肝功能异常为首发表现的嗜血细胞性淋巴组织细胞增生症临床特征分析

Clinical features of hemophagocytic lymphohistiocytosis with abnormal liver function as the initial manifestation

目的探讨以肝功能异常为首发表现的嗜血细胞性淋巴组织细胞增生症(HLH)的临床及实验室特征,提高对本病的认识。方法对北京佑安医院2011年11月-2017年10月以肝功能异常就诊并确诊为HLH的11例患者的病史、病原学、临床表现、实验室检查结果以及转归进行回顾性分析。结果病原学以感染相关HLH最多见(9/11,81. 8%),临床表现以发热(11/11,100%)和脾脏增大(9/11,72. 7%)最常见。实验室检查结果显示11例患者均有不同程度肝功能异常,其中ALT升高者10例(10/11,90. 9%),AST升高者11例(11/11,100%),TBil升高者10例(10/11,90. 9%),Alb下降者9例(9/11,81. 8%),胆碱酯酶(ChE)下降者10例(10/11,90. 9%),GGT升高者9例(9/11,81. 8%),ALP升高者10例(10/11,90. 9%),乳酸脱氢酶升高者5例(5/6,83. 3%),病程初期铁蛋白升高对本病的诊断最为敏感(11/11,100%),其次为甘油三酯> 3 mmoL/L(6/7,85. 7%),血细胞2系以上下降和纤维蛋白原下降在病程早期阳性率分别为54. 5%和45. 4%,在动态监测中所有患者均出现2系以上血细胞下降。所有患者均可见嗜血现象,7例患者检测NK细胞活性及可溶性IL-2受体(s CD25)水平,均表现为NK细胞活性降低及s CD25水平升高。结论 HLH部分诊断指标早期阳性率不高,对于不明原因肝功能异常伴有持续发热患者,即使早期未出现明显血细胞下降仍不能排除HLH,需动态监测血细胞变化,尽早完善铁蛋白、血脂等实验室检查,及早诊断和治疗。

Objective To investigate the clinical and laboratory features of hemophagocytic lymphohistiocytosis（ HLH） with abnormal liver function as the initial manifestation,and to increase the awareness of this disease. Methods A retrospective analysis was performed for the clinical data of 11 patients who attended the hospital due to abnormal liver function from November 2011 to October 2017 and were diagnosed with HLH,including their medical history,etiology,clinical manifestation,laboratory examination results,and prognosis. Results Of all11 patients,9（ 81. 8%） had infection as the etiology of HLH,and as for clinical manifestation,11（ 100%） had pyrexia and 9（ 81. 8%）had splenomegaly. Laboratory examination showed varying degrees of abnormal liver function in all patients,among whom 10（ 90. 9%） had elevated alanine aminotransferase,11（ 100%） had elevated aspartate aminotransferase,10（ 90. 9%） had an increase in total bilirubin,9（ 81. 8%） had a reduction in albumin,10（ 90. 9%） had a reduction in cholinesterase,9（ 81. 8%） had an increase in gamma-glutamyl transpeptidase,10（ 90. 9%） had an increase in alkaline phosphatase,and 5（ 83. 3%） had an increase in lactate dehydrogenase. Elevated ferritin in the early course of the disease had the highest sensitivity（ 11/11,100%） in the diagnosis of this disease,followed by triglyceride 3 mmol/L（ 6/7,85. 7%）. In the early course of the disease,the positive rates of peripheral cytopenia of two or more lineages and reduced fibrinogen were 54. 5% and 45. 4%,respectively. Dynamic monitoring showed that all patients experienced peripheral cytopenia of two or more lineages. Hemophagocytosis was observed in all patients. NK cell activity and soluble CD25（ s CD25） level were measured for 7 patients,and they all had a reduction in NK cell activity and an increase in s CD25 level. Conclusion Some diagnostic indices of HLH have a low positive rate in the early course of the disease. For patients with unexplained abnormal liver function and persistent fever,HLH cannot be excluded even if no significant peripheral cytopenia is observed in the early stage. The change in blood cells should be monitored,and laboratory examination including ferritin and blood lipids should be performed as early as possible to assist early diagnosis and treatment.