Lu Yangguang, Yu Bohuai, Bu Yiran, Lou Jialing, Jin Yan
The First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou, China.
Department of Infectious Diseases, Tongde Hospital of Zhejiang Province, Hangzhou, China.
Front Med (Lausanne). 2024 Apr 5;11:1293336. doi: 10.3389/fmed.2024.1293336. eCollection 2024.
The efficacy of Pegbelfermin (PGBF) in treating non-alcoholic steatohepatitis (NASH) remains controversial. Therefore, we conducted a dose-response meta-analysis to explore the effect and pattern of PGBF at different dosages and treatment durations on transaminase reduction in NASH patients.
We conducted searches on PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov, and supplemented the search with gray literature and manual searches. Randomized controlled trials (RCTs) evaluating the efficacy of PGBF in NASH patients were included. Risk of bias was assessed by Cochrane Risk of Bias Tool 2.0. We used random-effects models, generalized least squares regression, constrained maximum likelihood, and restricted cubic splines to explore the dose-response relationship. Egger's linear regression was employed to assess publication bias. The study is registered with PROSPERO, CRD42023448024.
Four RCT studies from the period 2018-2023, involving 546 participants, were included. No participants discontinued PGBF treatment due to adverse events. High-dose PGBF treatment significantly reduced transaminase levels in NASH patients compared to the low-dose group (ALT %: MD = 14.94, 95% CI = 2.11-27.77; AST %: MD = 9.05, 95% CI = 3.17-14.92). Longer treatment duration further decreased transaminase levels (ALT%: MD = 8.81, 95% CI = 4.07-13.56; AST%: MD = 6.72, 95% CI = 2.62-10.81). Egger's test did not reveal significant publication bias ( > 0.05). Further investigation indicated a ceiling effect of PGBF dosage on transaminase reduction at 30 mg/week, and NASH patients experienced a rebound in transaminase levels after 28 weeks of continuous treatment.
There is a positive correlation between PGBF dosage and transaminase reduction within a certain range, showing an overall non-linear dose-response relationship. This finding provides guidance for the clinical application of PGBF. Clinicians should be mindful of the dosage ceiling at 30 mg/week and monitor changes in transaminase levels after 28 weeks for timely adjustments in PGBF dosage.
PROSPERO, CRD42023448024. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=448024.
培格贝美（PGBF）治疗非酒精性脂肪性肝炎（NASH）的疗效仍存在争议。因此，我们进行了一项剂量反应荟萃分析，以探讨不同剂量和治疗持续时间的PGBF对NASH患者转氨酶降低的影响及模式。
我们在PubMed、Embase、Cochrane图书馆、科学网和ClinicalTrials.gov上进行了检索，并用灰色文献和手工检索进行补充。纳入评估PGBF对NASH患者疗效的随机对照试验（RCT）。采用Cochrane偏倚风险工具2.0评估偏倚风险。我们使用随机效应模型、广义最小二乘回归、约束最大似然法和受限立方样条来探索剂量反应关系。采用Egger线性回归评估发表偏倚。该研究已在PROSPERO注册，注册号为CRD42023448024。
纳入了2018 - 2023年期间的4项RCT研究，涉及546名参与者。没有参与者因不良事件而停止PGBF治疗。与低剂量组相比，高剂量PGBF治疗显著降低了NASH患者的转氨酶水平（谷丙转氨酶百分比：MD = 14.94，95%CI = 2.11 - 27.77；谷草转氨酶百分比：MD = 9.05，95%CI = 3.17 - 14.92）。更长的治疗持续时间进一步降低了转氨酶水平（谷丙转氨酶百分比：MD = 8.81，95%CI = 4.07 - 13.56；谷草转氨酶百分比：MD = 6.72，95%CI = 2.62 - 10.81）。Egger检验未显示显著的发表偏倚（P>0.05）。进一步研究表明，PGBF剂量在30mg/周时对转氨酶降低存在天花板效应，且NASH患者在连续治疗28周后转氨酶水平出现反弹。
在一定范围内，PGBF剂量与转氨酶降低呈正相关，呈现总体非线性剂量反应关系。这一发现为PGBF的临床应用提供了指导。临床医生应注意30mg/周的剂量上限，并在28周后监测转氨酶水平变化，以便及时调整PGBF剂量。
PROSPERO，CRD42023448024。https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=448024。
