Primary Sclerosing Cholangitis (PSC)
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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.
Primary Sclerosing Cholangitis (PSC)
- 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.
- 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.
Editor's Notes
- #7: Abberant lymphocyte homing. Activation of immune reponse to bacterial pathogen. Toxic bile.
- #12: Approximately 75% of patients have involvement with both small and large ducts; 15% have only small duct and 10% have only large duct disease. Patients with small duct disease have a more favorable prognosis.
- #13: Patients with small duct disease have a more favorable prognosis.
- #14: Patient can present only with vague symptoms of fatigue, abdominal pain and pruritus.
- #16: Take care of bilirubin.
- #17: A proportion of individuals will present with features consistent with PSC and extensive biliary changes; however, they will suffer from a closely related condition termed IgG4 related disease which is a distinct entity characterised by dense lymphoplasmacytic infiltrates that are rich in IgG positive plasma cells. Those patients suffer also for autoimmune pancreatitis. IgG4 related disease can affect nearly all organs. IgG4 sclerosing cholangitis, unlike PSC, may respond to steroid therapy. Therefore this condition needs to be differentiated from PSC.
- #21: Cholangiographic features in primary sclerosing cholangitis. Multifocal strictures with intervening saccular dilation (“beads-on-astring” appearance) of both intrahepatic and extraheaptic bile ducts are shown. Liver biopsy is the only way to diagnose small duct PSC
- #23: FISH of normal (A) and maligant (B) bile duct cells. Normal cells display duplicate color for each chromosomal probe while malignant cells reveal multiple gains of chromosomes (i.e., polysomy).
- #24: a Normal bile duct epithelium (reticular network with thin dark branching band<20 μm). b Malignant cholangiocarcinoma (reticular structure with thick dark band).
- #25: The diagnosis of cholangiocarcinoma can be very diffcult. Its early diagnosis is essential for any chance of successful therapy. Most cases of cholangiocarcinoma are diagnosed within 10 years of the diagnosis of PSC. Patients with PSC and IBD have an increased risk of colorectal carcinoma.
- #28: Successful endoscopic or radiologically guided balloon dilatation or placement of a stent across a dominant stricture may lead to symptomatic and biochemical improvement in some. Studies have not shown whether this translates to improvement in survival. Those with jaundice or recurrent bouts of cholangitis may also be candidates for such therapy.