Alcoholic Liver Disease: Diagnostics and Therapeutics

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (30 October 2019) | Viewed by 39843

Special Issue Editors

Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Goethe University, 999035 Frankfurt, Germany
Interests: alcoholic liver disease; alcoholic liver injury; alcohol metabolism; microsomal ethanol-oxidizing system; drug induced liver injury; herb induced liver injury; herbal traditional Chinese medicine (TCM); dietary supplements; causality assessment
Special Issues, Collections and Topics in MDPI journals
Centre of Liver- and Alcohol Diseases, Ethianum Clinic Heidelberg, Germany
Interests: alcohol metabolism and toxicity; carcinogenesis; liver disease;
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Alcoholic liver disease (ALD) is basically a molecular rather than a nutritional disease. It results from disturbances in hepatic functions and subcellular structures due to the metabolism of ethanol as a short-chain chemical derived from natural plant resources, such as grapes. In addition, gut-derived endotoxins further contribute to the disease. Whereas small amounts of alcohol ingested for a short period are well-handled by the liver, prolonged alcohol abuse commonly leads initially to alcoholic fatty liver disease (AFLD) or perhaps alcoholic steatohepatitis (ASH). More severe stages include alcoholic hepatitis (AH), alcoholic cirrhosis (AC), and alcoholic hepatocellular carcinoma (AHCC). Patients with early stages of ALD are commonly asymptomatic, a condition that rarely allows for a timely diagnosis and the recommendation to abstain from alcohol use, which may lead to clinically more severe stages of the disease. For instance, severe AH, which commonly presents as an acute or chronic disease, is a particular clinical challenge for which several options of pharmacotherapy with limited success are available. Thus, liver transplantation, although discussed controversially, is currently under consideration. AC represents the end stage of ALD, and its complications, such as bleeding of esophageal varices, hepatic encephalopathy, or ascites, require specific treatment. Most of these complications can be handled conservatively; however, in a few patients, a liver transplantation may have to be considered. Finally, AHCC occurs rarely and commonly develops from AC. Patients with AHCC have a poor prognosis despite medical treatment, local interventions, or liver transplantation. In essence, ALD is clinical disorder that requires early diagnosis at the AFLD stage or the ASH stage to achieve abstinence from alcohol use and to prevent the late stages of the disease that are irreversible and life-threatening. This special issue is intended to bring together experts in the field to present their views on specific issues that may yet be a matter of uncertainty and under discussion. Apart from solicited authors, other contributors are welcome to submit abstracts that will be fairly assessed with the potential for encouragement to submit a full-length paper.

Prof. Dr. Rolf Teschke
Prof. Dr. Helmut K. Seitz
Guest Editors

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Keywords

  • Alcoholic liver disease
  • Alcoholic fatty liver disease
  • Alcoholic hepatitis
  • Alcoholic cirrhosis
  • Alcoholic hepatocellular carcinoma
  • Alcohol abstinence
  • Pharmacotherapy options
  • Liver transplantation

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Published Papers (4 papers)

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Research

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10 pages, 1517 KiB  
Article
Global Burden of Alcohol Use Disorders and Alcohol Liver Disease
by Jürgen Rehm and Kevin D. Shield
Biomedicines 2019, 7(4), 99; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines7040099 - 13 Dec 2019
Cited by 91 | Viewed by 11072
Abstract
Alcohol use is a major risk factor for burden of mortality and morbidity. Alcoholic liver disease (ALD) and alcohol use disorders (AUDs) are important disease outcomes caused by alcohol use. We will describe the global mortality and burden of disease in disability-adjusted life [...] Read more.
Alcohol use is a major risk factor for burden of mortality and morbidity. Alcoholic liver disease (ALD) and alcohol use disorders (AUDs) are important disease outcomes caused by alcohol use. We will describe the global mortality and burden of disease in disability-adjusted life years for ALD and AUDs, based on data from the comparative risk assessment of the World Health Organization for 2016. AUDs have a limited impact on mortality in this assessment, since alcohol poisonings are almost the only disease category directly attributable to AUDs; most other alcohol-related deaths are indirect, and the cause which directly led to the death, such as liver cirrhosis, is the one recorded on the death certificate. Burden of disease for AUDs is thus mainly due to disability resulting from alcohol use. In contrast to AUDs, ALD is one of the major lethal outcomes of alcohol use, and burden of disease is mainly due to (premature) years of life lost. Many of the negative outcomes attributable to both AUDs and ALD are due to their interactions with other factors, most notably economic wealth. To avoid alcohol-attributable morbidity and mortality, measures should be taken to reduce the AUDs and ALD burden globally, especially among the poor. Full article
(This article belongs to the Special Issue Alcoholic Liver Disease: Diagnostics and Therapeutics)
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28 pages, 10030 KiB  
Review
Alcoholic-Hepatitis, Links to Brain and Microbiome: Mechanisms, Clinical and Experimental Research
by 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 and Opris Mihaiadd Show full author list remove Hide full author list
Biomedicines 2020, 8(3), 63; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8030063 - 18 Mar 2020
Cited by 13 | Viewed by 4727
Abstract
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) [...] Read more.
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. Full article
(This article belongs to the Special Issue Alcoholic Liver Disease: Diagnostics and Therapeutics)
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16 pages, 500 KiB  
Review
Alcohol Metabolizing Enzymes, Microsomal Ethanol Oxidizing System, Cytochrome P450 2E1, Catalase, and Aldehyde Dehydrogenase in Alcohol-Associated Liver Disease
by Yanchao Jiang, Ting Zhang, Praveen Kusumanchi, Sen Han, Zhihong Yang and Suthat Liangpunsakul
Biomedicines 2020, 8(3), 50; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8030050 - 04 Mar 2020
Cited by 90 | Viewed by 17995
Abstract
Once ingested, most of the alcohol is metabolized in the liver by alcohol dehydrogenase to acetaldehyde. Two additional pathways of acetaldehyde generation are by microsomal ethanol oxidizing system (cytochrome P450 2E1) and catalase. Acetaldehyde can form adducts which can interfere with cellular function, [...] Read more.
Once ingested, most of the alcohol is metabolized in the liver by alcohol dehydrogenase to acetaldehyde. Two additional pathways of acetaldehyde generation are by microsomal ethanol oxidizing system (cytochrome P450 2E1) and catalase. Acetaldehyde can form adducts which can interfere with cellular function, leading to alcohol-induced liver injury. The variants of alcohol metabolizing genes encode enzymes with varied kinetic properties and result in the different rate of alcohol elimination and acetaldehyde generation. Allelic variants of these genes with higher enzymatic activity are believed to be able to modify susceptibility to alcohol-induced liver injury; however, the human studies on the association of these variants and alcohol-associated liver disease are inconclusive. In addition to acetaldehyde, the shift in the redox state during alcohol elimination may also link to other pathways resulting in activation of downstream signaling leading to liver injury. Full article
(This article belongs to the Special Issue Alcoholic Liver Disease: Diagnostics and Therapeutics)
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12 pages, 540 KiB  
Review
Alcoholic Liver Disease: Current Mechanistic Aspects with Focus on Their Clinical Relevance
by Rolf Teschke
Biomedicines 2019, 7(3), 68; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines7030068 - 05 Sep 2019
Cited by 44 | Viewed by 5354
Abstract
The spectrum of alcoholic liver disease (ALD) is broad and includes alcoholic fatty liver, alcoholic steatohepatitis, alcoholic hepatitis, alcoholic fibrosis, alcoholic cirrhosis, and alcoholic hepatocellular carcinoma, best explained as a five-hit sequelae of injurious steps. ALD is not primarily the result of malnutrition [...] Read more.
The spectrum of alcoholic liver disease (ALD) is broad and includes alcoholic fatty liver, alcoholic steatohepatitis, alcoholic hepatitis, alcoholic fibrosis, alcoholic cirrhosis, and alcoholic hepatocellular carcinoma, best explained as a five-hit sequelae of injurious steps. ALD is not primarily the result of malnutrition as assumed for many decades but due to the ingested alcohol and its metabolic consequences although malnutrition may marginally contribute to disease aggravation. Ethanol is metabolized in the liver to the heavily reactive acetaldehyde via the alcohol dehydrogenase (ADH) and the cytochrome P450 isoform 2E1 of the microsomal ethanol-oxidizing system (MEOS). The resulting disturbances modify not only the liver parenchymal cells but also non-parenchymal cells such as Kupffer cells (KCs), hepatic stellate cells (HSCs), and liver sinusoidal endothelial cells (LSECs). These are activated by acetaldehyde, reactive oxygen species (ROS), and endotoxins, which are produced from bacteria in the gut and reach the liver due to gut leakage. A variety of intrahepatic signaling pathways and innate or acquired immune reactions are under discussion contributing to the pathogenesis of ALD via the five injurious hits responsible for disease aggravation. As some of the mechanistic steps are based on studies with in vitro cell systems or animal models, respective proposals for humans may be considered as tentative. However, sufficient evidence is provided for clinical risk factors that include the amount of alcohol used daily for more than a decade, gender differences with higher susceptibility of women, genetic predisposition, and preexisting liver disease. In essence, efforts within the last years were devoted to shed more light in the pathogenesis of ALD, much has been achieved but issues remain to what extent results obtained from experimental studies can be transferred to humans. Full article
(This article belongs to the Special Issue Alcoholic Liver Disease: Diagnostics and Therapeutics)
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