Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada.
Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada.
BMJ Open. 2023 Aug 22;13(8):e076547. doi: 10.1136/bmjopen-2023-076547.
Advanced chronic liver disease (ACLD) is a major cause of death for people with HIV (PWH). While viral hepatitis coinfections are largely responsible for this trend, metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging concern for PWH. We aimed to assess the contribution of MASLD to incident ACLD in PWH.
This multicentre prospective observational cohort study will enrol 968 consecutive HIV monoinfected patients from four Canadian sites, excluding subjects with alcohol abuse, liver disease other than MASLD, or ACLD at baseline. Participants will be followed annually for 4 years by clinical evaluation, questionnaires, laboratory testing and Fibroscan to measure liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). The primary outcome will be incidence of ACLD, defined as LSM>10 kPa, by MASLD status, defined as CAP≥285 dB/m with at least one metabolic abnormality, and to develop a score to classify PWH according to their risk of ACLD. Secondary outcomes will include health-related quality of life (HRQoL) and healthcare resource usage. Kaplan-Meier survival method and Cox proportional hazards regression will calculate the incidence and predictors of ACLD, respectively. Propensity score methods and marginal structural models will account for time-varying exposures. We will split the cohort into a training set (to develop the risk score) and a validation set (for validation of the score). HRQoL scores and healthcare resource usage will be compared by MASLD status using generalised linear mixed effects model.
This protocol has been approved by the ethics committees of all participating institutions. Written informed consent will be obtained from all study participants. The results of this study will be shared through scientific publications and public presentations to advocate for the inclusion of PWH in clinical trials of MASLD-targeted therapies and case-finding of ACLD in PWH.
慢性肝病（ACLD）是 HIV 感染者（PWH）死亡的主要原因。虽然病毒性肝炎合并感染在很大程度上导致了这一趋势，但代谢功能障碍相关脂肪性肝病（MASLD）是 PWH 面临的一个新兴问题。我们旨在评估 MASLD 在 PWH 中导致 ACLD 发病的作用。
这项多中心前瞻性观察队列研究将从加拿大的四个地点招募 968 名连续的 HIV 单感染患者，排除基线时有酒精滥用、除 MASLD 以外的肝脏疾病或 ACLD 的患者。参与者将每年通过临床评估、问卷调查、实验室检查和 Fibroscan 进行随访，以测量肝脏硬度测量值（LSM）和受控衰减参数（CAP）。主要结局将根据 MASLD 状态定义为 LSM>10kPa 的 ACLD 发病率，MASLD 定义为 CAP≥285dB/m 且至少存在一种代谢异常，并制定一种评分方法来根据 PWH 的 ACLD 风险对其进行分类。次要结局将包括健康相关生活质量（HRQoL）和医疗保健资源使用情况。Kaplan-Meier 生存法和 Cox 比例风险回归将分别计算 ACLD 的发病率和预测因素。倾向评分方法和边缘结构模型将考虑随时间变化的暴露情况。我们将把队列分为训练集（开发风险评分）和验证集（验证评分）。将使用广义线性混合效应模型根据 MASLD 状态比较 HRQoL 评分和医疗保健资源使用情况。
该方案已获得所有参与机构的伦理委员会的批准。将从所有研究参与者处获得书面知情同意。本研究的结果将通过科学出版物和公开演讲共享，以倡导将 PWH 纳入 MASLD 靶向治疗的临床试验和 PWH 中 ACLD 的病例发现。
