21st April 2024

Disorders of the biliary system

Primary biliary cholangitis

Primary biliary cholangitis (PBC) is an autoimmune disease which damages the biliary epithelial cells, causing cholestatic liver injury, and can eventually lead to liver cirrhosis. For PBC, remember the “Rule of Ms” – middle aged females, raised IgM, and anti-mitochondrial antibody positive (M2 subtype is highly specific) in the majority of patients. It affects females to males at a 9:1 ratio.

Features

The classic presentation is itching and fatigue in a middle-aged female. Other features may include right upper quadrant pain, xanthelasma, clubbing, hepatosplenomegaly, and clinical signs of liver cirrhosis if advanced disease. There is a high association with other autoimmune conditions such as Sjogren’s, rheumatoid arthritis, systemic sclerosis, and thyroid disease.

Diagnosis

• MRCP to exclude extrahepatic biliary obstruction
• Liver screen bloods – presence of anti-mitochondrial antibodies is highly specific for PBC
• Note that many patients will have a raised ANA titre as for many autoimmune conditions

Management

• Ursodeoxycholic acid is virtually the only licensed medication shown to slow progression of PBC and is first line
• Cholestyramine is often used for itch (sequestrates bile acid salts in the enteric lumen, preventing reabsorption)
• Fat soluble vitamin supplementation
• Many need transplantation if the disease progresses to end-stage liver disease

Complications

• Cirrhosis and portal hypertension (ascites, varices, splenomegaly)
• Osteomalacia and osteoporosis
• Increased risk HCC (20x increased risk)

Primary Sclerosing Cholangitis

Primary Sclerosing Cholangitis (PSC) is heavily associated with Ulcerative Colitis. It causes inflammation and scarring of intra and extra hepatic ducts, leading to cholestasis, bile duct strictures and hepatic fibrosis, which may eventually cause features associated with cirrhosis and portal hypertension (ascites, varices etc). It classically presents as jaundice and itch. Patients will have a raised ALP and gamma GT. 4% of patients with UC have PSC, whilst approximately 80% of patients with PSC have UC. It is also associated with Crohn’s, but to a much lesser degree. There is also an association between PSC and HIV.

Features

PSC is often asymptomatic in the early stages of the disease. Patients may be diagnosed incidentally (i.e. abnormal liver biochemistry found incidentally, leading to further investigation). In later stages of the disease, patients may present with one or more of the following: right upper quadrant pain, itch, fatigue, raised bilirubin/jaundice, fever, or unintentional weight loss. Patients also often have a raised ALP and gamma-GT. A raised bilirubin is a marker of a poorer prognosis.

There is a high risk of colorectal cancer in patients with PSC and colitis. There is also a high risk of cholangiocarcinoma in patients with PSC who have not undergone liver transplantation.

Diagnosis

• MRCP is the first line and will show beaded appearance of the biliary tree
• ERCP is reserved for patients who may need endoscopic intervention, e.g. biliary dilatation or tissue sampling

Management

• There is no licensed drug therapy for PSC (note that ursodeoxycholic acid is not recommended, nor are immunosuppressants such as steroids)
• Cholestyramine for symptomatic relief of pruritus
• Must investigate for underlying colitis with colonoscopy and biopsy (colonic)
• Liver transplant if advanced disease and suitable candidate
• Fat soluble vitamin supplementation
• Screen for osteoporosis

Ascending Cholangitis

Ascending cholangitis is caused by bacterial infection of the biliary tree. The most common cause is E. coli. The biggest predisposing factor is gallstones. Charcot’s triad occurs in many patients (right upper quadrant pain, fever, and jaundice). Reynold’s pentad includes the addition of hypotension and confusion.

Features

Commonly, features include Charcot’s triad, deranged LFTs and the patient is often unwell.

Diagnosis

• Abdominal ultrasound to look for biliary dilation is the most common initial investigation

Management

• Adequate resuscitation with IV antibiotics and IV fluids
• ERCP once the patient is stable enough for definitive management (usually within 24 – 48 hours of presentation) to relieve obstruction or CBD stones/debris
• Percutaneous transhepatic cholangiogram (PTC) may be done if the patient is unfit for ERCP

References

• British Medical Journal.(2022) Chronic pancreatitis. [Online]. BMJ Best Practice. Last Updated: May 2022. Available at: https://bestpractice.bmj.com/topics/en-gb/67 [Accessed 4 October 2022]
• British Medical Journal (30 August 2022) Dubin-Johnson syndrome. [Online] BMJ Best Practice. Last Updated: 30 August 2022. Available at: https://bestpractice.bmj.com/topics/en-gb/1151 [Accessed 7 February 2023]
• British Medical Journal (6 September 2022) Gilbert syndrome. [Online] BMJ Best Practice. Last Updated: 6 September 2022. Available at: https://bestpractice.bmj.com/topics/en-gb/346 [Accessed 7 February 2023]
• British Medical Journal (11 November 2022) Pancreatic Cancer. [Online]. BMJ Best Practice. Last Updated: 11 November 2022. Available at: https://bestpractice.bmj.com/topics/en-gb/265 [Accessed 7 February 2023]
• Chapman MH, Thorburn D, Hirschfield GM, et al. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut 2019;68:1356-1378
• Farrugia A, Arasaradnam R. Bile acid diarrhoea: pathophysiology, diagnosis and management. Frontline Gastroenterology 2021;12:500-507
• Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut 2018;67:1568-1594
• Liang Y, Yang Z, Zhong R. Primary biliary cirrhosis and cancer risk: a systematic review and meta-analysis. Hepatology. 2012 Oct;56(4):1409-17