Contents
Introduction
Autoimmune, slowly progressive, cholestatic, liver disease characterized by a triad of chronic cholestasis, circulating anti-mitochondrial antibodies (AMA), and characteristic liver biopsy findings.
History:
The first report of the disease dates back 1851 by Addison and Gull who described a clinical picture of progressive jaundice in the absence of mechanical obstruction of the large bile ducts. Ahrens et al. in 1950 published the first detailed description of 17 patients with this condition and coined the term “primary biliary cirrhosis”. In 1959, Dame Sheila Sherlock reported a further series of PBC patients and recognised that the disease could be diagnosed in a pre-cirrhotic stage and proposed the term “chronic intrahepatic cholestasis” as more appropriate description of this disease. However, this nomenclature failed to gain acceptance and the term “primary biliary cirrhosis” lasted for decades. In 2014, to correct the inaccuracy and remove the social stigmata of cirrhosis as well as all the misunderstanding, disadvantages and discrimination emanating from this misnomer in daily life for patients, International liver associations agreed to rename the disease “primary biliary cholangitis”, as it is known nowadays.
Aetiology
Being one of the first conditions in which specific autoantibodies were recognized, PBC is regarded as a “model autoimmune disease. Both environmental factors and inherited genetic predisposition appear to contribute to its pathogenesis

Associated autoimmune disorders:
These disorders generally precede the onset of PBC by about 4 years
- Autoimmune thyroid disorders
- Raynaud syndrome
- Sjogren syndrome
Pathophysiology
It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build up in the liver causing cholestasis. Further slow damage to the liver tissue can lead to scarring, fibrosis, and eventually cirrhosis.
Natural history:


Clinical features
More than half of patients diagnosed today with PBC are asymptomatic at presentation.
- Fatigue (85%): Excessive manganese deposits in globus pallidum, elevated inflammatory cytokines
- Pruritis (70%): Cholestasis, increased opioidergic tone
- Xanthelasma: Hypercholesterolemia and hyperlipidemia
- Osteoporosis: Disturbances in bone remodeling due to metabolic changes in PBC
- Dyslipidemia: Reduction in biliary secretion of cholesterol. Toxic effects of unconjugated bilirubin
- Jaundice (late sign): Cholestasis

Complications
- Oesophageal varices
- Ascites
- Spontaneous bacterial peritonitis
- Hepatorenal syndrome
- Hepatoma formation
Diagnosis
Biochemical tests:
Biochemical markers of cholestasis, particularly alkaline phosphatase, are elevated persistently for more than 6 months in the presence of serum AMA and in the absence of an alternative explanation
- ↑ Serum ALP & γGT (> 6 months)
- ↑ AMA (Anti-mitochondrial antibodies) (M/specific serological marker)
Mayo Risk score:
M/C used and best prognostic system
Mayo Risk score = 0.04 (Age) + 10.87 Loge (Bilirubin) – 22.53 Loge (Albumin) + 12.38 Loge (Prothrombin time) + 10.86 (Edema score)
Liver biopsy:
Histologic hallmark of the disease is a loss of biliary epithelial cells and small intrahepatic bile ducts with portal infiltration of T cells, B cells, macrophages, eosinophils, and natural killer cells
- Nonsuppurative destructive cholangitis
- Interlobular bile duct destruction

Differential Diagnosis
- Primary Sclerosing Cholangitis (PSC)
- AMA (-)
Management
The aim of PBC therapy is to reverse injury from bile duct inflammation to relieve symptoms, prevent disease progression, relieve laboratory abnormalities, and prevent the consequences of chronic cholestasis, including pruritus, fatigue, osteoporosis, and fat-soluble vitamin deficiencies
- Ursodeoxycholic acid (first-line): Protection of cholangiocytes, stimulation of biliary secretions of bile acids
- Corticosteroids (budesonide): Anti-inflammatory, especially useful for interface hepatitis
- Obeticholic acid: Reduces bile acid synthesis, downregulates bile acid uptake proteins
- Fibrates: Activates peroxisome proliferator-activated receptors

Liver transplantation:
Definitive therapy for advanced disease, with about 70% 10-year survival after transplantation.
Management of complications:
- Pruritis: Local skin care, dermatologist referral, avoiding potential pruritogens, cholestyramine, and possibly opioid antagonists, sertraline, or rifaximin
- Osteoporosis: Life-style modifications, calcium and vitamin D, alendronate, statins
- Sjogren’s syndrome: Artificial tears, cyclosporine ophthalmic emulsion (stimulate tear production), saliva substitutes, cholinergic agents, and scrupulous oral and dental care