Elsevier

The Lancet

Volume 348, Issue 9039, 23 November 1996, Pages 1399-1402
The Lancet

Articles
Natural history of early primary biliary cirrhosis

https://doi.org/10.1016/S0140-6736(96)04410-8Get rights and content

Summary

Background

In 1986, we reported a group of 29 patients who were positive in serum for antimitochondrial antibody (AMA), the disease-specific marker for primary biliary cirrhosis (PBC), but who had normal liver function test results and no symptoms of liver disease. However, liver histology was diagnostic or compatible with PBC in 24 patients and normal in only two. The aims of this 10-year follow-up study were to establish whether patients with AMA have very early PBC, to assess the outlook for such patients, and to follow the progression of the disease.

Methods

All patients were assessed every year at our PBC clinic: records were reviewed, cause of death verified when applicable, and current clinical and biochemical data collected, including repeat liver histology as indicated. Serum samples from the original study were located. Original and follow-up serum samples were tested by ELISA for E2 components of pyruvate dehydrogenase complex and 2-oxoglutarate dehydrogenase complex.

Findings

Five patients died during follow-up; no deaths were attributable to liver disease. Median follow-up of patients who survived was 17·8 years (range 11·0–23·9) from firstdetected AMA to the last follow-up review. Overall, 22 (76%) developed symptoms of PBC and 24 (83%) had liver function tests persistently showing cholestasis. Repeat liver biopsy samples were obtained from ten patients; among these patients PBC progressed from Scheuer grade 1 to grade 2 in two and from grade 1 to grade 3 in two. No patient developed clinically apparent cirrhosis. ELISA of baseline serum samples from 27 patients was positive in 21, all of whom had original liver histology compatible with or diagnostic of PBC. Of the six patients who tested negative, only one had an original liver biopsy sample that was compatible with PBC.

Interpretation

This study confirms that before the advent of any clinical or biomedical indications, individuals positive for AMA do have PBC. This finding extends the natural history of PBC back in some cases for many years. What determines the eventual progression to biochemically and clinically apparent disease is not yet understood. During our study no patient developed clinically apparent portal hypertension or cirrhosis. Thus, although the finding of a solitary persistently raised AMA is confirmation of a diagnosis of PBC, patients with AMA but no other signs or symptoms of PBC seem to have slow progression of the disease.

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.

Section snippets

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)

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