Neonatal Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK.
Division of Neonatology, Department of Pediatrics, Keck School of Medicine, Los Angeles County Medical Center, University of Southern California, Los Angeles, USA.
Eur J Pediatr. 2017 Oct;176(10):1295-1303. doi: 10.1007/s00431-017-2956-2. Epub 2017 Jul 24.
Therapeutic hypothermia (TH) is now provided as standard care to infants with moderate-severe hypoxic ischemic encephalopathy (HIE). The role of TH in limiting neuronal injury is well recognized, but its effect on hepatic injury which occurs frequently in neonatal HIE is not known. Our objective was to characterize biomarkers of liver injury and function in the setting of neonatal HIE and to describe whether HIE severity and provision of TH influence these hepatic biomarkers. We performed a multicenter retrospective study and compared hepatic biomarkers obtained during the first postnatal week, according to the severity of HIE and whether treated with TH. Of a total of 361 infants with HIE, 223 (62%) received TH and 138 (38%) were managed at normal temperature. Most hepatic biomarkers and C-reactive protein (CRP) were significantly associated with the severity of HIE (p < 0.001). Infants treated with TH had lower peak alanine aminotransferase (ALT) concentrations (p = 0.025) and a delay in reaching peak CRP concentration (p < 0.001).
We observed a significant association between the clinical grade of HIE and biomarkers of liver metabolism and function. Therapeutic hypothermia was associated with delayed CRP responses and with lower ALT concentrations and so may have the potential to modulate hepatic injury. What is Known: • Ischemic hepatic injury occurs frequently as a part of multiorgan dysfunction in infants with hypoxic ischemic encephalopathy (HIE). • The neuroprotective role of therapeutic hypothermia in management of infants with HIE is well recognized, but the potential hepato-protective effects of hypothermia are unclear. What is New/What this study adds: • Therapeutic hypothermia was associated with lower alanine aminotransferase and albumin concentrations and a delayed C-reactive protein (CRP) response and so may have the potential to modulate hepatic injury. • An elevated CRP concentration during the first postnatal week may be regarded as an expected finding in moderate and severe HIE and, in the overwhelming majority of cases, occurs secondary to hepatic hypoxia-ischemia in the absence of blood culture-positive sepsis.
描述新生儿缺氧缺血性脑病（HIE）中肝损伤和肝功能的生物标志物特征，并探讨 HIE 严重程度和是否采用亚低温治疗对这些肝生物标志物的影响。
我们进行了一项多中心回顾性研究，比较了根据 HIE 严重程度和是否采用亚低温治疗，在生后第 1 周获得的肝生物标志物。在总共 361 例 HIE 患儿中，223 例（62%）接受了亚低温治疗，138 例（38%）在正常体温下治疗。大多数肝生物标志物和 C 反应蛋白（CRP）与 HIE 的严重程度显著相关（p<0.001）。接受亚低温治疗的患儿丙氨酸氨基转移酶（ALT）峰值浓度较低（p=0.025），且达到 CRP 峰值浓度的时间延迟（p<0.001）。
我们观察到 HIE 临床分级与肝代谢和功能的生物标志物之间存在显著关联。亚低温治疗与 CRP 反应延迟以及 ALT 浓度降低相关，因此可能具有调节肝损伤的潜力。
• 缺氧缺血性脑病（HIE）患儿常发生多器官功能障碍，其中包括肝损伤。
• 亚低温治疗在管理 HIE 患儿中的神经保护作用已得到充分认识，但亚低温治疗的潜在肝保护作用尚不清楚。
新发现/本研究新增内容：
• 亚低温治疗与较低的丙氨酸氨基转移酶和白蛋白浓度以及 CRP 反应延迟相关，因此可能具有调节肝损伤的潜力。
• 在生后第 1 周，CRP 浓度升高可能被视为中重度 HIE 的预期发现，且在绝大多数情况下，发生于肝脏缺氧缺血，而非血培养阳性脓毒症。
