Letter: Lubiprostone Treatment for MASLD—Gender Imbalance and Blinding Considerations. Authors' Reply

IF 6.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Mohamed El-Kassas, Hala Mostafa, Hongqun Liu, Samuel S. Lee
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引用次数: 0

Abstract

We appreciate the comments of Drs. Li and Shen [1] on our recent study [2] investigating the effects of lubiprostone in metabolic dysfunction-associated steatotic liver disease (MASLD). Their concerns regarding gender imbalance and blinding considerations provide an opportunity to further clarify our study design and findings.

First, we acknowledge that our study population had a higher proportion of female participants, with 83% in the control group and 91% in the lubiprostone group. This gender distribution reflects real-world epidemiological patterns, where MASLD is increasingly prevalent among women, particularly in regions with high obesity and metabolic syndrome rates [3]. Recent data from Egypt indicate that obesity prevalence in adults is among the highest globally, with significantly higher rates in females (49.5%) compared to males (29.5%) [4].

Secondly, while oestrogen may play a role in MASLD pathophysiology [5], the randomization process in our study ensured an equal distribution of potential confounders across both groups. Furthermore, baseline characteristics—including BMI, lipid profiles, and liver enzymes—were comparable, minimising the likelihood that hormonal differences influenced our results. Future studies may benefit from stratified randomisation based on menopausal status or direct oestrogen level assessments to explore this aspect further.

Additionally, Li and Shen raise concerns regarding the potential for participants to infer their treatment allocation due to lubiprostone's well-documented gastrointestinal effects. While we recognise that laxatives may induce a noticeable physiological response [6], our study adhered to a rigorous double-blind design in which both patients and healthcare providers were unaware of group allocation. Importantly, patient-reported outcomes were not a primary endpoint, reducing the potential for subjective bias. Although the suggestion of incorporating a dummy laxative as a control arm is theoretically appealing, it presents ethical and logistical challenges, including potential confounding effects. That said, future trials incorporating validated blinding assessment tools could provide additional reassurance regarding the robustness of blinding procedures.

Finally, our trial focused on MASLD patients without advanced fibrosis, with liver enzyme levels below 40 U/L. This was an intentional design choice to examine lubiprostone's effects on hepatic steatosis in a relatively homogenous population. We agree that studying patients with more severe MASLD, including those with elevated ALT and significant fibrosis, is crucial. The long-term safety of lubiprostone, particularly in patients with metabolic comorbidities, warrants further study in larger, multi-centre trials with extended follow-up periods.

Mohamed El-Kassas: conceptualization, writing – original draft, writing – review and editing. Hala Mostafa: writing – original draft, writing – review and editing. Hongqun Liu: writing – original draft, writing – review and editing. Samuel S. Lee: conceptualization, writing – original draft, writing – review and editing.

IRB approval was not required because no data was collected for this article.

The authors declare no conflicts of interest.

This article is linked to El-Kassas et al papers. To view these articles, visit https://doi.org/10.1111/apt.18478 and https://doi.org/10.1111/apt.70089.

信:卢比前列酮治疗 MASLD--性别失衡和盲法注意事项。作者回复
我们感谢博士的评论。Li和Shen b[1]对我们最近的研究b[1]调查了脂prostone在代谢功能障碍相关脂肪变性肝病(MASLD)中的作用。他们对性别失衡和盲性考虑的担忧为进一步阐明我们的研究设计和发现提供了机会。首先,我们承认我们的研究人群中女性参与者的比例较高,对照组为83%,润滑油前列素组为91%。这种性别分布反映了现实世界的流行病学模式,其中MASLD在妇女中越来越普遍,特别是在肥胖和代谢综合征发生率高的地区。来自埃及的最新数据表明,埃及成年人的肥胖患病率是全球最高的,其中女性的肥胖率(49.5%)明显高于男性(29.5%)。其次,虽然雌激素可能在MASLD病理生理[5]中发挥作用,但我们研究中的随机化过程确保了两组中潜在混杂因素的均匀分布。此外,基线特征(包括BMI、脂质谱和肝酶)具有可比性,将激素差异影响结果的可能性降至最低。未来的研究可能会受益于基于绝经状态的分层随机化或直接雌激素水平评估来进一步探索这方面。此外,Li和Shen还提出了一些担忧,即由于卢比前列酮的胃肠道效应,参与者可能会推断他们的治疗分配。虽然我们认识到泻药可能会引起明显的生理反应b[6],但我们的研究坚持严格的双盲设计,其中患者和医疗保健提供者都不知道组分配。重要的是,患者报告的结果不是主要终点,减少了主观偏倚的可能性。虽然将虚拟泻药作为控制臂的建议在理论上很有吸引力,但它提出了伦理和后勤方面的挑战,包括潜在的混淆效应。也就是说,未来的试验纳入了经过验证的盲法评估工具,可以为盲法程序的稳健性提供额外的保证。最后,我们的试验重点是无晚期纤维化、肝酶水平低于40 U/L的MASLD患者。这是一项有意的设计选择,目的是在相对均匀的人群中检验润滑前列素对肝脂肪变性的影响。我们同意,研究更严重的MASLD患者,包括ALT升高和显著纤维化的患者是至关重要的。lubiprostone的长期安全性,特别是对于有代谢合并症的患者,值得在更大规模的多中心试验中进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
15.60
自引率
7.90%
发文量
527
审稿时长
3-6 weeks
期刊介绍: Alimentary Pharmacology & Therapeutics is a global pharmacology journal focused on the impact of drugs on the human gastrointestinal and hepato-biliary systems. It covers a diverse range of topics, often with immediate clinical relevance to its readership.
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