广东地区新型冠状病毒Delta变异株感染并发肝功能异常患者的临床特征分析

Clinical features of patients with severe acute respiratory syndrome coronavirus 2 Delta variant infection and abnormal liver function in Guangdong Province,China

目的总结分析广东地区新型冠状病毒(SARS-CoV-2)Delta变异株感染并发肝功能异常患者的临床特征。方法选取2021年5月21日—2021年6月18日广州医科大学附属市八医院收治的广东地区(广州市和佛山市)同一传播链的SARS-CoV-2 Delta变异株感染者,肝功能指标判定标准:ALT(男/女)>50/40 U/L,AST>40 U/L,TBil>26μmol/L,GGT>60 U/L,ALP>125 U/L。上述指标其中1项异常,即定义为肝功能异常并纳入分析(<18岁的患者ALP单项轻中度升高不纳入分析)。比较肝功能正常者与肝功能异常者临床资料的差异,并分析肝功能异常的病因及转归。计量资料2组间比较采用Mann-Whitney U检验。计数资料2组间比较采用χ^(2)检验。结果166例SARS-CoV-2 Delta变异株感染者中,32例(19.3%)患者出现肝功能异常,肝功能指标均为轻度至中度升高,肝功能异常组危重型患者占比明显高于肝功能正常组(χ^(2)=38.689,P<0.001),前者年龄、炎症指标(C反应蛋白、血清淀粉样蛋白A和IL-6)水平亦明显高于肝功能正常组(P值均<0.05)。在32例肝功能异常患者中,13例患者入院时即出现肝功能异常(原发组),19例患者在入院时肝功能指标正常,但经治后复查发现肝功能异常(继发组)。原发组3例(3/13,23.1%)患者未发现其他引起肝功能异常的证据,考虑SARS-CoV-2感染直接相关的中毒性肝损伤可能性大;继发组中,轻/普通型9例(47.4%),危重型10例(52.6%),危重型患者均存在炎症因子(C反应蛋白、血清淀粉样蛋白A和IL-6)水平明显升高和低氧血症等间接引起肝损伤的证据,继发组仅1例(1/19,5.3%)患者未发现其他引起肝功能异常的证据,考虑SARS-CoV-2感染直接相关的中毒性肝损伤可能性大。32例肝功能异常的患者经护肝等治疗后肝功能指标均较峰值明显下降。结论在本次广东地区同一传播链的SARS-CoV-2 Delta变异株感染者中,危重型患者肝功能异常的占比明显高于其他临床分型,其肝损伤病因以SARS-CoV-2感染以外的其他因素及间接损伤为主。

Objective To investigate the clinical features of patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Delta variant infection and abnormal liver function in Guangdong Province,China.Methods The patients with SARS-CoV-2 Delta variant infection who belonged to the same chain of transmission in Guangdong Province(Guangzhou and Foshan)and were admitted to Guangzhou Eighth People’s Hospital,Guangzhou Medical University from May 21 to June 18,2021 were enrolled in this study,and the judgment criteria for liver function were alanine aminotransferase(male/female)>50/40 U/L,aspartate aminotransferase>40 U/L,total bilirubin>26μmol/L,gamma-glutamyl transpeptidase>60 U/L,and alkaline phosphatase(ALK)>125 U/L.Abnormality in any one item of the above criteria was defined as abnormal liver function,and such patients were included in analysis(the patients,aged<18 years,who had a mild or moderate increase in ALP alone were not included in analysis).Clinical data were compared between the patients with normal liver function and those with abnormal liver function,and the etiology and prognosis of abnormal liver function were analyzed.The Mann-Whitney U test was used for comparison of continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.Results Among the 166 patients with SARS-CoV-2 Delta variant infection,32(19.3%)had abnormal liver function with mild-to-moderate increases in liver function parameters,and compared with the normal liver function group,the abnormal liver function group had a significantly higher proportion of critical patients(χ^(2)=38.689,P<0.001)and significantly higher age and inflammatory cytokines[C-reactive protein type,serum amyloid A,and interleukin-6(IL-6)](all P<0.05).Among the 32 patients with abnormal liver function,13 patients had abnormal liver function on admission(defined as primary group),while 19 patients had normal liver function on admission but were found to have abnormal liver function by reexamination after treatment(defined as secondary group).For the primary group,the evidence of abnormal liver function was not found for 3 patients(3/13,23.1%),and the possibility of toxic liver injury directly associated with SARS-CoV-2 infection was considered.Among the 19 patients in the secondary group,9(47.4%)had mild/common type and 10(52.6%)had critical type,and all critical patients had the evidence of liver injury indirectly caused by the significant increases in C-reactive protein type,serum amyloid A,and IL-6 and hypoxemia;the evidence of abnormal liver function was not found for only 1 patient(1/19,5.3%),and the possibility of toxic liver injury directly associated with SARS-CoV-2 infection was considered.All 32 patients with abnormal liver function had significant reductions in liver function parameters after treatment including liver protection.Conclusion As for the patients with SARS-CoV-2 Delta variant infection who belong to the same chain of transmission in Guangdong Province,the critical patients show a significantly higher proportion of patients with abnormal liver function than the patients with other clinical types,and other factors except SARS-CoV-2 infection and indirect injury caused by SARS-CoV-2 infection are the main cause of liver injury.