scholarly journals The Propensity of the Human Liver to Form Large Lipid Droplets Is Associated with PNPLA3 Polymorphism, Reduced INSIG1 and NPC1L1 Expression and Increased Fibrogenetic Capacity

2021 ◽  
Vol 22 (11) ◽  
pp. 6100
Author(s):  
Flaminia Ferri ◽  
Simone Carotti ◽  
Guido Carpino ◽  
Monica Mischitelli ◽  
Alfredo Cantafora ◽  
...  
Keyword(s):  
Human Liver ◽  
Stellate Cell ◽  
Linear Regression Models ◽  
Hepatic Expression ◽  
Predominant Type ◽  
Lipid Droplet Size ◽  
Liver Biopsies ◽  
Niemann Pick ◽  
One Year ◽  
Macrovesicular Steatosis

In nonalcoholic steatohepatitis animal models, an increased lipid droplet size in hepatocytes is associated with fibrogenesis. Hepatocytes with large droplet (Ld-MaS) or small droplet (Sd-MaS) macrovesicular steatosis may coexist in the human liver, but the factors associated with the predominance of one type over the other, including hepatic fibrogenic capacity, are unknown. In pre-ischemic liver biopsies from 225 consecutive liver transplant donors, we retrospectively counted hepatocytes with Ld-MaS and Sd-MaS and defined the predominant type of steatosis as involving ≥50% of steatotic hepatocytes. We analyzed a donor Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism, hepatic expression of proteins involved in lipid metabolism by RT-PCR, hepatic stellate cell (HSC) activation by α-SMA immunohistochemistry and, one year after transplantation, histological progression of fibrosis due to Hepatitis C Virus (HCV) recurrence. Seventy-four livers had no steatosis, and there were 98 and 53 with predominant Ld-MaS and Sd-MaS, respectively. In linear regression models, adjusted for many donor variables, the percentage of steatotic hepatocytes affected by Ld-MaS was inversely associated with hepatic expression of Insulin Induced Gene 1 (INSIG-1) and Niemann-Pick C1-Like 1 gene (NPC1L1) and directly with donor PNPLA3 variant M, HSC activation and progression of post-transplant fibrosis. In humans, Ld-MaS formation by hepatocytes is associated with abnormal PNPLA3-mediated lipolysis, downregulation of both the intracellular cholesterol sensor and cholesterol reabsorption from bile and increased hepatic fibrogenesis.

scholarly journals Efficiency of Machine Learning Algorithms for the Determination of Macrovesicular Steatosis in Frozen Sections Stained with Sudan to Evaluate the Quality of the Graft in Liver Transplantation

Sensors ◽  
2021 ◽  
Vol 21 (6) ◽  
pp. 1993
Author(s):  
Fernando Pérez-Sanz ◽  
Miriam Riquelme-Pérez ◽  
Enrique Martínez-Barba ◽  
Jesús de la Peña-Moral ◽  
Alejandro Salazar Nicolás ◽  
...  
Keyword(s):  
Machine Learning ◽  
Liver Transplantation ◽  
Learning Algorithms ◽  
Selection Procedure ◽  
Machine Learning Algorithms ◽  
Liver Biopsies ◽  
Convenient Technique ◽  
End Stage ◽  
Macrovesicular Steatosis

Liver transplantation is the only curative treatment option in patients diagnosed with end-stage liver disease. The low availability of organs demands an accurate selection procedure based on histological analysis, in order to evaluate the allograft. This assessment, traditionally carried out by a pathologist, is not exempt from subjectivity. In this sense, new tools based on machine learning and artificial vision are continuously being developed for the analysis of medical images of different typologies. Accordingly, in this work, we develop a computer vision-based application for the fast and automatic objective quantification of macrovesicular steatosis in histopathological liver section slides stained with Sudan stain. For this purpose, digital microscopy images were used to obtain thousands of feature vectors based on the RGB and CIE L*a*b* pixel values. These vectors, under a supervised process, were labelled as fat vacuole or non-fat vacuole, and a set of classifiers based on different algorithms were trained, accordingly. The results obtained showed an overall high accuracy for all classifiers (>0.99) with a sensitivity between 0.844 and 1, together with a specificity >0.99. In relation to their speed when classifying images, KNN and Naïve Bayes were substantially faster than other classification algorithms. Sudan stain is a convenient technique for evaluating ME in pre-transplant liver biopsies, providing reliable contrast and facilitating fast and accurate quantification through the machine learning algorithms tested.

scholarly journals Collagen proline hydroxylase activity and 35S sulphate uptake in human liver biopsies

Gut ◽  
1974 ◽  
Vol 15 (4) ◽  
pp. 260-267 ◽  
Author(s):  
J. OD. McGee ◽  
R. S. Patrick ◽  
M. C. Rodger ◽  
C. M. Luty
Keyword(s):  
Human Liver ◽  
Hydroxylase Activity ◽  
Sulphate Uptake ◽  
Human Liver Biopsies ◽  
Liver Biopsies ◽  
Proline Hydroxylase

scholarly journals Single Cell, Single Nucleus and Spatial RNA Sequencing of the Human Liver Identifies Hepatic Stellate Cell and Cholangiocyte Heterogeneity

2021 ◽  
Author(s):  
Tallulah S Andrews ◽  
Jawairia Atif ◽  
Jeff C Liu ◽  
Catia T Perciani ◽  
Xue-Zhong Ma ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Human Liver ◽  
Stellate Cell ◽  
Parenchymal Cell ◽  
Cell Types ◽  
Cell Populations ◽  
Healthy Human ◽  
Single Nucleus

The critical functions of the human liver are coordinated through the interactions of hepatic parenchymal and non-parenchymal cells. Recent advances in single cell transcriptional approaches have enabled an examination of the human liver with unprecedented resolution. However, dissociation related cell perturbation can limit the ability to fully capture the human liver's parenchymal cell fraction, which limits the ability to comprehensively profile this organ. Here, we report the transcriptional landscape of 73,295 cells from the human liver using matched single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq). The addition of snRNA-seq enabled the characterization of interzonal hepatocytes at single-cell resolution, revealed the presence of rare subtypes of hepatic stellate cells previously only seen in disease, and detection of cholangiocyte progenitors that had only been observed during in vitro differentiation experiments. However, T and B lymphocytes and NK cells were only distinguishable using scRNA-seq, highlighting the importance of applying both technologies to obtain a complete map of tissue-resident cell-types. We validated the distinct spatial distribution of the hepatocyte, cholangiocyte and stellate cell populations by an independent spatial transcriptomics dataset and immunohistochemistry. Our study provides a systematic comparison of the transcriptomes captured by scRNA-seq and snRNA-seq and delivers a high-resolution map of the parenchymal cell populations in the healthy human liver.

scholarly journals Evaluation of determinants of the serological response to the split-inactivated influenza vaccine

2021 ◽  
Author(s):  
Shaohuan Wu ◽  
Ted M. Ross ◽  
Michael A. Carlock ◽  
Elodie Ghedin ◽  
Hyungwon Choi ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Regression Models ◽  
Seasonal Influenza ◽  
Vaccine Dose ◽  
Serological Response ◽  
Linear Regression Models ◽  
Negative Effects ◽  
Categorical Response ◽  
One Year ◽  
The Impact

AbstractThe seasonal influenza vaccine is only effective in half of the vaccinated population. To identify determinants of vaccine efficacy, we used data from >1,300 vaccination events to predict the response to vaccination measured as seroconversion as well as hemagglutination inhibition (HAI) levels one year after. We evaluated the predictive capabilities of age, body mass index (BMI), sex, race, comorbidities, prevaccination history, and baseline HAI titers, as well as vaccination month and vaccine dose in multiple linear regression models. The models predicted the categorical response for >75% of the cases in all subsets with one exception. Prior vaccination, baseline titer level, and age were the strongest determinants on seroconversion, all of which had negative effects. Further, we identified a gender effect in older participants, and an effect of vaccination month. BMI played a surprisingly small role, likely due to its correlation with age. Comorbidities, vaccine dose, and race had negligible effects. Our models can generate a new seroconversion score that is corrected for the impact of these factors which can facilitate future biomarker identification.

scholarly journals Acute Kidney Injury Patterns Following Transplantation of Steatotic Liver Allografts

2020 ◽  
Vol 9 (4) ◽  
pp. 954 ◽  
Author(s):  
Caroline Jadlowiec ◽  
Maxwell Smith ◽  
Matthew Neville ◽  
Shennen Mao ◽  
Dina Abdelwahab ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Patient Survival ◽  
Kidney Injury ◽  
Allograft Survival ◽  
Injury Patterns ◽  
Initiation Of Dialysis ◽  
One Year ◽  
End Stage ◽  
The Impact ◽  
Macrovesicular Steatosis

Background: Steatotic grafts are increasingly being used for liver transplant (LT); however, the impact of graft steatosis on renal function has not been well described. Methods: A total of 511 allografts from Mayo Clinic Arizona and Minnesota were assessed. We evaluated post-LT acute kidney injury (AKI) patterns, perioperative variables and one-year outcomes for patients receiving moderately steatotic allografts (>30% macrovesicular steatosis, n = 40) and compared them to non-steatotic graft recipients. Results: Post-LT AKI occurred in 52.5% of steatotic graft recipients versus 16.7% in non-steatotic recipients (p < 0.001). Ten percent of steatotic graft recipients required new dialysis post-LT (p = 0.003). At five years, there were no differences for AKI vs. no AKI patient survival (HR 0.95, 95% CI 0.08–10.6, p = 0.95) or allograft survival (HR 1.73, 95% CI 0.23–13.23, p = 0.59) for those using steatotic grafts. Lipopeliosis on biopsy was common in those who developed AKI (61.0% vs. 31.6%, p = 0.04), particularly when the Model for End-Stage Liver Disease (MELD) was ≥20 (88.9%; p = 0.04). Lipopeliosis was a predictor of post-LT AKI (OR 6.0, 95% CI 1.1–34.6, p = 0.04). Conclusion: One-year outcomes for moderately steatotic grafts are satisfactory; however, a higher percentage of post-LT AKI and initiation of dialysis can be expected. Presence of lipopeliosis on biopsy appears to be predictive of post-LT AKI.

LIPOGRANULOMAS IN HUMAN LIVER BIOPSIES WITH FATTY CHANGE

2009 ◽  
Vol 79A (2) ◽  
pp. 150-158
Author(s):  
Per Christoffersen ◽  
Otto Braendstrup ◽  
Erik Juhl ◽  
Hemming Poulsen
Keyword(s):  
Human Liver ◽  
Fatty Change ◽  
Human Liver Biopsies ◽  
Liver Biopsies
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