Combined alcoholic and non-alcoholic steatohepatitis

Wandji, Line Carolle Ntandja; Gnemmi, Viviane; Louvet, Alexandre

doi:10.1016/j.jhepr.2020.100101

Cited by 53 publications

(47 citation statements)

References 142 publications

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“…Long-term drinking causes hepatic inflammation and hepatocyte injury by multiple mechanisms, including accumulation of reactive oxygen species (ROS) causing oxidative stress, and toxicity of both lipopolysaccharide and acetaldehyde [ 9 ]. Moreover, pathology is also exacerbated by coexisting conditions such as viral hepatitis, obesity and environmental toxins, among others [ 6 ].…”

Section: Alcohol-associated Liver Diseasementioning

confidence: 99%

“…ALD includes a wide spectrum of liver conditions ranging from hepatic steatosis to steatohepatitis and fibrosis, which could progress to liver cirrhosis and even hepatocellular carcinoma ( Figure 1 ) [ 6 ]. Alcohol-associated fatty liver (AFL) is the earliest stage of ALD, and it occurs in almost 90% of alcohol consumers [ 13 ].…”

Section: Alcohol-associated Liver Diseasementioning

confidence: 99%

“…Alcohol-associated steatohepatitis (ASH) is a form of hepatic injury manifesting microscopically as inflammation with ballooning of hepatocytes [ 17 ]. Obesity is increasingly recognized as a prominent coexisting risk factor [ 6 , 18 , 19 , 20 ]. ASH occurs due to ongoing hepatic inflammation which triggers the release of damage-associated molecular patterns (DAMPs), which lead to stimulation and recruitment of inflammatory cells such as polymorphonuclear leukocytes (PMNLs) and T cells as well as stimulation of Kupffer cells (KCs).…”

Section: Alcohol-associated Liver Diseasementioning

confidence: 99%

“…Long-term heavy drinking causes liver damage via several mechanisms, such as oxidative stress with accumulation of reactive oxygen species (ROS) generated from alcohol metabolism; lipopolysaccharide-induced inflammatory response; acetaldehyde toxicity; and nicotinamide adenine dinucleotide (NAD) depletion, to name a few [ 5 ]. ALD could be exacerbated by other coexisting liver conditions such as chronic viral hepatitis and non-alcoholic fatty liver disease (NAFLD) [ 6 ]. There is no FDA-approved therapy available for any stage of ALD, and standard of care includes alcohol abstinence and nutritional support as the conventional treatment strategies for ALD in the clinic [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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cAMP Signaling in Pathobiology of Alcohol Associated Liver Disease

et al. 2020

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The importance of cyclic adenosine monophosphate (cAMP) in cellular responses to extracellular signals is well established. Many years after discovery, our understanding of the intricacy of cAMP signaling has improved dramatically. Multiple layers of regulation exist to ensure the specificity of cellular cAMP signaling. Hence, disturbances in cAMP homeostasis could arise at multiple levels, from changes in G protein coupled receptors and production of cAMP to the rate of degradation by phosphodiesterases. cAMP signaling plays critical roles in metabolism, inflammation and development of fibrosis in several tissues. Alcohol-associated liver disease (ALD) is a multifactorial condition ranging from a simple steatosis to steatohepatitis and fibrosis and ultimately cirrhosis, which might lead to hepatocellular cancer. To date, there is no FDA-approved therapy for ALD. Hence, identifying the targets for the treatment of ALD is an important undertaking. Several human studies have reported the changes in cAMP homeostasis in relation to alcohol use disorders. cAMP signaling has also been extensively studied in in vitro and in vivo models of ALD. This review focuses on the role of cAMP in the pathobiology of ALD with emphasis on the therapeutic potential of targeting cAMP signaling for the treatment of various stages of ALD.

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Section: Alcohol-associated Liver Diseasementioning

confidence: 99%

Section: Alcohol-associated Liver Diseasementioning

confidence: 99%

Section: Alcohol-associated Liver Diseasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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cAMP Signaling in Pathobiology of Alcohol Associated Liver Disease

et al. 2020

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“…The changing scenario is attributed to improved antiviral therapy for virus-related HCC (50). With the growing inclination towards western dietary pattern, sociocultural changes and the lifestyle with limited or no physical activity has sharply increased the incidence rates of NAFLD-and AFLD-associated HCC across the continents (51,52). The pathological spectra of liver injury in promoting HCC development are similar in these two fatty liver diseases despite having divergent pathogenic origin with yet some key distinct features ( Figure 2).…”

Section: Fatty Liver Disease and Hccmentioning

confidence: 99%

Etiology of Hepatocellular Carcinoma: Special Focus on Fatty Liver Disease

2020

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Hepatocellular Carcinoma (HCC) is a highly aggressive cancer with mortality running parallel to its incidence and has limited therapeutic options. Chronic liver inflammation and injury contribute significantly to the development and progression of HCC. Several factors such as gender, age, ethnicity, and demographic regions increase the HCC incidence rates and the major risk factors are chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), carcinogens (food contaminants, tobacco smoking, and environmental toxins), and inherited diseases. In recent years evidence highlights the association of metabolic syndrome (diabetes and obesity), excessive alcohol consumption (alcoholic fatty liver disease), and high-calorie intake (nonalcoholic fatty liver disease) to be the prime causes for HCC in countries with a westernized sedentary lifestyle. HCC predominantly occurs in the setting of chronic liver disease and cirrhosis (80%), however, 20% of the cases have been known in patients with non-cirrhotic liver. It is widely believed that there exist possible interactions between different etiological agents leading to the involvement of diverse mechanisms in the pathogenesis of HCC. Understanding the molecular mechanisms of HCC development and progression is imperative in developing effective targeted therapies to combat this deadly disease. Noteworthy, a detailed understanding of the risk factors is also critical to improve the screening, early detection, prevention, and management of HCC. Thus, this review recapitulates the etiology of HCC focusing especially on the nonalcoholic fatty liver disease (NAFLD)- and alcoholic fatty liver disease (AFLD)-associated HCC.

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DDIT4 S‐Nitrosylation Aids p38‐MAPK Signaling Complex Assembly to Promote Hepatic Reactive Oxygen Species Production

Zhao

et al. 2021

Advanced Science

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Mitogen-activated protein kinase (MAPK) signaling plays a significant role in reactive oxygen species (ROS) production. The authors have previously shown that Brahma-related gene 1 (BRG1), a chromatin remodeling protein, contributes to hepatic ROS accumulation in multiple animal and cellular models of liver injury. Here it is reported that DNA damage-induced transcript 4 (DDIT4) is identified as a direct transcriptional target for BRG1. DDIT4 overexpression overcomes BRG1 deficiency to restore ROS production whereas DDIT4 knockdown phenocopies BRG1 deficiency in suppressing ROS production in vitro and in vivo. Mechanistically, DDIT4 coordinates the assembly of the p38-MAPK signaling complex to drive ROS production in an S-nitrosylation dependent manner. Molecular docking identifies several bioactive DDIT4-inteacting compounds including imatinib, nilotinib, and nateglinide, all of which are confirmed to attenuate hepatic ROS production, dampen p38-MAPK signaling, and ameliorate liver injury by influencing DDIT4 S-nitrosylation. Importantly, positive correlation between ROS levels and BRG1/DDIT4/S-nitrosylated DDIT4 levels is detected in human liver biopsy specimens. In conclusion, the data reveal a transcription-based signaling cascade that contributes to ROS production in liver injury.

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Combined alcoholic and non-alcoholic steatohepatitis

Cited by 53 publications

References 142 publications

cAMP Signaling in Pathobiology of Alcohol Associated Liver Disease

cAMP Signaling in Pathobiology of Alcohol Associated Liver Disease

Etiology of Hepatocellular Carcinoma: Special Focus on Fatty Liver Disease

DDIT4 S‐Nitrosylation Aids p38‐MAPK Signaling Complex Assembly to Promote Hepatic Reactive Oxygen Species Production

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