Primary biliary cirrhosis (PBC)
Ongoing autoimmune damage to the intralobular bile ducts causing liver failure.
5 per 100 000 population per annum.
20–80 years, mean age 50 years.
Associated with other autoimmune disorders and also HLA-DR8 haplotype. Antibodies to mitochondria are present; however, their exact role in pathogenesis is unclear as titres do not correlate with disease.
Environmental triggers suggested include enterobacteria such as E. coli.
Chronic inflammation of the small intrahepatic bile ducts leads to cholestasis and destruction of bile ducts. This leads on to portal tract fibrosis and cirrhosis. Duct epithelium in the pancreas, salivary and lacrimal glands are also affected.
Up to half of patients are asymptomatic at diagnosis. Patients may complain of fatigue and pruritus, followed some months later by jaundice. Any sign of liver disease may be present, such as clubbing, hepatomegaly, spider naevi, xanthomata. Asymptomatic patients are discovered through abnormal biochemical findings or during investigation of another autoimmune disorder such as thyroiditis.
Throughout the disease, copper accumulates due to the chronic cholestasis.
Stage I: Lymphocytic infiltration of small bile ducts and portal tracts with occasional granuloma formation.
Stage II: More widespread inflammation in the periportal parenchyma, leading to loss of bile ducts.
Stage III: Fibrous septa extend between triads and form fibrous bridges (bridging necrosis).
Stage IV: Cirrhosis with absent bile ducts, scarring, distorted architecture and nodular regeneration.
Oesophageal varices, osteoporosis, osteomalacia, pancreatic hyposecretion, renal tubular acidosis (possibly copper induced).
Increased risk of hepatocellular carcinoma and breast cancer.
Associated with many other disorders, such as Sjogren’s,¨ hypothyroidism, systemic lupus erythematosus, scleroderma, dermatomyositis.
Definitive diagnosis is made on liver biopsy. Anti-mitochondrial antibodies (AMA) are present in >99%. Raised alkaline phosphatase suggests damage to bile ducts. Raised cholesterol and raised total IgM are also found.
Supportive treatment involves ursodeoxycholic acid (which helps the pruritus), calcium and vitamin supplementation, management of complications such as varices, hyperlipidaemia. The disease may recur after liver transplantation.
Asymptomatic patients may have a normal life expectancy. In symptomatic patients advancing age, hep-atomegaly, high bilirubin, low albumin and cirrhosis correlate with shortened survival (5–7 years in severe disease).