scholarly journals Liver Zonation – Revisiting Old Questions With New Technologies

2021 ◽  
Vol 12 ◽  
Author(s):  
Rory P. Cunningham ◽  
Natalie Porat-Shliom
Keyword(s):  
Liver Disease ◽  
Spatial Organization ◽  
New Technologies ◽  
Single Cell Analysis ◽  
Normal Liver ◽  
Alcoholic Fatty Liver ◽  
Liver Zonation ◽  
Hepatocyte Heterogeneity ◽  
Glucose And Lipid Homeostasis ◽  
Technological Limitations

Despite the ever-increasing prevalence of non-alcoholic fatty liver disease (NAFLD), the etiology and pathogenesis remain poorly understood. This is due, in part, to the liver’s complex physiology and architecture. The liver maintains glucose and lipid homeostasis by coordinating numerous metabolic processes with great efficiency. This is made possible by the spatial compartmentalization of metabolic pathways a phenomenon known as liver zonation. Despite the importance of zonation to normal liver function, it is unresolved if and how perturbations to liver zonation can drive hepatic pathophysiology and NAFLD development. While hepatocyte heterogeneity has been identified over a century ago, its examination had been severely hindered due to technological limitations. Recent advances in single cell analysis and imaging technologies now permit further characterization of cells across the liver lobule. This review summarizes the advances in examining liver zonation and elucidating its regulatory role in liver physiology and pathology. Understanding the spatial organization of metabolism is vital to further our knowledge of liver disease and to provide targeted therapeutic avenues.

Gastroenterology and hepatology

2016 ◽  
Keyword(s):  
Liver Disease ◽  
Basic Science ◽  
Gastrointestinal Haemorrhage ◽  
Normal Liver ◽  
Gastrointestinal Infections ◽  
Alcoholic Fatty Liver ◽  
Gastrointestinal Problems ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Chapter 9 covers the basic science and clinical topics relating to gastroenterology and hepatology which trainees are required to learn as part of their basic training and demonstrate in the MRCP. It covers basic science, gastrointestinal investigation, malabsorption and malnutrition, inflammatory bowel disease, acute upper gastrointestinal haemorrhage, lower gastrointestinal bleeding and related disorders, gastrointestinal infections, gastrointestinal cancer, miscellaneous gastrointestinal problems, normal liver and biliary function, variceal disease, hepatic tumours, acute (fulminant) liver failure, haemochromatosis, Wilson disease (hepatolenticular degeneration), Alpha-1 antitrypsin deficiency, alcohol-induced liver disease, hepatitis, biliary diseases, and non-alcoholic fatty liver disease.

scholarly journals Metabolic Syndrome and Nonalcoholic Fatty Liver Disease

2019 ◽  
Vol 16 (1) ◽  
pp. 51-58
Author(s):  
Oana Irina Gavril ◽  
Lidia Iuliana Arhire ◽  
Ovidiu Mitu ◽  
Radu Sebastian Gavril ◽  
Alexandra Mastaleru ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Normal Liver ◽  
Liver Fat ◽  
Equal Distribution ◽  
Alcoholic Fatty Liver ◽  
Hepatic Expression ◽  
The Metabolic Syndrome

AbstractIntroduction. Non-alcoholic fatty liver disease (NAFLD) is regarded as the hepatic expression of the metabolic syndrome, both conditions presenting similar clinical features.Aim. The aim of this study was to evaluate, among diabetic subjects, the relationship between fatty liver load and the presence of metabolic syndrome criteria.Methods. An observational study was conducted on 92 subjects with type 2 diabetes. We followed anthropometric measurments, lipid profile, blood pressure and the degree of hepatic steatosis using ultrasonography.Results. The average age of the study group was 60,38 ± 10,37 years, with an approximately equal distribution by gender (48% male and 52% female). More than half of the subjects presented hypercholesterolemia, hypertriglyceridemia, and low HDL cholesterol level. Most of the patients included in the study had varying degrees of liver fat load (only 9,89% of cases of apparently normal liver on ultrasound), and met the criteria for metabolic syndrome (81,31%). It was found that the frequency of the cases with fatty liver impairment was significantly higher in subjects with metabolic syndrome (32,43% compared to 5,88% for those without metabolic syndrome, p = 0,01) and the frequency of the cases with normal liver were significantly higher in subjects without metabolic syndrome (23,53% to 6,76%, p=0,02).Conclusion. We can say that NAFLD is a risk factor for the presence of metabolic syndrome and it can be considered the hepatic expression of this syndrome.

scholarly journals Autophagy and Non-Alcoholic Fatty Liver Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Vanessa J. Lavallard ◽  
Philippe Gual
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Severe Disease ◽  
Normal Liver ◽  
Autophagic Flux ◽  
Unfolded Proteins ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Autophagy, or cellular self-digestion, is a catabolic process that targets cell constituents including damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Autophagy is crucial for development, differentiation, survival, and homeostasis. Important links between the regulation of autophagy and liver complications associated with obesity, non-alcoholic fatty liver disease (NAFLD), have been reported. The spectrum of these hepatic abnormalities extends from isolated steatosis to non-alcoholic steatohepatitis (NASH), steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. NAFLD is one of the three main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to steatosis and then more severe disease are complex and still unclear. The regulation of the autophagic flux, a dynamic response, and the knowledge of the role of autophagy in specific cells including hepatocytes, hepatic stellate cells, immune cells, and hepatic cancer cells have been extensively studied these last years. This review will provide insight into the current understanding of autophagy and its role in the evolution of the hepatic complications associated with obesity, from steatosis to hepatocellular carcinoma.

scholarly journals Endothelial-immune crosstalk contributes to vasculopathy in non-alcoholic fatty liver disease

2021 ◽  
Author(s):  
Chun-Yi Ng ◽  
Khang Leng Lee ◽  
Mark Dhinesh Muthiah ◽  
Kan Xing Wu ◽  
Florence Chioh ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Single Cell Analysis ◽  
Human Leukocyte ◽  
Cardiovascular Complications ◽  
Alcoholic Fatty Liver ◽  
Leukocyte Antigens ◽  
Alcoholic Fatty Liver Disease

The top cause of mortality in patients with non-alcoholic fatty liver disease (NAFLD) is cardiovascular complications. However, the mechanisms of NAFLD-associated vasculopathy remain understudied. We developed blood outgrowth endothelial cell (BOEC) models from NAFLD and healthy subjects. NAFLD BOECs exhibited global transcriptional upregulation of chemokine hallmarks and human leukocyte antigens. In mouse models of diet-induced NAFLD, we further confirmed enhanced endothelial expressions of CXCL12 in the aortas and liver vasculatures. To elucidate endothelial-immune crosstalk, we performed immunoprofiling by single-cell analysis, uncovering T cell intensification and potentially T-helper type 1 inflammation in NAFLD patients. Functionally, interference of the CXCL12-CXCR4 axis by small molecule AMD3100 selectively modulated the chemotaxis of patient-derived CD4+ T cells and natural killer cells towards NAFLD BOECs, restoring endothelial barrier integrity. Clinically, we detected three folds more circulating damaged endothelial cells in NAFLD patients than healthy controls. Our work provides insights for modulation of interactions with effector immune subsets to mitigate endothelial injury in NAFLD.

scholarly journals Liver zonation in children with non-alcoholic fatty liver disease: Associations with dietary fructose and uric acid concentrations

2018 ◽  
Vol 38 (6) ◽  
pp. 1102-1109 ◽  
Author(s):  
Valerio Nobili ◽  
Antonella Mosca ◽  
Rita De Vito ◽  
Massimiliano Raponi ◽  
Eleonora Scorletti ◽  
...  
Keyword(s):  
Uric Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Liver Zonation ◽  
Dietary Fructose ◽  
Disease Associations ◽  
Alcoholic Fatty Liver Disease

scholarly journals Association of circulating miR-20a, miR-27a, and miR-126 with non-alcoholic fatty liver disease in general population

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yoshitaka Ando ◽  
Mirai Yamazaki ◽  
Hiroya Yamada ◽  
Eiji Munetsuna ◽  
Ryosuke Fujii ◽  
...  
Keyword(s):  
Liver Disease ◽  
General Population ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Reference Group ◽  
Normal Liver ◽  
Health Examination ◽  
Cross Sectional ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) is closely associated with obesity, metabolic syndrome, and type II diabetes mellitus. Recently, circulating microRNAs (miRNAs) have been proposed as useful disease biomarkers. We examined whether circulating miRNAs, such as miR-20a, miR-27a, and miR-126, were useful biomarkers for NAFLD. We conducted a cross-sectional analysis of 527 subjects aged 39 years or older who had undergone a health examination in the Yakumo Study. Of the residents, 92 were diagnosed with NAFLD using a registered medical sonographer. Serum miR-20a, miR-27a and miR-126 levels were measured by quantitative real-time PCR. We then calculated the odds ratios for serum miRNA level changes according to the severity of NAFLD using normal liver status as the reference group. Serum levels of miR-20a and 27a, but not miR-126, were significantly lower in NAFLD subjects than normal subjects. Serum miR-20a and miR-27a levels were significantly lower in both male and female severe NAFLD subjects. Logistic regression analysis showed a significant relationship between low circulating miR-20a and 27a levels and severe NAFLD. Down-regulated circulating miR-20a and 27a levels were significantly associated with severe NAFLD in the general population. Circulating miR-20a and miR-27a may be useful biomarkers for severe NAFLD.

scholarly journals Characterization of Patients with Biopsy-Proven Non-Alcoholic Fatty Liver Disease and Normal Aminotransferase Levels

2019 ◽  
Vol 28 (4) ◽  
pp. 427-431 ◽  
Author(s):  
Celal Ulasoglu ◽  
Feruze Yilmaz Enc ◽  
Eda Kaya ◽  
Yusuf Yilmaz
Keyword(s):  
Diabetes Mellitus ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Enzymes ◽  
Normal Liver ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Elevated Liver Enzymes ◽  
Alcoholic Fatty Liver Disease

Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is one of the major causes of abnormal liver function tests in hepatology practice. However, not all patients with NAFLD have increased aminotransferase levels. The aim of this study was to compare the clinical and histologic characteristics of patients with biopsyproven NAFLD showing normal versus elevated aminotransferase levels. Methods: We retrospectively reviewed 515 patients with biopsy-proven NAFLD. Patients with ALT ≤ 40 U/L and AST ≤ 37 U/L were considered as having normal liver enzymes. A histological fibrosis score F ≥ 3 was used to define advanced fibrosis. Results: Of the 515 study participants, 107 (20.8%) had normal liver enzymes. Compared with patients showing elevated liver enzymes, those with normal aminotransferase levels were older and most commonly women. Moreover, they had a higher body mass index and more frequently showed metabolic risk factors (metabolic syndrome, diabetes mellitus, hypertension, higher waist and hip circumferences). Although liver histology tended to be less severe in patients with normal liver enzymes, the prevalence of advanced fibrosis was similar in the two groups. Diabetes mellitus (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.46−3.91, p < 0.001) and age (OR = 1.14, 95% CI = 1.07−1.24, p < 0.05) were identified as independent predictors of advanced fibrosis in patients with normal aminotransferase levels. Conclusions: NAFLD with normal aminotransferase levels is characterized by a severe metabolic profile and a prevalence of advanced fibrosis similar to that identified in cases with elevated aminotransferase levels.

scholarly journals One-year outcomes for lung transplantation recipients with non-alcoholic fatty liver disease

2021 ◽  
pp. 00103-2021
Author(s):  
Anil J. Trindade ◽  
Tany Thaniyavarn ◽  
Nikroo Hashemi ◽  
Antonio Coppolino ◽  
John C. Kennedy ◽  
...  
Keyword(s):  
Liver Disease ◽  
Lung Transplantation ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Normal Liver ◽  
Alcoholic Fatty Liver ◽  
Post Transplant ◽  
Index Hospital ◽  
Secondary Outcomes ◽  
Alcoholic Fatty Liver Disease

Advanced hepatic fibrosis and cirrhosis are absolute contraindications to lung transplantation. [1] However, whether fatty liver disease with mild-moderate fibrosis contributes to increased adverse outcomes post-lung transplantation remains unknown.We present a retrospective analysis of patients transplanted at Brigham and Women's Hospital between 2015–2017 to identify whether patients with mild-moderate non-alcoholic fatty liver disease (NAFLD) experience increased short-term complications compared to patients with normal liver architecture. Patients with advanced (F3–F4) fibrosis and/or cirrhosis were considered non-suitable transplant candidates, a priori. This study was powered for a difference in index hospital-free days within the first 30 days of 25% (alpha=0.05, beta=0.8). Secondary outcomes included index intensive care unit (ICU) free days within the first 10 days post-transplant, perioperative blood product transfusion, incidence of index hospitalisation arrhythmias and delirium, need for insulin on discharge post-transplant, tacrolimus dose required to maintain a trough of 8–12 ng·mL−1 at index hospital discharge, and 1-year post-transplant incidence of insulin-dependent diabetes, acute kidney injury, acute cellular rejection, unplanned hospital readmissions, and infection.One hundred fifty patients underwent lung transplantation between 2015–2017 and were included in the analysis; of these patients 40 (27%) had evidence of NAFLD. Median index hospital-free days for patients with NAFLD were non-inferior to those without (16 days, IQR 10.5–19.5 versus 12 days, IQR 0–18.0, p= 0.03). Regarding secondary outcomes, both index hospitalisation and 1-year outcomes were non-inferior between patients with NAFLD and those with normal liver architecture.This study demonstrates that mild-moderate severity NAFLD may not be a contraindication to lung transplantation.

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