Priority Medicines for Europe and the World "A Public Health Approach to Innovation" Update on 2004 Background Paper Written by Warren Kaplan, Ph.D, JD, MPH Background Paper 6.14 Harmful use of Alcohol Alcohol Use Disorders and Alcoholic Liver Diseases By Rene Soria Saucedo (MD, MPH, PhDc) January 2013 Update on 2004 Background Paper, BP 6.14 Alcohol Use Disorders Table of Contents Abbreviations: ..................................................................................................................................................... 5 Executive Summary ............................................................................................................................................ 6 Burden of Disease ............................................................................................................................................ 6 Treatment Options ........................................................................................................................................... 7 1. Introduction ................................................................................................................................................. 8 1.1 Alcohol Consumption (ACo) and its relationship with Alcohol Use Disorders (AUD) ........... 8 1.2 Alcohol Use Disorders (AUD) .......................................................................................................... 9 1.3 Alcoholic Liver Diseases (ALD) ...................................................................................................... 10 1.3.1 Alcoholic Fatty Liver .................................................................................................................... 10 1.3.2 Alcoholic Hepatitis (AH) ............................................................................................................. 11 1.3.3 Alcoholic Cirrhosis (AC) ............................................................................................................. 11 1.4 Definition of AUD: Search for a consensus ................................................................................... 11 1.4.1 ICD Criteria ................................................................................................................................... 11 1.4.2 The DSM Criteria .......................................................................................................................... 12 2. What is the size and nature of the disease burden that is caused by ACo, AUD, and ALD? .... 12 2.1 General Epidemiological trends for Europe and the World ....................................................... 12 2.1.1 Unintentional injuries .................................................................................................................. 13 2.1.2 Intentional injuries ....................................................................................................................... 13 2.2 Prevalence of Alcohol Use Disorders (AUD) ................................................................................ 13 2.3 Prevalence of Alcohol Liver Disease (ALD) .................................................................................. 16 2.4 The European Burden of ACo, AD and ALD ............................................................................... 16 2.5 Several Specific Epidemiologic Issues related to AUD and ALD. ............................................. 20 2.5.1 Data collection challenges ........................................................................................................... 20 2.5.2 Alcohol and co-occurring chronic diseases............................................................................... 20 2.5.3 Immunomodulatory effects of alcohol ...................................................................................... 23 2.5.4 Alcohol and its carcinogen effect ............................................................................................... 24 2.5.5 Alcohol and the elderly ............................................................................................................... 24 2.5.6 Alcohol and women ..................................................................................................................... 24 2.5.7 Alcohol and genetics .................................................................................................................... 26 2.5.8 AUD diagnosis and biochemical markers ................................................................................ 26 3. What is the Control Strategy?................................................................................................................. 27 3.1 Alcohol policy ................................................................................................................................... 27 3.2 Remediation of Alcohol Use Disorders (AUD) ............................................................................ 29 3.2.1 Disulfiram (Antabuse): ................................................................................................................ 30 3.2.2 Oral naltrexone: ............................................................................................................................ 30 3.2.3 Extended-release naltrexone (monthly injection): ................................................................... 33 3.2.4 Acamprosate: ................................................................................................................................ 33 3.3 Alcoholic Liver Disease (ALD) ....................................................................................................... 34 3.3.1 Oxidative stress and hepatocyte membrane injury ................................................................. 36 3.3.2 Extracorporeal Liver Support (ELS). ......................................................................................... 36 6.14-2 Update on 2004 Background Paper, BP 6.14 Alcohol Use Disorders 3.4 Alcoholic Cirrhosis (AC) .................................................................................................................. 37 3.4.1 Antioxidants .................................................................................................................................. 37 3.4.2 Propylthiouracil (PTU) ................................................................................................................ 37 3.4.3 Colchicine ...................................................................................................................................... 38 3.4.4 Anabolic-androgenic steroids (AAS) ......................................................................................... 38 3.5 Transplantation ................................................................................................................................. 38 4. What is known of the Economic Burden, Feasibility, and Sustainability of the Control Strategy? .............................................................................................................................................................. 39 4.1 Economic burden .............................................................................................................................. 39 4.2 Feasibility and sustainability .......................................................................................................... 40 5. Why Does the Disease Burden Persist? ................................................................................................ 41 6. What can be learnt from past/current research into pharmaceutical interventions for this Condition? .......................................................................................................................................................... 42 6.1 Alcohol Use Disorders (AUD) ........................................................................................................ 42 6.2 Alcohol Liver Disease (ALD) .......................................................................................................... 42 7. What is the Current “Pipeline” of Products that Are to Be Used for this Particular Condition? .. ...................................................................................................................................................................... 43 7.1 Alcohol Use Disorders (AUD) ........................................................................................................ 43 7.1.1 Opioid antagonists ....................................................................................................................... 43 7.1.2 Serotonergics ................................................................................................................................. 43 7.1.3 Dopaminergics .............................................................................................................................. 44 7.1.4 GABA targeting ............................................................................................................................ 44 7.1.5 Other interventions ...................................................................................................................... 44 7.2 Alcoholic Liver Disease (ALD) ....................................................................................................... 45 7.3 “Spillovers” from the Hepatitis C pipeline and Other Fibrotic Conditions ............................. 47 8. What is the Current