US Gastroenterology & Hepatology Review, 2006;(1):1-4
Primary biliary cirrhosis (PBC) is characterized by inflammatory destruction of the small bile ducts within the liver. It is, generally, a slowly progressive disease that leads to cirrhosis of the liver. The cause of PBC is unknown but, primarily because of the presence of specific auto-antibodies in virtually all cases, it is thought to be an autoimmune disease.The disease predominantly affects women at a ratio of approximately 10 to 1.The age of diagnosis is typically between 40 and 60 years. The prevalence of PBC for women and men combined is approximately 30 to 40 per 100,000, based on studies from the US and the UK.1,2 Despite being relatively rare, PBC constitutes an economic burden, resulting in yearly costs of US$69 million to US$115 million dollars for hospital charges alone, as estimated by the Healthcare Cost and Utilization Project (HCUP).3
Etiology
The causes of PBC are unknown. Most investigators presume a genetic predisposition to the disease. Exposure to certain environmental factors in genetically susceptible individuals may then lead to breakdown of immunological tolerance and disease. This is suggested by the results of a recent controlled interview-based epidemiological study of 1,032 patients in the US.4 This study demonstrated that having a first-degree relative with PBC significantly increased an individual’s risk of having the disease. In addition, environmental factors, possibly including infectious agents through urinary tract infections or chemicals contained in cigarette smoke, were associated with the disease.Therefore, it appears that exposure of genetically susceptible individuals to certain environmental agents induces PBC.
Diagnosis
The diagnosis of PBC is based on clinical features, laboratory abnormalities, the presence of auto-antibodies, and liver histology.
Clinical Features
More than 90% of patients with PBC are women. Most present in their middle years, but the diagnosis is sometimes made in older and younger individuals. Perhaps the most common presentation is an abnormal serum alkaline phosphatase activity picked up on routine laboratory testing or during work-up of an unrelated problem. Another common presentation is pruritus (itching), which occurs in approximately 80% of patients with PBC.5 Some patients first present with symptoms of advanced liver disease, including jaundice or problems related to chronic portal hypertension. None of these clinical features are specific for PBC, but their occurrence in women without other obvious causes of cholestatic liver disease are suggestive of the diagnosis.
Laboratory Abnormalities
Virtually all patients with PBC have an abnormally elevated serum alkaline phosphatase activity. As there are other sources of serum alkaline phosphatase, a confirmatory test that the bile ducts are the origin should be performed, such as serum gammaglutamyltranspeptidase (GGT) activity, which will also be elevated. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities are usually normal or only moderately elevated. The serum bilirubin concentration is normal early in the disease, but increases as the disease progresses. Most patients have an elevated serum total cholesterol concentration, which is largely contained in an abnormal lipoprotein, termed lipoprotein X, produced in patients with cholestasis.6 The total gamma-globulin concentration is usually normal until late in the disease when cirrhosis develops. However, almost all patients with PBC have an isolated elevated serum immunoglobulin (Ig)M concentration. The prothrombin time and serum albumin concentration are normal until cirrhosis develops late in the course of disease.
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