Primary Sclerosing Cholangitis (PSC)

This is a chronic cholestatic liver disease with obliterative inflammatory fibrosis of the bile ducts. The term 'primary' is used to distinguish this condition from bile duct strictures that are secondary to bile duct injury, cholelithiasis or ischaemia.

• The aetiology is unknown but an autoimmune basis is suspected.
• It may also be related to infection and the ability of certain organisms to traverse the bowel wall in inflammatory bowel disease.
• It is associated with certain HLA types.
• One small study found a 100-fold increase in the risk of acquiring PSC in first degree relatives of patients, suggesting a genetic component.¹

• PSC is rare. It seems most common in Northern Europe.²
• Peak incidence is around age 40 years, but PSC can also occur in infants and children.³ There is a 2:1 male preponderance.⁴
• Of those with PSC, 75% have inflammatory bowel disease, usually ulcerative colitis. The PSC may precede the onset of bowel disease.⁴
• There is an association with coeliac disease.⁵

Symptoms:

• May be asymptomatic (presenting with abnormal LFTs or hepatomegaly)
• Jaundice and pruritus
• Right upper quadrant abdominal pain
• Fatigue, weight loss, fevers and sweats
• May present with complications (see below)

Signs:

• Jaundice
• Hepatomegaly (may also have splenomegaly at presentation)
• Later stages: signs of cirrhosis, portal hypertension or hepatic failure

• Autoimmune hepatitis
• Overlap syndromes, e.g. autoimmune hepatitis-primary sclerosing cholangitis⁶
• Hepatitis - infectious or chronic active hepatitis
• Other bile duct diseases: acute and chronic cholangitis, strictures, cholangiocarcinoma
• Gall stones
• Hepatomegaly (see our dedicated record)
• Primary biliary cirrhosis

Blood tests

• Abnormal liver function tests are usual. The commonest abnormality is elevation of alkaline phosphatase or gamma glutamyltransferase (GGT) level.
• Serum transaminase levels (SGOT) may be normal or elevated to several times normal.
• Bilirubin is raised in advanced PSC.
• Serum albumin and prothrombin time (PTT) become abnormal as the disease progresses.
• IgG, IgM and the serum globulin fraction levels may be raised.
• Anti-neutrophil cytoplasmic antibodies (ANCA) have been found in 60% of patients with PSC. The presence of ANCA is associated with a more severe course of autoimmune liver disease.⁷

Other investigations

• Ultrasound is the initial investigation and may show bile duct dilatation, liver and splenic changes; however, it is not diagnostic for PSC.
• ERCP is the ‘first choice’ test for diagnosis, but is invasive.
• Transhepatic cholangiography can be used if ERCP is unsuccessful, but again is invasive.
• Magnetic resonance cholangio-pancreatography (MRCP) is a non-invasive alternative to ERCP, which is increasingly used.
• MRI may be useful to exclude other disease and evaluate the biliary system.
• Liver biopsy may be needed for staging the disease. However, the usefulness of serial liver biopsy in monitoring the disease is limited: there is considerable variability with place of sampling, as the disease is not homogenous.⁸
• A new technique, transient elastography (FibroScan), has potential as a non-invasive method for detection of cirrhosis in patients with chronic liver disease.⁹

Histological staging

There are 4 histological stages of the disease. They have limited value in predicting survival from PSC, perhaps due to the high degree of sampling variability.⁸

Mayo clinic risk score¹⁰

• A multivariate statistical survival model from long-term survival data has been developed at the Mayo Clinic.
• It computes the score on the basis of the patient's age, history of variceal bleeding, and serum levels of albumin, bilirubin, and aspartate aminotransferase.
• This scoring system has advantages over histological staging, in that it is non-invasive and was found to be well correlated to actual survival.
• It also performed better than the well-known Child-Pugh classification for cirrhosis, which did not predict survival with PSC.¹¹

Pruritus:

• SSRI anti-depressants such as sertraline may improve symptoms.¹²
• One patient found phototherapy helpful.¹³

• As with other cholestatic disorders, supplements for the fat-soluble vitamins (vitamins A, D, E, K) may be required.
• In children, nutritional support may be needed to ensure adequate growth.

• Systematic reviews have evaluated corticosteroids¹⁴ and penicillamine,¹⁵ but found no evidence of benefit.
• Ursodeoxycholic acid:¹⁶
  • This gives a a significant improvement in liver biochemistry and is well tolerated.
  • However, it has not so far been shown to give any clinical benefit. A Cochrane review concluded that there is insufficient evidence to either support or refute its clinical effects in PSC.
• Overlap syndromes: patients with the autoimmune hepatitis-primary sclerosing cholangitis overlap syndrome may respond to immunosuppressant treatment.⁶
• Avoid alcohol (a risk factor for cholangiocarcinoma development, see below).

• Strictures causing recurrent cholangitis can be treated by balloon dilatation (endoscopic or percutaneous). Stents are also used.¹⁷
• Surgical drainage procedures are possible, but do not alter prognosis because of the intrahepatic component of the disease. There is a postoperative risk of cholangitis, and the procedures may make later transplantation more difficult.³ However, some authors suggest there is a role for extrahepatic biliary resection.¹⁸
• Liver transplantation (see below).

Biliary complications:

• Biliary obstruction due to stones or strictures - treat with endoscopic or drainage procedures (above).
• Bacterial cholangitis, acute or chronic - treat with antibiotics.

Cirrhosis and associated complications:

• Ascites.
• Portal hypertension.
• Oesophageal varices (these can also occur early in PSC, without established cirrhosis).¹⁹
• Hepatic failure - orthotopic liver transplant is the ideal treatment for PSC patients with significant cirrhosis or liver failure.^5,18

Related cancers:

• Cholangiocarcinoma develops in some PSC patients. One study found a 7% rate of cholangiocarcinoma over 11 years. Alcohol consumption and variceal bleeding are risk factors for developing cholangiocarcinoma with PSC.^3,20
• In patients with ulcerative colitis, having PSC is an additional risk factor for bowel cancer. Folate may be protective.²¹

• There is a slow progression to cirrhosis.
• The Mayo clinic staging (above) helps indicate prognosis.
• PSC can be classified into small-duct or large-duct types, which seems to affect prognosis:²²
  • Small-duct PSC has a better prognosis, with longer transplant-free survival.
  • Also, it appears that cholangiocarcinoma is unlikely with small-duct PSC.
• Prognosis after liver transplant:^6,22,23
  • The outcome for liver transplant in PSC is good, with a 5 year survival of 75-80%.
  • PSC can recur after transplantation, and a retransplant may be required.