scholarly journals NASH and Systemic Complications: From Basic to Clinical Research

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1913
Author(s):  
Sabine Baumgartner ◽  
Ronit Shiri-Sverdlov

Nonalcoholic fatty liver disease (NAFLD) is known as the hepatic manifestation of the metabolic syndrome, and while most patients develop simple steatosis, up to one-third can develop nonalcoholic steatohepatitis (NASH). [...]

2003 ◽  
Vol 98 (9) ◽  
pp. 2064-2071 ◽  
Author(s):  
Arun J. Sanyal ◽  
Melissa J. Contos ◽  
Richard K. Sterling ◽  
Velimir A. Luketic ◽  
Mitchell L. Shiffman ◽  
...  

2019 ◽  
Vol 316 (4) ◽  
pp. G462-G472 ◽  
Author(s):  
Malte P. Suppli ◽  
Kristoffer T. G. Rigbolt ◽  
Sanne S. Veidal ◽  
Sara Heebøll ◽  
Peter Lykke Eriksen ◽  
...  

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of conditions ranging from simple steatosis (NAFL), over nonalcoholic steatohepatitis (NASH) with or without fibrosis, to cirrhosis with end-stage disease. The hepatic molecular events underlying the development of NAFLD and transition to NASH are poorly understood. The present study aimed to determine hepatic transcriptome dynamics in patients with NAFL or NASH compared with healthy normal-weight and obese individuals. RNA sequencing and quantitative histomorphometry of liver fat, inflammation and fibrosis were performed on liver biopsies obtained from healthy normal-weight ( n = 14) and obese ( n = 12) individuals, NAFL ( n = 15) and NASH ( n = 16) patients. Normal-weight and obese subjects showed normal liver histology and comparable gene expression profiles. Liver transcriptome signatures were largely overlapping in NAFL and NASH patients, however, clearly separated from healthy normal-weight and obese controls. Most marked pathway perturbations identified in both NAFL and NASH were associated with markers of lipid metabolism, immunomodulation, extracellular matrix remodeling, and cell cycle control. Interestingly, NASH patients with positive Sonic hedgehog hepatocyte staining showed distinct transcriptome and histomorphometric changes compared with NAFL. In conclusion, application of immunohistochemical markers of hepatocyte injury may serve as a more objective tool for distinguishing NASH from NAFL, facilitating improved resolution of hepatic molecular changes associated with progression of NAFLD. NEW & NOTEWORTHY Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. NAFLD is associated with the metabolic syndrome and can progress to the more serious form, nonalcoholic steatohepatitis (NASH), and ultimately lead to irreversible liver damage. Using gold standard molecular and histological techniques, this study demonstrates that the currently used diagnostic tools are problematic for differentiating mild NAFLD from NASH and emphasizes the marked need for developing improved histological markers of NAFLD progression.


2005 ◽  
Vol 90 (3) ◽  
pp. 1578-1582 ◽  
Author(s):  
F. Angelico ◽  
M. Del Ben ◽  
R. Conti ◽  
S. Francioso ◽  
K. Feole ◽  
...  

Background/Aims: An association of nonalcoholic fatty liver disease with the insulin-resistant metabolic syndrome has been suggested. The aim of the study was to assess the association of fatty liver to different degrees of insulin resistance and secretion. Methods and Results: The study was performed in 308 alcohol- and virus-negative consecutive patients attending a metabolic clinic, who underwent a complete clinical and biochemical work-up including oral glucose tolerance test and routine liver ultrasonography. Steatosis was graded as absent/mild, moderate, and severe. In nondiabetic subjects, a progressive (P < 0.05) increase in mean homeostasis model of insulin resistance was recorded from the group without steatosis to the groups with mild/moderate and severe steatosis. Severe steatosis was associated with the clustering of the five clinical and biochemical features proposed for the clinical diagnosis of the metabolic syndrome. Subjects with the metabolic syndrome with a more pronounced insulin resistance had a higher prevalence of severe steatosis (P < 0.01) compared with those with homeostasis model of insulin resistance below the median. Conclusions: The findings stress the heterogeneous presentation of patients with the metabolic syndrome when the diagnosis is based on the broad Adult Treatment Panel III clinical criteria and demonstrate that those who are more insulin resistant have a higher prevalence of severe steatosis.


2009 ◽  
Vol 35 (03) ◽  
pp. 277-287 ◽  
Author(s):  
Giovanni Targher ◽  
Michel Chonchol ◽  
Luca Miele ◽  
Giacomo Zoppini ◽  
Isabella Pichiri ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Stefan Chiriac ◽  
Carol Stanciu ◽  
Irina Girleanu ◽  
Camelia Cojocariu ◽  
Catalin Sfarti ◽  
...  

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most frequent cause of liver disease worldwide, comprising a plethora of conditions, ranging from steatosis to end-stage liver disease. Cardiovascular disease (CVD) has been associated with NAFLD and CVD-related events represent the main cause of death in patients with NAFLD, surpassing liver-related mortality. This association is not surprising as NAFLD has been considered a part of the metabolic syndrome and has been related to numerous CVD risk factors, namely, insulin resistance, abdominal obesity, dyslipidemia, hyperuricemia, chronic kidney disease, and type 2 diabetes. Moreover, both NAFLD and CVD present similar pathophysiological mechanisms, such as increased visceral adiposity, altered lipid metabolism, increased oxidative stress, and systemic inflammation that could explain their association. Whether NAFLD increases the risk for CVD or these diagnostic entities represent distinct manifestations of the metabolic syndrome has not yet been clarified. This review focuses on the relation between NAFLD and the spectrum of CVD, considering the pathophysiological mechanisms, risk factors, current evidence, and future directions.


2008 ◽  
Vol 132 (11) ◽  
pp. 1761-1766 ◽  
Author(s):  
Grace Guzman ◽  
Elizabeth M. Brunt ◽  
Lydia M. Petrovic ◽  
Gregorio Chejfec ◽  
Thomas J. Layden ◽  
...  

Abstract Context.—Hepatocellular carcinoma (HCC) is recognized as a complication of cirrhosis related to nonalcoholic fatty liver disease (NAFLD). Diabetes and the metabolic syndrome are also associated with HCC. However, it is not clear whether NAFLD predisposes patients to HCC in the absence of cirrhosis. Objective.—To seek evidence that HCC can develop in NAFLD unaccompanied by cirrhosis. Design.—Retrospective case study was performed on cases from 2004 to 2007 at the University of Illinois at Chicago Medical Center, using the key words hepatocellular carcinoma, liver explant, and liver resection. The diagnosis of HCC was identified and confirmed by hematoxylin-eosin–stained slides in 50 cases. Cause of liver disease was determined by review of liver histology, clinical history, and laboratory data. Results.—Three patients presented with advanced HCC with features of metabolic syndrome, including an elevated body mass index. Each patient had bland steatosis on liver biopsy, without fibrosis or cirrhosis. None of the 3 patients had evidence of any cause for liver disease other than NAFLD. Conclusions.—The cases presented here suggest that NAFLD may predispose patients to HCC in the absence of cirrhosis. Further studies are needed to confirm this potentially important observation.


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