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PRIMARY SCLEROSING CHOLANGITIS

Department of Medicine

Definition

• Primary Sclerosing Cholangitis = a chronic progressive disorder of unknown etiology that is characterized by inflammation, fibrosis, and stricturing of medium and large ducts in the intrahepatic and/or extrahepatic biliary tree

Epidemiology

• Incidence rate 1 case per 100,000 person-years• 70% (men)• 90% with PSC also have Ulcerative Colitis• 10% with Ulcerative Colitis have PSC

Risk Factors

• Male gender• Inflammatory bowel disease (ulcerative colitis > crohn’s)• First-degree relatives of patients with PSC

Pathogenesis

• Unknown etiology however likely that immunologically-mediated bile duct injury is a major mechanism leading to PSC

Symptoms

• Fatigue• Pruritus• Jaundice• Episodic cholangitis symptoms (biliary obstruction)

– Fevers– Chills– Night sweats– right upper quadrant pain

• 50% asymptomatic – diagnosed during investiation for abnormal LFT’s

Signs

• Excoriations• Jaundice• Hepatomegaly• Splenomegaly

• 50% Normal Physical Exam

Differential Diagnosis

• Alcoholic liver disease• Nonalcoholic fatty liver disease• Viral Hepatitis

– Chronic hepatitis C– Chronic hepatitis B

• Autoimmune hepatitis• Primary sclerosing cholangitis• Medications

– Methotrexate– Amiodarone– isoniazid

• Hereditary– Hereditary hemochromatosis– Wilson disease– Alpha-1-antitrypsin deficiency

investigations

Abnormal LFT’s “cholestatic pattern”• Elevated alkaline phosphatase• Elevated 5'-nucleotidase• Elevated gammaglutamyl transpeptidase• Normal or Slightly elevated ALT (< 300 IU)• Normal or Slightly elevated AST (< 300 IU)• Elevated bilirubin

• Liver Ultrasound– abnormal bile ducts

• Cholangiogram– multifocal stricturing and dilation of intrahepatic and/or extrahepatic bile ducts

• magnetic resonance cholangiopancreatography (MRCP) (1st line)• endoscopic retrograde cholangiopancreatography (ERCP) (2nd line)• percutaneous transhepatic cholangiography (PTC) (3rd line)

Investigation

Investigations

• liver biopsy (Not Indicated For Diagnosis)– staging the disease– determining prognosis

PSC Histology

Stage Zero Normal Liver

Stage one Enlargement, edema, and scarring of the portal triads

Stage two Expansion of portal triads with fibrosis extending into the surrounding parenchyma

Stage three Bridging fibrosis

Stage four Cirrhosis

Investigations

Screening• Annual Abdominal Ultrasound

– gallbladder (Gallbladder carcinoma)– liver (Cholangiocarcinoma)

• carcinoembryonic antigen (CEA)• CA 19-9 • Annual Colonscopy (Colorectal carcinoma)• 2 yearly DEXA bone density Scan

If cirrhosis• Annual α-Feto protein (Hepatocellular Carcinoma)• Annual Liver Ultrasound (Hepatocellular carcinoma)

Treatment

Pruritis / Jaundice• No proven role for medical therapy• Endoscopic treatment of dominant strictures dilate and/or stent

• Liver transplantation

Complications

• Fat soluble vitamin deficiencies (A, D, E, and K)• Metabolic bone disease• Cholangitis and cholelithiasis• Cholangiocarcinoma• Gallbladder cancer• Hepatocellular carcinoma (in patients with cirrhosis)• Colon cancer (in patients with concomitant ulcerative colitis)

Prognosis

• Median survival without liver transplantation after diagnosis is 10 to 12 years

References

• Tung, BY, Brentnall, T, Kowdley, KV, et al. Diagnosis and prevalence of ulcerative colitis in patients with sclerosing cholangitis. Hepatology. 1996; 24:169

• UpToDate• American Association for the Study of Liver diseases Guidelines 2010

Sample MCQ

A 60 year old man with a history of 15 year ulcerative colitis, presents to his family doctor with 3 month progressive history of fatigue, pruritus, jaundice. On examination he has scratch marks on his arms and abdomen, scleral icterus, hepatomegaly and splenomegaly. His Liver function tests are abnormal with elevated Bilirubin, elevated alkaline phosphatase and yGT but normal ALT / AST. What is the most likely investigation to identify the underlying condition?

a)Anti-mitochondrial antibody

b)Hepatitis B Serology

c)HIV Serology

d)Liver Biopsy

e)MRCP

Answer = e

A 60 year old man with a history of 15 year ulcerative colitis, presents to his family doctor with 3 month progressive history of fatigue, pruritus, jaundice. On examination he has scratch marks on his arms and abdomen, scleral icterus, hepatomegaly and splenomegaly. What treatment is most appropriate given the scenario above

a)Cholestyramine

b)Liver transplantation

c)Naltrexone

d)Rifampicin

e)Ursodeoxycholic acid

Answer = b

Sample MCQ

A 60 year old man with a history of 15 year ulcerative colitis, presents to his family doctor with 3 month progressive history of fatigue, pruritus, jaundice. On examination he has scratch marks on his arms and abdomen, scleral icterus, hepatomegaly and splenomegaly. Which is the most appropriate imaging to diagnose Primary Sclerosing Cholangitis?

a)ERCP

b)MRCP

c)PTC

d)US Abdomen

e)CT Abdomen

Answer = b

Sample MeQ

A 60 year old man with a history of 15 year ulcerative colitis, presents to his family doctor with 3 month progressive history of fatigue, pruritus, jaundice. On examination he has scratch marks on his arms and abdomen, scleral icterus, hepatomegaly and splenomegaly.

a)Name 5 differential Diagnosis of primary sclerosing cholangitis ( 5 marks)

See slide 8

b)List 4 complications of primary sclerosing cholangitis ( 4 marks)

See slide 14

c)Name 2 treatment options for Primary sclerosing cholangitis ( 4 marks)

Endoscopic treatment of dominant strictures dilate and/or stent

Liver transplantation

d)Name 1 autoimmune test that distinguishes primary sclerosing cholangitis from primary biliary cirrhosis ( 3 marks)

Anti-mitochondrial antibody