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直接作用抗病毒疗法治疗老年人慢性丙型肝炎病毒感染的安全性和有效性

Safety and efficacy of directly-acting antiviral therapy for chronic hepatitis C virus in elderly people.

作者信息

De Santis Adriano, Maggi Daniela, Lubrano Lobianco Federica

机构信息

Department of Translational and Precision Medicine Sapienza University Rome Italy.

出版信息

Aging Med (Milton). 2021 Dec 21;4(4):304-316. doi: 10.1002/agm2.12190. eCollection 2021 Dec.

Abstract

INTRODUCTION

In Italy, the prevalence of hepatitis C virus (HCV) infection is higher in the elderly, although the efficacy and safety of treatment in this population has not been extensively studied. Moreover, little is known about how much pharmacological interaction affects eligibility to treatment and to what extent the treatment affects subsequent outcomes.

METHODS

We retrospectively analyzed the efficacy and safety of directly acting antivirals (DAAs), drug-to-drug interactions, and post-treatment outcomes in 138 patients with HCV aged 70 years or older, who were consecutively treated in our center between 2015 and 2020.

RESULTS

The mean age was 77 years old (range = 70-95 years old). The Cumulative Illness Rating Scale of pretherapy severity was classified as moderate to severe in 65% of patients. Fifty-five patients (40%) presented compensated cirrhosis, eight of which were complicated by hepatocellular carcinoma (HCC) and all were cured before treatment. One hundred two patients (74%) were taking two or more drugs (range = 0-5 concomitant drugs registered) and in 29 patients (21%) we found potential drug-to-drug interaction. In 11 of those 29 patients (38%), we were forced to change the chronic therapy, when all therapeutic regimens were equal in terms of efficacy and interactions, to avoid potentially serious drug interactions. One serious adverse event occurred in our sample population (i.e., diverticular bleeding due to interaction with direct oral anticoagulants [DOACs]), whereas mild side effects occurred in 37% of patients. The undetectability of HCV RNA at the end of treatment was achieved in 97% of patients, whereas a sustained virological response (SVR) 12 and SVR 24 were obtained in 98% of patients. When comparing pretherapy with post-therapy data, after a medium follow-up of 15 months (median = 1 year, minimum = 2 months, and maximum = 4 years), we observed a reduction in the incidence of episodes of liver decompensation in patients with cirrhosis and a slight increase in the incidence of HCC (with 6 recurrent and 5 de novo HCC), diagnosed within 13 months from the end of therapy. In all patients, we found a significant improvement in all ultrasound variables and a significant reduction in the elastographic measurements. No significant differences in outcomes were observed dividing the population into patients aged ≥ 80 and < 80 years old.

CONCLUSIONS

Directly acting antiviral therapy was found to be safe and effective in elderly people, and, despite the large number of concomitant drugs, pharmacological interactions appeared to not affect the adherence to therapy or the incidence of adverse events. Side effects were mostly independent from the type of DAA used and from the burden of comorbidity. In long-term follow-up, the benefit of DAA therapy mainly concerned liver pathology and should be strongly advised in patients with cirrhosis. The therapy was found to not affect extrahepatic comorbidities but allowed to end follow-up in noncirrhotic patients with savings in terms of resources. Finally, patients should not be excluded based on age if they have a good performance status.

摘要

引言

在意大利,丙型肝炎病毒(HCV)感染的患病率在老年人中更高,尽管该人群治疗的有效性和安全性尚未得到广泛研究。此外,关于药物相互作用对治疗资格的影响程度以及治疗对后续结果的影响程度知之甚少。

方法

我们回顾性分析了2015年至2020年期间在我们中心连续接受治疗的138例70岁及以上HCV患者中直接抗病毒药物(DAA)的疗效和安全性、药物相互作用以及治疗后结果。

结果

平均年龄为77岁(范围 = 70 - 95岁)。65%的患者治疗前严重程度的累积疾病评定量表被分类为中度至重度。55例患者(40%)出现代偿性肝硬化,其中8例合并肝细胞癌(HCC),且所有患者在治疗前均已治愈。102例患者(74%)正在服用两种或更多药物(范围 = 0 - 5种合并用药记录),29例患者(21%)存在潜在的药物相互作用。在这29例患者中的11例(38%),当所有治疗方案在疗效和相互作用方面相当时,我们被迫改变慢性治疗方案,以避免潜在的严重药物相互作用。我们的样本人群中发生了1例严重不良事件(即因与直接口服抗凝剂[DOACs]相互作用导致的憩室出血),而37%的患者出现了轻微副作用。97%的患者在治疗结束时实现了HCV RNA不可检测,98%的患者获得了持续病毒学应答(SVR)12和SVR 24。在对治疗前和治疗后数据进行比较时,经过15个月的中位随访(中位数 = 1年,最小值 = 2个月,最大值 = 4年),我们观察到肝硬化患者肝失代偿发作的发生率有所降低,HCC的发生率略有增加(6例复发和5例新发HCC),在治疗结束后13个月内确诊。在所有患者中,我们发现所有超声变量均有显著改善,弹性成像测量值显著降低。将人群分为年龄≥80岁和<80岁的患者,结果未观察到显著差异。

结论

直接抗病毒治疗在老年人中被发现是安全有效的,并且,尽管有大量合并用药,但药物相互作用似乎并未影响治疗依从性或不良事件的发生率。副作用大多与所使用的DAA类型和合并症负担无关。在长期随访中,DAA治疗的益处主要涉及肝脏病理,对于肝硬化患者应强烈建议进行治疗。该治疗被发现不影响肝外合并症,但允许非肝硬化患者结束随访并节省资源。最后,如果患者的体能状态良好,不应基于年龄将其排除。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cc3/8711222/0b052bae81ea/AGM2-4-304-g002.jpg

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