Inflammation: Driving Force of NASH
Previous single-point cross-sectional studies have identified components of the metabolic syndrome to be associated with NASH and fibrosis.[33–39] These prevalence studies identify at-risk populations, but do not clarify cause and effect. In a recent systematic review of serial liver biopsy studies, Argo et al. demonstrated that age and presence of acinar and/or portal inflammation of any type (acute or chronic) on the initial biopsy were the sole independent predictors of the development of advanced fibrosis in NASH. These data imply that inflammation is the key predictor of eventual histological progression to fibrosis and cirrhosis and, thus, potentially a major therapeutic target in NASH. Interestingly, parameters of the metabolic syndrome (BMI, obesity, waist–hip ratio, insulin resistance and Type 2 diabetes) were not statistically significant predictors on multivariate analysis. It is logical to assume that altering the inflammatory injury may modify the clinical course of disease; however, this has yet to be demonstrated. Potential mechanisms driving inflammation in NASH implicate systemic lipotoxicity as a result of overnutrition, lipid metabolites, visceral adipose tissue and production of proinflammatory cytokines and adipokines, gut bacteria and oxidation.
Expert Rev Gastroenterol Hepatol. 2011;5(2):189-200. © 2011 Expert Reviews Ltd.