Fakhreddine Ali Y, Bagsic Samantha, Fujioka Ken, Frenette Catherine T
Division of Gastroenterology and Hepatology Scripps Clinic La Jolla California USA.
Scripps Whittier Diabetes Institute Scripps Health La Jolla California USA.
Obes Sci Pract. 2020 Dec 2;7(2):159-167. doi: 10.1002/osp4.469. eCollection 2021 Apr.
Obesity poses unique risks in patients with advanced liver fibrosis; however, given surgical risks of bariatric surgery in cirrhosis treatment recommendations are currently limited to lifestyle interventions. This study seeks to inform a potential treatment gap by describing the safety and efficacy of pharmacologic weight loss in patients with advanced liver disease.
A retrospective chart review of the electronic medical record was conducted for all patients in the Scripps Health system from 2005 to 2017 with established advanced liver fibrosis that were prescribed medications associated with weight loss. The primary outcome was safety as defined by the model for end-stage liver disease (MELD) score. Secondary outcomes included total body weight loss, reasons for medication discontinuation, medication adverse events, and hospitalization before and after medication initiation.
Thirty-eight patients and 63 prescriptions were included in the final analysis. The most frequently prescribed medication associated with weight loss was metformin (63%, = 24) followed by a GLP-1 agonist (39%, = 15). There was no significant effect of weight-loss medication on MELD score ( > 0.18) or number of hospitalizations when adjusting for subject ( > 0.26). There was a significant adjusted mean weight loss of 2.2 kg ( < 0.02) following prescription of a medication associated with weight loss. The Federal Drug Administration-approved anti-obesity medications as a group resulted in a significant adjusted weight loss of 7.22 kg ( < 0.013). In a linear mixed-effects model accounting for subjects, weight loss was not independently associated with a change in MELD ([51] = -1.972, > 0.05).
Pharmacologic weight loss in patients with advanced liver fibrosis appears feasible based on preliminary safety and efficacy outcomes in this study. Future prospective studies are warranted to evaluate a potential significant treatment gap in the management of obesity in this vulnerable population.
肥胖给晚期肝纤维化患者带来独特风险；然而，鉴于肥胖症手术在肝硬化治疗中的手术风险，目前治疗建议仅限于生活方式干预。本研究旨在通过描述药物减肥在晚期肝病患者中的安全性和有效性，来揭示潜在的治疗差距。
对2005年至2017年斯克里普斯健康系统中所有确诊为晚期肝纤维化且开具了与减肥相关药物的患者的电子病历进行回顾性图表审查。主要结局是由终末期肝病模型（MELD）评分定义的安全性。次要结局包括总体体重减轻、停药原因、药物不良事件以及用药前后的住院情况。
最终分析纳入了38例患者和63份处方。最常开具的与减肥相关的药物是二甲双胍（63%，n = 24），其次是胰高血糖素样肽-1（GLP-1）激动剂（39%，n = 15）。调整受试者因素后，减肥药物对MELD评分（P > 0.18）或住院次数无显著影响（P > 0.26）。开具与减肥相关药物后，调整后的平均体重显著减轻2.2千克（P < 0.02）。一组经美国食品药品监督管理局批准的抗肥胖药物导致调整后的体重显著减轻7.22千克（P < 0.013）。在考虑受试者的线性混合效应模型中，体重减轻与MELD变化无独立相关性（β[51] = -1.972，P > 0.05）。
基于本研究的初步安全性和有效性结果，晚期肝纤维化患者的药物减肥似乎是可行的。未来有必要进行前瞻性研究，以评估这一脆弱人群肥胖管理中潜在的重大治疗差距。
