Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH) require validation in patients with hepatitis D virus (HDV)-related compensated advanced chronic liver disease (cACLD). Therefore, we aimed to validate existing NIT algorithms for CSPH in this context. Patients with HDV-cACLD (LSM ≥10 kPa or histological METAVIR F3/F4 fibrosis) who underwent paired HVPG and NIT assessment at Medical University of Vienna or Hannover Medical School between 2013 and 2023 were retrospectively included. Liver stiffness measurement (LSM), von Willebrand factor to platelet count ratio (VITRO), and spleen stiffness measurement (SSM) were assessed. Individual CSPH risk was calculated according to previously published models (ANTICIPATE, 3P/5P). The diagnostic performance of Baveno VII criteria and refined algorithms (Baveno VII-VITRO, Baveno VII-SSM) was evaluated. The prognostic utility of NITs was investigated in the main cohort and an independent, multicenter, validation cohort. Fifty-one patients (HVPG ≥10 mmHg/CSPH prevalence: 62.7%, varices: 42.2%) were included. Patients with CSPH had significantly higher LSM (25.8 [17.2-31.0] 14.0 [10.5-19.8] kPa; < 0.001), VITRO (n = 31, 3.5 [2.7-4.5] 1.3 [0.6-2.0] %/[G/L]; < 0.001), and SSM (n = 20, 53.8 [41.7-75.5] 24.0 [17.0-33.9] kPa; < 0.001). Composite CSPH risk models yielded excellent AUROCs (ANTICIPATE: 0.885, 3P: 0.903, 5P: 0.912). Baveno VII criteria ruled out CSPH with 100% sensitivity and ruled in CSPH with 84.2% specificity. The Baveno VII ‘grey zone’ (41.1%) was significantly reduced by Baveno VII-VITRO or Baveno VII-SSM algorithms, which maintained diagnostic accuracy. Hepatic decompensation within 2 years only occurred in patients who had CSPH or met Baveno VII rule-in criteria. The prognostic value of NITs was confirmed in the validation cohort comprising 92 patients. Standalone and composite NIT/diagnostic algorithms are useful for CSPH diagnosis in patients with HDV-cACLD. Thus, NITs may be applied to identify and prioritize patients with CSPH for novel antiviral treatments against chronic hepatitis D. Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH) have been developed to identify patients with compensated advanced chronic liver disease (cACLD) at risk of decompensation, but conflicting data has been published regarding the accuracy of liver stiffness measurement (LSM) for the staging of fibrosis in patients infected with hepatitis D virus (HDV). In our study, including 51 patients with HDV-cACLD, LSM- and lab-based NITs yielded high AUROCs for CSPH. Moreover, only patients with CSPH or high non-invasively assessed CSPH risk were at risk of decompensation within 2 years, with the prognostic value of NITs confirmed in a validation cohort. Thus, NITs should be applied and updated in yearly intervals in clinical routine to identify patients with HDV-cACLD at short-term risk of clinical events; NITs may also guide prioritization for novel antiviral treatment options.

中文翻译：

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验证 Baveno VII 标准和其他非侵入性诊断算法对丁型肝炎有临床意义的门脉高压

对于具有临床意义的门脉高压 (CSPH) 的无创检测 (NIT) 需要在丁型肝炎病毒 (HDV) 相关代偿性晚期慢性肝病 (cACLD) 患者中进行验证。因此，我们旨在在此背景下验证 CSPH 的现有 NIT 算法。回顾性纳入 2013 年至 2023 年间在维也纳医科大学或汉诺威医学院接受 HVPG 和 NIT 配对评估的 HDV-cACLD（LSM ≥10 kPa 或组织学 METAVIR F3/F4 纤维化）患者。评估了肝脏硬度测量（LSM）、冯维勒布兰德因子与血小板计数比率（VITRO）和脾硬度测量（SSM）。个人 CSPH 风险根据之前发布的模型（ANTICIPATE、3P/5P）计算。对 Baveno VII 标准和改进算法（Baveno VII-VITRO、Baveno VII-SSM）的诊断性能进行了评估。 NIT 的预后效用在主要队列和独立的多中心验证队列中进行了研究。纳入 51 名患者（HVPG ≥10 mmHg/CSPH 患病率：62.7%，静脉曲张：42.2%）。 CSPH 患者的 LSM 显着升高 (25.8 [17.2-31.0] 14.0 [10.5-19.8] kPa; < 0.001)，VITRO (n = 31, 3.5 [2.7-4.5] 1.3 [0.6-2.0] %/[G/L ]; < 0.001) 和 SSM (n = 20, 53.8 [41.7-75.5] 24.0 [17.0-33.9] kPa; < 0.001)。复合 CSPH 风险模型产生了出色的 AUROC（预期：0.885，3P：0.903，5P：0.912）。 Baveno VII 标准排除 CSPH 的敏感性为 100%，排除 CSPH 的特异性为 84.2%。 Baveno VII-VITRO 或 Baveno VII-SSM 算法显着减少了 Baveno VII 的“灰色区域”（41.1%），从而保持了诊断准确性。 2年内肝代偿失调仅发生在患有CSPH或符合Baveno VII入组标准的患者中。 NIT 的预后价值在由 92 名患者组成的验证队列中得到了证实。独立和复合 NIT/诊断算法可用于 HDV-cACLD 患者的 CSPH 诊断。因此，NIT 可用于识别 CSPH 患者并优先考虑针对慢性丁型肝炎的新型抗病毒治疗。针对临床上显着的门脉高压 (CSPH) 的无创检测 (NIT) 已被开发用于识别患有代偿性晚期慢性肝病的患者。 cACLD）有失代偿的风险，但关于肝脏硬度测量（LSM）对丁型肝炎病毒（HDV）感染患者纤维化分期的准确性，已经发表了相互矛盾的数据。在我们的研究中，包括 51 名 HDV-cACLD 患者，LSM 和基于实验室的 NIT 对 CSPH 产生了高 AUROC。此外，只有患有 CSPH 或经非侵入性评估的高 CSPH 风险的患者在 2 年内有失代偿的风险，NIT 的预后价值在验证队列中得到证实。因此，应在临床常规中每年应用和更新 NIT，以识别具有短期临床事件风险的 HDV-cACLD 患者； NIT 还可以指导新型抗病毒治疗方案的优先顺序。