Dataset Information

Liver Stiffness Values in Persons with Normal Histology.

ABSTRACT:

Background and aims

Most studies to date have focused on liver stiffness measurement (LSM) in patients with different chronic liver diseases, and normal LSM is defined based on normal liver function tests or the absence of fibrosis. Very few studies have defined LSM based on completely normal liver biopsies. The current study was done to define the distribution of LSM values in individuals with normal liver biopsies.

Methods

All prospective liver donors presenting to Medanta, the Medicity hospital between September 2020 and September 2021 fulfilling the eligibility criteria were included in this study.

Results

A total of 63 donors (36 females and 27 males) were included in the study, 37 (58.7%) donors had normal liver biopsies, and 26 (41.2%) donors showed the presence of non-alcoholic fatty liver disease. LSM values in the normal liver histology group were 5.01 ± 1.99 kPa by the M probe and 5.34 ± 2.25 kPa by the XL probe. Even though the correlation was weak (r = 0.29, P = 0.03), M probe LSM correlated positively with body mass index. There was a good correlation between the LSM measured by the M probe and the XL probe (r = 0.73, P = <0.001).

Conclusions

LSM value in the biopsy-proven normal liver histology group was 5.01 ± 1.99 by the M probe and 5.34 ± 2.25 by the XL probe.

SUBMITTER: Sharma D

PROVIDER: S-EPMC9840077 | biostudies-literature | 2023 Jan-Feb

REPOSITORIES: biostudies-literature

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Publications

Liver Stiffness Values in Persons with Normal Histology.

Sharma Deepak D Choudhary Narendra S NS Dhampalwar Swapnil S Saraf Neeraj N Duseja Ajay A Gautam Dheeraj D Soin Arvinder S AS Sud Randhir R

Journal of clinical and experimental hepatology 20221103 1

<h4>Background and aims</h4>Most studies to date have focused on liver stiffness measurement (LSM) in patients with different chronic liver diseases, and normal LSM is defined based on normal liver function tests or the absence of fibrosis. Very few studies have defined LSM based on completely normal liver biopsies. The current study was done to define the distribution of LSM values in individuals with normal liver biopsies.<h4>Methods</h4>All prospective liver donors presenting to Medanta, the ...[more]

PMID: 36647399

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Project description:Background Stiffness thresholds for liver MR elastography in children vary between studies and may differ from thresholds in adults. Normative liver stiffness data are needed to optimize diagnostic thresholds for children. Purpose To determine normal liver stiffness, and associated normal ranges for children, as measured with MR elastography across vendors and field strengths. Materials and Methods This was a prospective multicenter cohort study (ClinicalTrials.gov identifier: NCT03235414). Volunteers aged 7-17.9 years without a known history of liver disease were recruited at four sites for a research MRI and blood draw between February 2018 and October 2019. MRI was performed on three vendor platforms and at two field strengths (1.5 T and 3.0 T). All MRI scans were centrally analyzed; stiffness, proton density fat fraction (PDFF), and R2* values were expressed as means of means. Mean and 95% confidence intervals (CIs) for liver stiffness were calculated. Pearson correlation coefficient (r), two-sample t test, or analysis of variance was used to assess univariable associations. Results Seventy-one volunteers had complete data and no documented exclusion criterion (median age, 12 years; interquartile range [IQR], 10-15 years; 39 female participants). Median body mass index percentile was 54% (IQR, 32.5%-69.5%). Mean liver stiffness was 2.1 kPa (95% CI: 2.0, 2.2 kPa) with mean ± 1.96 kPa standard deviation of 1.5-2.8 kPa. Median liver PDFF was 2.0% (IQR, 1.7%-2.6%). There was no association between liver stiffness and any patient variable or MRI scanner factor. Conclusion Mean liver stiffness measured with MR elastography in children without liver disease was 2.1 kPa (similar to that in adults). The 95th percentile of normal liver stiffness was 2.8 kPa. Liver stiffness was independent of sex, age, or body mass index and did not vary with MRI scanner vendor or field strength. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Yin in this issue.

Project description:Antifibrotic drug screening requires evaluating the inhibitory effects of drug candidates on fibrotic cells while minimizing any adverse effects on normal cells. It is challenging to create organ-specific vascularized organoids that accurately model fibrotic and normal tissues for drug screening. Our previous studies have established methods for culturing primary microvessels and epithelial cells from adult tissues. In this proof-of-concept study, we used rats as a model organism to create a two-dimensional vascularized liver organoid model that comprised primary microvessels, epithelia, and stellate cells from adult livers. To provide appropriate substrates for cell culture, we engineered ECMs with defined stiffness to mimic the different stages of fibrotic tissues and normal tissues. We examined the effects of two TGFβ signaling inhibitors, A83-01 and pirfenidone, on the vascularized liver organoids on the stiff and soft ECMs. We found that A83-01 inhibited fibrotic markers while promoting epithelial genes of hepatocytes and cholangiocytes. However, it inhibited microvascular genes on soft ECM, indicating a detrimental effect on normal tissues. Furthermore, A83-01 significantly promoted the expression of markers of stem cells and cancers, increasing the potential risk of it being a carcinogen. In contrast, pirfenidone, an FDA-approved compound for antifibrotic treatments, did not significantly affect all the genes examined on soft ECM. Although pirfenidone had minor effects on most genes, it did reduce the expression of collagens, the major components of fibrotic tissues. These results explain why pirfenidone can slow fibrosis progression with minor side effects in clinical trials. In conclusion, our study presents a method for creating vascularized liver organoids that can accurately mimic fibrotic and normal tissues for drug screening. Our findings provide valuable insights into the potential risks and benefits of using A83-01 and pirfenidone as antifibrotic drugs. This method can be applied to other organs to create organ-specific vascularized organoids for drug development.

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Dataset Information

Liver Stiffness Values in Persons with Normal Histology.

Background and aims

Methods

Results

Conclusions

Publications

Liver Stiffness Values in Persons with Normal Histology.

Similar Datasets

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