Alcoholic-Hepatitis, Links to Brain and Microbiome: Mechanisms, Clinical and Experimental Research
Manuela G. Neuman,
Helmut Karl Seitz,
Samuel W. French,
Stephen Malnick,
Heidekazu Tsukamoto,
Lawrence B. Cohen,
Paula Hoffman,
Boris Tabakoff,
Michael Fasullo,
Laura E. Nagy,
Pamela L. Tuma,
Bernd Schnabl,
Sebastian Mueller,
Jennifer L. Groebner,
French A. Barbara,
Jia Yue,
Afifiyan Nikko,
Mendoza Alejandro,
Tillman Brittany,
Vitocruz Edward,
Kylie Harrall,
Laura Saba,
Opris Mihai
Affiliations
Manuela G. Neuman
In Vitro Drug Safety and Biotechnology, Toronto, ON M5G 1L5, Canada
Helmut Karl Seitz
Department of Medicine, Centre of Alcohol Research, University of Heidelberg, Salem Medical Centre, 337374 Heidelberg, Germany
Samuel W. French
Department of Pathology, Harbor-UCLA Medical Center and Los Angeles BioMedical Institute, Torrance, CA Harbor-UCLA Medical Center, Torrance, CA 90509, USA
Stephen Malnick
Department Internal Medicine C, Kaplan Medical Centre and Hebrew University of Jerusalem, Rehovot 76100, Israel
Heidekazu Tsukamoto
Southern California Research Center for ALPD and Cirrhosis, Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089-5311, USA
Lawrence B. Cohen
Division of Gastroenterology, Sunnybrook Health Sciences Centre, Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON M4N 3M5, Canada
Paula Hoffman
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045-0511, USA
Boris Tabakoff
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045-0511, USA
Michael Fasullo
College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, NY 12205, USA
Laura E. Nagy
Departments of Pathobiology and Gastroenterology, Center for Liver Disease Research, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Pamela L. Tuma
Department of Biology, The Catholic University of America, Washington, DC 20064, USA
Bernd Schnabl
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Sebastian Mueller
Department of Medicine, Centre of Alcohol Research, University of Heidelberg, Salem Medical Centre, 337374 Heidelberg, Germany
Jennifer L. Groebner
Department of Biology, The Catholic University of America, Washington, DC 20064, USA
French A. Barbara
Department of Pathology, Harbor-UCLA Medical Center and Los Angeles BioMedical Institute, Torrance, CA Harbor-UCLA Medical Center, Torrance, CA 90509, USA
Jia Yue
Department of Pathology, Harbor-UCLA Medical Center and Los Angeles BioMedical Institute, Torrance, CA Harbor-UCLA Medical Center, Torrance, CA 90509, USA
Afifiyan Nikko
Department of Pathology, Harbor-UCLA Medical Center and Los Angeles BioMedical Institute, Torrance, CA Harbor-UCLA Medical Center, Torrance, CA 90509, USA
Mendoza Alejandro
Department of Pathology, Harbor-UCLA Medical Center and Los Angeles BioMedical Institute, Torrance, CA Harbor-UCLA Medical Center, Torrance, CA 90509, USA
Tillman Brittany
Department of Pathology, Harbor-UCLA Medical Center and Los Angeles BioMedical Institute, Torrance, CA Harbor-UCLA Medical Center, Torrance, CA 90509, USA
Vitocruz Edward
Department of Pathology, Harbor-UCLA Medical Center and Los Angeles BioMedical Institute, Torrance, CA Harbor-UCLA Medical Center, Torrance, CA 90509, USA
Kylie Harrall
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045-0511, USA
Laura Saba
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045-0511, USA
Opris Mihai
In Vitro Drug Safety and Biotechnology, Toronto, ON M5G 1L5, Canada
The following review article presents clinical and experimental features of alcohol-induced liver disease (ALD). Basic aspects of alcohol metabolism leading to the development of liver hepatotoxicity are discussed. ALD includes fatty liver, acute alcoholic hepatitis with or without liver failure, alcoholic steatohepatitis (ASH) leading to fibrosis and cirrhosis, and hepatocellular cancer (HCC). ALD is fully attributable to alcohol consumption. However, only 10−20% of heavy drinkers (persons consuming more than 40 g of ethanol/day) develop clinical ALD. Moreover, there is a link between behaviour and environmental factors that determine the amount of alcohol misuse and their liver disease. The range of clinical presentation varies from reversible alcoholic hepatic steatosis to cirrhosis, hepatic failure, and hepatocellular carcinoma. We aimed to (1) describe the clinico-pathology of ALD, (2) examine the role of immune responses in the development of alcoholic hepatitis (ASH), (3) propose diagnostic markers of ASH, (4) analyze the experimental models of ALD, (5) study the role of alcohol in changing the microbiota, and (6) articulate how findings in the liver and/or intestine influence the brain (and/or vice versa) on ASH; (7) identify pathways in alcohol-induced organ damage and (8) to target new innovative experimental concepts modeling the experimental approaches. The present review includes evidence recognizing the key toxic role of alcohol in ALD severity. Cytochrome p450 CYP2E1 activation may change the severity of ASH. The microbiota is a key element in immune responses, being an inducer of proinflammatory T helper 17 cells and regulatory T cells in the intestine. Alcohol consumption changes the intestinal microbiota and influences liver steatosis and liver inflammation. Knowing how to exploit the microbiome to modulate the immune system might lead to a new form of personalized medicine in ALF and ASH.
