ArticlesNatural history of early primary biliary cirrhosis
Introduction
Patients who have liver function test results showing cholestasis and who are positive for antimitochondrial antibody (AMA) would generally be diagnosed as having primary biliary cirrhosis (PBC), irrespective of the presence or absence of liver-related symptoms.1 Long-term follow-up studies2, 3, 4, 5, 6, 7 have confirmed that in up to two thirds of initially symptom-free patients with cholestasis, AMA, and a liver histology biopsy sample compatible with or diagnostic of PBC, the remaining characteristic of the classic clinical picture of PBC (liver-related symptoms) will appear within 5 years. The consensus has been that once symptoms have developed the outlook for a patient will be similar to that for any other patient with symptomatic PBC and will be associated with the same prognostic indicators8.
The earliest stage of PBC and the implications of the presence of AMA when there are no symptoms of liver disease or abnormality of liver function are little understood. Do patients with AMA but no other signs have very early PBC, and if so, what is their outlook and the expected progression of the disease? In 1986, we reported 29 patients who were positive for AMA and had normal liver function and no symptoms of liver disease; liver histology was diagnostic of or compatible with PBC in 24 and normal in only two.9 To answer the questions posed above we now report 10-year follow-up of this cohort.
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Methods
Seven of the 29 patients had been referred to the liver clinic at Freeman Hospital, Newcastle upon Tyne, UK, for investigation of an incidental finding of positive AMA tests during investigations for other diseases. The other 22 were found by examination of all antibody screen results at the Northern Regional Immunology Laboratory, between 1970 and 1984, to seek individuals with positive AMA results (reciprocal titre ⩾40 by indirect immunofluorescence). Full clinical, biochemical,
Results
Table 1, Table 2 show follow-up data for all patients. Of the 29 patients in the original study, five (17%) had died (patients 1, 2, 4, 9, and 11). The median time from first positive AMA test to death was 11·7 years (range 6·4–16·8) and median age at death was 78·0 years (72·1–83·6). No death was attributable to liver disease. Patient 1 died of lung cancer, patient 2 of breast cancer, patient 4 of cricoid cancer, patient 9 of heart failure, and patient 11 of pneumonia.
The median follow-up of
Discussion
This study offers new evidence about the early natural history of PBC and confirms the hypothesis that individuals who are repeatedly AMA positive, but who have normal liver biochemistry and no symptoms of the disease, do have very early PBC, which will progress to classic PBC in most cases.2, 9 Our findings show a development from those of our earlier paper,12 in which we suggested that such patients may never develop PBC. However, the progression of PBC in our cohort was slow. Of the ten
References (17)
- et al.
Symptom development and prognosis in primary cirrhosis: a study in two centres.
Gastroenterology
(1990) - et al.
Updating prognosis in primary biliary cirrhosis using a time dependent Cox regression model.
Gastroenterology
(1993) - et al.
Primary biliary cirrhosis: quantitation of autoantibodies to purified mitochondrial enzymes and correlation with disease progression.
Gastroenterology
(1990) - et al.
Primary biliary cirrhosis—identification of two major M2 mitochondrial autoantigens.
Lancet
(1988) - et al.
Presentation and course of asymptomatic primary biliary cirrhosis.
Gastroenterology
(1977) - et al.
Primary biliary cirrhosis: clinicopathological characteristics and outcome
J Gastroenterol Hepatol
(1990) - et al.
Primary biliary cirrhosis: survival of a large cohort of symptomatic and asymptomatic patients followed for 24 years.
J Hepatol
(1994) - et al.
The prognostic importance of clinical and histological features in asymptomatic and primary biliary cirrhosis.
N Engl J Med
(1983)
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