Perspectives in clinical gastroenterology and hepatologyPrimary Sclerosing Cholangitis: Diagnosis, Prognosis, and Management
Section snippets
Epidemiology and Risk Factors
The incidence of PSC is estimated at 1 per 100,000 population, with evidence that the incidence is increasing over time based on a recent meta-analysis of population-based studies from Northern Europe, the United Kingdom, the United States, and Canada.9 The highest annual incidence is reported in Norway (1.3 per 100,000), with a prevalence of 8.5 per 100,000,10 and in this population PSC is the leading indication for LT.11 In the United States, the overall age- and sex-adjusted incidence of PSC
Pathogenesis
The pathogenesis of PSC continues to be elusive, and is reviewed in detail elsewhere.16 It is believed to be a complex immune-mediated disease rather than a true autoimmune disease given the lack of classic features (male rather than female predisposition, lack of response to immunosuppressive medications, and lack of highly selective and pathogenic auto-antibodies).16 The most commonly accepted theory is that in a genetically predisposed individual, an initial insult to cholangiocytes through
Clinical Manifestations
The majority of patients (44%–56%) are asymptomatic at the time of diagnosis,1, 6 and the discovery of PSC increasingly is based on the investigation of abnormal serum liver tests and/or the incidental discovery of intrahepatic bile duct dilatation on cross-sectional imaging. Notably, up to 17% of asymptomatic patients may have cirrhosis on liver biopsy at the time of diagnosis.27 In asymptomatic patients, the estimated survival without decompensated cirrhosis at 7 years is 75% in comparison
Small-Duct Primary Sclerosing Cholangitis
Small-duct PSC is diagnosed when patients have clinical, biochemical, and histologic features of PSC in the setting of a normal cholangiogram (Figure 2B). This represents approximately 11% to 17% of patients with PSC based on population-based studies.1, 12 The diagnosis is difficult to confirm in the absence of IBD. Long-term follow-up studies have shown that approximately 25% of subjects progress to large-duct PSC over time. These patients have significantly longer transplantation-free
Complications and Associated Conditions
Because of the markedly increased risk of cancer in patients with PSC, it should be considered a premalignant condition that warrants close surveillance.
Medical Management
To date, there are no medical therapies that have been proven to alter the natural course of PSC. The most comprehensively studied agent is ursodeoxycholic acid (UDCA), 7-β-epimer of chenodeoxycholic acid that improves hepatobiliary secretion, is hepatoprotective, has immunomodulatory properties, and is very effective in the management of primary biliary cirrhosis.84 An initial placebo-controlled, randomized, controlled trial showed that standard-dose UDCA (13–15 mg/kg/d) was no superior to
Prognosis
PSC is an insidious and slowly progressive disease without effective medical therapy. Although the median time from diagnosis to death or LT is 12 years,105 there is significant interpatient variability in prognosis depending on the stage of disease at diagnosis as well as inherent differences in the phenotype of PSC (small duct vs large duct). Several prognostic models for PSC have been described to determine risk factors for disease progression and the best time for LT.2, 3, 7, 45, 106, 107
Conclusions
PSC is a chronic cholestatic liver disease that impacts survival and quality of life of affected patients. Complications related to chronic cholestasis and portal hypertension from progressive disease as well as hepatobiliary and colorectal cancer occur in a significant number of patients. To date, no medical therapies have been shown to modify the natural course of PSC except for LT.
References (108)
- et al.
Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community
Gastroenterology
(2003) - et al.
Natural history and prognostic variables in primary sclerosing cholangitis
Gastroenterology
(1991) - et al.
Incidence, clinical patterns, and outcomes of primary sclerosing cholangitis in south Wales, United Kingdom
Gastroenterology
(2004) - et al.
Hepatic and extrahepatic malignancies in primary sclerosing cholangitis
J Hepatol
(2002) - et al.
Primary sclerosing cholangitis is associated with nonsmoking: a case-control study
Gastroenterology
(1996) - et al.
Risk of primary sclerosing cholangitis is associated with nonsmoking behavior
Gastroenterology
(1996) - et al.
Pathogenesis of primary sclerosing cholangitis
Best Pract Res Clin Gastroenterol
(2011) - et al.
Increased prevalence of primary sclerosing cholangitis among first-degree relatives
J Hepatol
(2005) - et al.
Genome-wide association analysis in primary sclerosing cholangitis
Gastroenterology
(2010) - et al.
Susceptibility to primary sclerosing cholangitis is associated with polymorphisms of intercellular adhesion molecule-1
J Hepatol
(2004)
A functional polymorphism of the stromelysin gene (MMP-3) influences susceptibility to primary sclerosing cholangitis
Gastroenterology
Homing of mucosal lymphocytes to the liver in the pathogenesis of hepatic complications of inflammatory bowel disease
Lancet
Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice
Gastroenterology
Patients with asymptomatic primary sclerosing cholangitis frequently have progressive disease
Gastroenterology
Clinicopathologic features of the syndrome of primary sclerosing cholangitis
Gastroenterology
Serum autoantibodies in patients with primary sclerosing cholangitis
J Hepatol
Magnetic resonance cholangiography in patients with biliary disease: its role in primary sclerosing cholangitis
J Hepatol
Diagnostic accuracy of magnetic resonance and endoscopic retrograde cholangiography in primary sclerosing cholangitis
Clin Gastroenterol Hepatol
Is there a role for liver biopsy in primary sclerosing cholangitis?
Am J Gastroenterol
The natural history of small-duct primary sclerosing cholangitis
Gastroenterology
Overlap of autoimmune hepatitis and primary sclerosing cholangitis: an evaluation of a modified scoring system
J Hepatol
Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy
Gastroenterology
High lifetime risk of cancer in primary sclerosing cholangitis
J Hepatol
Advanced cytologic techniques for the detection of malignant pancreatobiliary strictures
Gastroenterology
Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review
J Hepatol
Primary sclerosing cholangitis and disease distribution in inflammatory bowel disease
Clin Gastroenterol Hepatol
A unique clinical phenotype of primary sclerosing cholangitis associated with Crohn's disease
J Crohns Colitis
Peristomal varices after proctocolectomy in patients with primary sclerosing cholangitis
Gastroenterology
Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis
Gastrointest Endosc
AGA medical position statement on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease
Gastroenterology
Colon neoplasms develop early in the course of inflammatory bowel disease and primary sclerosing cholangitis
Clin Gastroenterol Hepatol
Gallbladder disease in patients with primary sclerosing cholangitis
J Hepatol
Pruritus in chronic cholestatic liver disease
Clin Liver Dis
Bone disease in patients with primary sclerosing cholangitis
Gastroenterology
Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis
Gastroenterology
Balloon dilation compared to stenting of dominant strictures in primary sclerosing cholangitis
Am J Gastroenterol
Impact of endoscopic therapy on the survival of patients with primary sclerosing cholangitis
Gastrointest Endosc
Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers
Gastroenterology
Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis
Gut
Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population
Gut
Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: a single center study
Am J Gastroenterol
Primary sclerosing cholangitis: natural history, prognostic factors and survival analysis
Hepatology
Incidence of primary sclerosing cholangitis: a systematic review and meta-analysis
Hepatology
Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population
Scand J Gastroenterol
The Nordic liver transplant registry
Annu Rep
The burden of large and small duct primary sclerosing cholangitis in adults and children: a population-based analysis
Am J Gastroenterol
Cigarette smoking, appendectomy, and tonsillectomy as risk factors for the development of primary sclerosing cholangitis: a case control study
Gut
Association of the tumour necrosis factor alpha −308 but not the interleukin 10 −627 promoter polymorphism with genetic susceptibility to primary sclerosing cholangitis
Gut
Etiopathogenesis of primary sclerosing cholangitis
Semin Liver Dis
Recurrence and rejection in liver transplantation for primary sclerosing cholangitis
World J Gastroenterol
Cited by (0)
Conflicts of interest The authors disclose no conflicts.