Thomsen Karen Louise, Macnaughtan Jane, Tritto Giovanni, Mookerjee Rajeshwar P, Jalan Rajiv
Liver Failure Group, UCL Institute for Liver and Digestive Health, University College London Medical School, London, United Kingdom.
PLoS One. 2016 Jan 8;11(1):e0146076. doi: 10.1371/journal.pone.0146076. eCollection 2016.
EASL/AASLD hepatic encephalopathy (HE) guidelines proposed the alternative use of the term 'Covert HE' combining minimal HE (mHE) and Grade 1 HE into a single entity. However, longitudinal data to indicate that these are indeed a single entity are lacking. The aims of this study were to determine whether the occurrence of complications of cirrhosis requiring hospital admission and mortality were similar in these sub-groups of patients.
Clinically-stable cirrhotic patients (n = 106) with no previous history of 'Overt HE' were included over a 2-year period and classified as having no HE (n = 23), mHE (n = 39) or Grade 1 HE (n = 44). Standard biochemistry, venous ammonia, bacterial DNA and neutrophil function were measured at inclusion and the patients were followed for a mean of 230±95 days.
Patients with Grade 1 HE had significantly more complications requiring hospitalisation (infection 9/18/34%; HE 4/8/18%; other 13/10/11%; P = 0.02) and significantly greater mortality (4/5/20%; P = 0.04) compared to patients with no HE or mHE respectively. Patients with mHE and grade 1 HE had similar ammonia levels, but higher than the no HE group (P<0.001). MELD score was similar between groups but Grade 1 HE patients had increased frequency of bacterial translocation (P = 0.06) and neutrophil spontaneous respiratory burst (P = 0.02) compared to patients with mHE.
The results of this study show for the first time that 'Covert HE' is a heterogeneous entity with significantly greater hospitalisations and mortality in the Grade 1 HE patients compared with mHE. Further prospective longer-term studies are required before EASL/AASLD guidance is fully implemented.
欧洲肝脏研究学会（EASL）/美国肝病研究学会（AASLD）的肝性脑病（HE）指南提议使用“隐匿性HE”这一术语，将轻微肝性脑病（mHE）和1级HE合并为一个单一实体。然而，缺乏纵向数据表明它们确实是一个单一实体。本研究的目的是确定在这些亚组患者中，需要住院治疗的肝硬化并发症的发生率和死亡率是否相似。
纳入106例临床稳定、既往无“显性HE”病史的肝硬化患者，随访2年，分为无HE组（n = 23）、mHE组（n = 39）或1级HE组（n = 44）。纳入时检测标准生化指标、静脉血氨、细菌DNA和中性粒细胞功能，患者平均随访230±95天。
与无HE或mHE的患者相比，1级HE患者需要住院治疗的并发症显著更多（感染9/18/34%；HE 4/8/18%；其他13/10/11%；P = 0.02），死亡率也显著更高（4/5/20%；P = 0.04）。mHE和1级HE患者的血氨水平相似，但高于无HE组（P<0.001）。各组间终末期肝病模型（MELD）评分相似，但与mHE患者相比，1级HE患者细菌移位频率增加（P = 0.06），中性粒细胞自发呼吸爆发增加（P = 0.02）。
本研究结果首次表明，“隐匿性HE”是一个异质性实体，与mHE相比，1级HE患者的住院率和死亡率显著更高。在全面实施EASL/AASLD指南之前，需要进一步进行前瞻性长期研究。
