Primary Biliary Cholangitis

Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is an autoimmune disease that primarily affects the liver. It is characterised by the slow, progressive destruction of the small bile ducts within the liver, leading to cholestasis, where bile and other toxins build up. This can result in scarring, fibrosis, and eventually cirrhosis.

Signs and Symptoms

PBC commonly presents with fatigue, which affects about 80% of patients and can significantly impact quality of life. Itching (pruritus) is another frequent symptom, occurring in 20-70% of cases, and can be intermittent and severe, particularly at night. Other symptoms include jaundice, dry skin, and dry eyes. Advanced cases may lead to complications such as ascites, enlarged spleen, oesophageal varices, and hepatic encephalopathy. Patients may also exhibit xanthelasma or xanthoma due to increased cholesterol levels. PBC is often associated with other autoimmune disorders like Sjögren's syndrome, thyroid disease, and rheumatoid arthritis.

Causes

PBC is classified as an autoimmune disorder, with more than 90% of patients displaying antimitochondrial antibodies (AMAs) against the pyruvate dehydrogenase complex (PDC-E2). Genetic predisposition plays a role, as evidenced by familial cases and concordance in identical twins. Environmental factors, such as the association with the Gram-negative bacterium Novosphingobium aromaticivorans, may also contribute. The exact mechanism involves cross-reactions between bacterial proteins and mitochondrial proteins in liver cells.

Diagnosis

Most diagnoses occur during routine blood tests revealing abnormal liver enzymes, particularly elevated gamma-glutamyl transferase (GGT) and alkaline phosphatase. The presence of AMAs is a hallmark, being found in 90-95% of patients. Liver biopsy can help confirm the diagnosis, especially when specific antibodies are absent or when other liver conditions are suspected. Imaging studies like ultrasound, MRCP, or CT scans are used to rule out other causes of biliary obstruction.

Treatment

Cholestasis

The primary treatment for PBC is ursodeoxycholic acid (UDCA), which improves liver enzyme levels, slows disease progression, and enhances liver transplant-free survival. For those unresponsive or intolerant to UDCA, obeticholic acid (OCA) is an option, acting as a farnesoid X receptor agonist to increase bile flow. Fibric acid derivatives, such as bezafibrate and fenofibrate, are also used, particularly in cases with inadequate response to UDCA.

Itching

Pruritus is commonly managed with anion-exchange resins like cholestyramine, colestipol, or colesevelam. If ineffective, alternative treatments include rifampicin, naltrexone, or sertraline. Care must be taken with rifampicin due to potential liver toxicity and drug interactions.

Other Therapies

• Fatigue: No specific therapies are licenced for PBC-related fatigue, but structured management and exercise programmes can help.
• Vitamin Supplementation: Patients may require supplementation for fat-soluble vitamins (A, D, E, and K).
• Osteoporosis Management: Regular screening and treatment are necessary due to the elevated risk.
• Liver Transplant: This remains the only curative therapy for advanced liver disease, with favourable outcomes.

Prognosis

The prognosis for PBC has improved with the use of UDCA. Patients who respond well to UDCA have a survival rate similar to the general population. However, those with persistent abnormal liver biochemistry on treatment have a poorer prognosis. The risk of hepatocellular carcinoma is relatively low but higher in non-responders and males. Post-liver transplant, recurrence rates are significant but manageable.

Epidemiology

PBC is more prevalent in women, with a female-to-male ratio of up to 9:1, and typically manifests between the ages of 30 and 60. Prevalence rates vary globally, with higher rates observed in North America and Northern Europe. Genetic and environmental factors contribute to its occurrence, and there is a notable familial predisposition.

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Self-assessment MCQs (single best answer)

What is the primary characteristic of Primary Biliary Cholangitis (PBC)?

Which of the following symptoms is most commonly associated with PBC?

What is the primary treatment for PBC?

Which antibody is commonly found in more than 90% of PBC patients?

Which environmental factor has been associated with PBC?

What is the purpose of using obeticholic acid (OCA) in PBC treatment?

Which condition is PBC often associated with?

What is the long-term curative option for advanced liver disease in PBC patients?

Which imaging study is commonly used to rule out other causes of biliary obstruction in PBC diagnosis?

What is a possible complication of advanced PBC?