Primary Sclerosing Cholangitis

A 38-year-old English male was investigated after he was found to have an abnormal liver function test during a health insurance medical check. He worked in an information technology firm. Apart from occasional fatigue he was well. He consumed less than 20 units of alcohol per week. The patient had only traveled out of Europe twice and on both occasions he had been to North America. He took very infrequent paracetamol for aches and pains in his ankles and knees. There was no history of hepatitis or transfusion or blood products. He had been married for 5 years.
Systemic inquiry revealed infrequent episodes of loose stool for almost 4 years.
On examination he appeared well. There were no stigmata of chronic liver disease.
Abdominal examination revealed a palpable liver edge 3 cm below the costal margin. There were no other masses.
Examination of the central nervous system was normal.
Investigations were as shown.

• Hb 12.6 g/dl ,WCC 8 109/l ,Platelets 210 109/l, MCV 90 fl
• Sodium 136 mmol/l, Potassium 4.1 mmol/l
• Urea 6 mmol/l , Creatinine 100 mmol/l 
• AST 60 iu/l (NR 10–40 iu/l) , ALT 78 iu/l (NR 5–30 iu/l)
• Alkaline phosphatase 350 iu/l (NR 25–100 iu/l)
• Bilirubin 22 mmol/l (NR 2–17 μmol/l)
• Albumin 38 g/l (NR 34–48 g/l)
• Total cholesterol 5.2 mmol/l , Triglyceride 3.1 mmol/l
• Blood glucose 6 mmol/l
• Ferritin 256 mg/l (NR 15–250 mg/l) , Serum Fe 28 mmol/l( NR 14–32 mmol/l) , TIBC 50 mmol/l (NR 40–80 mmol/l)
• Serum Slightly reduced caeruloplasmin , 24-hr urine copper Slightly elevated
• IgG 19 g/l (NR 7–18 g/l), IgA 4.2 g/l (NR 0.8–4.0 g/l) ,IgM 5.0 g/l (NR 0.4–2.5 g/l)
• Anti-nuclear Positive 1/32 antibodies ,Smooth muscle Not detected antibodies,  Antimitochondrial Not detected antibodies
• Hep B sAg Not detected , Hep C virus Not detected antibodies
• Abdominal ultrasound Normal

What is the most probable diagnosis?
a. Autoimmune hepatitis.
b. Primary sclerosing cholangitis.
c. Primary biliary cirrhosis.
d. Haemochromatosis.
e. Wilson’s disease.

Answer:

b. Primary sclerosing cholangitis.

Explanation: This is a relatively difficult question. The history of loose stool is crucial in making the diagnosis in this particular case in the absence of data from the ERCP. Diarrhoea and biochemical evidence of cholestasis (alkaline phosphatase greater than transaminases) should lead to the clinical suspicion of primary sclerosing cholangitis (PSC).

The aetiology of PSC is unknown but immunological destruction of intra- and extra-hepatic bile ducts is the main pathological feature. 90% of PSC is associated with inflammatory bowel disease, particularly ulcerative colitis, and hence the importance of the intermittent diarrhoea. Ulcerative colitis is the most frequent association with primary sclerosing cholangitis. A raised alkaline phosphatase level in a patient with ulcerative colitis (in the absence of bone disease) should raise the possibility of PSC. The frequency of PSC is inversely proportional to the severity of ulcerative colitis. Other associations of PSC include coeliac disease.

Clinical features: Patients with PSC may be asymptomatic at presentation but can present with advanced liver disease. Fatigue and pruritus are common complaints as with the other cholestatic disorders. Approximately one-fifth of the patients also complain of right upper quadrant pain.

The diagnosis is confirmed with ERCP that shows strictures within biliary ducts.

Complications are those of chronic cholestasis, notably statorrhoea, fat-soluble vitamin malabsorption, large biliary strictures, cholangitis, cholangiocarcinoma and colonic carcinoma.

Treatment:  There are no effective pharmacological agents that greatly retard the progression of the disorder. Patients are treated with cholestyramine to reduce pruritus. Fat-soluble vitamin supplementation is necessary owing to steatorrhoea. Antibiotic prophylaxis during instrumentation of the biliary tree is mandatory to reduce the risk of bacterial cholangitis. Ciprofloxacin is the prophylactic antibiotic drug of choice prior to ERCP. Biliary stenting may improve biochemistry and symptoms; however, the  definitive treatment for PSC is hepatic transplantation.


Brief Explanation Of Other choices in the question:
Although a cholestatic picture is also recognized in primary biliary cirrhosis, alcohol abuse and viral hepatitis there is nothing in the history or investigations to indicate these conditions as the cause of his illness.
Primary biliary cirrhosis affects mainly females in the fifth decade onwards. Furthermore, the absence of anti-mitochondrial antibodies is against the diagnosis.
The ferritin is modestly raised but not high enough to suggest hereditary haemochromatosis. High ferritin levels are also a feature of chronic viral hepatitis, alcohol-related hepatitis and non-alcoholic steato-hepatitis.
 Hyper gammaglobulinaemia and raised autoantibody titres are features of primary sclerosing cholangitis but also occur in other immunological liver disorders such as chronic active viral hepatitis, auto-immune hepatitis and biliary cirrhosis.
Patients with cholestasis also have lowish caeruloplasmin levels and increased blood and urine copper levels. The abnormal copper metabolism in this case should not lead to the candidate diagnosing Wilson’s disease, since there are many features above to indicate PSC. Furthermore, patients with Wilson’s disease usually have a hepatitic biochemistry picture and often have coexisting
neuro-psychiatric disease.