Avaliação da estrutura e função cardíaca em diferentes estágios da doença do fígado gorduroso não alcoólica

Abstract

Clinical evidences indicate that non-alcoholic fatty liver disease (NAFLD) affects cardiac structure and function. However, it is still unclear whether cardiac alteration is evident only in advanced NAFLD, for example, inflammation and fibrosis, or it also affects milder variations of the disease, such as isolated steatosis. Thus, the aim of the study was to evaluate the cardiac structure and function at different stages of the NAFLD using an animal model. The study protocol was approved by the Ethics Committee on the Use of Animals (CEUA) of the Federal University of Mato Grosso under nº. 23108.904930/2017-98. Male Wistar rats were divided into four groups: control (C), sucrose (S), control and thioacetamide (C+TAA), sucrose and thioacetamide (S+TAA). Group C received chow diet and natural water, while group S received chow diet and water with sucrose (300 g/L). The C+TAA and S+TAA groups received thioacetamide (100 mg/kg body weight, i.p., twice week, for 8 weeks), while the animals in groups C and S received saline. The liver condition was determined by histological analysis with H&E and determination of the ALT enzyme in the blood; the morphology and cardiac function were evaluated in vivo by the echocardiogram. Data were presented as mean and standard deviation or median and total amplitude. The comparison between the groups was performed using Two Way ANOVA or ANOVA on Ranks, with 95% confidence. Animals that received sucrose isolated showed obesity, hypertriglyceridemia and intense hepatic steatosis, but without any signs of inflammation and liver dysfunction. This condition was associated with left ventricular (LV) concentric hypertrophy and systolic dysfunction. The animals submitted to the hepatotoxic drug TAA presented reduction of the corporal weight, hypotriglyceridemia and an intense hepatic picture of inflammation and fibrosis in association to the increase of ALT in the blood; the animals presented LV eccentric hypertrophy and systolic dysfunction. The combination of the factors sucrose and TAA was associated with intense hepatic steatosis, however, moderate degree of inflammation and fibrosis, a condition accompanied by attenuation of liver dysfunction and most morphological and functional changes of the heart. The stages of nonalcoholic fatty liver disease demonstrated in this study were associated with indicators of LV systolic dysfunction. In the case of isolated steatosis, systolic dysfunction was accompanied by a concentric hypertrophy, while in severe hepatic inflammation/fibrosis there was eccentric LV hypertrophy. Morphological changes were milder in the presence of steatohepatitis. The findings of this animal study do not support the idea from clinical evidences that liver inflammation and fibrosis can lead to heart abnormalities, while steatosis appears to be just a mild form of nonalcoholic fatty liver disease.