儿童传染性单核细胞增多症与肝功能异常的相关性及长期预后分析

Liver function abnormalities in pediatric infectious mononucleosis: Risk factors and long-term outcomes

摘要:

目的 探讨儿童传染性单核细胞增多症（IM）合并肝功能异常的危险因素及长期预后，并分析其潜在机制。方法 回顾性分析2021年1月—2023年12月山西省儿童医院收治的80例IM住院患儿的临床资料。依据肝功能状态分为肝功能异常组（32例）和肝功能正常组（48例）。比较两组的一般临床特征及实验室指标，采用多因素一般Logistic回归模型分析IM合并肝功能异常的影响因素。随访12个月，评估患儿的肝功能恢复情况、复发率及并发症发生情况。结果 肝功能异常组丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶、总胆红素和直接胆红素水平均高于肝功能正常组（P <0.05）。两组患儿发热天数、肝脏肿大、皮疹、异形淋巴细胞比值、中性粒细胞与淋巴细胞比值（NLR）和CD4⁺/CD8⁺比值比较，差异均有统计学意义（P <0.05）。两组患儿性别构成、年龄、咽峡炎、淋巴结肿大、脾脏肿大、白细胞计数、血红蛋白、EB病毒DNA载量、EB病毒衣壳抗原抗体阳性和CD3⁺比较，差异均无统计学意义（P >0.05）。多因素一般Logistic回归分析结果显示：发热天数长［O^R=4.775（95% CI：1.550，14.709）］、肝脏肿大［O^R=5.438（95% CI：1.529，19.338）］、皮疹［O^R=5.370（95% CI：1.725，16.712）］、异形淋巴细胞比例大［O^R=6.234（95% CI：1.673，23.226）］、NLR水平低［O^R=0.315（95% CI：0.107，0.928）］、CD4⁺/CD8⁺水平低［O^R=0.384（95% CI：0.153，0.967）］均是IM患儿发生肝功能异常的危险因素（P <0.05）。肝功能异常组中87.50%（28/32）的患儿在3个月内肝酶及胆红素水平恢复正常；9.38%（3/32）的患儿在6个月内恢复；仅1例（3.13%）患儿在6个月后ALT仍轻度升高，但至12个月随访时已基本恢复正常。两组患儿均复发2例，均未出现典型慢性IM或慢性肝炎病例。结论 IM患儿易合并肝功能异常，其发生与发热持续时间长、肝脏肿大、皮疹、异形淋巴细胞比例升高、NLR降低及CD4⁺/CD8⁺比值下降关系密切。尽管部分患儿肝功能恢复较慢，但长期预后总体良好，未见严重慢性肝损伤。

Abstract:

Objective To investigate the risk factors and long-term prognosis of liver function abnormalities in children with infectious mononucleosis (IM) and to explore the potential underlying mechanisms.Methods A retrospective analysis was conducted on the clinical data of 80 hospitalized children diagnosed with IM at Shanxi Children's Hospital from January 2021 to December 2023. The patients were divided into the abnormal liver function group (n = 32) and the normal liver function group (n = 48) based on their liver function status. General clinical characteristics and laboratory indicators were compared between the two groups. Multivariable logistic regression analysis was performed to identify influencing factors associated with liver function abnormalities in IM. Patients were followed up for 12 months to assess liver function recovery, recurrence rate, and incidence of complications.Results The abnormal liver function group exhibited higher levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and direct bilirubin compared with those in the normal liver function group (P < 0.05). Significant differences were also observed between the two groups in terms of duration of fever, hepatomegaly, rash, the proportion of atypical lymphocytes, the neutrophil-to-lymphocyte ratio (NLR), and the CD4⁺/CD8⁺ ratio (P < 0.05). No significant differences were found in sex distribution, age, pharyngitis, lymphadenopathy, splenomegaly, white blood cell count, hemoglobin, EBV DNA load, EBV capsid antigen antibody positivity, or CD3⁺ levels (P > 0.05). Multivariable logistic regression analysis revealed that prolonged fever [O^R = 4.775 (95% CI: 1.550, 14.709) ], hepatomegaly [O^R = 5.438 (95% CI: 1.529, 19.338) ], rash [O^R = 5.370 (95% CI: 1.725, 16.712) ], higher proportion of atypical lymphocytes [O^R = 6.234 (95% CI: 1.673, 23.226) ], lower NLR [O^R = 0.315 (95% CI: 0.107, 0.928) ], and lower CD4⁺/CD8⁺ ratio [O^R = 0.384 (95% CI: 0.153, 0.967) ] were independent risk factors for liver function abnormalities in children with infectious mononucleosis (all P < 0.05). Regarding prognosis, 87.5% (28/32) of children with liver function abnormalities normalized their liver enzymes and bilirubin within 3 months, 9.38% (3/32) recovered within 6 months, and only one child (3.13%) had mildly elevated ALT beyond 6 months which normalized by 12-month follow-up. Both groups experienced two cases of recurrence, with no cases of typical chronic infectious mononucleosis or chronic hepatitis observed.Conclusions Children with IM are prone to developing liver function abnormalities, which is closely associated with prolonged fever, hepatomegaly, rash, increased proportion of atypical lymphocytes, decreased NLR, and a reduced CD4⁺/CD8⁺ ratio. Although some patients experience a slower recovery of liver function, the overall long-term prognosis is favorable, with no severe chronic liver damage observed.