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Cited by 421Liver Diseases and ImmunityPediatric Hepatobiliary Diseases and TreatmentsLiver Disease Diagnosis and Treatment

Natural history of early primary biliary cirrhosis

Metcalf, Jane V, Mitchison, Harriet C, Palmer, Jeremy M, Jones, David E, Bassendine, Margaret F, James, Oliver FW·1996·The Lancet
DOI 10.1016/s0140-6736(96)04410-8
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Abstract

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 first-detected 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.

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  • Cohort studies from the 1980s showed that such AMA-positive patients with normal LFTs had a high frequency of biliary features of PBC on liver biopsy, and the majority went on to develop classical PBC over prolonged follow-up (although notably not advanced liver disease).

    “Cohort studies from the 1980s showed that such AMA-positive patients with normal LFTs had a high frequency of biliary features of PBC on liver biopsy, and the majority went on to develop classical PBC over prolonged follow-up (although notably not advanced liver disease).83 84”

    From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [83]

  • Over 18 years of follow-up, none of the AMA+ normal LFT patients developed cirrhosis, needed transplant or died of PBC.

    “Over 18 years of follow-up, however, none developed cirrhosis, needed transplant or died of PBC.267”

    From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [267]

  • Patients positive for anti-mitochondrial antibodies and with normal alkaline phosphatase levels did not progress to cirrhosis after 17.8 years.

    “patients positive for anti-mitochondrial antibodies and with normal alkaline phosphatase levels did not progress to cirrhosis after 17•8 years 85”

    From Primary biliary cholangitis. (2024) · cites this paper as [85]

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Authors
Metcalf, J. V., Mitchison, H. C., Palmer, J. M., Jones, D. E., Bassendine, M. F., & James, O. F.
Affiliations
  • Newcastle University (GB)
  • City Hospitals Sunderland NHS Foundation Trust (GB)
Corresponding author
James, Oliver FW
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
1996-11
Volume
348
Issue
9039
Pages
1399-1402
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(96)04410-8
OpenAlex
W2159434940
Cited by
421
References
8
Citations by year
2026: 4 · 2025: 7 · 2024: 8 · 2023: 6 · 2022: 9 · 2021: 10 · 2020: 9 · 2019: 11 · 2018: 18 · 2017: 16 · 2016: 10 · 2015: 13 · 2014: 20 · 2013: 13 · 2012: 24
FWCI
7.51
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust
Topics
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
  • Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Keywords
primary biliary cirrhosis, antimitochondrial antibodies, natural history (disease), disease progression, cholestasis, liver histopathology, pyruvate dehydrogenase complex, 2-oxoglutarate dehydrogenase, long-term follow-up, portal hypertension
MeSH terms
Adult, Aged, Aged, 80 and over, Autoantibodies, Autoantigens, Cause of Death, Enzyme-Linked Immunosorbent Assay, Follow-Up Studies, Humans, Ketoglutarate Dehydrogenase Complex, Liver, Liver Cirrhosis, Biliary, Liver Function Tests, Middle Aged, Pyruvate Dehydrogenase Complex, Cohort Studies, Biomarkers, Disease Progression

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