Alcoholic steatohepatitis

Stickel, Felix; Seitz, Helmut K.

doi:10.1016/j.bpg.2010.07.003

Cited by 52 publications

(34 citation statements)

References 80 publications

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“…11,57,118-120 We briefly summarize the treatment of AH, focusing mainly on recently identified potential therapeutic targets (Figure 5). …”

Section: Pathogenesismentioning

confidence: 99%

“…141 Several liver transplantation centers have therefore proposed that this be a rescue option for patients with severe AH who do not respond to medical therapy and are unlikely to survive the mandatory, 6-month abstinence period but who fulfill all other standard criteria for transplantation, including a thorough psychosocial evaluation. 118,142 …”

Section: Pathogenesismentioning

confidence: 99%

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Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets

2011

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Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide and can lead to fibrosis and cirrhosis. The latest surveillance report published by the National Institute on Alcohol Abuse and Alcoholism showed that liver cirrhosis was the 12th leading cause of death in the United States, with a total of 29,925 deaths in 2007, 48% of which were alcohol related. The spectrum of ALD includes simple steatosis, alcoholic hepatitis, fibrosis, cirrhosis, and superimposed hepatocellular carcinoma. Early work on the pathogenesis of the disease focused on ethanol metabolism–associated oxidative stress and glutathione depletion, abnormal methionine metabolism, malnutrition, and production of endotoxins that activate Kupffer cells. We review findings from recent studies that have characterized specific intracellular signaling pathways, transcriptional factors, aspects of innate immunity, chemokines, epigenetic features, microRNAs, and stem cells that are associated with ALD, improving our understanding of its pathogenesis. Despite this progress, no targeted therapies are available. The cornerstone of treatment for alcoholic hepatitis remains as it was 40 years ago: abstinence, nutritional support, and corticosteroids. There is an urgent need to develop new pathophysiology-oriented therapies. Recent translational studies of human samples and animal models have identified promising therapeutic targets.

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“…11,57,118-120 We briefly summarize the treatment of AH, focusing mainly on recently identified potential therapeutic targets (Figure 5). …”

Section: Pathogenesismentioning

confidence: 99%

Section: Pathogenesismentioning

confidence: 99%

Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets

2011

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“…Excessive ethanol consumption can generate alcoholic liver disease (ALD) 7 , ranging from simple steatosis to severe forms of liver injury, such as steatohepatitis, cirrhosis, and hepatocellular carcinoma (1,2). Hepatic steatosis is the first manifestation of ALD, which is characterized by lipid accumulation in hepatocytes.…”

Section: Introductionmentioning

confidence: 99%

Luteolin Alleviates Alcoholic Liver Disease Induced by Chronic and Binge Ethanol Feeding in Mice

Liu

Zhang

Liu

et al. 2014

The Journal of Nutrition

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Ethanol consumption can lead to hepatic steatosis that contributes to late-stage liver diseases such as cirrhosis and hepatocellular carcinoma. In this study, we investigated the potential protective effect of a flavonoid, luteolin, on ethanol-induced fatty liver development and liver injury. Six-wk-old male C57BL/6 mice were divided into 3 groups: a control group; a group exposed to alcohol by using a chronic and binge ethanol feeding protocol (EtOH); and a group that was administered daily 50 mg/kg of luteolin in addition to ethanol exposure (EtOH + Lut). A chronic and binge ethanol feeding protocol was used, including chronic ethanol consumption (1%, 2%, and 4% for 3 d, and 5% for 9 d) and a binge (30% ethanol) on the last day. Compared with the control group, the EtOH group had a significant elevation in serum concentrations of alanine aminotransferase (ALT) (561%), triglyceride (TG) (47%), and LDL cholesterol (95%), together with lipid accumulation in the liver. Compared with the EtOH group, the EtOH + Lut group had significant reductions in serum concentrations of ALT (43%), TG (22%), LDL cholesterol (52%), and lipid accumulation in the liver. Ethanol elevated liver expression of lipogenic genes including sterol regulatory element-binding protein 1c (Srebp1c) (560%), fatty acid synthase (Fasn) (190%), acetyl-CoA carboxylase (Acc) (48%), and stearoyl-CoA desaturase 1 (Scd1) (286%). Luteolin reduced ethanol-induced expression of these genes in the liver: Srebp1c (79%), Fasn (80%), Acc (60%), and Scd1 (89%). In cultured hepatocytes, luteolin prevented alcohol-induced lipid accumulation and increase in the expression of lipogenic genes. The transcriptional activity of the master regulator of lipid synthesis, sterol regulatory element-binding protein (SREBP), was enhanced by ethanol treatment (160%) and reduced by luteolin administration (67%). In addition, ethanol-induced reduction of AMP-activated protein kinase and SREBP-1c phosphorylation was abrogated by luteolin. Collectively, our study indicates that luteolin is effective in ameliorating ethanol-induced hepatic steatosis and injury.

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“…Patients with severe AH who do not respond to medical are unlikely to survive the “mandatory” 6-month abstinence period as their risk of mortality is quite high 30,31 . However post-transplant outcomes appear to be good for highly selected patients with severe AH unresponsive to medical therapy with low rates of alcohol relapse 32,33 .…”

Section: Role Of Transplantation In Alcoholic Hepatitismentioning

confidence: 99%

New therapeutic targets in alcoholic hepatitis

2016

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Alcoholic liver disease (ALD) is a leading cause of liver related morbidity and mortality worldwide. ALD encompasses a spectrum of disorders including asymptomatic steatosis, steatohepatitis, fibrosis, cirrhosis and its related complications, and the acute on chronic state of alcoholic hepatitis. While multidisciplinary efforts continue to be aimed at curbing progression of this spectrum of disorders, there is an urgent need to focus our efforts on effective therapeutic interventions for alcoholic hepatitis (AH), the most severe form of ALD. AH is characterized by an abrupt development of jaundice and complications related to liver insufficiency and portal hypertension in patients with heavy alcohol intake. The mortality of patients with severe AH is very high (20–50% at 3 months). The current therapeutic regimens are limited. The development of new therapies requires translational studies in human samples and suitable animal models that reproduce clinical and histological features of human AH. This review article summarizes the clinical syndrome, pre-clinical translational tools, and pathogenesis of AH at a molecular and cellular level, with the aim to identify new targets of potential therapeutic intervention.

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Alcoholic steatohepatitis

Cited by 52 publications

References 80 publications

Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets

Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets

Luteolin Alleviates Alcoholic Liver Disease Induced by Chronic and Binge Ethanol Feeding in Mice

New therapeutic targets in alcoholic hepatitis

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