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Common variable immunodeficiency disorder (CVID)-related liver disease: assessment of the main histological aspects using novel semiquantitative scoring systems, image analysis and correlation with clinical parameters of liver stiffness and portal hypertension
  1. Hiroshi Silva1,
  2. Camila Gabriela Xavier de Brito1,
  3. Andrew Hall1,2,
  4. Nadia Eden2,3,
  5. Henry Somers2,3,
  6. Niall Burke2,3,
  7. Siobhan O Burns4,5,
  8. David Lowe4,5,
  9. Douglas Thorburn2,3,
  10. Neil Halliday2,3,
  11. Alberto Quaglia1,3
  1. 1Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, UK
  2. 2Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
  3. 3Institute for Liver and Digestive Health, University College London, London, UK
  4. 4Institute of Immunity and Transplantation, University College London, London, UK
  5. 5Department of Immunology, Royal Free London NHS Foundation Trust, London, UK
  1. Correspondence to Dr Camila Gabriela Xavier de Brito, Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, NW3 2QG, UK; camila.xbrito{at}


Aims We aimed to investigate the relationship between T-cell-mediated sinusoidal injury, nodular regenerative hyperplasia like changes (NRH-LC) and fibrosis, clinical measures of fibrosis and portal hypertension, and progression rate in common variable immunodeficiency disorder (CVID)-related liver disease.

Methods This is a retrospective single-centre study. Liver biopsies from CVID patients with liver disease were reviewed to assess for NRH-LC, fibrosis and elastosis, including collagen and elastin proportionate areas. CD3 positive T-cells infiltration and sinusoidal endothelial changes by CD34 expression were quantified by image analysis and a semiquantitative method, respectively. These findings were correlated with liver stiffness measurements (LSM) and hepatic venous pressure gradient (HVPG).

Results NRH-LC and pericellular elastosis were present in most biopsies (32/40 and 38/40, respectively). All biopsies showed fibrosis, which was limited to pericellular in 21/40 (52.5%) and included bridging fibrous septa in 19/40 (47.5%). 28/40 liver biopsies showed enhanced sinusoidal expression of CD34. There were more CD3 positive cells in biopsies with NRH-LC compared with those without. There was no significant correlation between LSM, HVPG and fibrosis/elastosis scores. Five of seven patients with at least two biopsies showed progression in fibrosis stage.

Conclusions NRH-LC and fibrosis in CVID patients often coexist along with the presence of sinusoidal endothelial changes and sinusoidal lymphocytic infiltration. Fibrosis progresses over time, and significant fibrosis can be observed in young patients (<30 years old), potentially reflecting a more aggressive form of CVID-related liver disease. Further studies are necessary to investigate the relationship between histological findings, clinical measures of fibrosis and portal hypertension and outcome.

  • fibrosis
  • Immune System Diseases

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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  • HS and CGXdB are joint first authors.

  • Handling editor Yoh Zen.

  • Contributors HSilva and AQ conceived the study design. HSilva, CGXdB and AQ reviewed and scored all slides; HSilva and CGXdB acquired and analysed data and contributed equally as co-first authors to drafting the manuscript, AH performed image analysis, immunohistochemistry and contributed to the writing and revising of the manuscript. NE, HSomers, NB, SOB, DL, NH and DT collected clinical data. NH was involved in interpretation of results, editing the manuscript and contributing to data analysis. AQ, NH and DL critically reviewed the manuscript. AQ is responsible for the overall content as the guarantor. All authors revised the content and have approved the final version for publication.

  • 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 declared.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.