274例青少年和成人传染性单核细胞增多症患者肝损伤临床特征分析

樊亚楠; 施逸怡; 徐京杭; 李妞妞; 程然; 秦利霞; 纪童童; 李雪迎; 于岩岩

doi:10.3969/j.issn.1001-5256.2021.03.026

274例青少年和成人传染性单核细胞增多症患者肝损伤临床特征分析

DOI: 10.3969/j.issn.1001-5256.2021.03.026

樊亚楠^1a,
施逸怡^1a,
徐京杭^1a, ,,
李妞妞^{1a, 2},
程然^1a,
秦利霞^1a,
纪童童^1a,
李雪迎^1b,
于岩岩^1a

1a.
北京大学第一医院感染疾病科, 北京 100034
1b.
北京大学第一医院医学统计室, 北京 100034
2.
深圳市第三人民医院肝病三科, 广东深圳 518000

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：樊亚楠、施逸怡、徐京杭、李妞妞、程然、秦利霞、纪童童负责提出选题，设计方案及采集整理数据；樊亚楠、施逸怡、徐京杭负责调研整理文献，论文书写并最终成文；施逸怡、徐京杭、李妞妞、李雪迎、于岩岩负责统计分析，获取研究经费及技术支持，并对研究进行指导。

详细信息

作者简介:
樊亚楠(1994—)，女，在读博士，主要从事感染病和肝病研究

施逸怡(1993—)，女，主治医师，主要从事感染病和肝病研究

通信作者:
徐京杭, ddcatjh@sina.com

二者对本文贡献相同，同为第一作者

中图分类号: R512.7;R575
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出版历程
- 收稿日期: 2020-11-17
- 录用日期: 2020-12-29
- 出版日期: 2021-03-20

Features of liver injury in adolescents and adults with infectious mononucleosis: A single-center retrospective clinical study of 274 cases

Yanan FAN^1a,
Yiyi SHI^1a,
Jinghang XU^{1a
, ,},
Niuniu LI^{1a, 2},
Ran CHENG^1a,
Lixia QIN^1a,
Tongtong JI^1a,
Xueying LI^1b,
Yanyan YU^1a

1a.
Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
1b.
Department of Medical Statistics, Peking University First Hospital, Beijing 100034, China
2.
Third Department of Liver Diseases, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518000, China

摘要

摘要: 目的分析青少年和成人传染性单核细胞增多症(IM)患者肝损伤的临床特征及影响因素。方法回顾性分析2005年1月1日—2018年12月31日北京大学第一医院住院的青少年和成人IM患者的肝损伤特征，按照年龄、血清EBV DNA水平、是否合并黄疸、是否合并巨细胞病毒及HEV感染分为不同亚组，比较亚组间的各项指标的差异。计量资料符合参数分析条件者2组间比较采用t检验，不符合参数分析条件者2组间比较采用Mann-Whitney U检验；计数资料2组间比较采用χ²检验或Fisher精确概率法。多因素分析采用logistic回归分析。结果共纳入274例患者，其中男154例(56.2%)，女120例(43.8%)；发病平均年龄为(22.3±6.7)岁。肝损伤(定义为ALT＞50 U/L和/或AST＞40 U/L)发生率为97.4%(267/274)，黄疸发生率27.6%(74/268)。年龄≥20岁者GGT更高(Z=2.070，P=0.038)。167例患者检测了血清EBV DNA，其中阳性组90例，阴性组77例。血清EBV DNA阳性组比阴性组的GGT(Z=3.005，P=0.003)及LDH(Z=2.162，P=0.031)水平更高。合并巨细胞病毒感染组ALP更高(Z=2.351，P=0.019)；合并HEV感染组GGT(Z=1.988，P=0.047)更高。AST(OR=1.006, 95%CI: 1.002~1.010, P=0.005)和ALP(OR=1.012, 95%CI: 1.005~1.020, P=0.001)为影响黄疸发生的独立危险因素。结论青少年和成人IM患者肝损伤发生率很高，其中年长者和血清EBV DNA阳性者的肝损伤更严重。
- 传染性单核细胞增多症 /
- 肝功能不全 /
- 青少年 /
- 成年人
Abstract: Objective To investigate the features of liver injury and related influencing factors in adolescents and adults with infectious mononucleosis (IM). Methods A retrospective analysis was performed to investigate the features of liver injury in adolescents and adults with IM who were hospitalized in Peking University First Hospital from January 1, 2005 to December 31, 2018, and the patients were divided into subgroups based on age, Epstein-Barr virus (EBV) DNA level, and presence or absence of jaundice or infection with cytomegalovirus or hepatitis E virus (HEV). The t-test was used for comparison of continuous data meeting analytical conditions between two groups, and the Mann-Whitney U test was used for comparison of continuous data which did not meet analytical conditions between two groups; the chi-square test was used for comparison of categorical data between two groups, and the Fisher's exact test was used for comparison of categorical data which did not meet the analytical conditions of the chi-square test. A logistic regression analysis was used for multivariate analysis. Results A total of 274 patients were enrolled, with 154 male patients (56.2%) and 120 female patients (43.8%), and the mean age of onset was 22.3±6.7 years. The incidence rate of liver injury [defined as alanine aminotransferase (ALT) > 50 U/L and/or aspartate aminotransferase (AST) > 40 U/L] was 97.4% (267/274), and that of jaundice was 27.6% (74/268). The patients, aged ≥20 years, tended to have a higher level of gamma-glutamyl transpeptidase (GGT) (Z=2.070, P=0.038). Serum EBV DNA was measured for 167 patients, among whom 90 had positive results and 77 had negative results. The positive serum EBV DNA group had significantly higher levels of GGT (Z=3.005, P=0.003) and lactate dehydrogenase (Z=2.162, P=0.031) than the negative serum EBV DNA group. The patients with cytomegalovirus infection tended to have a higher level of alkaline phosphatase (Z=2.351, P=0.019), and the patients with HEV infection presented with a higher level of GGT (Z=1.988, P=0.047). AST (odds ratio [OR]=1.006, 95% confidence interval [CI]: 1.002-1.010, P=0.005) and ALP (OR=1.012, 95%CI: 1.005-1.020, P=0.001) were independent risk factors for jaundice. Conclusion There is a high incidence rate of liver injury in adolescents and adults with IM, and the patients with an older age or positive serum EBV DNA tend to have more severe liver injury.
- Infectious Mononucleosis /
- Hepatic Insufficiency /
- Adolescent /
- Adult

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表 1 不同年龄组IM患者一般情况及肝损伤指标比较

指标	年轻组(n=116)	年长组(n=158)	统计值	P值
年龄(岁)	17.4±1.1	25.9±6.9	t=13.108	＜0.001
男性[例(%)]	61(52.6)	93(58.9)	χ²=1.070	0.301
住院天数(d)	12.0(8.3~16.0)	13.0(9.0~18.0)	Z=0.744	0.457
最高体温(℃)	39.0(38.5~39.5)	38.9(38.5~39.2)	Z=1.961	0.050
ALT首次升高距离发病时间(d)	8.0(6.0~13.0)	8.0(6.0~11.0)	Z=0.725	0.469
入院淋巴细胞百分数(%)	64.3±9.2	63.3±11.0	t=0.764	0.445
ALT(U/L)	254.5(149.0~393.0)	292.0(164.5~497.3)	Z=1.953	0.051
AST(U/L)	152.5(103.8~249.8)	199.5(92.5~343.3)	Z=1.870	0.061
TBil(μmol/L)	11.8(8.5~21.0)¹⁾	12.4(9.4~23.1)²⁾	Z=1.431	0.152
ALP(U/L)	143.0(96.8~201.8)¹⁾	160.0(97.5~235.8)³⁾	Z=0.915	0.360
GGT(U/L)	98.5(54.5~178.0)¹⁾	139.0(65.5~219.0)³⁾	Z=2.070	0.038
LDH(U/L)	483.0(338.0~613.5)⁴⁾	482.5(382.0~664.0)⁵⁾	Z=1.052	0.293
血清EBV DNA (log₁₀拷贝/ml)	3.2±0.9⁶⁾	3.0±0.5⁷⁾	t=1.852	0.066
淋巴细胞EBV DNA (log₁₀拷贝/ml)	4.6±1.2⁸⁾	4.3±1.2⁹⁾	t=1.441	0.152
注：1) n=114; 2) n=154; 3) n=156; 4) n=64; 5) n=100; 6) n=65; 7) n=106; 8) n=52; 9) n=83。

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表 2 不同血清EBV DNA组IM患者一般情况及肝损伤指标比较

指标	血清EBV DNA阴性组(n=77)	血清EBV DNA阳性组(n=90)	统计值	P值
年龄(岁)	21.0 (18.0~ 26.0)	20.5 (18.0~ 24.3)	Z=1.255	0.210
男性[例(%)]	44 (57.1)	51(56.7)	χ²=0.004	0.951
最高体温(℃)	38.8±0.7	39.0±0.7	t=1.523	0.130
ALT首次升高距离发病时间(d)	8.0(6.0~14.0)	8.0(5.0~12.0)	Z=0.155	0.877
入院淋巴细胞百分数(%)	60.9±12.0	66.3±9.1	t=3.317	0.001
ALT(U/L)	306.0(192.0~519.0)	285.0(192.0~424.0)	Z=0.242	0.808
AST(U/L)	205.0(91.0~380.0)	183.0(132.0~308.0)	Z=0.059	0.953
TBil(μmol/L)	11.2(8.80~ 19.70)	15.8(9.7~24.5)	Z=1.462	0.144
ALP(U/L)	146.0(104.0~ 204.0)	178.0(103.0~252.0)	Z=1.962	0.050
GGT(U/L)	95.0(63.0~ 178.0)	161.0(89.0~232.0)	Z=3.005	0.003
LDH(U/L)	438.0(313.0~651.0) ¹⁾	518.0(402.0~628.0)²⁾	Z=2.162	0.031
淋巴细胞EBV DNA(log₁₀拷贝/ml)	3.55(2.70~4.50)¹⁾	5.07(4.27~5.77)³⁾	Z=5.802	＜0.001
注：1) n=51；2) n=67；3) n=71。

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表 3 有无黄疸组IM患者的一般资料及临床特征比较

指标	无黄疸组(n=194)	黄疸组(n=74)	统计值	P值
男性[例(%)]	109(56.2)	44(59.5)	χ²=0.234	0.628
年龄(岁)	20.0(18.0~24.3)	21.5(18.0~25.3)	Z=0.655	0.512
超重[例(%)]	58(30.1)	17(30.0)	χ²=1.327	0.249
吸烟史[例(%)]	20(10.3)	8(10.8)	χ²=0.014	0.904
饮酒史[例(%)]	19(9.8)	8(10.8)	χ²=0.061	0.805
淋巴细胞比例(%)	64.4(59.1~70.0)	65.9(57.0~72.9)	Z=0.996	0.319
最高体温(℃)	39.0(38.5~39.4)	39.0(38.5~39.4)	Z=0.464	0.643
CD4/CD8	0.25(0.16~0.36)¹⁾	0.13(0.08~0.34)²⁾	Z=1.319	0.222
血清DNA (log₁₀拷贝/ml)	2.70(2.70~3.41)³⁾	2.72(2.70~3.28)⁴⁾	Z=0.671	0.502
淋巴细胞DNA (log₁₀拷贝/ml)	4.467(2.759~5.244)⁵⁾	4.888(3.804~5.486)⁶⁾	Z=1.412	0.158
ALT(U/L)	226.5(135.5~377.5)	443.5(298.8~568.3)	Z=6.738	＜0.001
AST(U/L)	140.5(81.8~238.3)	296.5(196.5~474.8)	Z=6.473	＜0.001
ALP(U/L)	123.0(92.0~182.5)	229.0(158.0~305.0)	Z=6.813	＜0.001
GGT(U/L)	94.0(51.5~167.0)	185.5(141.8~280.0)	Z=6.281	＜0.001
LDH(U/L)	446.0(335.0~566.0)⁷⁾	635.0(443.0~711.0)⁴⁾	Z=3.860	＜0.001
注：1) n =8；2) n=5；3) n=122；4) n=47；5) n=97；6) n=37；7) n=115。

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表 4 未合并与合并CMV感染IM患者的一般资料和临床特征比较

指标	未合并其他病毒感染组(n=214)	合并CMV感染组(n=26)	统计值	P值
男性[例(%)]	117(54.7)	14(53.8)	χ²=0.006	0.936
年龄(岁)	20.0(18.0~25.0)	20.0(17.8~24.5)	Z=0.051	0.959
入院淋巴细胞比例(%)	64.6(58.6~70.6)	65.4(58.5~69.6)	Z=0.317	0.751
入院异型淋巴细胞比例(%)	15.0(7.8~22.0)	19.5(14.8~24.3)	Z=2.169	0.030
最高体温(℃)	39.0(38.5~39.4)	38.9(38.2~39.6)	Z=0.269	0.788
发热持续时间(d)	11.5(8.0~17.0)	12.5(10.8~20.3)	Z=2.021	0.043
ALT(U/L)	266.0(151.3~409.0)	294.5(180.0~486.0)	Z=1.174	0.240
AST(U/L)	173.5(94.5~279.3)	198.5(112.0~369.0)	Z=1.258	0.208
TBil(μmol/L)	12.0(8.6~20.7)¹⁾	15.7(11.1~30.0)²⁾	Z=2.043	0.041
ALP(U/L)	137.5(94.0~204.3)³⁾	193.0(127.5~262.5)	Z=2.351	0.019
GGT(U/L)	108.0(54.5~182.0)³⁾	152.0(82.3~229.3)	Z=1.728	0.084
LDH(U/L)	455.0(347.3~637.5)⁴⁾	533.0(410.0~708.0)⁵⁾	Z=1.488	0.137
注：1) n=209; 2) n=25; 3) n=210; 4) n=126; 5) n=19。

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表 5 未合并与合并HEV感染IM患者的一般资料和临床特征比较

指标	未合并其他病毒感染组(n=214)	合并HEV感染组(n=24)	统计值	P值
男性[例(%)]	117(54.7)	16(66.7)	χ²=1.259	0.262
年龄(岁)	20.0(18.0~25.0)	22.0(20.0~26.5)	Z=1.692	0.091
入院淋巴细胞比例(%)	64.6(58.6~70.6)	66.6(63.0~68.0)	Z=0.746	0.456
入院异型淋巴细胞比例(%)	15.0(7.8~22.0)	20.0(12.3~34.5)	Z=2.240	0.025
最高体温(℃)	39.0(38.5~39.4)	39.0(38.6~39.5)	Z=0.907	0.364
发热持续时间(d)	11.5(8.0~17.0)	13.0(10.3~17.0)	Z=1.350	0.177
ALT(U/L)	266.0(151.3~409.0)	372.0(194.3~528.5)	Z=1.545	0.122
AST(U/L)	173.5(94.5~279.3)	205.0(101.3~333.3)	Z=1.147	0.251
TBil(μmol/L)	12.0(8.6~20.7)¹⁾	12.5(8.0~33.6)	Z=0.613	0.540
ALP(U/L)	137.5(94.0~204.3)²⁾	186.0(120.5~227.3)	Z=1.685	0.092
GGT(U/L)	108.0(54.5~182.0)²⁾	156.0(81.3~280.0)	Z=1.988	0.047
LDH(U/L)	455.0(347.3~637.5)³⁾	535.5(454.8~705.0)⁴⁾	Z=1.961	0.050
注：1) n=209; 2) n=210; 3) n=126; 4) n=16。

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表 6 未合并与合并脂肪肝IM患者的一般资料和临床特征比较

指标	未合并脂肪肝组(n=266)	合并脂肪肝组(n=8)	统计值	P值
男性[例(%)]	146(54.9)	8(100.0)		0.010
年龄(岁)	20.0(18.0~25.0)	27.0(24.5~34.0)	Z=3.351	0.001
体质量(kg)	62.0(53.5~73.5)	89.5(83.3~96.3)	Z=4.101	＜0.001
入院淋巴细胞(%)	65.0(59.1~70.3)	61.7(53.5~ 67.1)	Z=0.941	0.347
最高体温(℃)	39.0(38.5~39.4)	38.6(38.3~38.9)	Z=2.056	0.040
发热持续时间(d)	12.0(8.0~17.0)	12.5(9.0~17.0)	Z=0.166	0.869
ALT(U/L)	278.5(161.3~448.5)	222.5(114.8~420.8)	Z=0.840	0.401
AST(U/L)	180.5(95.8~304.0)	140.0(93.8~193.3)	Z=1.132	0.258
TBil(μmol/L)	12.3(8.8~22.0)¹⁾	11.5(10.8~16.8)	Z=0.206	0.837
ALP(U/L)	153.0(97.0~221.5)²⁾	132.5(83.0~231.0)	Z=0.416	0.677
GGT(U/L)	124.0(60.5~190.3)²⁾	157.5(58.8~248.3)	Z=0.646	0.518
LDH(U/L)	479.0(355.5~648.5)³⁾	529.0(411.5~633.0)⁴⁾	Z=0.477	0.633
注：1) n=260；2) n=262；3) n=158；4) n=6。

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