Alcohol and Acute-on-Chronic Liver Failure

Abstract

Acute-on-chronic liver failure (ACLF) is a clinical syndrome that occurs in patients with cirrhosis and is characterised by acute deterioration, organ failure and high short-term mortality. Alcohol is one of the leading causes of ACLF and the most frequently reported aetiology of underlying chronic liver disease. Among patients with alcoholic hepatitis (AH), ACLF is a frequent and severe complication. It is characterised by both immune dysfunction associated to an increased risk of infection and high-grade systemic inflammation that ultimately induce organ failure. Diagnosis and severity of ACLF determine AH prognosis, and therefore, ACLF prognostic scores should be used in severe AH with organ failure. Corticosteroids remain the first-line treatment for severe AH but they seem insufficient when ACLF is associated. Novel therapeutic targets to contain the excessive inflammatory response and reduce infection have been identified and are under investigation. With liver transplantation remaining one of the most effective therapies for severe AH and ACLF, adequate organ allocation represents a growing challenge. Hence, a clear understanding of the pathophysiology, clinical implications and management strategies of ACLF in AH is essential for hepatologists, which is narrated briefly in this review.

Keywords: ACLF, Acute-on-chronic liver failure; AH, alcoholic hepatitis; ALT, alanine aminotransferase; APASL, Asian Pacific Association for the Study of the Liver; AST, aspartate aminotransferase; DAMPs, damage-associated molecular patterns; EASL-CLIF, European Association for the Study of the Liver – Chronic Liver Failure Consortium; GAHS, Glasgow alcoholic hepatitis score; IL, interleukin; INR, international normalised ratio; MELD, model for end-stage liver disease; NAC, N-acetylcysteine; NACSELD, North American Consortium for the Study of End-Stage Liver Disease; PAMPs, pathogen-associated molecular patterns; TNF, tumour necrosis factor; WGO, World Gastroenterology Organization; acute-on-chronic liver failure; alcoholic hepatitis; cirrhosis.

Figure 1

Pathophysiological mechanism of alcoholic hepatitis acute-on-chronic liver failure. Abbreviations: pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs) and nitric oxide (NO).