Primary Sclerosing Cholangitis (PSC): Symptoms, Causes, Treatment, Diagnosis, Etiology, Epidemiology, and Complications

source:www.hopkinsmedicine.org

Definition of primary sclerosing cholangitis:

is a chronic, progressive, inflammatory disease of unknown etiology, that affect the biliary ducts of middle and large size intra- and extrahepatic.

This will lead to destruction of bile ducts, with the following complications:

-        Liver cirrhosis

-        Cholangitis/cholelithiasis

-        Cholangiocarcinoma

PSC is seen in 5% in patients with colitis ulcerosa, respectively up to 90% of patients with PSC have colitis ulcerosa.

Etiology:

The most plausible explanation for the pathogenesis of PSC is immunologic priming in a genetically pre-disposed individual.

Epidemiology:

USA 1-16/100000

60-70 % men at the age of 30-40

Clinical manifestation:

Most patients are asymptomatic at die Diagnosis. Clinical manifestations are mostly fatigue and pruritus.

Fever, chills, upper abdominal pain, night sweets may refer to complications such as cholangitis.

Diagnosis:

Laboratory:

-        Elevated liver function tests: with a cholestatic pattern (elevated APH, gGT and Direct Bilirubin), Transaminases usually don’t exceed 300 U/l

-        Autoimmune antibodies may be present with a low clinically significance:

1-     Hypergammaglobulinemia – 30%

2-     Increased serum IgM levels – 40-50%

3-     P-ANCA – 30-80%

4-     IgG4 in Autoimmune pancreatitis compared with PSC in 50%

5-     AMA is usually absent in PSC (and characteristic of primary biliary cirrhosis)

-        Signs of malabsorption:

1-     Vitamin A deficiency in 80%

2-     Vitamin E and D deficiency in 50%

3-     Vitamin K deficiency

Radiomorphology:

-        Characteristic and diagnostic are multifocal strictures and dilations in the bile ducts in ERCP, MRCP (intra-, extra- or intra- and extrahepatic)

-        Less common can just shallow ulcerations of bile ducts in early stages

-        Less common in (small-duct- PSC) with no strictures, but similar histological and biochemical findings.

Liver Biopsy:

Support the diagnosis but rarely diagnostic! it is to be recommended in patients with highly suspected PSC without typical radiological findings

Histologic can typically be seen:

-        fibrous obliteration of small bile ducts, with concentric replacement by connective tissue in an "onion skin" pattern

Differential Diagnosis:

Other causes of cholestasis such as:

-        PBC

-        Choledocholithiasis

-        bacterial cholangitis

-        carcinomas

-        autoimmune pancreatitis associated with stricturing of the pancreaticobiliary tract and elevated serum levels of IgG4: sclerosing pancreatocholangitis.

-        Autoimmunhepatitis: Further testing for autoimmune hepatitis is recommended for patients <25 years of age with PSC or those with higher-than-expected levels of aminotransferases usually 5 × upper limits of normal.

Therapy:

1-     UDCA (ursodeoxycholicacid) in doses 10-15 mg/kg/Day: it helps biochemical improvement with unclear clinical improvement.

2-     ERCP with balloon dilation by dominant strictures or Cholangitis/ Cytology is to be taken by dominate strictures to exclude malignancy/ Antibiotics prophylaxe is recommended for ERCP

3-     Biliary reconstruction by biliary-enteric drainage allows prolonged clinical improvement, with resolution of jaundice and cholangitis, but has a significant risk of cholangitis and increased rates of mortality

4-     Liver transplantation: referral to Liver-transplantation should be taken when MELD-Score>13

Prognosis:

Is a progressive disease that may end with end-stage liver failure and liver transplantation

Median survival without liver transplantation after diagnosis is 10 to 12 years. Survival is significantly worse for patients who are symptomatic at the time of diagnosis

Complications:

1-     Pruritus:

-         Mild pruritus may be treated with skin emollients and possibly antihistamines.

-         severe pruritus is best managed by bile acid sequestrants, such as cholestyramine 4–16 g/day is needed to maintain symptom control

-        Second-line therapies include rifampin, 50–300 mg twice daily (liver tests and serum bilirubin should be monitored during rifampin therapy to evaluate for hepatotoxicity), naltrexone (up to 50 mg/day), sertraline (75–100 mg per day) or phenobarbital (90 mg at bedtime) 

2-     fat-soluble vitamin deficiency K, E, D, A

3-     steatorrhea

4-     metabolic bone disease with osteoporosis/osteopenia:

-         Patients are advised to undergo weight-bearing exercise

-         calcium and vitamin D supplementation.

-         BMD is performed at diagnosis and every 2–4 years thereafter.

-         The role of bisphosphonates for the treatment of osteoporosis in PSC is not proven. 

9-     cholangitis/ cholelithiasis

10-  dominant biliary strictures:

-        up to 60% of Patients, 

-        One definition of a dominant stricture is stenosis with a diameter of ≤1.5 mm in the common bile duct or ≤1 mm in the hepatic ducts,

-        it is to be differentiated from cholangiocarcinoma, thus it is recommended to do biliary brush cytology

11-  cholangiocarcinoma:

-        Consider screening for cholangiocarcinoma with ultrasound or MR and serial CA 19-9 every 6–12 months

12-  Gallen bladder cancer:

-        Cholecystectomy should be performed for patients with PSC and gallbladder polyps >8 mm, to prevent the development of gallbladder adenocarcinoma.

13-  Hepatocellular carcinoma