Sponsored CPD: Diagnosis and management of primary biliary cholangitis

In this sponsored CPD module, head of research and education at the PBC Foundation Rebecca West, GP with special interest in liver disease Dr Helen Jarvis, honorary consultant hepatologist Dr George Mells and professor of liver immunology Professor David Jones provide a concise overview of primary biliary cholangitis (PBC), focusing on key aspects relevant to primary care. Complete the full module on Pulse 365 today.

Learning objectives

This module will extend your knowledge and enable you to:

• Recognise the typical clinical features and key risk factors for PBC in general practice.
• Understand the appropriate initial investigations and diagnostic approach for suspected PBC in primary care.
• Be aware of differential diagnoses when liver blood tests indicate a cholestatic pattern.
• Appreciate the importance of early identification and timely referral to Hepatology or Gastroenterology.
• Understand the general management principles of PBC including medications.
• Appreciate the role of third sector organisations in supporting people with PBC.

What is primary biliary cholangitis?

Primary biliary cholangitis (PBC) is a chronic autoimmune disease of the liver. It was previously known as primary biliary cirrhosis, but the name was changed as this former terminology was considered stigmatising and was erroneous as most patients do not have cirrhosis at presentation. 

It is characterised by progressive destruction of the small bile ducts within the liver. This leads to cholestasis (impaired bile flow), whereby bile acids and other toxic substances build up in the liver, damaging liver cells and eventually causing inflammation, fibrosis and cirrhosis. However, PBC can be regarded as a fully treatable disease provided it is diagnosed early and treated appropriately.

Epidemiology and risk factors

• Frequency: PBC is a rare disease.  In the UK, it has a prevalence of 39.6 cases per 100,000 population and an incidence of 2.47 per 100,000 population per year.  This means the average GP practice in the UK will have fewer than 5 PBC patients under follow-up. 
• Sex: PBC mainly affects women, the ratio being 9:1 (female to male)
• Age: Most people with PBC present between the ages of 35 and 55.
• Genetics: People with a family history of PBC or another autoimmune condition have increased risk of developing the disease.
• Associated conditions: Can coexist with other autoimmune diseases, such as autoimmune hepatitis, Sjögren’s syndrome, thyroid disease, and rheumatoid arthritis.

While the main demographic affected is women aged 35 to 55, both men and younger women are susceptible to PBC. Early diagnosis and treatment are vital to prevent disease progression and mitigate the risk of liver transplantation or premature death.

Clinical presentation and diagnosis in primary care

Common presenting features

PBC can be asymptomatic for many years and is often discovered after an incidental finding of abnormal liver blood tests.

Typical symptoms are as follows:

• Pruritus: This is a common symptom.  There is no rash, other than possible excoriations. Its severity is variable and does not correlate with the stage of disease. It often affects atypical areas such as the scalp, palms or soles. It is often described as deep or subdermal. Excoriations may be present because of scratching.
• Fatigue: Can be distressing and debilitating for patients, affecting their quality of life.
• Sicca syndrome: This consists of dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia). People with sicca syndrome may also have dryness of the skin, vagina, nose and throat.
• Xanthelasmas/xanthomas: Cholesterol deposits around the eyes or skin.
• Right upper quadrant discomfort.

People with advanced PBC can have features of end-stage liver disease, such as jaundice, fluid retention (dependent oedema or ascites) or hepatic encephalopathy.

Initial diagnostic approach

• Consider a diagnosis of PBC when patients present with fatigue or persistent pruritus without a rash, or the patient has abnormal liver function tests (LFTs) showing biochemical evidence of cholestasis (see points below).    
• Where PBC is a consideration, check LFTs (total bilirubin, alanine transaminase [ALT], alkaline phosphatase [ALP] and albumin).    
• In PBC, LFTs are abnormal with a cholestatic pattern, meaning the ALP is disproportionately elevated. In people with isolated elevation of ALP, check gamma glutamyl-transferase (GGT) to confirm that the elevated ALP is hepatobiliary in origin.     
• People with abnormal LFTs should have an ultrasound scan to look for biliary duct dilatation or a focal liver lesion, and a non-invasive liver screen to look for different causes of liver disease.
• In people with PBC, the ultrasound scan shows no focal liver lesions or biliary duct dilatation, and the non-invasive liver screen typically shows anti-mitochondrial antibodies (AMA).
• Antimitochondrial antibodies: These are present in 90-95% of PBC patients. They are highly sensitive and specific for the disease. A small proportion of PBC patients will be AMA negative. There are several variations of this test that different labs will use, including the ‘M2 antibody’. These all have the same significance.

It is important to also consider other possible causes of cholestatic liver enzyme elevation, including (but not restricted to):

• Drug-induced liver injury.
• Gallstones or bile duct obstruction.
• Primary sclerosing cholangitis (PSC).
• Sarcoidosis or amyloidosis.

Management principles

Patients with suspected PBC (or persistently abnormal LFT of unclear cause) should be referred to a Hepatologist or Gastroenterologist with an interest in liver disease.  In secondary care, the diagnosis of PBC is confirmed based on persistent elevation of ALP combined with positive AMA. A liver biopsy is needed to confirm the diagnosis in AMA-negative cases. In patients with confirmed PBC, the goals of management are as follows:

• Delay progression of PBC.
• Avoid or postpone cirrhosis and/or its complications.
• Alleviate symptoms and enhance quality of life.

In secondary care, patients will be managed with disease-modifying medication, symptomatic control through lifestyle, nutrition and medications, and appropriate treatment of related conditions.

The British Society of Gastroenterology (BSG), UK-PBC, and the PBC Foundation have produced a PBC care bundle providing a standardised approach to care, aimed at ensuring patients receive consistent and evidence-based management regardless of where they are seen in the NHS.

Rebecca West is head of research and education at the PBC Foundation; Dr Helen Jarvis is a GP with specialist clinical and academic interest in liver disease and liver lead at the Primary Care Society for Gastroenterology; Dr George Mells is clinical senior lecturer, Newcastle University and honorary consultant hepatologist, Newcastle upon Tyne Hospitals NHS Foundation Trust; and Professor David Jones is consultant honorary hepatologist and professor of liver immunology at Newcastle University