Complications, morbidity and mortality of nonalcoholic fatty liver disease

Mantovani, Alessandro; Scorletti, Eleonora; Mosca, Antonella; Alisi, Anna; Byrne, Christopher D.; Targher, Giovanni

doi:10.1016/j.metabol.2020.154170

Cited by 309 publications

(267 citation statements)

References 145 publications

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“…The chronic accumulation of hepatic triglycerides and saturated fatty acids increases oxidative stress and inflammation that activate hepatic stellate cells. This leads to fibrosis in NASH that can advance to hepatic cirrhosis [90][91][92]. Given its important role in energy expenditure and mitochondrial activity, the activation of ESRRA and its downstream pathways could be therapeutically beneficial for NAFLD.…”

Section: Esrra As a Target For Nafldmentioning

confidence: 99%

“…It is a hallmark of type 2 diabetes and is a major contributor to the development of NAFLD and vice versa [102]. While obesity is associated with chronic inflammation that leads to insulin resistance and NAFLD [90], mitochondrial dysfunction is involved in all three metabolic disorders [102][103][104][105]. Most notably, mitochondrial defects in FAO lead to the accumulation of intracellular fatty acid metabolites such as dihydroxyglycerol and ceramides that adversely affect insulin signaling in various tissues [106][107][108].…”

Section: Esrra As a Target For Insulin Resistance And Type 2 Diabetesmentioning

confidence: 99%

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Estrogen-Related Receptor Alpha: An Under-Appreciated Potential Target for the Treatment of Metabolic Diseases

Tripathi

Yen

Singh

2020

IJMS

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The estrogen-related receptor alpha (ESRRA) is an orphan nuclear receptor (NR) that significantly influences cellular metabolism.ESRRA is predominantly expressed in metabolically-active tissues and regulates the transcription of metabolic genes, including those involved in mitochondrial turnover and autophagy. Although ESRRA activity is well-characterized in several types of cancer, recent reports suggest that it also has an important role in metabolic diseases. This minireview focuses on the regulation of cellular metabolism and function by ESRRA and its potential as a target for the treatment of metabolic disorders.

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Section: Esrra As a Target For Nafldmentioning

confidence: 99%

Section: Esrra As a Target For Insulin Resistance And Type 2 Diabetesmentioning

confidence: 99%

Estrogen-Related Receptor Alpha: An Under-Appreciated Potential Target for the Treatment of Metabolic Diseases

Tripathi

Yen

Singh

2020

IJMS

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“…Non-alcoholic steatohepatitis (NASH), the most serious condition in the Non-Alcoholic Fatty Liver Disease (NAFLD) spectrum, is a liver disease characterized by serologic markers of hepatocyte injury as well as distinct histological features 1 . NASH is associated with significant morbidity and mortality [2][3][4] . Patients with NASH are at increased risk of progressive fibrosis with end-stage liver disease characterized by reduced hepatic synthetic function, portal hypertension, encephalopathy, and malignancy such as hepatocellular carcinoma.…”

Section: Introductionmentioning

confidence: 99%

A Large-Scale Internal Validation Study of Unsupervised Virtual Trichrome Staining Technologies on Non-alcoholic Steatohepatitis Liver Biopsies

Levy

Azizgolshani

Andersen

et al. 2020

Preprint

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AbstractNon-alcoholic steatohepatitis (NASH) is a type of fatty liver disease characterized by accumulation of fat in hepatocytes and concurrent inflammation. It is associated with significant morbidity as it can progress to cirrhosis and liver failure and increases the risk of developing hepatocellular carcinoma. NASH has become increasingly prevalent in the US and is a leading cause of liver transplantation for end stage liver disease and a significant public health burden. Grading and staging NASH involves liver core biopsy, followed by microscopic examination of histologic preparations of the tissue. Tissue sections are stained with hematoxylin and eosin (H&E) to grade NASH activity, and stained with trichrome to help stage fibrosis. Methods to computationally transform one stain into another on digital whole slide images (WSI) can reduce the need for additional physical staining besides H&E, alleviating personnel, equipment, and time costs. Recent computational techniques have shown promise and success for virtual staining of tissue. We conducted a large-scale validation study of the viability of virtual staining technologies for H&E to trichrome conversion on WSI (n=574). Our results demonstrate that virtual trichrome technologies present an immediate software solution that can be readily employed in the clinical setting as a diagnostic decision aid.

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“…The burden of NAFLD is strongly influenced by the global epidemics of obesity and type 2 diabetes mellitus, and the prevalence of these conditions is expected to dramatically increase in the forthcoming decades. Thus, NAFLD is an important cause of a poor quality of life for many patients and results in a considerable global health and economic burden for healthcare providers [ 3 , 4 ].…”

mentioning

confidence: 99%

“…Indeed, the deleterious effects of NAFLD extend far beyond the liver, with an accumulating body of clinical evidence now supporting the notion that NAFLD may precede and/or promote the development of cardiovascular disease and type 2 diabetes mellitus [ 15 ]. Furthermore, it has been demonstrated that the risk of developing these cardio-metabolic complications parallels the underlying severity of NAFLD, and especially the severity of liver fibrosis [ 4 , 15 , 16 , 17 ].…”

mentioning

confidence: 99%

What’s Past Is Prologue: History of Nonalcoholic Fatty Liver Disease

Targher

2020

Metabolites

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Since the initial descriptions in the early 1980s by Dr. Ludwig et al. and Drs. Schaffner and Thaler, who firstly coined the terms nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), this liver disease has become a global health problem worldwide, causing considerable liver-related and extra-hepatic morbidity and mortality. Based on pathophysiological insights gained from the past decades, it has been clearly established that NAFLD is a metabolic liver disease whose etiology and pathogenesis extends beyond the liver and that NAFLD has important clinical implications, especially in terms of an increased risk of developing both cardiovascular disease (which represents the leading cause of death in this patient population) and other extra-hepatic manifestations, such as type 2 diabetes mellitus, chronic kidney disease, and some extra-hepatic cancers. The aim of this brief commentary is to discuss a recent review article written by Dr. Lonardo and colleagues, who raised awareness of the history of NAFLD. Since “What’s past is prologue”, I believe that this review article focusing on the history of NAFLD may contribute to better understanding the disease itself, as well as to anticipating the lines of the future clinical and pharmacological research of this common and burdensome liver disease.

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Complications, morbidity and mortality of nonalcoholic fatty liver disease

Cited by 309 publications

References 145 publications

Estrogen-Related Receptor Alpha: An Under-Appreciated Potential Target for the Treatment of Metabolic Diseases

Estrogen-Related Receptor Alpha: An Under-Appreciated Potential Target for the Treatment of Metabolic Diseases

A Large-Scale Internal Validation Study of Unsupervised Virtual Trichrome Staining Technologies on Non-alcoholic Steatohepatitis Liver Biopsies

What’s Past Is Prologue: History of Nonalcoholic Fatty Liver Disease

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