Interpretation of Serum Visfatin Level in Relation to Hepatic Injury is Probably Gender Dependent in Nonalcoholic Fatty Liver Disease

Abstract

Background: Studies on the association between visfatin and nonalcoholic fatty liver disease (NAFLD) have contradictory results and the role of this adipokine in NAFLD pathogenesis has remained unclear. In vitro studies indicate that visfatin expression could be regulated by sex hormones. Testosterone down-regulates visfatin expression in pre-adipocytes and estrogen increases its expression in adipocytes. Objectives: This study aimed at exploring whether the association between serum visfatin and markers of hepatic injury is the same for both genders in patients with NAFLD. Methods: In this cross-sectional study, 62 consecutive patients (32 males and 30 females) with NAFLD were recruited. Fasting serum visfatin, caspase-cleaved cytokeratin 18 (cCK18), total soluble cytokeratin 18 (CK18), liver enzymes (AST and ALT), insulin, and lipid-glucose profile was measured. Anthropometric measurements, fibroscan and assessment of dietary intake and physical activity level, were performed for each participant. Two independent sample t tests, chi-square test, univariate, and multiple linear regression (to adjust for confounding factors) were used to analyze the data. Results: In males, serum visfatin had a significant positive association with serum Aspartate Aminotransferase (AST) (B = 0.47, P = 0.009), alanine aminotransferase (ALT) (B = 0.40, P = 0.035), CK18 (B = 0.50, P = 0.008), and cCK18 (B = 0.47, P = 0.012). In females, serum visfatin only had a weak association with CK18 (B = 0.37, P = 0.045). Instead, higher body mass index (BMI) was significantly associated with increased serum CK18 (B = 0.44, P = 0.02), cCK18 (B = 0.42, P = 0.02), controlled attenuation parameter (CAP) (B = 0.39, P = 0.049), and liver stiffness measurement (LSM) (B = 0.40, P = 0.03) in females. Higher waist to hip ratio was also significantly related to serum AST (B = 0.37, P = 0.04), ALT (B = 0.50, P = 0.02), CK18 (B = 0.41, P = 0.03), cCK18 (B = 0.37, P = 0.04), and CAP (B = 0.39, P = 0.04) in this group. In this study, females were significantly older (47.83 ± 81.10 vs 39.84 ± 12.10, P = 0.008) and had higher BMI (32.31 ± 4.56 vs 29.42 ± 4.89, P = 0.02) compared to males, thus the associations were adjusted for age, BMI, and other confounders. Conclusions: Interpretation of serum visfatin level in relation to hepatic injury was probably gender-dependent in NAFLD. While its increased serum level could be an indicator for more hepatic injury in males, this was not the case in females. Body Mass Index and waist to hip ratio were stronger predictors for hepatic injury in females.