Reviews and PerspectivesReviews in Basic and Clinical Gastroenterology and HepatologyPathogenesis of Primary Sclerosing Cholangitis and Advances in Diagnosis and Management
Section snippets
Serum Markers
An increased serum level of alkaline phosphatase is the most common biochemical abnormality detected in patients with PSC. In some cases, it is the only biochemical alteration observed, such as in patients with intrahepatic involvement with PSC.12 However, the level of alkaline phosphatase can vary throughout the disease course and may be normal.18 Although serum aminotransferase levels are frequently normal, in some patients they can be 2-to 3-fold above the upper limit of normal.12 Higher
Small Duct PSC
Among cases with suspected PSC and normal cholangiography, liver biopsy analysis is recommended to rule out small duct PSC.12 Nearly 6% of patients with chronic cholestasis, a normal cholangiogram, and IBD have concurrent small-duct PSC.49 Patients with small duct PSC have symptoms and laboratory results similar to those of subjects with classic PSC.49 However, patients with small duct PSC survive longer and have a lower cumulative risk of cholangiocarcinoma than patients with large duct
Ursodeoxycholic Acid
All randomized controlled trials of agents designed to prevent the progression of PSC have produced negative results, despite promising results from open-label precursor studies. The most commonly studied agent is ursodeoxycholic acid (UDCA), which significantly slows progression of other chronic biliary diseases such as primary biliary cirrhosis (Table 2).99, 100, 101, 102, 103 A European study did not show increased survival times of patients with PSC treated with 17–23 mg · kg−1 · day−1 UDCA
Endoscopic Therapy
New or worsening symptoms in patients with PSC typically warrant investigation to exclude a dominant extrahepatic biliary stricture. A dominant stricture is defined as a stenosis ≤1.5 mm in the common bile duct or ≤1 mm in the hepatic duct.12 When present, it should raise concern for cholangiocarcinoma. Although the prevalence of dominant strictures in patients with PSC is unknown, it has been approximated at 50%.111 Symptomatic dominant strictures are less common, forming in approximately 10%
Liver Transplantation
PSC is a leading indication for liver transplantation in some Scandinavian countries, and it is the fifth most frequent indication for liver transplantation in the United States.115 With 1- and 5-year rates of survival exceeding 90% and 80%, respectively, patients with PSC have among the most successful outcomes after liver transplantation.116 Typically, a Roux-en-Y choledochojejunostomy is the method of choice for biliary reconstruction during liver transplant.117
Indications for transplants
Cholangiocarcinoma
Cholangiocarcinoma occurs in 1% to 2% of patients annually after a diagnosis of PSC, with a lifetime risk of 5% to 10%.124 Cholangiocarcinoma is frequently detected within the first 1 to 3 years after the initial diagnosis of PSC.125 The presence of advanced fibrosis is not required for development of cholangiocarcinoma, unlike hepatocellular carcinoma, which is typically found in conjunction with cirrhosis. Increased levels of bilirubin, duration of IBD, and history of IBD-associated CRN have
Novel Pharmacological Therapies
Thus far, antibodies against TNF have been ineffective in patients with PSC.108, 150 The role of biologic agents such as ustekinumab and vedolizumab in the treatment of IBD is being investigated, and their role in treatment of PSC-IBD remains to be seen.151, 152 Given the possible role of lymphocyte trafficking in the pathogenesis of PSC, monoclonal antibodies that alter this process could have a potential therapeutic benefit.
Janus kinase (JAK) is a tyrosine kinase component of signaling
Conclusions
PSC is a rare but important cholestatic liver disease that reduces patient survival and quality of life. Management of patients involves early recognition of the disorder, implementation of routine screening protocols to identify complications (Figure 4), and treating comorbid conditions. In the absence of effective medical therapy for the disease itself, treatment centers on endoscopic management and referral for liver transplantation when necessary.
Although our understanding of PSC and its
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Conflicts of interest The authors disclose no conflicts.