Recent advances in alcohol-related liver disease (ALD): summary of a Gut round table meeting

Abstract

Alcohol-related liver disease (ALD), which includes a range of disorders of different severity and is one of the most prevalent types of liver disease worldwide, has recently regained increased attention. Among other reasons, the realisation that any alcohol intake, regardless of type of beverage represents a health risk, and the new therapeutic strategies tested in recently published or undergoing clinical trials spur scientific interest in this area.In April 2019, Gut convened a round table panel of experts during the European Association for the Study of the Liver International Liver Congress in Vienna to discuss critical and up-to-date issues and clinical trial data regarding ALD, its epidemiology, diagnosis, management, pathomechanisms, possible future treatments and prevention. This paper summarises the discussion and its conclusions.

Keywords: alcohol; alcoholic liver disease; cirrhosis; fibrosis; liver transplantation.

Figure 1

The natural course of alcohol-related liver disease. HCC, hepatocellular carcinoma. Adapted from. Published with permission from Springer nature.

Figure 2

Annual age-standardised overall mortality rates for chronic liver disease in the USA from 2007 through to 2016. ALD, alcohol-related liver disease; HCV, hepatitis C virus; HBV, hepatitis B virus; NAFLD, non-alcoholic fatty liver disease. Published with permission from Elsevier.

Figure 3

Algorithm for the management of alcoholic hepatitis (provided by Ramon Bataller, original figure). ASAT/ALAT, aspartate amino transferase/alanine amino transferase ratio; GGT, gamma-glutamyl transferase; MCV, mean corpuscular volume; mDF, Maddrey’s discriminant function; MELD, Model for End-Stage Liver Disease.

Figure 4

Cumulative incidence of death in patients with severe alcoholic hepatitis and without acute-on-chronic liver failure (ACLF) or with ACLF grades 1, 2 or 3. Published with permission from Elsevier.

Figure 5

Response rate to corticosteroids using the Lille model in patients with severe alcoholic hepatitis and without acute-on-chronic liver failure (ACLF) and among grades of ACLF. Published with permission from Elsevier.

Figure 6

Experimental models for various stages of alcohol-related liver disease (ALD), representing steatosis, subclinical alcoholic steatohepatitis (ASH), and alcoholic hepatitis (AH) in patients. Ab lib, Ab libitum; ALAT, alanine aminotransferase; ASAT, aspartate transaminase; CCI, carbon tetrachloride; DDC,3,5-diethoxycarbonyl-1,4-dihydrocollidine; EtOH,ethanol; GGT, γ-glutamyl transferase; HFD, high fat diet; iG, intragastric infusion of ethanol diet; INR, international normalised ratio; L/D, Lieber-DeCarli ethanol diet; LPS, lipopolysaccharide; MDB, Mallory-Denk body; SIRS, systemic inflammatory response syndrome. Modified from with permission from Wiley.

Figure 7

Contribution of intestinal microbiota to alcohol-relatedliver disease. LCFA, long-chain fatty acids; SCFA, short-chain fatty acids.

Figure 8

Overview of future therapeutic targets targeting hepatoprotection, inflammation and intestinal dysbiosis and gut permeability. FXR,farnesoid X receptor; G-CSF,granulocyte-colony stimulating factor; IL, interleukin; miRNA, micro ribonucleic acid; PAMPs,pathogen-associated molecular patterns; Syk,spleen tyrosine kinase.