目的

探讨1例乙型肝炎病毒（HBV）合并丁型肝炎病毒（HDV）感染婴儿的临床特点及诊治经过，并进行文献复习。

方法

选择2021—2023年3次于四川大学华西第二医院住院治疗的1例HBV 合并HDV 感染婴儿为研究对象。采用回顾性研究法，对其临床表现、诊疗过程及预后等临床资料进行分析。分别以“乙型肝炎” “丁型肝炎” “婴儿”与“hepatitis B” “hepatitis D” “infant”为中、英文关键词，在中国知网、万方知识服务平台及Pub Med数据库中，检索婴儿HBV 合并HDV 感染相关研究文献，文献检索时间设定为2010年1月1日至2024年10月31日，对检索到的相关文献进行复习。本研究遵循的程序符合四川大学华西第二医院伦理委员会规定，通过该伦理委员会的审批［审批文号：医学科研2024伦审批第（225）号］。

结果

本例婴儿为男性，8个月+26 d龄，于同一家医院进行3次住院治疗经过如下。①2021年8月26日，因“皮肤淤斑14 d，皮肤黄染10 d”，住院治疗。肝功能检查结果显示，丙氨酸转氨酶（ALT）水平正常，天冬氨酸氨基转移酶（AST）水平为87 U/L（较正常值稍增高）；而总胆红素（TB）浓度为90.8μmol/L，直接胆红素（DBIL）浓度为62.0μmol/L，总胆汁酸（TBA）浓度为202.8μmol/L，均较正常值增高；HBV DNA 水平为2.05×10⁸ copies/m L。本例婴儿的出院诊断为：婴儿胆汁淤积性肝病、维生素K 依赖因子缺乏症、HBV 感染；拟诊为希特林蛋白缺乏症、线粒体能量代谢异常或其他。对本例婴儿采取肌内注射维生素K1、口服复方甘草酸苷与熊去氧胆酸胶囊等药物保肝治疗，以及补充维生素AD、E等后，皮肤黄疸减轻，ALT、AST 下降，皮肤淤斑消退，患儿接受肝脏穿刺活检后（尚未出结果）出院。出院后，患儿肝脏穿刺活检结果显示，中度慢性乙型肝炎（CHB）（G2-3S3），并见界面性肝炎（+3），淋巴及浆细胞浸润（+1），肝细胞花环样结构（+1），胆管病变（-3），不排除合并胆汁淤积性肝病可能。②2021年10月13日，本例婴儿因皮肤黄染加重，监测肝功能异常指标较第1次出院时增高，再次住院治疗。肝功能检查结果显示，ALT 水平正常，而AST 水平为120 U/L，TB浓度为49.3μmol/L，DBIL浓度为38.1μmol/L，均较正常值增高；本次入院诊断为CHB（重度）。对其加用口服拉米夫定34 mg/次×1次/d抗HBV 治疗，并辅助使用熊去氧胆酸片降低胆汁酸水平，皮肤黄疸减轻后出院。出院后持续采取上述药物治疗方案治疗。③2022年5月11日，患儿因抗HBV 治疗效果差第3次入院治疗。对其采取HDV 抗原及免疫球蛋白（Ig）M 抗体检测结果均呈阳性，分别为23.25 S/CO 和88.71 S/CO；乙型肝炎耐药基因测序及基因分型结果显示，存在M204I突变，对拉米夫定及替比夫定耐药，停用拉米夫定，加用口服替诺福韦联合肌内注射干扰素抗病毒治疗，调整药物治疗方案后病情稳定出院。本次出院诊断为CHB、丁型肝炎。出院后，针对其丁型肝炎继续采取口服替诺福韦联合肌内注射干扰素抗病毒治疗，并持续门诊随访监测HBV 抗原定量及DNA 载量，均显著降低，肝酶及胆汁酸指标均正常。④文献复习结果：根据本研究设定的文献检索策略，检索到22篇HBV 合并HDV 感染相关研究文献，国外、国内文献分别为16、6篇。仅1篇文献报道HBV 与HDV 合并感染患儿的临床症状为发热、恶心、腹泻，其余文献均未报道HBV 合并HDV 感染后的临床症状。上述22 篇文献均未报道婴儿HBV 合并HDV 感染率及其治疗结局。

结论

对于婴儿HBV 合并HDV 感染，可使用替诺福韦联合干扰素抗病毒治疗，控制患儿病情。目前对于HBV 合并HDV 感染研究，仅少部分报道婴儿合并感染情况，缺乏对该病患儿详细的临床症状和治疗结局文献报道。

Objective

To explore the clinical characteristics，diagnosis，and treatment process of an infant with hepatitis B virus（HBV）and hepatitis D virus（HDV）co-infection，and to conduct a literature review.

Methods

A retrospective study was conducted on an infant with HBV and HDV co-infection who visited West China Second University Hospital，Sichuan University，three times between 2021 and 2023.The clinical manifestations，diagnosis，treatment，and prognosis of the infant were analyzed.Chinese and English keywords，including"viral hepatitis B""viral hepatitis D"and"infant"were used to search relevant literature published between January 1，2010，and October 31，2024，in the CNKI，Wanfang Data Knowledge Service Platform，and Pub Med databases.The study was approved by the Ethics Committee of West China Second University Hospital，Sichuan University（Approval No.2024-225）.

Results

The infant，an 8-month and 26-day-old male，was hospitalized three times at the same hospital，his specific diagnosis and treatment process was as follows.①On August 26，2021，the infant was hospitalized for the first time at the case collection hospital due to"skin ecchymosis for 14 d and jaundice for 10 d".Liver function tests showed that his alanine aminotransferase（ALT）was normal，aspartate aminotransferase（AST）was 87 U/L （slightly higher than normal），total bilirubin（TB）was 90.8μmol/L，direct bilirubin （DBIL）was 62.0μmol/L，and total bile acid（TBA）was 202.8 μmol/L，and all were higher than normal.HBV DNA was 2.05×10⁸ copies/m L.The discharge diagnosis of this infant was infantile cholestatic liver disease，vitamin K-dependent factor deficiency，and HBV infection；the suspected diagnosis was citrin deficiency，abnormal mitochondrial energy metabolism，or others.The infant was treated with intramuscular vitamin K1，oral compound glycyrrhizin，and ursodeoxycholic acid，along with vitamin AD and E supplementation.After treatment，his symptoms improved，and the infant was discharged after a liver biopsy.After discharge，the liver biopsy indicated moderate chronic hepatitis B（CHB）（G2-3S3）with interface hepatitis（+3），lymphocytic and plasma cell infiltration（+1），hepatocyte rosette formation（+1），and no significant bile duct changes（-3）.②On October 13，2021，the infant was hospitalized again due to worsening jaundice and elevated liver function markers.Liver function tests showed that his ALT was normal，AST was 120 U/L，TB concentration was 49.3μmol/L，and DBIL concentration was 38.1μmol/L，and all were higher than normal.The diagnosis was updated to severe CHB.On October 22，2021，oral lamivudine at a dose of 34 mg per administration，once daily，was started for anti-HBV treatment，and ursodeoxycholic acid tablets were additionally administed to reduce to bile acid levels.The infant was discharged after the skin jaundice was relieved，and continued to take the above-mentioned drug t reatment regimen after discharge.③On May 11，2022，the infant was hospitalized for the third time due to poor response to previous HBV treatment.HDV antigen and immunoglobulin（Ig）M antibody tests were positive （23.25 S/CO and 88.71 S/CO，respectively）.HBV resistance gene sequencing revealed an M204I mutation，indicating resistance to lamivudine and telbivudine.So lamivudine was discontinued，and tenofovir combined with interferon was initiated.After adjusting the medication，the infant was discharged from hospital in a stable condition.The diagnosis was updated to CHB and hepatitis D.After discharge，the infant continued this regimen，showing significant reductions in HBV antigen and DNA levels，with normalized liver enzymes and bile acids during outpatient follow-up.④Literature review results：based on the search strategy，22 relevant articles were identified（16 international and 6 domestic）.Only one article reported symptoms of fever，nausea，and diarrhea in children with HBV and HDV co-infection.None of the 22 articles reported the co-infection rate or outcomes in infants.

Conclusions

Tenofovir combined with interferon is effective in managing HBV and HDV co-infection in infants.Current research on HBV and HDV co-infection in infants is limited，with few reports on clinical symptoms and treatment outcomes.