Primary sclerosing cholangitis is a chronic progressive disease characterized by inflammation and fibrosis of the bile ducts. It has unknown causes but likely involves genetic and immunological factors. The disease varies in progression and can result in complications like end-stage liver disease, portal hypertension, cholangitis, or cholangiocarcinoma. While most patients with primary sclerosing cholangitis have inflammatory bowel disease, only a minority of inflammatory bowel disease patients develop primary sclerosing cholangitis. There are no proven effective treatments, so management focuses on supportive care and transplantation may be considered for complications.

1. Primary Sclerosing Cholangitis
Usama Ragab Youssif
Assistant Lecturer of Medicine
Moday, 2-4-2018

4. Definition
 Chronic progressive fibro-obliterative bile duct
inflammation that can involve any part of the
biliary tree.

5. Epidemiology
 The incidence of the disease ranges from 0.5 to
1.25 cases/100 000.
 The prevalence of the disease ranges between
six and 20 cases/100 000.
 Men are more likely to be affected (70%).
 Prevalence of PSC may be increased in first
degree relatives of PSC patients.

6. Etiologies
 Unknown.
 Many Hypothesis.
 Genetic element: HLA B8.
 Environmental triggers in genetic susceptible
individuals.

7. Predictive/risk factors
Risk Factor Frequency
Male sex 70%
IBD (pancolitis) 70-90%
HLA B8 60-80%

8. “Typical” PSC patient
 Thus, the ‘‘typical” PSC patient is a young to
middle-aged man with IBD who presents with
biochemical and/or clinical signs of a
cholestatic liver disease.

9. Screening
 Any patient with a repeatedly abnormal
cholestatic pattern of liver chemistries should
be evaluated.
 Likewise, patients with IBD and abnormal
liver chemistries should be evaluated for PSC
though only 2.4–7.5% will have or develop
PSC.

10. Associated Conditions
 PSC is frequently associated with
inflammatory bowel disease (80% with
ulcerative colitis). The clinical course of these
conditions is not correlated.
 HLA-A1, B8, & DR3
 Type 1 DM (10 %)
 Thyroid disorders (8%)
 Others: psoriasis, rheumatoid, SLE,
sarcoidosis, celiac disease.

11. Classification
 Small duct disease is defined as typical
histologic features of PSC with a normal
cholangiogram.
 In large duct PSC, characteristic strictures of
the biliary tree can be detected by
cholangiography.

12. Survival in patients with small-duct and large-duct PSC. Survival free of liver transplantation is
significantly longer in patients with small-duct PSC. Modified from Bjornsson et al.
Gastroenterology 2008;134(4)

13. Presentation
 The physical examination fndings of PSC are
non-specifc: fatigue, abdominal pain, pruriuts.
 Most patients with PSC present with abnormal
liver chemistries in a cholestatic pattern.
 Rarely patients will be diagnosed with PSC
after a bout of cholangitis or after presenting
with ESLD or cholangiocarcinoma.

14. Disease severity classifcation
 The Mayo Model can be used to help predict
the probability of survival based on several
parameters including bilirubin, AST, albumin,
history of variceal bleeding and age of the
patient
(www.mayoclinic.org/girst/mayomodel3.html).

15. Disease severity classifcation
R = 0.03 × age +
0.54 × loge(bilirubin) +
0.54 × loge(AST) +
1.24 × variceal bleeding -
0.84 × albumin

16. Differential Diagnosis
Condition Comment
AIDS Cholangiopathy Hx of HIV positive, risk factors
Bile Duct neoplasm Can be diffcult to distinguish. Brushings
and biopsy of the bile duct make the
diagnosis
Surgery/Stricture History of prior biliary surgery
IgG4 sclerosing cholangitis Distinguished based on laboratory testing
and history of pancreatitis
Congenital Early presentation

17. Work Up – Laboratory
 Elevated AP and GGT predominate.
 Serum aminotransferase levels are typically
less than 200 IU/L
 Bilirubin may be elevated.
 Albumin is typically normal except in those
with active IBD.
•

18. Work Up – Laboratory
 ANA & ASMA is positive in up to 50% of
cases in AIH-PSC overlap, and perinuclear
antineutrophil cytoplasmic antibody (p-
ANCA) is positive in 80% of cases.
Antibody Prevalence
Anti-neutrophil cytoplasmic antibody 50%–80%
Anti-nuclear antibody 7%–77%
Anti-smooth muscle antibody 13%–20%
Anti-endothelial cell antibody 35%
Anti-cardiolipin antibody 4%–66%
Thyroglobulin 4%
Thyroperoxidase 7%–16%
Rheumatoid factor 15%

19. Work Up – Imaging
 MRCP is preferred over endoscopic retrograde
cholangiopancreatography (ERCP) to establish
a diagnosis of PSC.
 Liver ultrasound may be useful in establishing
the diagnosis if ductal dilation is present.
 Annual abdominal ultrasonography should be
considered for gallbladder abnormalities
Case courtesy of Dr Chris O'Donnell, Radiopaedia.org, rID: 26879

20. Work Up – Procedure
 ERCP: characteristic beading, stricture.
 Liver biopsy: onion skininng appearance.
 Cytological brushing: FISH
 Total Colonoscopy.
Case courtesy of Dr Natalie Yang, Radiopaedia.org, rID: 6868

22. Cholangiocarcinoma Screening
 FISH: Flouresence in situ hybridization.
Brush cytology using EUS-FNA.
Cholangioscopy.
From Lazaridis and Gores, Elsevier.
World J Gastroenterol. Nov 21, 2012; 18(43): 6197-6205.

23. Confocal Biliary Endomicroscopy

25. Management
 UDCA (20 to 30 mg/kg/day) may be beneficial in improving
liver biochemistries; no sufficient data yet. (ACG, 2015:
Ursodeoxycholic acid (UDCA) in doses >28 mg/kg/day should
not be used for the management of patients with PSC.)
 Corticosteroids and other immunosuppressants are not
indicated for treatment of PSC in adults unless there is
evidence of an overlap syndrome or IgG4 associated PSC.
 Episodes of cholangitis should be managed with IV antibiotics
and endoscopic therapy: ciprofloxacin (oral vancomycin??).

26. Management
 Pruritis can be managed by cholestyramine 4g/day with other
options e.g. rifampicin 150 – 300 mg/day.
 In patients with hepatic osteopenia, use of calcium 1.0-1.5 g
and vitamin D 1,000 IU daily for therapy.
 In patients with hepatic osteoporosis, use of bisphosphonate
therapy in addition to calcium and vitamin D supplementation.
 In patients with osteoporosis and esophageal varices, use of
parenteral forms of bisphosphonate therapy rather than oral
formulations.

27. Other Therapies
 ERCP can be performed to dilate and stent dominant strictures.
R = 0.03 × age + 0.54 × loge(bilirubin) + 0.54 × loge(AST) +
1.24 × variceal bleeding - 0.84 × albumin
 Refer patients with ESLD for liver transplantation.

28. When to hospitalize
 Evidence or suspicion of bacterial cholangitis.
 Life-threatening complications of portal hypertension or
cirrhosis.

29. Final Bottom Line
 PSC is a cholestatic liver disease characterized by
inflammation and fbrosis of the biliary system that
can result in the formation of multifocal biliary
strictures.
 Though the etiology of the disease remains elusive,
evidence suggests the role of genetic and
immunologic factors.

30. Final Bottom Line
 Disease progression varies from patient to patient; the
disease can result in complications of ESLD, portal
hypertension, cholangitis and/or the development of
cholangiocarcinoma.
 While the majority of patients with PSC have or
develop IBD (70–90%; mainly ulcerative colitis), a
minority of patients with IBD have or will develop
PSC (2.4–7.5%).

31. Final Bottom Line
 No specifc therapy is of proven beneft and treatment
is supportive.
 Liver transplantation is a viable option and should be
considered early for those that have complications of
their disease.