Lipotoxicity as the Leading Cause of Non-Alcoholic Steatohepatitis

Branković, Marija; Jovanović, Igor; Dukić, Marija; Radonjić, Tijana; Oprić, Svetlana; Klašnja, Slobodan; Zdravković, Marija

doi:10.3390/ijms23095146

Cited by 33 publications

(29 citation statements)

References 169 publications

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“…Steatosis is characterized by the accumulation of triglycerides (TGs) as a compensatory response to an increase in free fatty acids (FFAs) within the cell. Moreover, the FFAs are partitioned into an inert and stable lipid, preventing the injury of hepatocytes ( Kawano and Cohen, 2013 ; Branković et al, 2022 ). As a matter of fact, there have been abundant reviews of the mechanisms underlying steatosis development elsewhere.…”

Section: Inflammation and Fibrosis In Nafldmentioning

confidence: 99%

Roles of hepatic stellate cells in NAFLD: From the perspective of inflammation and fibrosis

Wang¹,

Xu³

et al. 2022

Front. Pharmacol.

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Non-alcoholic fatty liver disease (NAFLD) has become one of the most common diseases and severe problems worldwide because of the global increase in obesity, dyslipidemia, hypertension, and type 2 diabetes mellitus. NAFLD includes a wide spectrum of liver diseases, the histological forms of which range from non-alcoholic fatty liver (NAFL), which is generally nonprogressive, to non-alcoholic steatohepatitis (NASH), which can progress to chronic hepatitis, liver cirrhosis (LC), and sometimes hepatocellular carcinoma (HCC). Unlike NAFL, as the progressive form of NAFLD, NASH is characterized by the presence of inflammation with or without fibrosis in addition to hepatic steatosis. Although it is widely known and proved that persistent hepatic injury and chronic inflammation in the liver activate quiescent hepatic stellate cells (HSCs) and lead to hepatic fibrosis, the three-step process of “inflammation-fibrosis-carcinoma” in NAFLD has not been investigated and clarified clearly. In this process, the initiation of inflammation in the liver and the function of various liver inflammatory cells have been discussed regularly, while the activated HSCs, which constitute the principal cells responsible for fibrosis and their cross-talk with inflammation, seem not to be investigated specifically and frequently. Also, accumulated evidence suggests that HSCs can not only be activated by inflammation but also participate in the regulation of liver inflammation. Therefore, it is necessary to investigate the unique roles of HSCs in NAFLD from the perspective of inflammation and fibrosis. Here, we review the pivotal effects and mechanisms of HSCs and highlight the potential value of HSC-targeted treatment methods in NAFLD.

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Section: Inflammation and Fibrosis In Nafldmentioning

confidence: 99%

Roles of hepatic stellate cells in NAFLD: From the perspective of inflammation and fibrosis

Wang¹,

Xu³

et al. 2022

Front. Pharmacol.

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“…Studies have shown that the frequency of developing liver cirrhosis in patients with NAFLD increases with age and that patients older than 50 years are at a higher risk for developing severe fibrosis [ 118 , 119 ]. NAFLD has a tendency to progress to NASH which is associated with obesity, metabolic syndrome, type 2 diabetes, insulin resistance and cardiovascular diseases [ 120 ]. The frequency of most of the mentioned conditions increases with age [ 3 ].…”

Section: Liver Diseases and Agingmentioning

confidence: 99%

Aging of Liver in Its Different Diseases

Radonjić

Dukić

Jovanović

et al. 2022

IJMS

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The proportion of elderly people in the world population is constantly increasing. With age, the risk of numerous chronic diseases and their complications also rises. Research on the subject of cellular senescence date back to the middle of the last century, and today we know that senescent cells have different morphology, metabolism, phenotypes and many other characteristics. Their main feature is the development of senescence-associated secretory phenotype (SASP), whose pro-inflammatory components affect tissues and organs, and increases the possibility of age-related diseases. The liver is the main metabolic organ of our body, and the results of previous research indicate that its regenerative capacity is greater and that it ages more slowly compared to other organs. With age, liver cells change under the influence of various stressors and the risk of developing chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH) and hepatocellular carcinoma (HCC) increases. It has been proven that these diseases progress faster in the elderly population and in some cases lead to end-stage liver disease that requires transplantation. The treatment of elderly people with chronic liver diseases is a challenge and requires an individual approach as well as new research that will reveal other safe and effective therapeutic modalities.

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“…As the incidence of non-alcoholic fatty liver disease (NAFLD) is galloping, it is crucial to focus on it as an emerging issue, since it could progress to non-alcoholic steato-hepatitis (NASH) which can be a further predisposing factor for chronic liver complications [ 7 ]. NAFLD frequently overlaps with one or more elements of metabolic syndrome including obesity, insulin resistance, dyslipidemia, and arterial hypertension [ 8 ], which all are known to have a significant impact on the severity of COVID-19 infection.…”

Section: Introductionmentioning

confidence: 99%

Elevated Transaminases as Predictors of COVID-19 Pneumonia Severity

et al. 2022

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Background: This study aimed to calculate the frequency of elevated liver enzymes in hospitalized patients with coronavirus disease 2019 (COVID-19) infection and to test if liver enzyme biochemistry levels on admission could predict the computed tomography (CT) scan severity score of bilateral interstitial pneumonia. Methods: This single-center study comprised of 323 patients including their demographic data, laboratory analyses, and radiological findings. All the information was taken from electronic health records, followed by statistical analysis. Results: Out of 323 patients, 115 of them (35.60%) had aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) over 40 U/L on admission. AST was the best predictor of CT scan severity score of bilateral interstitial pneumonia (R2 = 0.313, Adjusted R2 = 0.299). CT scan severity score in the peak of the infection could be predicted with the value of AST, neutrophils, platelets, and monocytes count (R2 = 0.535, Adjusted R2 = 0.495). Conclusion: AST, neutrophils, platelets, and monocytes count on admission can account for almost half (49.5%) of the variability in CT scan severity score at peak of the disease, predicting the extensiveness of interstitial pneumonia related to COVID-19 infection. Liver enzymes should be closely monitored in order to stratify COVID-19 patients with a higher risk of developing severe forms of the disease and to plan the beforehand step-up treatment.

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Lipotoxicity as the Leading Cause of Non-Alcoholic Steatohepatitis

Cited by 33 publications

References 169 publications

Roles of hepatic stellate cells in NAFLD: From the perspective of inflammation and fibrosis

Roles of hepatic stellate cells in NAFLD: From the perspective of inflammation and fibrosis

Aging of Liver in Its Different Diseases

Elevated Transaminases as Predictors of COVID-19 Pneumonia Severity

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