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Manuela G. Neuman1,2

1In Vitro Drug Safety and Biotechnology,
2Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

Alcohol metabolism involves several enzymes, including alcohol dehydrogenase, acetaldehyde dehydrogenase and CYP2E1. Since the risk of developing ALD is mediated by genetic polymorphisms in these enzymes, an understanding of the genetic predisposition of the individual is required. Moreover, CYP2E1 is involved in the metabolism of various other drugs, potentiating drug-drug interactions. Another important aspect of ALD progression is its co-morbidity with chronic viral hepatitis. The interaction between alcohol and medications used to treat HCV can exacerbate the degree of hepatotoxicity.
Nonalcoholic fatty liver disease (NAFLD) refers to liver damage in absence of alcohol abuse or viral hepatitis, ranging from fat inclusion in the liver (steatosis) to liver inflammation, and non-alcoholic steatohepatitis (NASH) leading to liver cancer. Progression from one stage to the next can be triggered by genetic or environmental factors and their interaction. In addition, NAFLD represents the hepatic manifestation of the metabolic syndrome. The association of obesity, type 2 diabetes mellitus, hyper-triglyceridemia and hypertension with insulin resistance has been recognized. A better understanding of predisposing immuno-genetic factors will lead to progress in diagnostic and predictive tests for NAFLD-NASH. The fibrosis pathways, as well as the degree of fibrosis, further determine disease progression both in ALD and in NAFLD. It is crucial to recognize that, because of the ALD process, some of the nutritional requirements change. Alcohol may induce activation of the innate immune system and autoimmunity through recognition of acetaldehyde-modified proteins, which may be implicated in the pathogenicity of acute alcoholic hepatitis. Therefore, anti-inflammatory agents may also be required as add-on therapy. The relationship between alcohol consumption and changes in the gut microbiota must also be considered. Also in NAFLD, change in microbiome may be considered as therapy. Finally, since excess drinking is the core of the issue, anti-craving agents should be incorporated in any contemplated therapeutic plan for ALD. In addition to treating the underlying disease, counseling can help increase alcohol or unhealthy food abstinence, thereby improving the quality of life and increasing survival rates among ALD/NAFLD patients.