Prediction of Poor Outcome in Patients with Acute Liver Failure—Systematic Review of Prediction Models

IntroductionAcute liver failure is a rare disease with high mortality and liver transplantation is the only life saving therapy. Accurate prognosis of ALF is crucial for proper intervention. AimTo identify and characterize newly developed prognostic models of mortality for ALF patients, assess study quality, identify important variables and provide recommendations for the development of improved models in the future. MethodsThe online databases MEDLINE® (1950–2012) and EMBASE® (1980–2012) were searched for English-language articles that reported original data from clinical trials or observational studies on prognostic models in ALF patients. Studies were included if they developed a new model or modified existing prognostic models. The studies were evaluated based on an existing framework for scoring the methodological and reporting quality of prognostic models. ResultsTwenty studies were included, of which 18 reported on newly developed models, 1 on modification of the Kings College Criteria (KCC) and 1 on the Model for End-Stage Liver Disease (MELD). Ten studies compared the newly developed models to previously existing models (e.g. KCC); they all reported that the new models were superior. In the 12-point methodological quality score, only one study scored full points. On the 38-point reporting score, no study scored full points. There was a general lack of reporting on missing values. In addition, none of the studies used performance measures for calibration and accuracy (e.g. Hosmer-Lemeshow statistics, Brier score), and only 5 studies used the AUC as a measure of discrimination. ConclusionsThere are many studies on prognostic models for ALF but they show methodological and reporting limitations. Future studies could be improved by better reporting and handling of missing data, the inclusion of model calibration aspects, use of absolute risk measures, explicit considerations for variable selection, the use of a more extensive set of reference models and more thorough validation.

引言：急性肝衰竭（Acute Liver Failure, ALF）是一种罕见且高死亡率的疾病，肝移植是唯一的救命治疗手段。准确预测ALF患者的预后对于采取恰当的干预措施至关重要。研究目的：本研究旨在识别并表征针对ALF患者死亡率的新型预后模型，评估相关研究的质量，明确关键变量，并为未来优化预后模型的开发提供建议。研究方法：我们检索了在线数据库MEDLINE®（1950–2012年）与EMBASE®（1980–2012年）中，以英文发表的、报道了ALF患者预后模型相关临床试验或观察性研究原始数据的文献。纳入标准为开发了新型预后模型或对现有预后模型进行改良的研究。本研究采用现有评分框架，对预后模型的方法学质量与报告质量进行评估。研究结果：最终共纳入20项研究，其中18项报道了新型预后模型，1项针对国王学院标准（Kings College Criteria, KCC）进行改良，1项针对终末期肝病模型（Model for End-Stage Liver Disease, MELD）展开研究。10项研究将新型预后模型与既往模型（如KCC）进行了对比，所有研究均显示新型模型更具优势。在12分制的方法学质量评分中，仅1项研究获得满分；在38分制的报告质量评分中，无研究获得满分。整体来看，相关研究普遍缺乏对缺失值的报告。此外，所有研究均未使用校准与准确度相关的性能指标（如Hosmer-Lemeshow统计量、Brier评分），仅5项研究采用受试者工作特征曲线下面积（AUC）作为区分度评估指标。结论：目前针对ALF预后模型的研究数量较多，但均存在方法学与报告层面的局限性。未来的研究可通过以下方式加以改进：完善缺失数据的报告与处理流程、纳入模型校准相关维度、采用绝对风险评估指标、明确考虑变量选择环节、使用更全面的参考模型集，以及开展更全面的验证工作。