Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC(PSC) is an uncommon inflammatory condition, which that affects the biliary tree resulting in multiple strictures, liver damage, and eventually cirrhosis.

The diagnosis can be made when there are classical imaging features in the correct clinical context, and secondary causes of cholangitis have been excluded ¹⁶. 

Epidemiology

Primary sclerosing cholangitis is strongly associated with inflammatory bowel disease (IBD) (in 70% of cases ⁶), especially ulcerative colitis, and thus shares similar demographics: young to middle-aged males (~4^th decade) are most frequently affected ⁴.

Associations

• ulcerative colitis 

  • 70-80% of patients with PSCprimary sclerosing cholangitis develop inflammatory bowel disease

    • 87% of these develop ulcerative colitis ¹⁸

• autoimmune hepatitis (AIH-PSC overlap)

• Sjogren

  Sjögren syndrome ⁶

• retroperitoneal fibrosis ⁶

• mediastinal fibrosis

• Riedel thyroiditis

• orbital pseudotumour

Clinical presentation

The average age of diagnosis of primary sclerosing cholangitis is 54 years (range 6-93) with increased occurrence in men (63%) ¹⁵. A large number of asymptomatic individuals are identified upon investigation of persistently deranged liver function tests. Symptomatic individuals commonly present non-specifically with fatigue. More specific symptoms include pruritus, jaundice or GIgastrointestinal bleeding ¹⁶.

Pathology

Unfortunately, no histological findings are pathognomonic for primary sclerosing cholangitis ². Frequent findings include ^2-4:

• periductal fibrosis (onion skin lesions)

• periportal eosinophilic infiltrate

• paucity of ducts

Markers

Unlike primary biliary cholangitis, antibody titres are usually absent or low ⁴. Liver function tests will usually have a cholestatic pattern with an elevated alkaline phosphatase (ALP) and bilirubin ².

Radiographic features

The entire biliary tree (both intra- and extrahepatic) may be involved, with multiple strictures scattered along its length. In ~20% only the intrahepatic and proximal extrahepatic bile ducts are involved ⁴.

The end result of primary sclerosing cholangitis is cirrhosis which is usually characterised by a markedly distorted biliary tract and atrophy of the entire liver with the exception of the caudate lobe which is hypertrophied in almost all cases (68-98%) ^1-5. Atrophy involving the left lobe is a feature whichthat somewhat distinguishes it from cirrhosis from other causes, in which the left lobe is usually hypertrophied ¹.

Ultrasound

Ultrasound is able to demonstrate both the changes of cirrhosis and irregularity of bile duct calibre. Additionally, brightly echogenic portal triads may be visible.

Primary sclerosing cholangitis is a risk factor for developing gallbladder cancer, so gallbladder polyps should be considered malignancy until proven otherwise.

CT

• contour abnormalities and atrophy (see above)

• marked caudate lobe hypertrophy

• the atrophied liver is of lower density than the hypertrophied caudate lobe ¹

• multiple linear discontinuous low-density regions representing dilated intrahepatic bile duct segments ¹

MRCP and ERCP

ERCP has traditionally been the gold standard for the depiction of the biliary tree, and also offers the ability to perform cholangioplasty, if necessary. In practice, however, MRCP is used before ERCP since it is noninvasivenon-invasive, can visualise the liver, and it avoids the 10% risk of hospitalisation from ERCP in PSCprimary sclerosing cholangitis patients ¹⁷.

The characteristic findings on direct imaging of the biliary tree are ^2,3,5:

• multiple segmental strictures

  • typically short segment

  • intervening segments are of normal calibre or slightly dilated (beading)

• biliary dilatation: may be present in ~85% of cases ⁹

  • general: ~35%

  • segmental: ~50%

• biliary diverticula

• mural irregularities

• distortion of the biliary tree due to associated cirrhosis

Treatment and prognosis

The only cure available at present is orthotopic liver transplantation (OLT) with 5-year survival rates approaching 80% ^10,11. However, there is evidence that PSCprimary sclerosing cholangitis may recur in 5-20% of patients post-transplantation ^10-12.

No medical therapy has stood the test of time, with ursodeoxycholic acid, immunosuppression, chelation and antifibrolytic therapy unable to demonstrate consistent benefits over placebo ⁸.

Percutaneous cholangioplasty of dominant strictures is usually performed in a retrograde fashion via ERCP or via a transhepatic approach ^6,7.

Complications

• hepatic osteodystrophy

• cholangiocarcinoma develops in ~15% of patients ⁶

• colorectal cancer ¹⁴

  • 4x greater risk compared to IBD patients without PSCprimary sclerosing cholangitis

  • 10x greater risk compared to general population

• hepatocellular carcinoma: appears to be not increased beyond other causes of cirrhosis ¹⁴

• gallbladder carcinoma

Differential diagnosis

General imaging differential considerations include:

• cirrhosis from other causes

  • caudate lobe not as frequently or as markedly enlarged

  • left lobe usually also hypertrophied

• IgG4-related sclerosing cholangitis

  • these patients tend to be older and more symptomatic with involvement of other systems besides the bile ducts ¹⁷

  • IgG4 levels 4x normal; ratio of IgG4 to immunoglobulin 1 of >0.24 ¹⁷

  • responds to steroid therapy

• secondary sclerosing cholangitis

  • AIDS-associated cholangitis

  • biliary strictures from other causes, e.g. surgery, ischaemia

• cholangiocarcinoma (can also occur as a later complication)

• primary biliary cholangitis

  • especially difficult to distinguish when PSCprimary sclerosing cholangitis is limited to the intrahepatic biliary tree

  • young women more frequently affected

  • high antibody titres ⁴

• Alagille syndrome (arteriohepatic dysplasia)

• hepatic sarcoidosis: see abdominal manifestations of sarcoidosis