Article Text

Download PDFPDF
Quantifying and monitoring fibrosis in non-alcoholic fatty liver disease using dual-photon microscopy
  1. Yan Wang1,
  2. Grace Lai-Hung Wong2,3,
  3. Fang-Ping He4,
  4. Jian Sun1,
  5. Anthony Wing-Hung Chan5,
  6. Jinlian Yang1,
  7. Sally She-Ting Shu2,3,
  8. Xieer Liang1,
  9. Yee Kit Tse2,3,
  10. Xiao-Tang Fan6,
  11. Jinlin Hou1,
  12. Henry Lik-Yuen Chan2,3,
  13. Vincent Wai-Sun Wong2,3
  1. 1 State Key Laboratory of Organ Failure Research, Guangdong Provincial Research Center for Liver Fibrosis, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
  2. 2 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
  3. 3 State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
  4. 4 Department of Infectious Diseases, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
  5. 5 Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China
  6. 6 Department of Hepatology, The First Affliated Hospital of Xinjiang Medical University, Urumqi, China
  1. Correspondence to Dr Vincent Wai-Sun Wong, Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, Hong Kong; wongv{at}cuhk.edu.hk

Abstract

Objective Fibrosis stage is strongly associated with liver-related outcomes and is a key surrogate endpoint in drug trials for non-alcoholic steatohepatitis. Dual-photon microscopy allows automated quantification of fibrosis-related parameters (q-FPs) and may facilitate large-scale histological studies. We aim to validate the performance of q-FPs in a large histological cohort.

Design 344 patients with non-alcoholic fatty liver disease (NAFLD) underwent 428 liver biopsies (240 had paired transient elastography examination). Fibrosis stage was scored using the NASH Clinical Research Network system, and q-FPs were measured by dual-photon microscopy using unstained slides. Patients were randomly assigned to the training and validation cohorts to test the performance of individual q-FPs and derive optimal cut-offs.

Results Over 25 q-FPs had area under the receiver-operating characteristics curves >0.90 for different fibrosis stages. Among them, the perimeter of collagen fibres and number of long collagen fibres had the highest accuracy. At the best cut-offs, the two q-FPs had 88.3%–96.2% sensitivity and 78.1%–91.1% specificity for different fibrosis stages in the validation cohort. q-FPs and histological scoring had nearly identical correlations with liver stiffness measurement, suggesting that the accuracy of q-FPs approached that of histological assessment. Among patients with paired liver biopsies, changes in the same q-FPs were associated with changes in fibrosis stage. At a median follow-up of 5.6 years, baseline q-FPs predicted liver-related events.

Conclusion q-FP is highly accurate in the assessment of fibrosis in NAFLD patients. This automated platform can be used in future studies as objective and reliable evaluation of histological fibrosis.

  • non-alcoholic steatohepatitis
  • liver fibrosis
  • cirrhosis
  • liver biopsy
View Full Text

Statistics from Altmetric.com

Footnotes

  • Contributors YW and VW-SW designed the study. GL-HL-HW, SS and VW-SW (HK cohort), and FH and X-TF (Urumqi cohort) collected the clinical data. YW and JY performed dual-photon microscopy. AWHC evaluated and scored all liver biopsy samples. YKT and VW-SW performed statistical analysis. YW, YKT and VW-SW drafted the manuscript. JS, XL, JH and HLYC provided administrative support. All authors contributed to and approved the final version of the manuscript.

  • Funding This study was partly supported by the National Natural Science Foundation of China (81670522) to YW and the Guangzhou Science and Technology Plan Project (201607020019) to JH.

  • Competing interests VW-SW has served as an advisor/consultant for AbbVie, Allergan, Echosens, Gilead Sciences, Janssen, Novo Nordisk, Perspectum Diagnostics, Pfizer and Terns; and a speaker for Bristol-Myers Squibb, Echosens, Gilead Sciences and Merck. GL-HL-HW and HLYC have served as speakers for Echosens. The other authors report no conflict of interests.

  • Patient consent for publication Not required.

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

  • Data availability statement Data are available upon reasonable request.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.