A total of 2%–10% of patients with vascular liver disease (VLD) have paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab reduces complement-mediated haemolytic activity in PNH. This study was aimed at assessing the impact of eculizumab on VLD outcome. Retrospective cohort of PNH patients, in Valdig registry, who had VLD diagnosed between 1997 and 2019 is considered. Eculizumab was the exposure of interest. Studied outcomes were death, venous thrombosis, bleeding, arterial ischemic event, infection, and liver-related complications. We compared survival and new thrombotic events from PNH/VLD cohort to Envie2 non-PNH cohort. Sixty-two patients (33 women), median age 35 years (28–48) and median follow-up VLD diagnosis 4.7 years (1.2–9.5), were included. Clone size was 80% (70–90), median hemoglobin concentration was 10.0 g/dl (8–11), and lactate dehydrogenase (LDH) was 736 IU (482–1744). Forty-two patients (68%) had eculizumab; median exposure time was 40.1 [9.3–72.6] months. Mortality was significantly lower in exposed versus nonexposed period: 2.6 versus 8.7 per 100 (PY), incidence rate ratio (IRR) was 0.29, 95% CI (0.1–0.9), p = .035. Thrombosis recurrence occurred less frequently during the exposure to eculizumab: 0.5 versus 2.8 per 100 PY, IRR 0.22 (0.07–0.64). Other secondary end points (i.e., bleeding, arterial ischemic lesions, infection, and liver complications) were less common during the exposure to eculizumab, although not reaching statistical significance. Six-year thrombosis-free survival was 70%, 95% CI [0.60–0.83] for PNH cohort and 83%, 95% CI [0.70–1.00] for non-PNH Envie 2 patients, (p < .001). In conclusion, patients with PNH and VLD are at higher risk of recurrent thrombosis than non-PNH patients. Eculizumab is significantly associated with a lower mortality and less thrombotic recurrence in patients with PNH and VLD.

中文翻译：

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阵发性睡眠性血红蛋白尿和血管性肝病：依库珠单抗治疗可降低死亡率和血栓并发症

总共有 2%–10% 的血管性肝病 (VLD) 患者有阵发性睡眠性血红蛋白尿症 (PNH)。Eculizumab 降低 PNH 中补体介导的溶血活性。本研究旨在评估依库珠单抗对 VLD 结果的影响。考虑了在 Valdig 登记处在 1997 年至 2019 年间诊断出 VLD 的 PNH 患者的回顾性队列。Eculizumab 是感兴趣的暴露。研究结果包括死亡、静脉血栓形成、出血、动脉缺血事件、感染和肝脏相关并发症。我们比较了 PNH/VLD 队列与 Envie2 非 PNH 队列的生存率和新血栓形成事件。包括 62 名患者（33 名女性），中位年龄 35 岁（28-48）和中位随访 VLD 诊断 4.7 年（1.2-9.5）。克隆大小为 80% (70–90)，血红蛋白浓度中位数为 10.0 g/dl (8–11)，乳酸脱氢酶 (LDH) 为 736 IU (482–1744)。42 名患者 (68%) 使用依库珠单抗；中位暴露时间为 40.1 [9.3–72.6] 个月。暴露期与非暴露期的死亡率显着降低：每 100 人 (PY) 为 2.6 对 8.7，发病率比 (IRR) 为 0.29，95% CI (0.1–0.9)，p  = .035。在暴露于依库珠单抗期间，血栓形成的复发率较低：每 100 PY 0.5 对 2.8，IRR 0.22 (0.07–0.64)。其他次要终点（即出血、动脉缺血性病变、感染和肝脏并发症）在依库珠单抗暴露期间较少见，但未达到统计学显着性。PNH 队列的六年无血栓形成生存率为 70%，95% CI [0.60-0.83]，非 PNH Envie 2 患者为 83%，95% CI [0.70-1.00]，( p  < .001)。总之，与非 PNH 患者相比，PNH 和 VLD 患者的血栓复发风险更高。在 PNH 和 VLD 患者中，依库珠单抗与较低的死亡率和较少的血栓复发显着相关。