Gastroenterology and Hepatology, Changi General Hospital, SingHealth, Singapore, Singapore.
SingHealth Duke-NUS Medicine Academic Clinical Program, Singapore, Singapore.
Hepatol Int. 2023 Oct;17(5):1150-1161. doi: 10.1007/s12072-023-10547-4. Epub 2023 Jun 5.
Current guidelines discourage the use of direct-acting antiviral (DAA) containing protease-inhibitor (PI) in advanced HCV cirrhosis. We aimed to compare the real-world tolerability of PI vs. non-PI DAA regimens in this population.
We identified advanced cirrhosis patients treated with DAA from the REAL-C registry. The primary outcome was significant worsening or improvement in CPT or MELD scores following DAA treatment.
From the REAL-C registry of 15,837 patients, we included 1077 advanced HCV cirrhosis patients from 27 sites. 42% received PI-based DAA. Compared to non-PI group, the PI group was older, had higher MELD and higher percentage with kidney disease. Inverse probability of treatment weighting (IPTW; matching on age, sex, history of clinical decompensation, MELD, platelet, albumin, Asia site, Asian ethnicity, hypertension, hemoglobin, genotype, liver cancer, ribavirin) was used to balance the two groups. In the IPTW-matched cohorts, the PI and non-PI groups had similar SVR12 (92.9% vs. 90.7%, p = 0.30), similar percentages of significant worsening in CTP or MELD scores at posttreatment week 12 and 24 (23.9% vs. 13.1%, p = 0.07 and 16.5% vs. 14.6%, p = 0.77), and similar frequency of new HCC, decompensating event, and death by posttreatment week 24. In multivariable analysis, PI-based DAA was not associated with significant worsening (adjusted odds ratio = 0.82, 95% CI 0.38-1.77).
Tolerability and treatment outcomes were not significantly different in advanced HCV cirrhosis treated with PI-based (vs. non-PI) DAA up to CTP-B or MELD score of 15. Safety of PI-based DAA in those with CTP-C or MELD beyond 15 awaits further data.
目前的指南不鼓励在晚期 HCV 肝硬化患者中使用含直接作用抗病毒（DAA）的蛋白酶抑制剂（PI）。我们旨在比较该人群中 PI 与非 PI DAA 方案的真实世界耐受性。
我们从 REAL-C 登记处确定了接受 DAA 治疗的晚期肝硬化患者。主要结局是 DAA 治疗后 CPT 或 MELD 评分的显著恶化或改善。
从 15837 例 REAL-C 登记患者中，我们纳入了来自 27 个地点的 1077 例晚期 HCV 肝硬化患者。42%接受了基于 PI 的 DAA。与非 PI 组相比，PI 组年龄较大，MELD 较高，且有更高比例的患者患有肾病。采用逆概率治疗加权（IPTW；匹配年龄、性别、临床失代偿史、MELD、血小板、白蛋白、亚洲地点、亚洲种族、高血压、血红蛋白、基因型、肝癌、利巴韦林）对两组进行平衡。在 IPTW 匹配队列中，PI 组和非 PI 组的 SVR12 相似（92.9% vs. 90.7%，p=0.30），治疗后 12 周和 24 周时 CTP 或 MELD 评分显著恶化的比例相似（23.9% vs. 13.1%，p=0.07 和 16.5% vs. 14.6%，p=0.77），且治疗后 24 周时新 HCC、失代偿事件和死亡的发生率也相似。多变量分析显示，基于 PI 的 DAA 与显著恶化无关（调整后的比值比=0.82，95%CI 0.38-1.77）。
在 CTP-B 或 MELD 评分达到 15 以下的晚期 HCV 肝硬化患者中，使用基于 PI（与非 PI）的 DAA 治疗的耐受性和治疗结局没有显著差异。PI 基于 DAA 在 CTP-C 或 MELD 超过 15 的患者中的安全性还需要进一步的数据。
