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 lipidglucose 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,

Serum Visfatin Levels in Nonalcoholic Fatty Liver Disease and Liver Fibrosis: Systematic Review and Meta-Analysis

“…Upon reviewing the references of included studies manually, one relevant article was recognized and included in our analysis. The total number of articles included in the qualitative synthesis was 21 articles, out of which 14 articles were included in the quantitative synthesis [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ].…”

“…Hepatic steatosis was assessed using liver biopsy for diagnosing NAFLD in most studies ( n = 11) [ 35 , 36 , 37 , 38 , 39 , 40 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ], while the remaining studies used ultrasonography [ 41 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. Moreover, four studies that used ultrasonography to evaluate hepatic steatosis used Fibroscan in order to assess liver stiffness [ 49 , 50 , 51 , 53 ].…”

“…Hepatic steatosis was assessed using liver biopsy for diagnosing NAFLD in most studies ( n = 11) [ 35 , 36 , 37 , 38 , 39 , 40 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ], while the remaining studies used ultrasonography [ 41 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. Moreover, four studies that used ultrasonography to evaluate hepatic steatosis used Fibroscan in order to assess liver stiffness [ 49 , 50 , 51 , 53 ]. Figure 2 summarizes the obtained meta-analysis results comparing serum visfatin levels in NAFLD vs. controls, biopsy-proven NAFLD vs. controls, and ultrasound evaluated hepatic steatosis vs. controls.…”

“…The NHLBI quality assessment tools were used to evaluate the methodological quality of eligible studies included in the qualitative assessment of our review, as demonstrated in Supplementary Table S2 . A total of 10 articles were evaluated using the NHLBI quality assessment of case-control studies [ 35 , 36 , 38 , 39 , 43 , 44 , 46 , 47 , 53 , 55 ] and 11 articles using the NHLBI quality assessment tool for observational cohort and cross-sectional studies [ 37 , 40 , 41 , 42 , 45 , 48 , 49 , 50 , 51 , 52 , 54 ].…”

“…There were several issues that we found regarding the presence of bias in the evaluated articles. Eleven articles received an overall rating of “fair” [ 38 , 39 , 41 , 42 , 44 , 45 , 47 , 49 , 51 , 52 , 53 ], while five articles were rated as “good” [ 36 , 46 , 48 , 54 , 55 ], and five studies were rated as “poor” [ 35 , 37 , 40 , 43 , 50 ]. In general, all included articles had a clearly stated research question or objective.…”