Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a progressive chronic inflammation of both the intrahepatic and extrahepatic bile ducts. While the exact etiology is unknown, there is a strong association with autoimmune diseases, particularly ulcerative colitis (UC). In the early stages, PSC is usually asymptomatic. Later in the course of the disease, patients present with symptoms of cholestasis (e.g., pruritus, jaundice). Laboratory abnormalities include elevated liver function tests and autoantibodies (pANCA in up to 80% of cases). Magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) is performed to confirm the diagnosis. Management is primarily symptomatic, with liver transplantation reserved for end-stage liver disease.

• Sex: ♂ > ♀ (2:1)
• Age: The median age at diagnosis is ∼ 40.

References:^[1]

Epidemiological data refers to the US, unless otherwise specified.

• Associations
  • Chronic inflammatory bowel diseases (IBD)
    • ∼ 90% of PSC patients have IBD (from these patients, 87% have ulcerative colitis (UC) and 13% have Crohn's disease
    • However, only ∼ 5% of patients with UC and < 5% of patients with Crohn's disease develop PSC.
  • HLA-B8 and HLA-DR3
  • Other autoimmune conditions (e.g., hypergammaglobulinemia IgM)

The majority of PSC patients also have ulcerative colitis! References:^[2][3][1][4]

• Often initially asymptomatic
• Signs of cholestasis
  • Jaundice/scleral icterus
  • Pruritus
  • Fatigue
  • Acute cholangitis (fever, chills, right upper quadrant pain)
• Later stages: signs of cirrhosis
  • Hepatomegaly
  • Portal hypertension
  • Liver failure
• Symptoms of chronic inflammatory bowel disease, which is frequently associated with PSC, or other associated comorbidities

References:^[2][3]

Laboratory findings

• Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) are present in up to 80% of cases
• ↑ ALP, GGT, conjugated bilirubin
• Potentially, ↑ transaminases (however, they are usually < 300 U/L)
• Hypergammaglobulinemia in approx. 30% of cases
• ↑ Serum immunoglobulin M (IgM) in approx. 45% of cases

Imaging

• Cholangiography
  • Method of choice: magnetic resonance cholangiopancreatography (MRCP)
  • Alternatives
    • Endoscopic retrograde cholangiopancreatography (ERCP)
      • More invasive but also more accurate than MRCP
      • Good alternative for patients who cannot undergo MRI testing (e.g., patients with pacemaker)
    • Percutaneous transhepatic cholangiography (PTC)
      • Most invasive test
      • For patients who cannot undergo ERCP
  • Findings: multifocal strictures alternating with dilation and beading of bile ducts
• Ultrasound
  • Irregular diameter of the bile duct
  • Diffuse thickening of the wall of the common hepatic and bile ducts
• Following diagnosis → colonoscopy (to assess for UC)

Liver biopsy

• Not an essential part of the workup; usually done if small duct PSC is suspected, which is not always detectable via cholangiography
• Typical finding: "onion skin" scarring and fibrosis of bile ducts
• Antibiotics (e.g., ciprofloxacin) can be given before the procedure to decrease the risk of developing consecutive cholangitis.

If a patient with pre-existing chronic inflammatory bowel disease displays increased ALP, GGT, and conjugated bilirubin, always consider PSC!References:^[1][3][2][4]

Differential diagnoses of primary cholangitis
	Primary sclerosing cholangitis	Primary biliary cholangitis
Epidemiology	More common among middle-aged men	More common among middle-aged women
Pathophysiology	Progressive chronic inflammation of both intrahepatic and extrahepatic bile ducts	Progressive destruction of only intrahepatic small and medium-sized bile ducts
Clinical presentation	Pruritus Fatigue Jaundice Hepatomegaly	Similar to PSC Potentially xanthomas and xanthelasma
Laboratory tests	pANCA ↑ ALP, GGT, and conjugated bilirubin	Anti-mitochondrial antibodies (AMA) ↑ ALP, GGT, and conjugated bilirubin
Associated conditions	Ulcerative colitis and cholangiocarcinoma	Autoimmune conditions

The differential diagnoses listed here are not exhaustive.

• Symptomatic
  • Ursodeoxycholic acid and immunosuppressives (e.g., tacrolimus): may decrease transaminases, ALP, and serum bilirubin, but do not prevent disease progression
  • Treatment of pruritus (e.g., cholestyramine, rifampicin, naltrexone)
  • Supplementation of fat-soluble vitamins (see “Complications” below)
  • In the case of bile duct stenosis: ERCP with duct dilation; potentially, stent placement
• Surgical: Liver transplantation is the only curative option and is performed in the case of advanced liver cirrhosis.

References:^{[5][6][7][8][3]}

• Steatorrhea and deficiency of fat-soluble vitamins
• Liver cirrhosis
• Cholangiocarcinoma (∼ 10–15% of cases)
• Increased risk of hepatocellular, colorectal, pancreatic, and gallbladder cancer

References:^[2]

We list the most important complications. The selection is not exhaustive.