Dataset Information

SHG/TPEF-based image technology improves liver fibrosis assessment of minimally sized needle biopsies.

ABSTRACT:

Background and aims

Sampling size variability of liver biopsy remains a major limitation in the assessment of liver fibrosis. We aimed to evaluate the diagnostic value of a fully quantitative method (second harmonic generation/two-photon excitation fluorescence, SHG/TPEF based) in "short" liver biopsy samples.

Methods

Liver biopsy samples from chronic hepatitis B (CHB) patients were constructed into "virtual" biopsies with different lengths. The original and "virtual" samples were measured by SHG/TPEF-based technology to obtain qFibrosis score, respectively. Here, ?qFibrosis was defined as difference of qFibrosis between original biopsy and "virtual" biopsy. Equivalence test was used to compare ?qFibrosis with the clinically acceptable error (deviation of 0.50) in each group.

Results

In real-world practice, qFibrosis score increased significantly with fibrosis progression in???1.5-cm-, 1.0-1.5-cm-, and 0.5-1.0-cm-long specimens (p??0.05). In virtual biopsy samples with specified length, the equivalence was confirmed in 0.5-1.0-cm- and 1.0-1.5-cm-long specimens (0.27 vs. 0.22, p??0.05). The number of cross-linked collagen fibers, the total and aggregated collagen proportionate area, and the collagen strings in number, length, width and perimeter showed excellent consistency with original biopsy samples in 0.5-1.0-cm- and 1.0-1.5-cm-long specimens (ICC?>?0.90).

Conclusions

The use of SHG/TPEF-based image technology may give useful suggestive information in evaluation of CHB-related liver fibrosis for the short sample (biopsy length?>?0.5 cm).

SUBMITTER: Wang B

PROVIDER: S-EPMC6661026 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

SHG/TPEF-based image technology improves liver fibrosis assessment of minimally sized needle biopsies.

Wang Bingqiong B Sun Yameng Y Zhou Jialing J Wu Xiaoning X Chen Shuyan S Shi Yiwen Y Wu Shanshan S Liu Hui H Ren Yayun Y Ou Xiaojuan X Jia Jidong J You Hong H

Hepatology international 20190611 4

<h4>Background and aims</h4>Sampling size variability of liver biopsy remains a major limitation in the assessment of liver fibrosis. We aimed to evaluate the diagnostic value of a fully quantitative method (second harmonic generation/two-photon excitation fluorescence, SHG/TPEF based) in "short" liver biopsy samples.<h4>Methods</h4>Liver biopsy samples from chronic hepatitis B (CHB) patients were constructed into "virtual" biopsies with different lengths. The original and "virtual" samples were ...[more]

PMID: 31187402

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Project description:UNLABELLED: BACKGROUND:The possibility of extracting RNA and measuring RNA expression from paraffin sections can allow extensive investigations on stored paraffin samples obtained from diseased livers and could help with studies of the natural history of liver fibrosis and inflammation, and in particular, correlate basic mechanisms to clinical outcomes. RESULTS:To address this issue, a pilot study of multiplex gene expression using branched-chain DNA technology was conducted to directly measure mRNA expression in formalin-fixed paraffin-embedded needle biopsy samples of human liver. Twenty-five genes were selected for evaluation based on evidence obtained from human fibrotic liver, a rat BDL model and in vitro cultures of immortalized human hepatic stellate cells. The expression levels of these 25 genes were then correlated with liver fibrosis and inflammation activity scores. Statistical analysis revealed that three genes (COL3A1, KRT18, and TUBB) could separate fibrotic from non-fibrotic samples and that the expression of ten genes (ANXA2, TIMP1, CTGF, COL4A1, KRT18, COL1A1, COL3A1, ACTA2, TGFB1, LOXL2) were positively correlated with the level of liver inflammation activity. CONCLUSION:This is the first report describing this multiplex technique for liver fibrosis and has provided the proof of concept of the suitability of RNA extracted from paraffin sections for investigating the modulation of a panel of proinflammatory and profibrogenic genes. This pilot study suggests that this technique will allow extensive investigations on paraffin samples from diseased livers and possibly from any other tissue. Using identical or other genes, this multiplex expression technique could be applied to samples obtained from extensive patient cohorts with stored paraffin samples in order to correlate gene expression with valuable clinically relevant information. This method could be used to provide a better understanding of the mechanisms of liver fibrosis and inflammation, its progression, and help development of new therapeutic approaches for this indication.

Project description:Technologies for digitizing tissues provide important quantitative data for liver histopathology investigation. We aimed to assess liver fibrosis degree with quantitative morphometric measurements of histopathological sections utilizing digital image analysis (DIA) and to further investigate if a correlation with histopathologic scoring (Scheuer staging) exists. A retrospective study of patients with at least two post-liver transplant biopsies having a Scheuer stage of ? 2 at baseline were gathered. Portal tract fibrotic percentage (%) and size (?m2) were measured by DIA, while clinical fibrosis score was measured by the Scheuer system. Correlations between DIA measurements and Scheuer scores were computed by Spearman correlation analysis. Differences between mean levels of fibrosis (score, size, and percentage) at baseline versus second visit were computed by Student's t-test. P values < 0.05 were considered significant. Of 22 patients who met the study criteria, 54 biopsies were included for analysis. Average levels ±standard error [S.E.] of portal tract fibrotic percentage (%) and size (?m2) progressed from 46.5 ± 3.6% at baseline to 61.8 ± 3.8% at the second visit (P = 0.005 by Student's t-test), and from 28,075 ± 3,232 ?m2 at base line to 67,146 ± 10,639 ?m2 at the second visit (P = 0.002 by Student's t-test), respectively. Average levels of Scheuer fibrosis scores progressed from 0.55±0.19 at baseline to 1.14±0.26 at the second visit (P = 0.02 by Student's t-test). Portal tract fibrotic percentage (%) and portal tract fibrotic size were directly correlated with clinical Scheuer fibrosis stage, with Spearman correlation coefficient and P value computed as r = 0.70, P < 0.0001 and r = 0.41, P = 0.002, respectively. Digital quantitative assessment of portal triad size and fibrosis percentage demonstrates a strong correlation with visually assessed histologic stage of liver fibrosis and complements the standard assessment for allograft monitoring, suggesting the utility of future WSI analysis.

Dataset Information

SHG/TPEF-based image technology improves liver fibrosis assessment of minimally sized needle biopsies.

Background and aims

Methods

Results

Conclusions

Publications

SHG/TPEF-based image technology improves liver fibrosis assessment of minimally sized needle biopsies.

Similar Datasets

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