Kowdley KV, Harrison ME. American College of Gastroenterology. 2015; ACG clinical guideline: primary sclerosing cholangitis. Am J Gastroenterol. 110:646–659. DOI: 10.1038/ajg.2015.112. PMID: 25869391.
Article
20. European Association for the Study of the Liver. 2009; EASL clinical practice guidelines: management of cholestatic liver diseases. J Hepatol. 51:237–267. DOI: 10.1016/j.jhep.2009.04.009. PMID: 19501929.
21. Aabakken L, Karlsen TH, Albert J, et al. 2017; Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) clinical guideline. Endoscopy. 49:588–608. DOI: 10.1055/s-0043-107029. PMID: 28420030.
Article
22. Muratori P, Muratori L, Ferrari R. 2003; Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis. Am J Gastroenterol. 98:431–437. DOI: 10.1111/j.1572-0241.2003.07257.x. PMID: 12591064.
Article
23. Chazouillères O, Wendum D, Serfaty L, Montembault S, Rosmorduc O, Poupon R. 1998; Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatology. 28:296–301. DOI: 10.1002/hep.510280203. PMID: 9695990.
Article
24. Bairy I, Berwal A, Seshadri S. 2017; Autoimmune hepatitis - primary biliary cirrhosis overlap syndrome. J Clin Diagn Res. 11:OD07–OD09. DOI: 10.7860/JCDR/2017/25193.10242. PMID: 28892963. PMCID: PMC5583830.
Article
25. Hirschfield GM, Dyson JK, Alexander GJM. 2018; The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 67:1568–1594. DOI: 10.1136/gutjnl-2017-315259. PMID: 29593060. PMCID: PMC6109281.
Article
26. Kim KA, Jeong SH. 2011; The diagnosis and treatment of primary biliary cirrhosis. Korean J Hepatol. 17:173–179. DOI: 10.3350/kjhep.2011.17.3.173. PMID: 22102382. PMCID: PMC3304651.
Article
27. Angulo P, Lindor KD, Therneau TM, et al. 1999; Utilization of the Mayo risk score in patients with primary biliary cirrhosis receiving ursodeoxycholic acid. Liver. 19:115–121. DOI: 10.1111/j.1478-3231.1999.tb00020.x. PMID: 10220741.
Article
28. Parés A, Caballería L, Rodés J. 2006; Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic acid. Gastroenterology. 130:715–720. DOI: 10.1053/j.gastro.2005.12.029. PMID: 16530513.
Article
29. Corpechot C, Abenavoli L, Rabahi N, et al. 2008; Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology. 48:871–877. DOI: 10.1002/hep.22428. PMID: 18752324.
Article
30. Kuiper EM, Hansen BE, de Vries RA, et al. 2009; Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid. Gastroenterology. 136:1281–1287. DOI: 10.1053/j.gastro.2009.01.003. PMID: 19208346.
Article
31. Kumagi T, Guindi M, Fischer SE, et al. 2010; Baseline ductopenia and treatment response predict long-term histological progression in primary biliary cirrhosis. Am J Gastroenterol. 105:2186–2194. DOI: 10.1038/ajg.2010.216. PMID: 20502446.
Article
32. Corpechot C, Chazouillères O, Poupon R. 2011; Early primary biliary cirrhosis:biochemical response to treatment and prediction of long-term outcome. J Hepatol. 55:1361–1367. DOI: 10.1016/j.jhep.2011.02.031. PMID: 21703194.
33. Azemoto N, Abe M, Murata Y, et al. 2009; Early biochemical response to ursodeoxycholic acid predicts symptom development in patients with asymptomatic primary biliary cirrhosis. J Gastroenterol. 44:630–634. DOI: 10.1007/s00535-009-0051-9. PMID: 19370305.
Article
34. Carbone M, Sharp SJ, Flack S, et al. 2016; The UK-PBC risk scores:derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cholangitis. Hepatology. 63:930–950. DOI: 10.1002/hep.28017. PMID: 26223498. PMCID: PMC6984963.
35. Lammers WJ, Hirschfield GM, Corpechot C, et al. 2015; Development and validation of a scoring system to predict outcomes of patients with primary biliary cirrhosis receiving ursodeoxycholic acid therapy. Gastroenterology. 149:1804–1812.e4. DOI: 10.1053/j.gastro.2015.07.061. PMID: 26261009.
Article
36. Poupon RE, Lindor KD, Cauch-Dudek K, Dickson ER, Poupon R, Heathcote EJ. 1997; Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology. 113:884–890. DOI: 10.1016/S0016-5085(97)70183-5.
Article
37. Lammers WJ, van Buuren HR, Hirschfield GM, et al. 2014; Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study. Gastroenterology. 147:1338–1349.e5. DOI: 10.1053/j.gastro.2014.10.032. PMID: 24954664.
38. Beuers U, Trauner M, Jansen P, Poupon R. 2015; New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond. J Hepatol. 62(1 Suppl):S25–S37. DOI: 10.1016/j.jhep.2015.02.023. PMID: 25920087.
Article
39. Nevens F, Andreone P, Mazzella G, et al. 2016; A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med. 375:631–643. DOI: 10.1056/NEJMoa1509840. PMID: 27532829.
40. Corpechot C, Chazouillères O, Rousseau A, et al. 2018; A placebo-controlled trial of bezafibrate in primary biliary cholangitis. N Engl J Med. 378:2171–2181. DOI: 10.1056/NEJMoa1714519. PMID: 29874528.
41. Adam R, Karam V, Delvart V, et al. 2012; Evolution of indications and results of liver transplantation in Europe. A report from the European Liver Transplant Registry (ELTR). J Hepatol. 57:675–688. DOI: 10.1016/j.jhep.2012.04.015. PMID: 22609307.
42. Singal AK, Guturu P, Hmoud B, Kuo YF, Salameh H, Wiesner RH. 2013; Evolving frequency and outcomes of liver transplantation based on etiology of liver disease. Transplantation. 95:755–760. DOI: 10.1097/TP.0b013e31827afb3a. PMID: 23370710.
Article
43. Carbone M, Neuberger JM. 2014; Autoimmune liver disease, autoimmunity and liver transplantation. J Hepatol. 60:210–223. DOI: 10.1016/j.jhep.2013.09.020. PMID: 24084655.
Article
44. Sylvestre PB, Batts KP, Burgart LJ, Poterucha JJ, Wiesner RH. 2003; Recurrence of primary biliary cirrhosis after liver transplantation:histologic estimate of incidence and natural history. Liver Transpl. 9:1086–1093. DOI: 10.1053/jlts.2003.50213. PMID: 14526404.
Full Text Links
  • KJG
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr