Liver Research Center, 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. 2021 Dec;12(1):270-280. doi: 10.1080/21505594.2020.1870080.
Involvement of extracellular nicotinamide phosphoribosyltransferase (eNAMPT, i.e., visfatin or pre-B-cell colony-enhancing factor), a cancer metabokine, in chronically hepatitis C virus (HCV)-infected (CHC) patients with sustained virological responses (SVRs) remains elusive. This 8-year prospective cohort study evaluated eNAMPT profiles of 842 consecutive CHC patients, including 519 who had completed an anti-HCV therapy course and pre-therapy and 24-week post-therapy surveys. For 842 patients, pre-therapy associations were HCV RNA, homeostatic model assessment for insulin resistance (HOMA-IR) index, and body mass index with eNAMPT levels, and NAMPT-rs61330082 T allele with total cholesterol levels. NAMPT-rs10953502, NAMPT-rs2058539, and NAMPT-rs61330082 were in a linkage disequilibrium block, which was associated with total cholesterol levels. Compared to pre-therapy levels, at 24 weeks post-therapy, decreased eNAMPT and increased lipid levels were observed in SVR patients (n = 427). Among SVR patients, higher cumulative incidences of cardiovascular events occurred in those with a NAMPT-rs61330082 TT genotype than those with non-TT genotypes (28.2% vs. 8.4%, < 0.001). NAMPT-rs61330082 TT genotype was independently associated with incident cardiovascular events (95% CI hazard ratio (HR): 1.88-10.37; HR: 4.415); no eNAMPT profiles were associated with incident malignancies. Of CHC patients, hepatic vascular endothelial cells and baseline peripheral leukocytes expressed higher eNAMPT levels than controls, and peripheral eNAMPT-positive leukocyte proportions decreased after SVR. During HCV infection, eNAMPT involvement in glucose metabolism was modulated by HCV RNA linked to lipid metabolism and NAMPT-associated SNPs. Hepatic endothelial cells and peripheral leukocytes potentially secrete eNAMPT. Caution is required for incident cardiovascular events in SVR patients with NAMPT-rs61330082 TT genotype.
细胞外烟酰胺磷酸核糖转移酶（eNAMPT，即内脏脂肪素或前 B 细胞集落增强因子）是一种癌症代谢物，其在慢性丙型肝炎病毒（HCV）感染并获得持续病毒学应答（SVR）的患者中的作用仍不清楚。本项为期 8 年的前瞻性队列研究评估了 842 例连续的 CHC 患者的 eNAMPT 谱，其中包括 519 例完成抗 HCV 治疗疗程并进行了治疗前和 24 周治疗后调查的患者。对于 842 例患者，治疗前与 eNAMPT 水平相关的因素包括 HCV RNA、稳态模型评估的胰岛素抵抗指数（HOMA-IR）和体重指数，以及 NAMPT-rs61330082 T 等位基因与总胆固醇水平相关。NAMPT-rs10953502、NAMPT-rs2058539 和 NAMPT-rs61330082 位于一个连锁不平衡块中，与总胆固醇水平相关。与治疗前水平相比，在 24 周治疗后，SVR 患者（n=427）的 eNAMPT 降低，脂质水平升高。在 SVR 患者中，NAMPT-rs61330082 TT 基因型患者的心血管事件累积发生率高于非 TT 基因型患者（28.2% vs. 8.4%，<0.001）。NAMPT-rs61330082 TT 基因型与心血管事件的发生独立相关（95%CI 风险比（HR）：1.88-10.37；HR：4.415）；eNAMPT 谱与恶性肿瘤的发生无关。与对照组相比，慢性丙型肝炎患者的肝血管内皮细胞和基线外周白细胞表达更高的 eNAMPT 水平，SVR 后外周 eNAMPT 阳性白细胞比例下降。在 HCV 感染期间，eNAMPT 参与葡萄糖代谢的情况受与脂质代谢和 NAMPT 相关 SNP 相关的 HCV RNA 调节。肝内皮细胞和外周白细胞可能分泌 eNAMPT。对于 NAMPT-rs61330082 TT 基因型的 SVR 患者，需要注意心血管事件的发生。
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