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直接作用抗病毒药物抗病毒治疗后肝移植患者的组织学动态、肾功能及糖尿病评估:丙型肝炎病毒复发的治疗

Evaluation of histological dynamics, kidney function and diabetes in liver transplant patients after antiviral treatment with direct-acting antivirals: Therapy of HCV-recurrence.

作者信息

Teegen Eva M, Dürr Michael, Maurer Max M, Eurich Franziska, Vollbort Antonia, Globke Brigitta, Bahra Marcus, Blaeker Hendrik, Pratschke Johann, Eurich Dennis

机构信息

Department of Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Department of Internal Medicine, Division of Nephrology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

出版信息

Transpl Infect Dis. 2019 Feb;21(1):e13020. doi: 10.1111/tid.13020. Epub 2018 Nov 27.

Abstract

BACKGROUND

Direct-acting antivirals allow efficient and safe treatment of hepatitis C (HCV) before and after liver transplantation (LT). However, the impact of sofosbuvir on the graft, diabetes, and on kidney function is not answered yet. Primary endpoint of this analysis was the evaluation of kidney function after antiviral treatment (AVT). Secondary endpoints were the assessment of extrahepatic manifestation of HCV-infection by diabetes mellitus and the histopathological changes in terms of inflammation, content of fat, and fibrosis stage.

METHODS

From 2014 to 4/2015, 100 patients with HCV-recurrence after LT were successfully treated with AVT. Ninety-eight received a sofosbuvir-based regimen. Indication was based on genotype, transplant fibrosis stage, and urgency. Biopsies were evaluated before and after treatment. Renal function and diabetes were assessed before, during, and after AVT.

RESULTS

All patients achieved sustained virological response. A significant improvement of inflammation (P = 0.001) and fibrosis stage (P = 0.031) were observed. Significantly less insulin was required in 32 patients with diabetes (P < 0.001) to keep Hb1Ac unchanged after AVT. Kidney function was stable during, 12 weeks after and 48 weeks after antiviral therapy. Stages of renal insufficiency were comparable before and after AVT.

CONCLUSION

Successful sofosbuvir-based AVT leads to a variety of positive development in transplant patients including a significant improvement of inflammation, fat content and fibrosis, a significant decrease in daily insulin dose and no significant impairment of kidney function.

摘要

背景

直接作用抗病毒药物可实现肝移植(LT)前后丙型肝炎(HCV)的高效安全治疗。然而,索磷布韦对移植物、糖尿病及肾功能的影响尚不清楚。本分析的主要终点是评估抗病毒治疗(AVT)后的肾功能。次要终点是通过糖尿病评估HCV感染的肝外表现以及炎症、脂肪含量和纤维化阶段方面的组织病理学变化。

方法

2014年至2015年4月,100例LT后HCV复发患者成功接受了AVT治疗。98例接受了基于索磷布韦的治疗方案。治疗指征基于基因型、移植纤维化阶段和紧迫性。在治疗前后对活检样本进行评估。在AVT前、治疗期间和治疗后评估肾功能和糖尿病情况。

结果

所有患者均实现持续病毒学应答。观察到炎症(P = 0.001)和纤维化阶段(P = 0.031)有显著改善。32例糖尿病患者在AVT后维持糖化血红蛋白(Hb1Ac)不变所需胰岛素显著减少(P < 0.001)。抗病毒治疗期间、治疗后12周和48周肾功能保持稳定。AVT前后肾功能不全阶段相当。

结论

基于索磷布韦的成功AVT可使移植患者出现多种积极变化,包括炎症、脂肪含量和纤维化显著改善,每日胰岛素剂量显著降低,且肾功能无显著损害。

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