RESUMO
BACKGROUND AND RATIONALE: Insulin resistance (IR), adipocytokines, oxidative stress and hepatic apoptosis play a pathogenetic role in nonalcoholic fatty liver disease (NAFLD). AIMS: The evaluation of specific adipocytokines and markers of IR, oxidative stress and apoptosis in NAFLD patients; the introduction of a combined non-invasive index for nonalcoholic steatohepatitis (NASH). MATERIAL AND METHODS: Thirty patients with biopsy-proven NAFLD (15 with simple nonalcoholic fatty liver [NAFL], 15 with NASH) and 24 controls were recruited. Blood samples for total and high molecular weight (HMW) adiponectin, visfatin and tumor necrosis factor (TNF)-α, the apoptotic by-product cytokeratin (CK)-18, the reactive oxygen metabolites (ROMs) and standard biochemical tests were measured. Homeostatic model of assessment - insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were calculated. MAIN RESULTS: Total and HMW adiponectin were significantly lower and TNF-α higher in either NAFL or NASH group compared to control group; CK-18 was significantly higher in NASH compared to either NAFL or control group. CHAI (an acronym of CK-18, HOMA-IR, AST Index) was calculated as the product of parameters being significantly different between NAFL and NASH groups. CHAI was significantly higher in NASH (24.2 [15.1-214.0]) compared to either NAFL (15.7 [6.8-22.7]) or control (5.1 [2.4-7.6]) group (p < 0.001) and significantly higher as the severity of steatosis, fibrosis, ballooning, lobular and portal inflammation advanced. CONCLUSION: CHAI was escalating from controls to NAFL and NASH and was higher by increasing the severity of all the main histological lesions. However, a validation study is needed before introducing CHAI in clinical practice.
Assuntos
Adiponectina/sangue , Fígado Gorduroso/sangue , Queratina-18/sangue , Adulto , Apoptose , Biomarcadores/sangue , Biópsia , Glicemia/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Citocinas/sangue , Fígado Gorduroso/patologia , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/sangue , Hepatopatia Gordurosa não Alcoólica , Estresse Oxidativo , Valor Preditivo dos Testes , Prognóstico , Espécies Reativas de Oxigênio/sangue , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangueRESUMO
Background and rational for the study. Nonalcoholic fatty liver disease (NAFLD) is regarded as the hepatic component of insulin resistance (IR) syndrome, but data on serum homocysteine (HCY) are limited. The aim of the study was the evaluation of serum HCY levels in patients with NAFLD. Material and methods. Thirty-one patients (54 ± 11 years, 8 males) with biopsy-proven NAFLD, 15 with simple nonalcoholic fatty liver (NAFL) and 16 with nonalcoholic steatohepatitis (NASH), and 22 healthy controls (52 ± 9 years, 5 males) matched for gender, age and body mass index (BMI), were recruited. Blood samples for HCY, folate, vitamin B12, insulin and standard biochemical tests were obtained after overnight fasting. Homeostatic model of assessment-insulin resistance (HOMA-IR) was calculated. Results. There was no difference in mean serum HCY levels between controls and NAFLD patients (12.6 ± 4.6 vs. 13.5 ± 2.6 mmol/L, respectively; p = 0.432). Serum folate and vitamin B12 were also similar between the study groups. Mean age, BMI, serum folate and vitamin B12 did not differ between NAFL and NASH patients. However, when compared with NAFL patients, NASH patients had lower mean serum HCY levels (12.3 ± 2.5 vs. 14.7 ± 2.1 mmol/L; p = 0.006). HCY was lower by increasing the grading of fibrosis (p = 0.005), portal inflammation (p = 0.029) and steatosis location (p = 0.021). In logistic regression analysis, HCY independently predicted NASH (p = 0.045) after adjustment for gender, age, BMI, AST, glucose and HOMA-IR. Conclusion. Our data suggest that serum HCY levels are lower in NASH compared with NAFL patients and can independently predict NASH. Serum HCY might represent another non-invasive marker for the assessment of NAFLD.