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.
Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou, Taiwan.
J Infect Public Health. 2024 Mar;17(3):486-494. doi: 10.1016/j.jiph.2024.01.010. Epub 2024 Jan 15.
BACKGROUND / AIMS: Effects of anti-hepatitis C virus (HCV) therapeutic regimens and mixed cryoglobulinemia on long-term renal function of HCV-infected patients with viral clearance have not been determined.
METHODS/MATERIALS: A prospective 10-year cohort study of 1212 HCV-infected patients (interferon-based therapy, n = 615; direct-acting antiviral (DAA) therapy, n = 434) was conducted.
At baseline, age, body mass index (BMI), hemoglobin (Hb) and uric acid (UA) levels, and fibrosis-4 score were associated with estimated glomerular filtration rates (eGFRs) in HCV-infected patients. At 24 weeks posttherapy, age, BMI, and Hb and UA levels were associated with eGFRs in patients with a sustained virological response (SVR) (n = 930). Compared with those at baseline, the eGFRs were lower in SVR patients at 24 weeks posttherapy, regardless of the therapeutic regimen. The eGFRs reverted to baseline levels in interferon-treated SVR patients up to 10 years posttherapy but remained decreased in DAA-treated SVR patients up to 4 years posttherapy. Longitudinally, repeated measures analyses with generalized estimating equations showed that the interactions between DAA-based therapy and mixed cryoglobulinemia (OR: 3.291) and Hb levels (1.778) were positively, while DAA-based therapy (0.442), age (0.956), UA levels (0.698), homeostasis model assessment-insulin resistance index (0.961) and complement 4 levels (0.9395) were negatively associated with the eGFR. Among DAA-treated SVR patients, the baseline eGFR (OR: 1.014; 95%CI OR: 1.004-1.023) and high-sensitivity C-reactive protein (HR: 1.082; 95%CI HR: 1.018-1.15) were associated with eGFR reduction at 24 weeks and 4 years posttherapy, respectively.
Hepatic fibrosis was an HCV-related factor for renal function. Longitudinally, DAA therapy was negatively, while the interaction between DAA therapy and mixed cryoglobulinemia was positively associated with renal function in SVR patients; deteriorated renal function was recovered in interferon-treated SVR patients. Particularly in DAA-treated SVR patients, baseline renal function and systemic inflammation were associated with short- and long-term reductions in renal function, respectively.
背景/目的：抗丙型肝炎病毒（HCV）治疗方案和混合性冷球蛋白血症对 HCV 感染患者病毒清除后长期肾功能的影响尚未确定。
方法/材料：对 1212 例 HCV 感染患者（基于干扰素的治疗，n=615；直接作用抗病毒（DAA）治疗，n=434）进行了一项前瞻性 10 年队列研究。
在基线时，年龄、体重指数（BMI）、血红蛋白（Hb）和尿酸（UA）水平以及纤维化-4 评分与 HCV 感染患者的估计肾小球滤过率（eGFR）相关。在治疗后 24 周时，年龄、BMI 和 Hb 及 UA 水平与持续病毒学应答（SVR）患者的 eGFR 相关（n=930）。与基线相比，无论治疗方案如何，SVR 患者在治疗后 24 周时的 eGFR 均较低。干扰素治疗的 SVR 患者的 eGFR 在治疗后 10 年内恢复到基线水平，但 DAA 治疗的 SVR 患者的 eGFR 在治疗后 4 年内仍降低。纵向分析采用广义估计方程的重复测量分析显示，DAA 为基础的治疗与混合性冷球蛋白血症（OR：3.291）和 Hb 水平（1.778）之间的交互作用呈正相关，而 DAA 为基础的治疗（0.442）、年龄（0.956）、UA 水平（0.698）、稳态模型评估-胰岛素抵抗指数（0.961）和补体 4 水平（0.9395）与 eGFR 呈负相关。在 DAA 治疗的 SVR 患者中，基线 eGFR（OR：1.014；95%CI OR：1.004-1.023）和高敏 C 反应蛋白（HR：1.082；95%CI HR：1.018-1.15）与治疗后 24 周和 4 年时的 eGFR 降低相关。
肝纤维化是 HCV 相关的肾功能因素。纵向分析显示，DAA 治疗呈负相关，而 DAA 治疗与混合性冷球蛋白血症之间的相互作用与 SVR 患者的肾功能呈正相关；干扰素治疗的 SVR 患者的肾功能得到恢复。特别是在 DAA 治疗的 SVR 患者中，基线肾功能和全身炎症与短期和长期肾功能下降分别相关。
