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Liver biopsy in primary biliary cholangitis: is sinusoidal fibrosis the missing key?
  1. Thomas Warnes1,
  2. Stephen Roberts2,
  3. Alexander Smith1,
  4. Najib Haboubi3,
  5. Raymond F McMahon4,5
  1. 1 Liver Unit, Department of Gastroenterology, Manchester Royal Infirmary, Manchester, Manchester, UK
  2. 2 Division of Population Health, Health Services Research & Primary Care (L5), University of Manchester, Manchester, UK
  3. 3 Department of Histopathology, Spire Healthcare Trust, Manchester, UK
  4. 4 Department of Histopathology, Manchester Royal Infirmary, Manchester, Manchester, UK
  5. 5 Division of Medical Education, University of Manchester, Manchester, UK
  1. Correspondence to Prof Raymond F McMahon, Histopathology, Manchester Royal Infirmary, Manchester M13 9WL, UK; ray.mcmahon{at}manchester.ac.uk

Abstract

Aims The role of liver biopsy in primary biliary cholangitis (PBC) is controversial, as is the optimal method of histological assessment. We compared the Ludwig and Ishak systems and three components of the Japanese (Nakanuma) staging system to evaluate their clinical and biochemical correlations and prognostic value.

Methods We reviewed biopsies from 106 patients with PBC, derived from a previous trial of colchicine therapy with 24–34 years’ follow-up, following which five clinical outcomes were evaluated: hepatic decompensation, cholestatic PBC death/liver transplant, portal hypertensive PBC death, all PBC deaths and overall survival.

Results Ludwig and Ishak stages correlated well with prognostically significant parameters, including serum bilirubin, and both Mayo and Child Scores. Serum aspartate aminotransferase correlated with interface hepatitis (IFH), and alkaline phosphatase with orcein deposition, bile duct (BD) loss and cholestasis. Ludwig correlated with all five clinical outcomes, while Ishak stage was only significantly correlated with two. While sinusoidal fibrosis, orcein deposition, BD loss and cholestasis all predicted hepatic death/transplant, after correction for Mayo Score, the only histological parameters predictive of clinical outcomes were IFH (associated with two) and sinusoidal fibrosis (associated with all five).

Conclusion Liver biopsy is required in the diagnosis of around 20% of patients with PBC. The Ludwig system is of more prognostic value than both Ishak and any of the three individual components of the Nakanuma staging system, but the major histological parameter providing independent prognostic value beyond the Mayo Score is sinusoidal fibrosis.

  • primary biliary cholangitis
  • liver biopsy
  • histological staging
  • prognosis
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Footnotes

  • Handling editor Runjan Chetty.

  • Contributors TW wrote the manuscript and was responsible for the care and follow-up of the patients in the study and for all aspects of the collection and coordination of the data. SR was responsible for the collation and analysis of the data and contributed to production of the manuscript. AS played a key role in the collection and organisation of the data and contributed to all stages of the project. NH and RFM were responsible for the histopathological analysis and were involved in the design of the study. All the authors participated in the critical revision of the manuscript for all intellectual content.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the hospital ethics committee of Manchester Royal Infirmary.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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