Predictors of steroid non-response and new approaches in severe alcoholic hepatitis

Sarin, Shiv Kumar; Sharma, Shvetank

doi:10.3350/cmh.2020.0196

Cited by 13 publications

(19 citation statements)

References 65 publications

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“…ALD is the most frequent cause of advanced chronic liver disease worldwide, contributing to 47.9% of all liver cirrhosis‐related deaths globally (Sarin & Sharma, 2020). Severe alcoholic hepatitis the most severe form of ALD, is a source of morbidity and mortality worldwide and has become a major economic burden and nonnegligible public health issues (Van Melkebeke et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, LAMP1 is important for the autophagy lysosome pathway and is thought to play a role in maintaining the structural integrity of the lysosome membrane by protecting it from the harsh intracavinal environment (Huynh et al, 2007). As shown in ALD is the most frequent cause of advanced chronic liver disease worldwide, contributing to 47.9% of all liver cirrhosis-related deaths globally (Sarin & Sharma, 2020). Severe alcoholic hepatitis the most severe form of ALD, is a source of morbidity and mortality worldwide and has become a major economic burden and nonnegligible public health issues (Van Melkebeke et al, 2021).…”

Section: Quercetin Activated Ampk-tfeb-mtormediated Lipid Metabolismmentioning

confidence: 99%

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Quercetin alleviates ethanol‐induced hepatic steatosis in L02 cells by activating TFEB translocation to compensate for inadequate autophagy

Zhao

Xue

Wang

et al. 2022

Phytotherapy Research

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This study aimed to investigate the therapeutic effect of quercetin on ethanol‐induced hepatic steatosis in L02 cells and elucidate the potential mechanism. In brief, L02 cells were pretreated with or without ethanol (3%) for 24 h, then treated quercetin (80, 40, 20 μM) for 24 h. The transfection procedure was performed with transcription factor EB (TFEB) small interfering RNA (siRNA TFEB) for 24 h. Our results showed that quercetin autophagic flux in the L02 cells, via upregulating of microtubule associated protein light chain 3B (LC3‐II) and lysosome‐associated membrane protein 1 (LAMP1), then downregulating of protein sequestosome 1 (SQSTM1/p62). Mechanistically, quercetin activated TFEB nuclear translocation, contributing to lysosomal biogenesis and autophagic activation. Accordingly, the genetic inhibition of TFEB‐dependent autophagy decreased ethanol‐induced fat accumulation in L02 cells via regulating fatty acid β oxidation and lipid synthesis. Subsequently, quercetin‐induced TFEB‐dependent autophagic activation was also linked to inhibit oxidative stress via suppressing reactive oxygen species (ROS), enhancing activities of antioxidant enzymes, and promoting nuclear transfer of the nuclear factor E2‐related factor 2 (Nrf2) translocation. Thus, we uncovered a novel protective mechanism against ethanol‐induced hepatic steatosis and oxidative stress through TFEB‐mediated lysosomal biogenesis and discovered insufficient autophagy as a novel previously unappreciated autophagic flux.

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Section: Discussionmentioning

confidence: 99%

Section: Quercetin Activated Ampk-tfeb-mtormediated Lipid Metabolismmentioning

confidence: 99%

Quercetin alleviates ethanol‐induced hepatic steatosis in L02 cells by activating TFEB translocation to compensate for inadequate autophagy

Zhao

Xue

Wang

et al. 2022

Phytotherapy Research

View full text Add to dashboard Cite

show abstract

“…Alcohol-related liver disease (ALD) is a chronic liver disease caused by long-term, high-frequency alcohol intake with poor treatment response, prognosis and survival [ 134 ]. Alcoholic hepatitis (AH) is a clinical form of ALD characterized by acute alcohol-induced liver injury as a pathological manifestation [ 135 ].…”

Section: Imbalance Of Liver Immune Microenvironment and Liver Diseasesmentioning

confidence: 99%

Mesenchymal stem cells-based therapy in liver diseases

Han

Jin

2022

Mol Biomed

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Multiple immune cells and their products in the liver together form a complex and unique immune microenvironment, and preclinical models have demonstrated the importance of imbalances in the hepatic immune microenvironment in liver inflammatory diseases and immunocompromised liver diseases. Various immunotherapies have been attempted to modulate the hepatic immune microenvironment for the purpose of treating liver diseases. Mesenchymal stem cells (MSCs) have a comprehensive and plastic immunomodulatory capacity. On the one hand, they have been tried for the treatment of inflammatory liver diseases because of their excellent immunosuppressive capacity; On the other hand, MSCs have immune-enhancing properties in immunocompromised settings and can be modified into cellular carriers for targeted transport of immune enhancers by genetic modification, physical and chemical loading, and thus they are also used in the treatment of immunocompromised liver diseases such as chronic viral infections and hepatocellular carcinoma. In this review, we discuss the immunological basis and recent strategies of MSCs for the treatment of the aforementioned liver diseases. Specifically, we update the immune microenvironment of the liver and summarize the distinct mechanisms of immune microenvironment imbalance in inflammatory diseases and immunocompromised liver diseases, and how MSCs can fully exploit their immunotherapeutic role in liver diseases with both immune imbalance patterns.

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“…Alcohol-related liver disease (ALD) is the most frequent cause of advanced chronic liver disease worldwide, contributing to 47.9% of all liver cirrhosis-related deaths globally [1]. Alcoholic hepatitis (AH) is an acute form of ALD that ranges from mild to severe disease states and usually presents on a background of cirrhosis [2].…”

Section: Introductionmentioning

confidence: 99%

“…Severe alcoholic hepatitis (sAH) is defined as a Maddrey discriminant function (MDF) of > 32 and/or a model for end-stage liver disease (MELD)-score of more than 20 in a patient with a recent onset of jaundice and a chronic alcohol use disorder [3]. sAH is the most severe manifestation of ALD with a 28-day mortality of 20-50% [1]. ALD has a complex pathogenesis, involving multiple mechanistic pathways [4].…”

Section: Introductionmentioning

confidence: 99%