Stimulating hepatocyte renewal: a new paradigm for the treatment of severe alcoholic hepatitis unresponsive to corticosteroids?

Patients with severe alcoholic hepatitis who are admitted to the hospital usually have evidence of decompensated cirrhosis with high serum bilirubin levels, low prothrombin time associated with dysfunction or failure of other organs/systems (kidney, brain, circulation).1 Spontaneous 1-month mortality is 35%.2 Pathophysiology of severe alcoholic hepatitis is incompletely understood.2–4 Alcohol consumption results in alterations of gut microbiome, increased intestinal permeability and subsequent translocation of Gram-negative bacteria. These bacteria may release pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS). In the liver, PAMPs stimulate Kupffer cells to produce high levels of proinflammatory chemokines (eg, interleukin-8 (IL-8)) or cytokines such as tumour necrosis factor α (TNF-α). TNF-α may activate cell death pathways and induce the production of reactive oxygen species (ROS) by hepatocyte mitochondria, leading to cell death. Acetaldehyde metabolism also contributes to hepatocyte ROS production. These findings led to the...
Source: Gut - Category: Gastroenterology Authors: Tags: Commentary Source Type: research