Primary sclerosing cholangitis

Primary sclerosing cholangitis

Description, Causes and Risk Factors:

Abbreviation: PSC.

Primary sclerosing cholangitis is a chronic cholestatic syndrome of unknown origin mostly found in males, and characterized by diffuse inflammation and fibrosis of both intra- and extra-hepatic bile ducts. So far, primary sclerosing cholangitis is considered as an autoimmune hepatobiliary disease.

The mean age at diagnosis is 40 years and men are affected about two times more than women. The natural history of the disease is variable from patient to patient although in most cases the progression towards liver failure is slow but irreversible. Currently, primary sclerosing cholangitis is the fifth most common indication for liver transplantation in the U.S., but in the Nordic countries, primary sclerosing cholangitis is the most important indication for orthotopic liver transplantation (OLT).

The prevalence of primary sclerosing cholangitis is currently unknown. About 75% are associated with inflammatory bowel disease (IBD), especially ulcerative colitis (UC). This theory is based on the frequent association of primary sclerosing cholangitis with IBD, especially UC. The combined activity of detergent bile acid with bacteria in a diseased colon may result in an increased mucosal permeability. The presence of bacteria and/or their toxins, and the increased concentration of potentially toxic bile acids in the portal vein may cause Kupffer cell (phagocytic cells of the mononuclear phagocyte series found on the luminal surface of the hepatic sinusoids) activation to produce TNF (tumor necrosis factor). Overproduction of TNF may ultimately result in bile duct inflammation and hepatobiliary lesions leading to portal fibrosis and primary sclerosing cholangitis.

The strong association of primary sclerosing cholangitis with a series of autoimmune diseases underscores the role of immunological alterations in the pathophysiology of the disease. Moreover, specific autoantibodies can be found in patients with primary sclerosing cholangitis i.e. antineutrophil cytoplasmic antibodies (p-ANCA), anticolon antibodies, antineutrophil nuclear antibodies with a high frequency, while anti-mitochondrial auto-antibodies (AMA), anti-nuclear auto-antibodies (ANA), anti-smooth muscle auto-antibodies (ASMA) with a lower frequency. Circulating immune complexes are found in as many as 80% of patients. Other immunological abnormalities may include hypergammaglobulinemia (30%), high serum IgM (50%), decreased circulating T cells, increased ratio of CD4:CD8, and decreased C3. At histology, it is possible to find lymphocytic.

Secondary causes may include:


  • Choledocholithiasis.

  • Diffuse intrahepatic metastasis.

  • Eosinophilic cholangitis.

  • Hepatic in?ammatory pseudotumor.

  • Histiocytosis X

  • IgG4-associated cholangitis.

  • Intra-arterial chemotherapy.

  • Ischemic cholangitis.

  • Mast cell cholangiopathy.

  • Portal hypertensive biliopathy.

  • Recurrent pancreatitis.

  • Recurrent pyogenic cholangitis.

  • Surgical biliary trauma.

In most cases the progression of primary sclerosing cholangitis towards liver cirrhosis and liver failure is slow but irreversible, and liver transplantation is currently the only definitive treatment.


Many people with primary sclerosing cholangitis do not get symptoms, especially in the early stages of the disease. When symptoms do occur the most common are fatigue, pruritus, or intense itching of the skin, and jaundice, a yellowing of the skin and eyes. These symptoms may come and go, but they may worsen over time. As the disease continues, the bile ducts may become infected, which can lead to episodes of fever, chills and abdominal pain.

In children, symptoms are highly variable. Patients often do not have symptoms but showliver function blood test abnormalities or an enlarged liver. Alternately, pediatric patientsmay present with fatigue, itching, fever, intermittent jaundice or weight loss. Whenprogression to cirrhosis is rapid, patients may show evidence of portal hypertension,including accumulations of abdominal fluid (ascites), esophageal bleeding, and enlargedspleen.

Other Findings:

Hypergammaglobulinemia occurs in one third of the patients with primary sclerosing cholangitis and IgM levels are increased in 50% of advanced cases. Other immunological changes include a decrease in circulating T cells and increased ratio of CD4 to CD8.

In the end stages, primary sclerosing cholangitis results in biliary cirrhosis, portal hypertension, and is associated with bile duct carcinoma with a high frequency (8%).


Diagnosis of primary sclerosing cholangitis may be difficult, especially at early stages,since patients are asymptomatic or poorly symptomatic.Diagnostic steps must include clinical assessment, laboratorytests, imaging, and histology. The ultimate diagnosis of primary sclerosing cholangitis requires that all secondary causes of cholangitis are ruled out,namely bacterial infections (chronic and acute, secondary tosurgery or to acquired immunodeficiency syndromes),abnormalities of the biliary tree, ischemic bile duct damage, and neoplasms.


Since the etiology and pathogenesis of primary sclerosing cholangitis are still unknown, establishing treatment strategies is difficult. Treatments should ultimately improve symptoms and aim to improve survival.

Studies using ursodeoxycholic acid (UDCA) and immunosuppressant therapy in combination shown some improvement and need further analysis.

Intense itching is often associated with primary sclerosing cholangitis and other cholestatic liver diseases. Some of the medications used to treat pruritus associated with cholestasis. These medications may include:

    Hydroxyzine (Atarax).

  • Ursodiol (Actigall, URSO).

  • Cholestyramine (Questran).

  • Rifampin (rifampicin).

  • Naltrexone (ReVia).

People with advanced primary sclerosing cholangitis are often deficient in the fat soluble vitamins A, D, E, K and replacement can be given. In osteoporosis, physical exercise and maintenance of adequate calcium and vitamin D be sufficient in the early stages.

Recurrent bacterial cholangitis should be treated with broad spectrum antibiotics.

Finally, liver transplant is an option in the treatment of primary sclerosing cholangitis for those who develop advanced disease. It is difficult to evaluate these patients with regard to timing of transplantation as disease course is unpredictable. At least 20% of patient undergoing liver transplantation development of recurrent sclerosing cholangitis within 5 years. Inflammatory bowel disease symptoms may become more severe post transplant.

NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.


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