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Exp Mol Pathol. 2014 Dec;97(3):492-510. doi: 10.1016/j.yexmp.2014.09.005. Epub 2014 Sep 11.

Alcoholic and non-alcoholic steatohepatitis.

Author information

1
In Vitro Drug Safety and Biotechnology, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: manuela.neuman@utoronto.ca.
2
Harbor-UCLA Medical Center, Torrance, CA, USA.
3
Centre of Alcohol Research, University of Heidelberg and Department of Medicine (Gastroenterology and Hepatology), Salem Medical Centre, Heidelberg, Germany.
4
Division of Gastroenterology, Sunnybrook Health Sciences Centre, Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
5
Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Internal Medicine, Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
6
Drug Health Services, Royal Prince Alfred Hospital, Centenary Institute of Cancer Medicine and Cell Biology, Camperdown, NSW 2050, Australia; Faculty of Medicine, The University of Sydney, Sydney, NSW 2006, Australia.
7
Office of Extramural Activities, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA.
8
Department of Surgery, Carolinas Medical Center, Charlotte, NC, USA.
9
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine and Department of Pharmacology; Toxicology, University of Louisville School of Medicine, Louisville, KY, USA.
10
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine and Department of Pharmacology; Toxicology, University of Louisville School of Medicine, Louisville, KY, USA; Robley Rex Veterans Medical Center, Louisville, KY, USA.
11
Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
12
In Vitro Drug Safety and Biotechnology, University of Toronto, Toronto, Ontario, Canada.
13
Division of Nephrology and Internal Medicine, Fundeni Clinical Institute and University of Medicine and Pharmacy, "Carol Davila", Bucharest, Romania.
14
In Vitro Drug Safety and Biotechnology, University of Toronto, Toronto, Ontario, Canada; Family Medicine Clinic CAR, Bucharest, Romania.
15
Department Internal Medicine, Kaplan Medical Centre and Hebrew University of Jerusalem, Rehovot, Israel.

Abstract

This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human immunodeficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible repair. We aim to (1) determine the immuno-pathology of alcohol-induced liver damage, (2) examine the role of genetics in the development of ASH, (3) propose diagnostic markers of ASH and NASH, (4) examine age differences, (5) develop common research tools to study alcohol-induced effects in clinical and pre-clinical studies, and (6) focus on factors that aggravate severity of organ-damage. The intention of these symposia is to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism.

KEYWORDS:

Alcoholic hepatitis; Alcoholic liver disease; CYP2E1; Hangover; Hepatocarcinogenesis; Human immunodeficiency virus; Immunohistochemistry; Laboratory markers; Mallory–Denk bodies; Methylation; Micronutrients; Mitochondrion; Nonalcoholic steatohepatitis; Viral hepatitis

PMID:
25217800
PMCID:
PMC4696068
DOI:
10.1016/j.yexmp.2014.09.005
[Indexed for MEDLINE]
Free PMC Article

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