Elevated hepatic SPARC levels are associated with increased risk of hepatocellular injury in severe obese patients with non-alcoholic fatty liver disease.

MAZZOLINI G; ATORRASAGASTI C; ONORATO A; PEIXOTO E; SCHLATTJAN M; SOWA JP; SYDOR S ; GERKEN G; CANBAY A

Boston, MA

Congreso; AASLD The liver meeting; 2016

American Association for the study of Liver diseases

Background and aims: Mechanisms that control progression from simple steatosis to steato-hepatitis and fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are still matter of investigation. SPARC, a secreted matricellular protein, is over-expressed in the liver under chronic injury. Contribution of SPARC accumulation to disease severity, and mechanisms involved, are largely unknown in NAFLD. We assessed the hypothesis that SPARC is increased in livers with more necrosis and inflammation and therefore at high risk of fibrosis.Methods: qrt-PCR, immunohistochemistry, and ELISA were employed to localize and quantify changes in SPARC in 62 morbidly obese patients with NAFLD and in a mouse model of diet-induced-NASH. Results were correlated with the severity of liver disease and progression from simple steatosis to NASH.Results: In obese patients 2 subgroups were identified with either high SPARC expression (n=20) or low SPARC expression (n=42) in liver tissue. High expression of SPARC paralleled more extensive hepatocellular necrosis, necroptosis, and increased pro-fibrogenic factors. In line with these findings, in the NASH animal model SPARC knockout mice were protected from inflammatory injury, and showed less inflammation and fibrosis.Conclusions: SPARC accumulation is associated with more severe liver injury and fibrogenic processes in NAFLD. SPARC may be a promising diagnostic and therapeutic target to monitor progression in NAFLD patients.