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Gastrointestinal (GI) System

Primary sclerosing cholangitis (PSC)

Disease of the bile ducts that causes inflammation and obliterative fibrosis of bile ducts inside and/or outside of the liver.

Disease of the bile ducts that causes inflammation and obliterative fibrosis of bile ducts inside and/or outside of the liver.

  • Type of Chronic Liver Disease (CLD)
  • 30-60 year age group

Etiology

Autoimmune associations:

  • IBD (1⁄3 PSC patients are affected with IBD): Ulcerative colitis (3-10%) > Crohn’s disease (~1%)
  • HLA association: HLA-B8, HLA-DR3, HLA-DRw52a
  • Hypergammaglobulinemia (↑ IgM)
  • ↑ p-ANCA association (80%)
Development of pathological changes in primary sclerosing sholangitis
Development of pathological changes in primary sclerosing sholangitis: Three key aspects define the microscopic changes-namely, subtle inflammation, portal firbrosis and cholangiocyte dysplasia. Several genetic and non-genetic factors probably interact multidirectionally to generate the portal microenvironment that drives the development of these three features. Genetic association studies have so far detected 16 common (i.e. occurring in >5% of the general population) genetic risk variants, half of which are associated with inflammatory bowel disease. Genetically determined immune dysregulation is probably implicated in the specific activation of T-cells capable of homing to the liver by hepatic expression of MADCAM1 and CCL25. Studies of secondary sclerosing cholangitis and sclerosing-cholangitis-like features in mice could show that environmental factors and infectious agents (potentially in the form of slight changes to commensal flora and genetic and non-genetic changes to bile homeostasis) might contribute to development of disease. | Hirschfield, G. M., Karlsen, T. H., Lindor, K. D. and Adams, D. H. (2017) ‘Primary sclerosing cholangitis’, The Lancet. Elsevier, 382(9904), pp. 1587–1599. doi: 10.1016/S0140-6736(13)60096-3.

Secondary sclerosing cholangitis:

Typical bile duct changes (of PSC) with a clear predisposing factor for duct fibrosis.
  • Previous bile duct surgery with stricturing & cholangitis
  • Bile duct stones causing cholangitis
  • Intrahepatic infusion of 5-fluorodeoxyuridine
  • Insertion of formalin into hepatic hydatid cysts
  • Insertion of alcohol into hepatic tumors
  • Parasitic infections (eg. Clonorchis)
  • Autoimmune pancreatitis/Ig64-associated cholangitis
  • AIDS (infective due to CMV or Cryptosporidium)

Presentation

Inflammation

Portal fibrosis

Gradual obliteration of intrahepatic & extrahepatic bile ducts

Biliary cirrhosis

Portal hypertension

Hepatic failure

Primary sclerosing cholangitis (PSC)
The Calgary Guide | http://calgaryguide.ucalgary.ca/

Complications

  • Liver:
    • Portal hypertension → Hepatosplenomegaly → Cirrhosis
  • Biliary system:
    • Cholangiocarcinoma (10-30% cases)
    • Gallbladder cancer
    • Recurrent cholangitis
  • Metabolic bone disease (eg. Osteoporosis)

Diagnosis

Diagnostic criteria:

  1. (Cholangiography) Generalized beading & stenosis of the biliary system
  2. (History) Absence of choledocholithiasis (or history of bile duct surgery)
  3. (Follow-up) Exclusion of bile duct cancer

Lab studies:

  • LFT: ↑ ALP, GGT, ↑ Serum bilirubin, absent urobilinogen
  • ↑ Atypical anti-p-ANCA antibodies
  • AMA titre (-)

Imaging:

  • ERCP (Endoscopic Retrograde Cholangiopancreatography) (M/accurate)
  • MRCP (Magnetic Resonance Cholangiopancreatography) (IOC)
    • Beading of ducts
Cholangiogram of primary sclerosing cholangitis
Cholangiogram of primary sclerosing cholangitis. | By Joy Worthington, Roger Chapman – Primary sclerosing cholangitis. Orphanet Journal of Rare Diseases 2006, 1:41doi:10.1186/1750-1172-1-41, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=2962999

Tissue biopsy:

  • Onion-skin fibrosis & inflammation around bile duct
  • Portal oedema
  • Bile ductular proliferation
  • Obliterative cholangitis: Vanishing bile duct syndrome
Typical focal lesion of primary sclerosing cholangitis
Typical focal lesion of primary sclerosing cholangitis demonstrating “onion skin” concentric fibrosis and chronic periductular inflammation. Notice significant edema in this relatively early phase of fibrosis. | Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis: a Review Featuring a Women’s Health Perspective. (2014). Journal of Clinical and Translational Hepatology, 2(4).

Differential diagnosis:

  • Primary Biliary Cholangitis (PBC)
    • AMA titre (+)
  • Secondary sclerosing cholangitis
  • Cholangiocarcinoma

Management

No cure. Only symptomatic management

Medical management:

  • Broad-spectrum antibiotics
  • Fat-soluble vitamin (A, D, E, K) replacement
  • Cholestyramine: Bile acid sequestrant
  • Large dose steroids
  • Immunosuppression therapy: Methotrexate, azathioprine, tacrolimus, cyclosporine
  • Ursodeoxycholic acid (UCDA)

Surgical management:

  • Stenting
  • T-tube drainage
  • Orthoropic liver transplantation (DEFINITIVE TREATMENT): In advanced liver disease
    • C/I: Cholangiocarcinoma

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