Retinol‐binding protein 4: A new marker of virus‐induced steatosis in patients infected with hepatitis c virus genotype 1

Abstract

Retinol-binding protein 4 (RBP4) is an adipocytokine associated with insulin resistance (IR).We tested serum levels of RBP4 to assess its link with steatosis in patients with genotype 1 chronic hepatitis C (CHC) or nonalcoholic fatty liver disease (NAFLD). Nondiabetic patients with CHC (n ‫؍‬ 143) or NAFLD (n ‫؍‬ 37) were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR by the homeostasis model assessment. Biopsies were scored by Scheuer classification for CHC, and Kleiner for NAFLD. Steatosis was tested as a continuous variable and graded as absent-mild <30%, or moderate-severe >30%. Thirty nondiabetic, nonobese blood donors served as controls. RBP4 levels were measured by a human competitive enzyme-linked immunosorbent assay kit (AdipoGen). Mean values of RBP4 were similar in NAFLD and CHC (35.3 ؎ 9.3 g/L versus 36.8 ؎ 17.6; P ‫؍‬ 0.47, respectively), and both were significantly higher than in controls (28.9 ؎ 12.1; P ‫؍‬ 0.02 and P ‫؍‬ 0.01, respectively). RBP4 was higher in CHC patients with steatosis than in NAFLD (42.1 ؎ 19.7 versus 35.2 ؎ 9.3; P ‫؍‬ 0.04). By linear regression, RBP4 was independently linked to steatosis only (P ‫؍‬ 0.008) in CHC, and to elevated body mass index (P ‫؍‬ 0.01) and low grading (P ‫؍‬ 0.04) in NAFLD. By linear regression, steatosis was independently linked to homeostasis model assessment score (P ‫؍‬ 0.03) and high RBP4 (P ‫؍‬ 0.003) in CHC. By logistic regression, RBP4 was the only variable independently associated with moderate-severe steatosis in CHC (odds ratio, 1.045; 95% confidence interval, 1.020 to 1.070; P ‫؍‬ 0.0004), whereas waist circumference was associated with moderate-severe steatosis in NAFLD (odds ratio, 1.095; 95% confidence interval, 1.007 to 1.192; P ‫؍‬ 0.03). Conclusion: In nondiabetic, nonobese patients with genotype 1 CHC, serum RBP4 levels might be the expression of a virus-linked pathway to steatosis, largely unrelated to IR. (HEPATOLOGY 2008;48:28-37.)

Insulin resistance is a risk factor for esophageal varices in hepatitis C virus cirrhosis

“…Our population had a low prevalence of obesity (15%), but nonetheless 26% of patients had diabetes, and the mean HOMA-IR score was approximately 4, higher than observed in our previous studies of subjects with chronic hepatitis C. 32,36 The high prevalence of diabetes and the high HOMA-IR values were not likely attributable to a "hepatogenous diabetes," 43 considering that they were found in a cohort of Child A patients. We identified an HOMA-IR score of greater than 3.5 as the cutoff value with the best sensitivity and specificity for predicting EV presence.…”

Upregulation of Calprotectin and Downregulation of Retinol Binding Protein in the Serum of Workers with Trichloroethylene‐induced Hypersensitivity Dermatitis

“…Additionally, both animal and human studies have shown that RBP4 might be involved in the development of insulin resis- tance and diabetes 24,25) . Furthermore, serum RBP4 levels have been shown to be associated with the degree of steatosis and fibrosis in liver diseases and chronic hepatitis C 26,27) . Considering the association between depressed serum RBP4 and hepatic damage, and the liver pathology of perivascular infiltrates and fibrosis in TCE-induced autoimmune hepatitis in MRL+/+ mice 28) , further studies are needed to investigate the precise role of RBP4 in the hepatotoxicity in THD.…”

Retinol and retinyl esters: biochemistry and physiology

“…Since 2005, the literature has suggested linkages between serum RBP4 concentrations, obesity, impaired insulin responsiveness (103)(104)(105)(106)(107)132 ), fatty liver development (134)(135)(136)(137)(138)(139)(140), vessel wall disease ( 141,142 ), and heart disease ( 143 ). At the molecular level, the best studied of these effects is the action of excessive RBP4 acting as a cytokine activating a signaling cascade within cells, which can eventually lead to both direct and indirect alterations in insulin signaling.…”