Primary Sclerosing Cholangitis (PSC)

Question 1

PSC

Answer 1

Primary sclerosing cholangitis is a biliary disease of unknown aetiology characterised by inflammation and fibrosis of intra and extra-hepatic bile ducts

Question 2

PSC - Associations

Answer 2

Associations
ulcerative colitis: 4% of patients with UC have PSC, 80% of patients with PSC have UC
Crohn’s (much less common association than UC)
HIV

Question 3

PSC - Features

Answer 3

Features
cholestasis: jaundice and pruritus
right upper quadrant pain
fatigue

Question 4

PSC - Ix

Answer 4

Investigation
ERCP is the standard diagnostic tool, showing multiple biliary strictures giving a ‘beaded’ appearance
ANCA may be positive
there is a limited role for liver biopsy, which may show fibrous, obliterative cholangitis often described as ‘onion skin’

Question 5

PSC - Cx

Answer 5

Complications
cholangiocarcinoma (in 10%)
increased risk of colorectal cancer

Question 6

PSC and UC - Example Question

Answer 6

A 45-year-old man with a 20-year history of ulcerative colitis was reviewed in the inflammatory bowel disease clinic. He opens his bowels once a day with no rectal bleeding. Aside from some fatigue, he is asymptomatic. He had required multiple courses of steroids over the past 4 years due to recurrent flare-ups of his colitis. He had gone into remission a year ago after receiving a course of infliximab. He had a colonoscopy 18 months ago which showed extensive left sided disease with friable mucosa and easy bleeding on contact with the endoscope. A repeat colonoscopy 6 months ago showed improved appearances and evidence of mucosal healing.

Blood tests done in clinic show:

Hb 102 g/l Na+ 139 mmol/l Bilirubin 63 µmol/l
Platelets 275 * 109/l K+ 4.2 mmol/l ALP 350 u/l
WBC 7.5 * 109/l Urea 3.2 mmol/l ALT 55 u/l
Neuts 4.2 * 109/l Creatinine 90 µmol/l γGT 136 u/l
Lymphs 1.2 * 109/l Albumin 33 g/l
INR 1.3

Which is the most appropriate investigation to confirm the cause of this patient’s abnormal LFTs?

Ultrasound liver
CT abdomen
Endoscopic retrograde cholangiopancreatography
> Magnetic resonance cholangiopancreatography
Liver biopsy

This patient has primary sclerosing cholangitis (PSC) which is associated with ulcerative colitis. Although endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance cholangiopancreatography (MRCP) and liver biopsy are all viable methods to diagnose PSC, the question asks for the most appropriate investigation. A MRCP is non-invasive unlike an ERCP and liver biopsy and does not expose the patient to radiation and thus is most appropriate in this case.

Question 7

PSC Diagnosis - Example Question

Answer 7

A 44-year-old male is referred to gastroenterology clinic by his GP. He had attended his GP surgery due to persistent episodes of loose stool. On further questioning, his only other symptom was mild fatigue. He is a non-smoker and his alcohol intake is within the recommended weekly allowance.

On examination his GP noted mild jaundice but no other stigmata of chronic liver disease. Palpation of his abdomen revealed mild hepatomegaly. All other systems were normal. Prior to being referred to clinic, the patient underwent a non-invasive liver screen (NILS). The results are as follows:

Hb 11.0 g/dl
Platelets 175 * 109/l
WBC 9.5 * 109/l

Na+ 139 mmol/l
K+ 4.9 mmol/l
Urea 6.7 mmol/l
Creatinine 87 µmol/l

Bilirubin 52 µmol/l
ALP 389 u/l
ALT 68 u/l
Albumin 40 g/l

Hep B sAg	Negative
Anti-Hep C Ab	Negative
Anti-nuclear Ab	Positive
Anti-mitochondrial Ab	Negative
Auto-smooth muscle Ab	Negative
Serum caeruloplasmin	28mg/dL (20-40mg/dL)
Serum ferritin	490mg/L (15-250mg/L)
Total iron binding capacity	62mmol/L (40-80mmol/L)

Abdominal ultrasound Mild hepatomegaly. Otherwise normal

What is the most likely diagnosis?

	Primary biliary cirrhosis
	Autoimmune hepatitis
	Wilson's disease
	> Primary sclerosing cholangitis
	Haemochromatosis

The mild fatigue, jaundice, abnormal LFTs and hepatomegaly are fairly non-specific and on their own are not enough to answer this question. The positive anti nuclear antibody result points towards an autoimmune pathology but the key is the history of persistent episodes of loose stool. When viewed in combination with the other abnormalities, the suggestion is that this patient is suffering with ulcerative colitis and primary sclerosing cholangitis. These two conditions which are known to be associated, and in combination tie all of the findings together.