Emerging concepts in alcoholic hepatitis

Abstract

Severe alcoholic hepatitis is implicated as a costly, worldwide public health issue with high morbidity and mortality. The one-month survival for severe alcoholic hepatitis is low with mortality rates high as 30%-50%. Abstinence from alcohol is the recommended first-line treatment. Although corticosteroids remain as the current evidence based option for selected patients with discriminant function > 32, improvement of short-term survival rate may be the only benefit. Identification of individuals with risk factors for the development of severe alcoholic hepatitis may provide insight to the diverse clinical spectrum and prognosis of the disease. The understanding of the complex pathophysiologic processes of alcoholic hepatitis is the key to elucidating new therapeutic treatments. Newer research describes the use of gut microbiota modification, immune modulation, stimulation of liver regeneration, caspase inhibitors, farnesoid X receptors, and the extracorporeal liver assist device to aid in hepatocellular recovery. Liver transplantation can be considered as the last medical option for patients failing conventional medical interventions. Although the preliminary data is promising in patients with low risk of recividism, controversy remains due to organ scarcity. This review article comprehensively summarizes the epidemiology, pathophysiology, risk factors, and prognostic indicators of severe alcoholic hepatitis with a focus on the current and emerging therapeutics.

Keywords: Alcoholic hepatitis; Apoptosis inhibitors; Extracorporeal liver assist device; Gut microbiota modification; Immune modulation.

Figure 1

Ethanol metabolism in the hepatocyte. ¹Ethanol inhibits the peroxisome-proliferator-activated receptor α and adenosine monophosphate activated protein kinase with stimulation of sterol regulatory element binding protein 1, a membrane bound transcript factor to promote lipogenesis. ADH: Alcohol dehydrogenase; ALDH: Aldehyde dehydrogenase; NADH: Nicotinamide adenine dinucleotide.

Figure 2

Acetaldehyde induced gut permeability with endotoxemia and inflammatory cascade. LPS: Lipopolysaccharide; TLR-4: Toll-like receptor type 4; ROS: Reactive oxygen species; NADPH: Nicotinamide adenine dinucleotide phosphate-oxidase; NFKB: Nuclear factor kappa beta; JNK: c-Jun N-terminal kinase; AP-1: Activator protein 1; ICAM-1: Intracellular adhesion molecule 1; VCAM-1: Vascular adhesion protein 1; IL-8: Interleukin 8; CCL 2: C-C motif ligand; TNFα: Tumor necrosis factor alpha; IL-1: Interleukin 1; IL-6: Interleukin 6.