Essay Example on Alcoholic Fatty Liver

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Alcoholic Fatty Liver The liver is a highly metabolic organ Viollet et al 2009 It acts as a pivot point between the fasting and feeding states and as such has both catabolic and anabolic capabilities These processes are implicated when an excess of alcohol results in inadequate metabolism endoplasmic reticulum stress and increased fatty acid and triglyceride synthesis all of which lead to steatosis The peroxisome proliferator activated receptor α is critical for alcohol metabolism and when down regulated or depleted results in massive fat accumulation Zeng et al 2012 Bala et al 2016 Sterol regulatory element binding proteins SREBP and 50 adenosine monophosphate activated protein kinase AMPK are also implicated in ALD since they play an important role in regulating lipid metabolism and their expression is altered under alcohol consumption Altamirano and Bataller 2011 Zhang et al 2015 Down regulation of AMPK by alcohol decreases its ability to inactivate SREBP and increases adenylyl cyclase activity contributing to steatosis Garcia et al 2008 



Recent advances in the field have shown that dietary lipids such as saturated and unsaturated fat play a critical role in alcohol induced liver pathology For a careful summary of recent advances on the role of dietary lipids in ALD Kirpich et al 2016 Lipid accumulation is a critical feature in ALD it also represents the early stage of the disease and it may be accompanied by inflammation fibrosis and cirrhosis and hepatocellular carcinoma Importantly steatosis will develop in the majority of individuals who regularly consume alcohol in excess of 40 g day Stickel et al 2017 In 10 35 of drinkers the presence of steatosis may be complicated by the development of inflammation and fibrosis where cirrhosis will likely develop in about 10 15 of these patients Teli et al 1995 and 1 2 of them progress to hepatocellular carcinoma HCC Stickel 2015 b Alcoholic Hepatitis Progressive inflammatory liver injury due to ethanol intake leads to AH characterized by poor liver function ductular reaction Sancho Bru et al 2012 Dubuquoy et al 2015 high levels of LPS and impaired hepatocyte proliferation Odena et al 2016 All these events along with sterile and non sterile inflammation Laursen et al 2016 are mechanisms involved in the pathogenesis of the disease AH has a significant short term mortality Key features are a significant increase in proinflammatory cytokines like tumor necrosis factor α TNF α and interleukins IL 1 and 6 Alcohol abstinence has demonstrated to benefit these patients by improving the prognosis in early and advanced stages Lackner et al 2016 Pentoxifylline and prednisolone improve short time survival of AH and continue to be the main treatment for these patients although corticosteroids could be detrimental since they increase the risk of bleeding and infections Garcia et al 2016

Thus assessment of early response to corticosteroids identification of novel biomarkers and or unique drugs targets for the treatment of moderate and severe AH are still required to adequately monitor and treat this disease c Alcoholic Fibrosis 3 ﻫﺎم Liver fibrosis is a wound healing response to virtually all forms of chronic liver injury it is characterizedby excessive accumulation of collagen and other extracellular matrix proteins Bataller and Brenner 2005 Friedman 2008 Activated HSCs are the major source of the increased production of extracellular matrix proteins along with portal fibroblasts and bone marrow derived myofibroblasts Hepatocellular damage increases levels of and activates many cytokines chemokines neuroendocrine factors angiogenic factors and components of the innate immune system that subsequently induce HSC activation and fibrogenesis Bataller and Brenner 2005 Friedman 2008 Most of these fibro genic mechanisms occur during alcoholic liver fibrogenesis whereas some unique mechanisms also contribute to alcoholic liver fibrosis Purohit and Brenner 2006 Cubero et al 2009 d Alcoholic Cirrhosis Excess alcohol consumption is the most frequent cause of cirrhosis in Europe Rehm et al 2013

 In the United States the prevalence of cirrhosis is 0 27 corresponding to 633 323 adults in 2015 Scaglione et al 2015 higher than previously estimated Thus liver cirrhosis is an important public health concern and a significant cause of morbidity and mortality worldwide In most cases in addition to alcohol consumption lifestyle gender ethnic and socioeconomic factors may contribute or synergize in the progression of the disease In patients with decompensated ALD cirrhosis is more frequent and features of hepatocellular damage lobular inflammation hepatocellular ballooning degeneration and hepatocyte drop out megamitochondria and the appearance of Mallory Denk bodies are more dominant Lackner et al 2016 Liver cirrhosis leads to severe complications such as variceal bleeding ascites and hepatic encephalopathy When cirrhosis occurs the sinusoidal space ensuring blood supply to the parenchyma decreases sinusoidal endothelial cell fenestrations collapse and numerous new vessels formed around the cirrhotic nodules bypass the obstructed normal route This vascular proliferation contributes to the remodeling of the liver architecture collateral flow and portal hypertension The latter is a frequent and severe complication of cirrhosis a leading cause of death and an indicator for liver transplantation Lemoinne et al 2015


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