Submit a Manuscript: http://www.wjgnet.com/esps/ World J Gastroenterol 2016 January 7; 22(1): 0000-0000 Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx ISSN 1007-9327 (print) ISSN 2219-2840 (online) DOI: 10.3748/wjg.v22.i1.0000 © 2016 Baishideng Publishing Group Inc. All rights reserved. TOPIC HIGHLIGHT 2016 Alcoholic Liver Disease: Global view Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination? Moon-Sun Kim, Madeleine Ong, Xianqin Qu Moon-Sun Kim, Madeleine Ong, XianQin Qu, School of disease (ALD) is defined by histological lesions on the Medical & Molecular Biosciences, University of Technology liver that can range from simple hepatic steatosis to Sydney, NSW 2007, Australia more advanced stages such as alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and liver failure. As Moon-Sun Kim, Faculty of Pharmacy, University of Sydney, one of the oldest forms of liver injury known to humans, NSW 2006, Australia ALD is still a leading cause of liver-related morbidity Author contributions: Qu X, Kim MS and Ong M contributed and mortality and the burden is exerting on medical to writing the manuscript. Kim MS produced the figures and systems with hospitalization and management costs Ong M thoroughly edited the manuscript rising constantly worldwide. Although the biological mechanisms, including increasing of acetaldehyde, Conflict-of-interest statement: No conflict of interest. oxidative stress with induction of cytochrome p450 2E1, inflammatory cytokine release, abnormal lipid Open-Access: This article is an open-access article which was metabolism and induction of hepatocyte apoptosis, selected by an in-house editor and fully peer-reviewed by external by which chronic alcohol consumption triggers serious reviewers. It is distributed in accordance with the Creative complex progression of ALD is well established, there Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this is no universally accepted therapy to prevent or work non-commercially, and license their derivative works on reverse. In this article, we have briefly reviewed the different terms, provided the original work is properly cited and pathogenesis of ALD and the molecular targets for the use is non-commercial. See: http://creativecommons.org/ development of novel therapies. This review is focused licenses/by-nc/4.0/ on current therapeutic strategies for ALD, including lifestyle modification with nutrition supplements, Correspondence to: Xianqin Qu, PhD, MD, School of Medical available pharmacological drugs and new agents that & Molecular Biosciences, University of Technology Sydney, PO are under development, liver transplantation, application Box 123, Broadway, NSW 2007, of complementary medicines, and their combination. Australia. [email protected] Telephone: +61-2-95147852 The relevant molecular mechanisms of each con- Fax: +61-2-95147852 ventional medication and natural agent have been reviewed according to current available knowledge in Received: April 28, 2015 the literature. We also summarized efficacy vs safety on Peer-review started: May 5, 2015 conventional and herbal medicines which are specifically First decision: June 23, 2015 used for the prevention and treatment of ALD. Through Revised: July 7, 2015 a system review, this article highlighted that the Accepted: November 13, 2015 combination of pharmaceutical drugs with naturally Article in press: occurring agents may offer an optimal management for Published online: January 7, 2016 ALD and its complications. It is worthwhile to conduct large-scale, multiple centre clinical trials to further prove the safety and benefits for the integrative therapy on ALD. Abstract Alcohol consumption is the principal factor in the Key words: Alcoholic liver disease; Alcohol hepatitis; pathogenesis of chronic liver diseases. Alcoholic liver Conventional medicines; Natural medicines; Hepatic WJG|www.wjgnet.com 1 January 7, 2016|Volume 22|Issue 1| Kim MS et al . Optimal management for alcoholic liver disease lipid metabolism; Hepatic inflammation; Combination expenses, there is a lack of effective treatments for therapy ALD, especially cirrhosis and HCC. Abstention from alcohol may reverse the early stage of ALD to a normal © The Author(s) 2016. Published by Baishideng Publishing condition. The treatment for ALD with conventional Group Inc. All rights reserved. medicines, mainly pharmaceutical medications, has limited success with side-effects. Recently, natural Core tip: The aim of this article is to review the medicines, which mainly apply herb-derived agents, impairment of hepatocellular dysfunction in alcoholic are emphasized as alternative therapies to manage the liver diseases and their prospective managements. various alcohol-related liver diseases. It is the aim of Specifically, we focused on the natural therapies this article to provide an overview of understanding the with their efficacies and safeties. Moreover, we mechanisms of ALD, which could generate therapeutic summarized molecular mechanisms of herbal therapy to treat alcoholic liver disease (ALD). With evidence- interventions with conventional medicines, natural based natural therapy, this article highlighted that the therapies and their combinations to reverse or retard combination of pharmaceutical drugs with naturally the progression of ALD. occurring agents may offer an optimal management for Pathogenesis of ALD is multifactorial. Strategically, this complex liver disease. It is worthwhile to conduct the liver is the most important organ to target as about [7] large-scale, multiple centre clinical trials further to 90% of alcohol intake is metabolized by the liver . prove the safety and benefits for the integrative Alcohol consumption can cause fatty liver by disrupting therapy on ALD. hepatic lipids and glucose metabolism. Furthermore, ethanol and its oxidative and non-oxidative metabolites have direct toxic effects on the liver[8]. Histologically, Kim MS, Ong M, Qu X. Optimal management for alcoholic fatty liver, or HS, is a malfunctioned fat accumulation liver disease: Conventional medications, natural therapy or in the parenchymal cells of the liver. HS is a reversible combination? World J Gastroenterol 2016; 22(1): 0000-0000 lesion. Fibrosis (or scar formation) is the subsequent Available from: URL: http://www.wjgnet.com/1007-9327/full/ result if liver injury persists. Fibrosis determined by v22/i1/0000.htm DOI: http://dx.doi.org/10.3748/wjg.v22.i1.0000 biopsy increases the likelihood of progression to cirrhosis and end-stage liver disease. Biochemically, alcohol abuse contributes to a serious complex phenomenon involving different molecular and biological mechanism INTRODUCTION to induce ALD. Many hypotheses have been investigated Alcohol is a psychoactive substance and has been and established to explain the pathogenic mechanisms widely used in many cultures for centuries. Alcoholic of ALD. These include: (1) activation of alcohol abuse causes a large range of diseases and is also dehydrogenase (ADH) and aldehyde dehydrogenase [9] a social and economic burden in world societies. (ALDH) to cause the over generation of acetate ; Reduction of alcohol consumption is now becoming (2) induction of cytochrome P450 2E1 (CYP2E1) for [10] the global strategy, with attempts to define “harmful alcoholic oxidative stress and hepatotoxicity ; (3) use” of alcohol by the World Health Organization abnormal lipid metabolism by increasing fatty acid (FA) [10] (WHO) to reduce the associated morbidity and synthesis and decreasing of FA oxidation ; (4) hepatic mortality. Alcohol intake is a principal etiological inflammation indicated by an increase of tumour [11] factor in chronic liver diseases. Alcoholic liver necrosis factor-α (TNF-α) and cytokine release ; (5) disease (ALD), which initially manifests as hepatic fat induction of hepatocyte apoptosis and subsequent accumulation, followed by an inflammatory response activation of Kupffer cells; (6) increased hepatic levels to induce final stage liver failure, is now a deleterious of cellular fibronectin and tissue growth factor-β (TGF-β) [12] health problem[1]. Alcohol abuse accelerates various related to the activation of hepatic stellate cells ; and [13,14] types of liver diseases, such as alcoholic fatty liver (7) ethanol-induction of gut endotoxins . Proposed disease (AFLD), alcoholic steatohepatitis, alcoholic mechanisms impacting hepatocellular dysfunction hepatitis (AH), progressive fibrosis, liver cirrhosis by alcohol exposure within ALD pathogenesis are and liver failure[2]. Patients with ALD, especially with summarized in Figure 1. To further improve current alcoholic cirrhosis, are associated with increased risk strategies for managing ALD, a deeper understanding of of hepatocellular carcinoma (HCC)[3,4]. the pathomechanisms of the disease is needed. Various The prevalence of ALD has increased in the last curative approaches based on these mechanisms could years, parallel with the increasing alcohol consumption prevent the progression of ALD and its downstream in the western world as well as in Asian counties[5]. sequelae. According to the WHO report in 2011, chronic alcohol consumption results in approximately 2.5 million deaths each year with much of the burden related to ALD[6]. CURRENT MANAGEMENT FOR ALD Though ALD significantly contributes to the rising General management of ALD should initially be morbidity and mortality statistics and related health