Chronic liver inflammation: Clinical implications beyond alcoholic liver disease

Abstract

Chronic alcohol exposure can lead to alcoholic liver disease, including hepatitis, cirrhosis and hepatocellular carcinoma, and chronic inflammation can simultaneously cause systemic medical illness. Recent evidence suggests that alcoholic liver disease is a predictor for liver-related diseases, cardiovascular disease, immunologic disease, and bone disease. Chronic inflammation in alcoholic liver disease is mediated by a direct inflammatory cascade from the alcohol detoxification process and an indirect inflammatory cascade in response to gut microflora-derived lipopolysaccharides (LPS). The pathophysiology of alcoholic liver disease and its related systemic illness is characterized by oxidative stress, activation of the immune cascade, and gut-liver interactions. Integrative therapeutic strategies for alcoholic liver disease include abstaining from alcohol consumption; general anti-inflammatories such as glucocorticoid, pentoxifylline, and tumour necrosis factor-α antagonist; antioxidants such as N- acetylcysteine; gut microflora and LPS modulators such as rifaximin and/or probiotics. This review focuses on the impact of chronic liver inflammation on systemic health problems and several potential therapeutic targets.

Keywords: Alcoholic liver disease; Oxidative stress; Cardiovascular disease; Immunologic disease; Bone disease

Core tip: Beyond the natural course in the liver, alcoholic liver disease can be implicated in many health problems that affect the quality of life and disease progression. Evidence suggests that alcoholic liver disease is a predictor for liver-related diseases, cardiovascular disease, immunologic disease, and bone disease. Chronic inflammation in alcoholic liver disease and related systemic illness is mediated by a direct response to alcohol and an indirect inflammatory response. Alcoholic liver disease should be considered from the perspective of chronic inflammation. Accordingly, integrative therapeutic strategies including anti-inflammatory targeting are needed for alcohol-induced liver inflammation management and prevention of systemic medical problems.