Inflammation in alcohol-associated liver disease progression

Chronic alcohol consumption induces stress and damage in alcohol metabolising hepatocytes, which leads to inflammatory and fibrogenic responses. Besides these direct effects, alcohol disrupts intestinal barrier functions and induces gut microbial dysbiosis, causing translocation of bacteria or microbial products through the gut mucosa to the liver and, which induce inflammation indirectly. Inflammation is one of the key drivers of alcohol-associated liver disease progression fromsteatosis to severe alcoholic hepatitis. The current standard of care for the treatment of severe alcoholic hepatitis is prednisolone, aiming to reduce inflammation. Prednisolone, however improves only short-term but not long-term survival rates in those patients, and even increases the risk for bacterial infections. Thus, recent studies focus on the exploration of more specific inflammatory targets for the treatment of severe alcoholic hepatitis. These comprise, among others interference with inflammatory cytokines, modulation of macrophage phenotypes or targeting of immune cell communication, as summarized in the present overview. Although several approaches give promising results in preclinical studies, data robustness and ability to transfer experimental results to human disease is still not sufficient for effective clinical translation.

Automated summary

Chronic alcohol consumption leads to stress and damage in liver cells, causing inflammation and fibrosis. Alcohol also disrupts intestinal barrier function and leads to gut microbial imbalance, indirectly causing inflammation in the liver. The current standard treatment for severe alcoholic hepatitis is prednisolone, but it only provides short-term improvement in survival rates and increases the risk of bacterial infections. Recent studies focus on finding more specific targets for inflammation to treat this liver disease effectively.