SeminarPrimary biliary cirrhosis
Section snippets
Prevalence
Estimates of disease prevalence vary between 20 and 240 cases per million population and for incidence between 4 and 30 per million per year.1 These variations are partly due to differences in methodology, but may reflect true variations in disease prevalence. PBC is reported only rarely in Africa and the Indian subcontinent. Clustering of cases has been reported. The reported incidence of PBC is increasing—eg, in northeast England, from 11·3/million per year between 1976 and 1980 to
Presentation
The commonest presenting symptom is pruritus, affecting about half the patients. Non-specific symptoms such as lethargy and right-upper-quadrant pain are the presenting symptoms in one quarter, and symptoms of hepatic decompensation (jaundice, ascites, variceal haemorrhage) in about 20%. Whereas itching is more common in men, the progression of disease is similar in the two sexes. Some patients present in pregnancy. On examination the patient may have skin pigmentation and scratch marks.
Prognosis
The increasing use of liver transplantation for patients with end-stage PBC has highlighted the need for accurate assessment of a patient's prognosis. Early studies demonstrated that serum bilirubin is a prognostic marker:23 once the serum bilirubin exceeds 170 μmol/L, the estimated survival is less than 18 months. Several more sophisticated models have been developed and validated, based on the retrospective application of Cox regression analysis to patients. The most widely used is the Mayo
Pathogenesis
The pathogenesis of PBC remains uncertain. The disease has been considered as an example of autoimmunity.26 Histological evidence suggests the involvement of immune mechanisms since most lymphocytes are CD4 but occasionally CD8 cells and B cells are seen. There is an increase in γδ T cells in the portal tracts. Analysis of liver-derived T-cell clones shows a slight preponderance of Th1 cells and considerable heterogeneity of the T-cell-receptor Vβ usage. The damaged bile-duct cells over-express
Symptoms and their treatment
Patients should be treated symptomatically; when there is cholestasis, fat-soluble vitamins (A, D, and K) should be given and fat malabsorption may be helped by the use of medium-chain triglycerides. Here I discuss only three symptoms of PBC: pruritus, lethargy, and bone disease.
Medical
In the absence of a known pathogenesis it is difficult to define a logical strategy for therapy. The long natural history of PBC and variable progression make adequate prospective studies difficult to do. The earlier trials used death as the end-point, but the increasing use of transplantation in some patients has invalidated this approach and alternative, surrogate, end-points have not been critically validated. Many therapies have been tried for the treatment of PBC (panel 3), but the fact
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