不明原因急性肝衰竭：专家委员会建立因果关系的全面系统方法。
Acute Liver Failure of Indeterminate Etiology: A Comprehensive Systematic Approach by An Expert Committee to Establish Causality.
机构信息
Department of Medicine, Division of Gastroenterology and Hepatology, Northwestern university Feinberg School of Medicine, Chicago, IL, uSA. Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA. Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA. Department of Medicine, UCSF San Francisco, San Francisco, CA, USA. Medical University of South Carolina, Charleston, SC, USA. Section of Hepatology Virginia Commonwealth University, Richmond, VA, USA. Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA. Hepatology and Liver Transplantation, University of Washington, Seattle, WA, USA. Section of Pediatric Pharmacology and Toxicology, Arkansas Children's Hospital and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA. Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
出版信息
Am J Gastroenterol. 2018 Sep;113(9):1319. doi: 10.1038/s41395-018-0160-2. Epub 2018 Jun 27.
OBJECTIVES
In the United States, the Acute Liver Failure Study Group (ALFSG) registry lists approximately 11% of cases as of indeterminate etiology (IND-ALF) as determined by the respective local site principal investigator (PI). Traditionally, IND-ALF has prompted concern that other viruses or toxins might be implicated. We hypothesized that many IND- ALF cases would have an identifiable etiology upon further investigation. Improving the identification process should reduce the number of truly indeterminate cases.
METHODS
Specific definitions for each etiology ("etiology-specific algorithms") were developed by a Causality Adjudication Committee that included six reviewers (each with 20 or more years of experience). Of 2718 patients with ALF, 303 initially deemed IND-ALF by site PIs underwent committee review guided by the algorithms. Acetaminophen (APAP) protein adducts were measured in sera when available, additional HEV testing was performed, and viral sequences sought by microarray analysis and metagenomic next-generation sequencing (mNGS). Study sites were asked to provide liver biopsy and/or explant reports and to update serological findings not reported previously.
RESULTS
Nearly half (142, 46.9%) of the 303 IND-ALF cases could be reassigned to a single, defined etiology and rated as highly likely or probable; 11 additional cases, upon review, did not meet ALF criteria. Amongst reassigned etiologies, 45 were previously unrecognized APAP, 34 autoimmune hepatitis (AIH), 24 drug-induced liver injury (DILI), 13 various viral causes, 12 ischemia, and 14 miscellaneous other etiologies. The remaining 150, deemed true IND-ALF, represented just 5.5%.
CONCLUSIONS
The indeterminate etiology in ALF includes patients with a diagnosis that is discernible after closer examination. Revision of etiologic diagnoses of indeterminate cases using added testing and expert opinion is useful in understanding all aspects of ALF.
目的
在美国，急性肝衰竭研究组 (ALFSG) 登记处列出了大约 11%的病例为病因不明（IND-ALF），这是由当地的主要研究者（PI）确定的。传统上，IND-ALF 引起了人们的关注，认为可能涉及其他病毒或毒素。我们假设，在进一步调查后，许多 IND-ALF 病例将有可识别的病因。改进识别过程应减少真正不确定病例的数量。
方法
由一个因果关系裁决委员会制定了每个病因的具体定义（“病因特异性算法”），该委员会包括六名评审员（每位评审员有 20 年或以上的经验）。在 2718 名 ALF 患者中，303 名最初被当地 PI 判定为 IND-ALF 的患者，由委员会根据算法进行了审查。当血清中可获得时，测量了对乙酰氨基酚（APAP）蛋白加合物，进行了额外的 HEV 检测，并通过微阵列分析和宏基因组下一代测序（mNGS）寻找病毒序列。研究地点被要求提供肝活检和/或移植组织报告，并更新之前未报告的血清学发现。
结果
在 303 例 IND-ALF 病例中，近一半（142 例，46.9%）可以重新分配到单一的、明确的病因，并被评为高度可能或很可能；在重新评估的 11 例病例中，不符合 ALF 标准。在重新分配的病因中，45 例为先前未被识别的 APAP，34 例为自身免疫性肝炎（AIH），24 例为药物性肝损伤（DILI），13 例为各种病毒性病因，12 例为缺血性病因，14 例为其他各种病因。其余 150 例被认为是真正的 IND-ALF，仅占 5.5%。
结论
ALF 的不确定病因包括通过更仔细的检查可以发现诊断的患者。使用附加的检测和专家意见修订不确定病例的病因诊断有助于了解 ALF 的各个方面。
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