What is the optimal first-line treatment of autoimmune hepatitis? A systematic review with meta-analysis of randomised trials and comparative cohort studies.

IF 3.3 Q2 GASTROENTEROLOGY & HEPATOLOGY
Dermot Gleeson, Marrissa Martyn-StJames, Ye Oo, Sarah Flatley
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引用次数: 0

Abstract

Objectives: Uncertainty remains about many aspects of first-line treatment of autoimmune hepatitis (AIH).

Design: Systemic review with meta-analysis (MA).

Data sources: Bespoke AIH Endnote Library, updated to 30 June 2024.

Eligibility criteria: Randomised controlled trials (RCTs) and comparative cohort studies including adult patients with AIH, reporting death/transplantation, biochemical response (BR) and/or adverse effects (AEs).

Data extraction and synthesis: Data pooled in MA as relative risk (RR) under random effects. Risk of bias (ROB) assessed using Cochrane ROB-2 and ROBINS-1 tools.

Results: From seven RCTs (five with low and two with some ROB) and 18 cohort studies (12 moderate ROB, six high for death/transplant), we found lower death/transplantation rates in (a) patients receiving pred+/-aza (vs no pred): overall (RR 0.38 (95% CI 0.20 to 0.74)), in patients without symptoms (0.38 (0.19-0.75)), without cirrhosis (0.30 (0.14-0.65)), and with decompensated cirrhosis (RR 0.38 (0.23-0.61)), and (b) patients receiving pred+aza (vs pred alone) (0.38 (0.22-0.65)). Patients receiving higher (vs lower) initial pred doses had similar BR rates (RR 1.07 (0.92-1.24)) and mortality (0.71 (0.25-2.05)) but more AEs (1.73 (1.17-2.55)). Patients receiving bud (vs pred) had similar BR rates (RR 0.99 (0.71-1.39)), with fewer cosmetic AEs (0.46 (0.34-0.62)). Patients receiving mycophenolate mofetil (MMF) (vs aza) had similar BR rates (RR 1.32 (0.73-2.38)) and fewer AEs requiring drug cessation (0.20 (0.09-0.43)).

Conclusions: Mortality is lower in pred-treated (vs untreated) patients, overall and in several subgroups, and in those receiving pred+aza (vs pred). Higher initial pred doses confer no clear benefit and cause more AEs. Bud (vs pred) achieves similar BR rates, with fewer cosmetic AEs. MMF (vs aza) achieves similar BR rates, with fewer serious AEs.

自身免疫性肝炎的最佳一线治疗方法是什么?对随机试验和比较队列研究进行荟萃分析的系统综述。
目的:自身免疫性肝炎(AIH)一线治疗的许多方面仍存在不确定性。设计:采用meta分析(MA)进行系统评价。数据来源:Bespoke AIH Endnote Library,更新至2024年6月30日。入选标准:随机对照试验(RCTs)和比较队列研究,包括报告死亡/移植、生化反应(BR)和/或不良反应(ae)的成年AIH患者。数据提取和综合:随机效应下MA中作为相对风险(RR)的数据汇集。使用Cochrane rob2和ROBINS-1工具评估偏倚风险(ROB)。结果:从7个随机对照试验(5个低ROB, 2个有部分ROB)和18个队列研究(12个中度ROB, 6个死亡率/移植率高)中,我们发现(a)接受pred+/-aza的患者(相对于没有pred):总体(RR 0.38 (95% CI 0.20至0.74))、无症状(0.38(0.19-0.75))、无肝硬化(0.30(0.14-0.65))和失代偿性肝硬化(RR 0.38(0.23-0.61))和(b)接受pred+aza的患者(相对于单独接受pred)(0.38(0.22-0.65))的死亡率/移植率较低。初始剂量较高(vs较低)的患者BR率(RR 1.07(0.92-1.24)和死亡率(0.71(0.25-2.05))相似,但ae较高(1.73(1.17-2.55))。接受bud治疗的患者BR率相似(RR 0.99(0.71-1.39)),美容ae更少(0.46(0.34-0.62))。接受霉酚酸酯(MMF)(与aza)治疗的患者BR率相似(RR为1.32(0.73-2.38)),需要停药的ae较少(0.20(0.09-0.43))。结论:总的来说,在几个亚组中,接受pred+aza治疗的患者死亡率低于未治疗的患者(与pred相比)。较高的初始剂量并不能带来明显的益处,反而会导致更多的不良反应。Bud(与pred)达到相似的BR率,美容ae更少。MMF(与aza相比)的BR率相似,严重ae更少。
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来源期刊
BMJ Open Gastroenterology
BMJ Open Gastroenterology GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
5.90
自引率
3.20%
发文量
68
审稿时长
2 weeks
期刊介绍: BMJ Open Gastroenterology is an online-only, peer-reviewed, open access gastroenterology journal, dedicated to publishing high-quality medical research from all disciplines and therapeutic areas of gastroenterology. It is the open access companion journal of Gut and is co-owned by the British Society of Gastroenterology. The journal publishes all research study types, from study protocols to phase I trials to meta-analyses, including small or specialist studies. Publishing procedures are built around continuous publication, publishing research online as soon as the article is ready.
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