乙肝相关性慢加急性肝衰竭的诊断标准与预后评分的建立

发布时间：2018-05-07 16:31

  本文选题：乙肝 + 慢加急性肝衰竭　； 参考：《浙江大学》2017年硕士论文

【摘要】：研究背景及目的:慢加急性肝衰竭(Acute-on-chronic liver failure,ACLF)概念已被国际广泛接受,但在以慢性乙型肝炎(Chronic hepatitis B,CHB)为常见病因的亚太地区,肝硬化是否应该作为ACLF诊断的关键指标争议颇大。本研究旨在通过多中心、大样本、前瞻性分析研究,系统阐明乙肝相关性慢加急性肝衰竭(HBV-related acute-on-chronic liver failure,HBV-ACLF)患者的特异性临床特征,并建立新的HBV-ACLF诊断标准与预后评价体系。研究方法采用多中心、前瞻性临床研究设计,全国13个中心统一收集入组患者,入组标准为乙肝肝硬化患者出现急性失代偿和慢乙肝患者出现急性严重肝损伤(总胆红素[total bilirubin,TB]≥ 5md/dL,合并国际标准化比值[internationalnormalized ratio,INR]≥ 1.5)。采集患者所有临床数据、预后指标,并结合血清巨噬细胞炎性蛋白-3α(serum macrophage inflammatory protein3α,MIP-3α),在此基础上建立HBV-ACLF诊断标准与预后模型,并重新入组符合新建HBV-ACLF诊断标准的患者,设立外部验证组以验证新建预后模型的预后价值。研究结果:自2013年6月至2016年10月,13个中心共入组患者2638例,排除相关病例后共计1322例患者进入研究分析,包括1031例乙肝相关性肝硬化急性失代偿(patients who have an HBV infection with acute decompensation of cirrhosis,HBV-AD-C)、171例慢乙肝基础上出现急性严重肝损(Patients who have an HBV infection with acute severe liver injury,HBV-ASI-NC)和 120 例非乙肝肝硬化急性失代偿(ACLF with cirrhosis caused by non-HBV pathogens,NonHBV-AD-C)患者。结合EASL-ACLF 诊断标准,HBV-AD-C、HBV-ASI-NC 和 NonHBV-AD-C 组分别有 271、92和28例被判断为ACLF,并分别定义为乙肝肝硬化ACLF(HBV-ACLF-C)、慢乙肝基础上ACLF(HBC-ACLF-NC)和非乙肝肝硬化ACLF(NonHBV-ACLF-C)。分析发现HBV-ACLF-C和HBV-ACLF-NC组短期(28天和90天)死亡率均显著高于NonHBV-ACLF-C组。在器官衰竭分布上,HBV-ACLF以肝功能和凝血功能衰竭为主。通过对1119例(83例接受肝移植术除外)乙肝患者的进一步研究发现,单一肝功能衰竭合并INR≥ 1.5应被纳入HBV-ACLF的诊断标准。新的HBV-ACLF定义能够有效地区分出高死亡率群体,并使19.3%的乙肝患者在入院时也被扩大诊断为HBV-ACLF。在此基础上建立的HBV-ACLF新预后模型也优于CLIF-C ACLFs及其它预后评分,这在实验组以及154例外部验证组ACLF患者中都得到验证。此外,MIP-3α血清学分析显示HBV-ACLF-C和HBV-ACLF-NC具有相似的生物学特性。结论:无论是否存在肝硬化,单一肝功能衰竭合并INR≥ 1.5的慢乙患者应该被诊断为HBV-ACLF。新的诊断标准不仅完善了 EASL-ACLF对于HBV-ACLF的诊断局限性,更使得约20%的慢乙肝患者在入院时就被诊断为ACLF并得到及时的诊治。
[Abstract]:Background and objective: the concept of Acute-on-chronic liver failure (ACLF) has been widely accepted in the world. However, in the Asia-Pacific region where chronic hepatitis B hepatitis (Chronic hepatitis) is a common cause, whether cirrhosis should be regarded as the key index for the diagnosis of ACLF is controversial. The purpose of this study was to systematically elucidate the specific clinical features of HBV-related acute-on-chronic liver failure in patients with chronic hepatitis B associated with acute liver failure by multi-center, large sample and prospective analysis, and to establish a new diagnostic criteria for HBV-ACLF and a prognostic evaluation system. Methods Multi-center, prospective clinical study design was used to collect patients in 13 centers in China. The admission criteria were acute decompensation in patients with hepatitis B cirrhosis and acute severe liver injury in patients with chronic hepatitis B (total bilirubin TB 鈮，

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