Primary sclerosing cholangitis (PSC)

Definition

PSC is a chronic, progressive cholestatic liver disease. Inflammation and fibrosis lead to strictures and dilatations of the intrahepatic and/or extrahepatic bile ducts. The diagnosis is based on typical bile duct changes on cholangiography after exclusion of other causes of secondary cholangitis.

Classification

• Classic PSC: involvement of large and small bile ducts, frequently with inflammatory bowel disease
• Small-duct PSC: about 5% of patients; only small bile ducts affected, normal cholangiogram, diagnosis by histology only; progression to the classic form is possible
• PSC with features of autoimmune hepatitis (overlap form)

Occurrence & epidemiology

Prevalence is about 10 per 100,000. More than 60% of patients are men; the disease usually manifests between the ages of 30 and 40 but also occurs in children and older people. PSC is found in 2.4–7.5% of patients with ulcerative colitis and in 1.2–3.4% of patients with Crohn's disease.

Aetiopathogenesis

The cause is unknown. Immune-mediated mechanisms are suggested by the close association with inflammatory bowel disease (in 60–80% of PSC patients in Northern Europe and North America) and the frequent detection of autoantibodies such as ANA and atypical pANCA. There is also a genetic component: first-degree relatives have a markedly increased risk of disease.

The accompanying bowel disease often shows a distinct pattern: pancolitis, rectal sparing and backwash ileitis are more common than in ulcerative colitis without PSC.

Clinical features

Up to 50% of patients are symptom-free at diagnosis and are noticed only because of raised liver values. Typical complaints are right upper quadrant pain, pruritus, jaundice, fatigue and exhaustion; episodes of fever point to bacterial cholangitis. On examination, hepatomegaly and splenomegaly are the main findings.

Complications over time:

• bacterial cholangitis (in about 40%) and gallstones or choledocholithiasis (in about 50%)
• dominant strictures of the large bile ducts
• cholangiocarcinoma in 10–20% of patients, and an increased risk of gallbladder carcinoma
• increased risk of colorectal carcinoma with coexisting inflammatory bowel disease
• biliary cirrhosis with portal hypertension

Diagnosis

• Laboratory tests: alkaline phosphatase and GGT usually raised; a normal ALP (in up to 20%) does not exclude PSC, and values often fluctuate. Aminotransferases usually only 2 to 3 times raised, bilirubin usually normal at first.
• Autoantibodies: ANA and pANCA frequently positive but not diagnostic; AMA negative
• IgG4 once at diagnosis to distinguish IgG4-associated cholangitis; however, raised IgG4 levels (above 1.4 g/L) also occur in 10–15% of PSC patients
• MRCP as the most important method of cholangiography: beaded pattern of strictures and upstream dilatations of the bile ducts
• Liver biopsy only if small-duct PSC or overlap with autoimmune hepatitis is suspected; concentric, onion-skin fibrosis around bile ducts is typical
• In known inflammatory bowel disease, persistently raised cholestatic enzymes suggest PSC; however, the bowel disease may also be diagnosed only after the PSC

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Further reading (open access)

1. DGVS/AWMF 021-027: S2k-Leitlinie Autoimmune Lebererkrankungen (Stand 2017)
2. MSD Manual Professional: Primary Sclerosing Cholangitis (PSC)

Cross-references