Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital , Taoyuan, Taiwan.
Department of Medicine, College of Medicine, Chang Gung University , Taoyuan, Taiwan.
Virulence. 2020 Dec;11(1):1501-1511. doi: 10.1080/21505594.2020.1838742.
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 (0.5162.036), triglycerides (0.030.127), neutrophil-to-lymphocyte ratio (NLR) (1.5617.327), 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 (0.6528.129), BMI (0.1991.254), triglycerides (0.0390.088), uric acid (0.5993.067), 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.
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 HCV 感染中 RBP4 与 IR 的关系仍不清楚。本研究对 842 例慢性 HCV 感染患者（842 例对照）的前瞻性队列进行了联合研究，并对 HCV 核心转基因小鼠进行了研究。在 842 例患者中，771 例完成了抗 HCV 治疗，667 例获得持续病毒学应答（SVR）。与对照组相比，CHC 患者的 RBP4 水平较低。在基线时，年龄（95%CIβ：-0.87-0.317）、BMI（0.5162.036）、甘油三酯（0.030.127）、中性粒细胞与淋巴细胞比值（NLR）（1.5617.327）和估计肾小球滤过率（eGFR）（-0.342-0.149）与 CHC 患者的 RBP4 水平相关。在治疗后 24 周时，男性（0.6528.129）、BMI（0.1991.254）、甘油三酯（0.0390.088）、尿酸（0.5993.067）、eGFR（-0.247-0.14）水平和纤维化 4（FIB-4）评分（-3.602~-0.039）与 SVR 患者的 RBP4 水平相关；与基线相比，除基因型 3 HCV 感染患者外，SVR 患者的 RBP4 水平升高，与对照组相当，而 SVR 后 HOMA-IR 指数没有变化。HCV 核心转基因小鼠表现为非肥胖性肝脂肪变性，肝 RBP4 表达升高，血清 RBP4 和甘油三酯水平升高，但与非转基因同窝仔鼠的 HOMA-IR 水平相当。结论：肝脂肪变性、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。除基因型 3 HCV 感染患者外，SVR 后 RBP4 水平的逆转是明显的。与 IR 无关的代谢改变导致了 HCV 感染患者的脂肪变性和炎症，决定了 RBP4 水平。
