Than Nwe Ni, Tomlinson Claire L, Haldar Debashis, King Andrew L, Moore David, Newsome Philip N
National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Birmingham Clinical Trials Unit, Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Syst Rev. 2016 Jun 14;5:100. doi: 10.1186/s13643-016-0277-6.
Chronic liver disease (CLD) is a major health burden worldwide. Liver cirrhosis, a form of CLD is the fifth most common cause of death in the UK. Acute-on-chronic liver failure (ACLF) is the result of an acute insult superimposed on patients with liver cirrhosis as a result of precipitating events such as infection or bleeding. ACLF has a high associated mortality as a result of multi-organ failure. The only effective treatment for CLD is liver transplantation, but the treatment is limited by shortage of donor organs. As a result, alternative treatments such as cell therapies have been studied in patients with liver diseases. This study will systematically review the evidence on clinical effectiveness of cell therapies in patients.
All types of study design that investigate the effectiveness of cell therapies (haematopoietic, mesenchymal and unsorted cell types) of autologous or allogeneic origin and/or the use of granulocyte colony-stimulating factor in patients with CLD including ACLF will be included (except case reports). Both autologous and allogenic cell types will be included. The primary outcomes of interest are survival, model for end-stage liver disease score, quality of life and adverse events. Secondary outcomes include liver function tests, Child-Pugh score and events of liver decompensation. A literature search will be conducted in the following databases: MEDLINE, MEDLINE in Process, EMBASE and Cochrane Library (CENTRAL, CDSR, DARE, HTA databases). Trial registers will be searched for ongoing trials, as will conference proceedings. Reference lists of relevant articles and systematic reviews will be screened. Randomised controlled trial (RCT) evidence is likely to be scant; therefore, controlled trials and concurrently controlled observational studies will be primarily analysed and uncontrolled observational studies will be analysed where primary outcomes are not reported in the control studies or where uncontrolled studies have longer follow-up. Initial screening of studies will be carried by one reviewer with a proportion checked by another reviewer. Full-text selection will be performed by two reviewers independently against the pre-defined selection criteria. The data collection and the risk of bias assessment will be completed by one reviewer and counter checked by another reviewer for all selected studies. Where appropriate, data will be meta-analysed for each study design, therapy and outcome. Data specifically on ACLF will be treated as a subgroup.
This systematic review will identify the available evidence on the effectiveness of cell therapies in patients with CLD and in ACLF subgroup. The findings will aid decision-making by clinicians and health service leaders.
PROSPERO CRD42016016104.
慢性肝病（CLD）是全球主要的健康负担。肝硬化作为CLD的一种形式，是英国第五大常见死因。慢加急性肝衰竭（ACLF）是在肝硬化患者基础上，因感染或出血等诱发事件导致急性损伤的结果。由于多器官功能衰竭，ACLF的相关死亡率很高。CLD唯一有效的治疗方法是肝移植，但该治疗受供体器官短缺的限制。因此，细胞疗法等替代治疗方法已在肝病患者中进行研究。本研究将系统评价细胞疗法对患者临床有效性的证据。
将纳入所有研究设计类型，这些研究旨在调查细胞疗法（造血细胞、间充质细胞和未分类细胞类型）对CLD患者（包括ACLF患者）的有效性，这些细胞疗法为自体或异体来源，和/或使用粒细胞集落刺激因子（病例报告除外）。自体和异体细胞类型均将纳入。主要关注的结局指标为生存率、终末期肝病模型评分、生活质量和不良事件。次要结局指标包括肝功能检查、Child-Pugh评分和肝失代偿事件。将在以下数据库中进行文献检索：MEDLINE、MEDLINE在研数据库、EMBASE和Cochrane图书馆（CENTRAL、CDSR、DARE、HTA数据库）。将检索试验注册库以查找正在进行的试验，会议论文集也将进行检索。将筛选相关文章和系统评价的参考文献列表。随机对照试验（RCT）证据可能很少；因此，将主要分析对照试验和同期对照观察性研究，在对照研究未报告主要结局指标或非对照研究随访时间更长时，将分析非对照观察性研究。研究的初步筛选将由一名评审员进行，另一评审员检查一部分。全文选择将由两名评审员根据预先确定的选择标准独立进行。数据收集和偏倚风险评估将由一名评审员完成，另一名评审员对所有选定研究进行核对。在适当情况下，将对每个研究设计、治疗方法和结局指标进行荟萃分析。关于ACLF的具体数据将作为一个亚组进行分析。
本系统评价将确定细胞疗法对CLD患者及ACLF亚组有效性的现有证据。研究结果将有助于临床医生和卫生服务领导者做出决策。
PROSPERO CRD42016016104。
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