ABSTRACT

Both hepatitis C virus (HCV) infection and retinol-binding protein 4 (RBP4) might contribute to insulin resistance (IR), how RBP4 links to IR in HCV infection remain elusive. A joint study of a prospective cohort of 842 chronically HCV-infected (CHC) patients (with 842 controls) and a line of HCV core transgenic mice was conducted. Of 842 patients, 771 had completed anti-HCV therapy and 667 had sustained virological responses (SVRs). Compared with controls, CHC patients had lower RBP4 levels. At baseline, age (95% CI β: −0.87~−0.317), BMI (0.516~2.036), triglycerides (0.03~0.127), neutrophil-to-lymphocyte ratio (NLR) (1.561~7.327), and estimated glomerular filtration rate (eGFR) (−0.342~−0.149) levels were associated with RBP4 levels in CHC patients. At 24-week post-therapy, male sex (0.652~8.129), BMI (0.199~1.254), triglycerides (0.039~0.088), uric acid (0.599~3.067), eGFR (−0.247 ~−0.14) levels, and fibrosis-4 (−3.602~−0.039) scores were associated with RBP4 levels in SVR patients; compared with baseline, except genotype 3 HCV-infected patients, SVR patients had increased RBP4 levels, which were comparable with controls, while no HOMA-IR index alteration was noted after SVR. The HCV core transgenic mice exhibited nonobese hepatic steatosis, had higher hepatic RBP4 expression, higher serum levels of RBP4 and triglycerides, but comparable HOMA-IR levels than non-transgenic littermates. In conclusion, steatosis, sex, age, uric acid, NLR, and FIB-4 levels were associated with HCV-related RBP4 levels; BMI, triglycerides, and eGFR levels were associated with non-HCV-related RBP4 levels. Reversal of low RBP4 levels after SVR was evident in non-genotype 3 HCV-infected patients. Steatosis and inflammation linked with metabolic alteration other than IR, determined RBP4 levels in HCV-infected patients.

摘要

丙型肝炎病毒 (HCV) 感染和视黄醇结合蛋白 4 (RBP4) 都可能导致胰岛素抵抗 (IR)，但 RBP4 如何与 HCV 感染中的 IR 相关联仍然难以捉摸。对 842 名慢性 HCV 感染 (CHC) 患者（有 842 名对照）和一系列 HCV 核心转基因小鼠的前瞻性队列进行了联合研究。在 842 名患者中，771 名完成了抗 HCV 治疗，667 名患者获得了持续病毒学应答 (SVR)。与对照组相比，CHC 患者的 RBP4 水平较低。基线时，年龄（95% CI β：-0.87~-0.317）、BMI（0.516~2.036）、甘油三酯（0.03~0.127）、中性粒细胞与淋巴细胞比率（NLR）（1.561~7.327）和估计的肾小球滤过率 (eGFR) (-0.342~-0.149) 水平与 CHC 患者的 RBP4 水平相关。治疗后 24 周，男性 (0.652~8.129)、BMI (0.199~1.254)、甘油三酯 (0.039~0.088)、尿酸（0.599~3.067）、eGFR（-0.247~-0.14）水平和纤维化4（-3.602~-0.039）评分与SVR患者的RBP4水平相关；与基线相比，除基因 3 型 HCV 感染患者外，SVR 患者的 RBP4 水平升高，与对照组相当，而 SVR 后未发现 HOMA-IR 指数变化。HCV 核心转基因小鼠表现出非肥胖肝脂肪变性，肝脏 RBP4 表达更高，血清 RBP4 和甘油三酯水平更高，但与非转基因同窝仔鼠相比，HOMA-IR 水平相当。总之，脂肪变性、性别、年龄、尿酸、NLR 和 FIB-4 水平与 HCV 相关的 RBP4 水平相关；BMI、甘油三酯和 eGFR 水平与非 HCV 相关的 RBP4 水平相关。在非基因 3 型 HCV 感染的患者中，SVR 后低 RBP4 水平的逆转是明显的。