Petta Salvatore, Cammà Calogero, Di Marco Vito, Alessi Nicola, Barbaria Francesco, Cabibi Daniela, Caldarella Rosalia, Ciminnisi Stefania, Licata Anna, Massenti Maria Fatima, Mazzola Alessandra, Tarantino Giuseppe, Marchesini Giulio, Craxì Antonio
Cattedra ed Unità Operativa di Gastroenterologia, University of Palermo, Palermo, Italy.
Hepatology. 2008 Jul;48(1):28-37. doi: 10.1002/hep.22316.
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 > or =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 microg/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).
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.
视黄醇结合蛋白4（RBP4）是一种与胰岛素抵抗（IR）相关的脂肪细胞因子。我们检测了1型慢性丙型肝炎（CHC）或非酒精性脂肪性肝病（NAFLD）患者的血清RBP4水平，以评估其与脂肪变性的关系。对非糖尿病的CHC患者（n = 143）或NAFLD患者（n = 37）进行肝活检以及人体测量和代谢指标测定，包括采用稳态模型评估法评估IR。CHC患者的活检标本按照Scheuer分类法评分，NAFLD患者的活检标本按照Kleiner分类法评分。将脂肪变性作为连续变量进行检测，并分为无-轻度（<30%）或中度-重度（≥30%）。30名非糖尿病、非肥胖的献血者作为对照。采用人竞争性酶联免疫吸附测定试剂盒（AdipoGen）测定RBP4水平。NAFLD和CHC患者的RBP4均值相似（分别为35.3±9.3μg/L和36.8±17.6μg/L；P = 0.47），且两者均显著高于对照组（28.9±12.1μg/L；P分别为0.02和0.01）。CHC合并脂肪变性患者的RBP4水平高于NAFLD患者（42.1±19.7μg/L对35.2±9.3μg/L；P = 0.04）。通过线性回归分析，在CHC中，RBP4仅与脂肪变性独立相关（P = 0.008），而在NAFLD中，RBP4与体重指数升高（P = 0.01）和低分级（P = 0.04）相关。通过线性回归分析，在CHC中，脂肪变性与稳态模型评估得分（P = 0.03）和高RBP4水平（P = 0.003）独立相关。通过逻辑回归分析，RBP4是CHC中与中度-重度脂肪变性独立相关的唯一变量（比值比，1.045；95%置信区间，1.020至1.070；P = 0.0004），而在NAFLD中，腰围与中度-重度脂肪变性相关（比值比，1.095；95%置信区间，1.007至1.192；P = 0.03）。
在非糖尿病、非肥胖的1型CHC患者中，血清RBP4水平可能是与脂肪变性相关的病毒介导途径的一种表现，很大程度上与IR无关。
