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Journal of Gastroenterology and Digestive Diseases | Volume 3
May 25-26, 2018 | New York, USA
World Liver Conference 2018
N
onalcoholic fatty liver disease (NAFLD), hepatic
manifestation of metabolic syndrome is now the
commonest chronic liver disease due to rising obesity and
diabetes. NAFLD progresses from simple steatosis (NAFL) to
steatohepatitis (NASH) and cirrhosis. In presence of suitable
genetic and environmental factors (diet/physical activity/
gut dysbiosis), insulin resistance (IR) and obesity results
in adipose dysfunction, which triggers proinflammatory
response, decreased lipolysis, increased de-novo lipogenesis
and further increased IR. These events increase free fatty acid
(FFA) flux to liver, which leads to triglyceride accumulation
(NAFL). Toxic levels of FFA in liver trigger increasedβ-oxidation
and mitochondrial dysfunction (MD). Obesity, homocysteine
and environmental factors trigger endoplasmic reticulum
stress (ERS). MD and ERS result in reactive oxygen species
(ROS) production. ROS activates antioxidant mechanisms
(consisting of enzymes like Superoxide dismutase, catalase,
glutathione peroxidase, glutathione reductase, glutathione
transferase; and non-enzymes like vitamin A, C, E, β-carotene
and glutathione) which scavenges them, but over production
ofROSresultsindepletionofantioxidants.Homocysteineadds
to ROS production and suppresses antioxidants. Oxidative
stress results in proinflammatory cytokine production, lipid
peroxidation (measured by Malonildialdehyde) and protein
adducts production leading to cell injury, inflammation and
cell death leading to NASH. In addition, it triggers hepatic
stellate cell activation leading to fibrosis and subsequently
cirrhosis. Oxidative stress also produces DNA damage
leading to future hepatocellular carcinoma. So, oxidative
stress remains central to development of NASH and cirrhosis.
In clinical practice, differentiating NAFL and NASH requires
liver biopsy because non-invasive scoring systems are not
sensitive. Measuring homocysteine and enzymes (like
glutathione transferase, glutathione peroxidase, catalase,
etc.) may prove helpful to define progress to NASH. Also
targeting these molecules by newer therapeutic strategies
may halt progression of NAFLD.
Speaker Biography
Nikhil D Patel (MD, DNB [Gastroenterology]) is practicing as a Consultant
Gastroenterologist since 12 years. He has around 50 publications in various journals.
He has presented more than 80 scientific papers in reputed conferences.
e:
niyopatel@yahoo.comRole of oxidative stress and homocysteine in non-alcoholic fatty liver disease
Nikhil D Patel
Jivandeep Hospital, India