Digital quantitation of bridging fibrosis and septa reveals changes in natural history and treatment not seen with conventional histology

IF 6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver International Pub Date : 2024-09-09 DOI:10.1111/liv.16092

Nikolai V. Naoumov, David E. Kleiner, Elaine Chng, Dominique Brees, Chandra Saravanan, Yayun Ren, Dean Tai, Arun J. Sanyal

{"title":"Digital quantitation of bridging fibrosis and septa reveals changes in natural history and treatment not seen with conventional histology","authors":"Nikolai V. Naoumov, David E. Kleiner, Elaine Chng, Dominique Brees, Chandra Saravanan, Yayun Ren, Dean Tai, Arun J. Sanyal","doi":"10.1111/liv.16092","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background and Aims</h3>\n \n <p>Metabolic dysfunction-associated steatohepatitis (MASH) with bridging fibrosis is a critical stage in the evolution of fatty liver disease. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence (AI) provides sensitive and reproducible quantitation of liver fibrosis. This methodology was applied to gain an in-depth understanding of intra-stage fibrosis changes and septa analyses in a homogenous, well-characterised group with MASH F3 fibrosis.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Paired liver biopsies (baseline [BL] and end of treatment [EOT]) of 57 patients (placebo, <i>n</i> = 17 and tropifexor <i>n</i> = 40), with F3 fibrosis stage at BL according to the clinical research network (CRN) scoring, were included. Unstained sections were examined using SHG/TPEF microscopy with AI. Changes in liver fibrosis overall and in five areas of liver lobules were quantitatively assessed by qFibrosis. Progressive, regressive septa, and 12 septa parameters were quantitatively analysed.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>qFibrosis demonstrated fibrosis progression or regression in 14/17 (82%) patients receiving placebo, while the CRN scoring categorised 11/17 (65%) as ‘no change’. Radar maps with qFibrosis readouts visualised quantitative fibrosis dynamics in different areas of liver lobules even in cases categorised as ‘No Change’. Measurement of septa parameters objectively differentiated regressive and progressive septa (<i>p</i> < .001). Quantitative changes in individual septa parameters (BL to EOT) were observed both in the ‘no change’ and the ‘regression’ subgroups, as defined by the CRN scoring.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>SHG/TPEF microscopy with AI provides greater granularity and precision in assessing fibrosis dynamics in patients with bridging fibrosis, thus advancing knowledge development of fibrosis evolution in natural history and in clinical trials.</p>\n </section>\n </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"44 12","pages":"3214-3228"},"PeriodicalIF":6.0000,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16092","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Liver International","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/liv.16092","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background and Aims

Metabolic dysfunction-associated steatohepatitis (MASH) with bridging fibrosis is a critical stage in the evolution of fatty liver disease. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence (AI) provides sensitive and reproducible quantitation of liver fibrosis. This methodology was applied to gain an in-depth understanding of intra-stage fibrosis changes and septa analyses in a homogenous, well-characterised group with MASH F3 fibrosis.

Methods

Paired liver biopsies (baseline [BL] and end of treatment [EOT]) of 57 patients (placebo, n = 17 and tropifexor n = 40), with F3 fibrosis stage at BL according to the clinical research network (CRN) scoring, were included. Unstained sections were examined using SHG/TPEF microscopy with AI. Changes in liver fibrosis overall and in five areas of liver lobules were quantitatively assessed by qFibrosis. Progressive, regressive septa, and 12 septa parameters were quantitatively analysed.

Results

qFibrosis demonstrated fibrosis progression or regression in 14/17 (82%) patients receiving placebo, while the CRN scoring categorised 11/17 (65%) as ‘no change’. Radar maps with qFibrosis readouts visualised quantitative fibrosis dynamics in different areas of liver lobules even in cases categorised as ‘No Change’. Measurement of septa parameters objectively differentiated regressive and progressive septa (p < .001). Quantitative changes in individual septa parameters (BL to EOT) were observed both in the ‘no change’ and the ‘regression’ subgroups, as defined by the CRN scoring.

Conclusion

SHG/TPEF microscopy with AI provides greater granularity and precision in assessing fibrosis dynamics in patients with bridging fibrosis, thus advancing knowledge development of fibrosis evolution in natural history and in clinical trials.

Abstract Image

查看原文本刊更多论文

对桥接纤维化和隔膜进行数字量化，可以发现自然病史和治疗方面的变化，而传统组织学检查则无法发现这些变化。

背景和目的：代谢功能障碍相关性脂肪性肝炎（MASH）伴有桥接纤维化是脂肪肝演变的关键阶段。带有人工智能（AI）的二次谐波发生/双光子激发荧光（SHG/TPEF）显微镜可对肝纤维化进行灵敏且可重复的量化。该方法用于深入了解同质、特征明确的 MASH F3 肝纤维化群体中肝纤维化的阶段内变化和隔膜分析：根据临床研究网络（CRN）的评分，57名患者（安慰剂17人，托吡酯40人）的肝脏活组织切片（基线[BL]和治疗结束[EOT]）在基线时处于F3纤维化阶段。使用SHG/TPEF显微镜和AI对未染色切片进行检查。用 qFibrosis 定量评估肝纤维化的整体变化和肝小叶五个区域的变化。结果：qFibrosis显示，14/17（82%）名接受安慰剂治疗的患者纤维化进展或退缩，而CRN评分将11/17（65%）名患者归类为 "无变化"。即使在被归类为 "无变化 "的病例中，带有qFibrosis读数的雷达图也能显示肝小叶不同区域的定量纤维化动态。隔膜参数的测量客观地区分了退行性隔膜和进行性隔膜（p 结论）：带人工智能的SHG/TPEF显微镜能更精细、更精确地评估桥接性肝纤维化患者的纤维化动态，从而促进自然史和临床试验中纤维化演变知识的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.