儿童慢性乙型肝炎合并代谢相关脂肪性肝病的临床特点及肝纤维化危险因素分析

Analysis of clinical characteristics and risk factors of hepatic fibrosis in children with chronic hepatitis B combined with metabolic-related fatty liver disease

目的比较儿童慢性乙型肝炎合并代谢相关脂肪性肝病(CHB-MAFLD)与单纯慢性乙型肝炎(单纯CHB)的临床及病理特征差异,探讨MAFLD对CHB肝纤维化进展的影响。方法连续性收集解放军总医院第五医学中心2010年1月-2021年12月收治并经肝活检证实的儿童CHB初治患者701例,根据是否合并MAFLD分为CHB-MAFLD组和单纯CHB组。采用回顾性病例对照研究,以CHB-MAFLD为病例组,按年龄、性别与单纯CHB组进行1∶2倾向性评分匹配,其中CHB-MAFLD组56例,单纯CHB组112例。比较两组患儿体质量指数(BMI)、代谢并发症、实验室指标及肝组织病理特征,采用二元logistic回归模型分析影响CHB肝脏疾病进展的相关因素。组间数据比较采用t检验、非参数秩和检验或χ^(2)检验。结果CHB-MAFLD组丙氨酸转氨酶(ALT,P=0.032)、天冬氨酸转氨酶(AST,P=0.003)水平低于单纯CHB组,而BMI(P<0.001)、甘油三酯(TG,P<0.001)、总胆固醇(P=0.016)水平及代谢综合征的发生率(P<0.001)较单纯CHB组高。两组HBsAg定量及HBV DNA载量的差异无统计学意义(P>0.05)。组织学上,CHB-MAFLD组显著肝纤维化(S2~S4)比例高于单纯CHB组(67.9%与49.1%,χ^(2)=5.311,P=0.021)。多因素回归结果显示BMI(OR=1.258,95%CI:1.145~1.381,P=0.001)和TG(OR=12.334,95%CI:3.973~38.286,P<0.001)是儿童CHB发生肝细胞脂肪变的独立危险因素;MAFLD(OR=4.104,95%CI:1.703~9.889,P=0.002)、肝脏炎症(OR=3.557,95%CI:1.553~8.144,P=0.003)和γ-谷氨酰转移酶(OR=1.019,95%CI:1.001~1.038,P=0.038)是儿童CHB显著肝纤维化的独立危险因素。结论在儿童CHB中,MAFLD的发生与患者代谢因素相关;合并MAFLD有可能促进CHB患者肝纤维化的进展。

Objective To compare the clinical and pathological features of children with chronic viral hepatitis B combined with metabolic-associated fatty liver disease(CHB-MAFLD)and chronic viral hepatitis B alone(CHB alone),and to further explore the effect of MAFLD on the progression of hepatic fibrosis in CHB.Methods 701 initially treated CHB children confirmed by liver biopsy admitted to the Fifth Medical Center of the PLA General Hospital from January 2010 to December 2021 were collected continuously.They were divided into CHB-MAFLD and CHB-alone groups according to whether they were combined with MAFLD.A retrospective case-control study was conducted.CHB-MAFLD was used as the case group,and 1:2 propensity score matching was performed with the CHB alone group according to age and gender,including 56 cases in the CHB-MAFLD group and 112 cases in the CHB alone group.The body mass index(BMI),metabolic complications,laboratory indicators,and pathological characteristics of liver tissue were compared between the two groups.The related factors affecting liver disease progression in CHB were analyzed by a binary logistic regression model.The measurement data between groups were compared using the t-test and rank sum test.Theχ^(2) test was used for the comparison of categorical data between groups.Results Alanine aminotransferase(ALT,P=0.032)and aspartate aminotransferase(AST,P=0.003)levels were lower in the CHB-MAFLD group than those in the CHB alone group,while BMI(P<0.001),triglyceride(TG,P<0.001),total cholesterol(P=0.016)and the incidence of metabolic syndrome(P<0.001)were higher in the CHB alone group.There were no statistically significant differences in HBsAg quantification or HBV DNA load between the two groups(P>0.05).Histologically,the proportion of significant liver fibrosis(S2-S4)was higher in the CHB-MAFLD group than that in the CHB alone group(67.9%vs.49.1%,χ^(2)=5.311,P=0.021).Multivariate regression results showed that BMI(OR=1.258,95%CI:1.145~1.381,P=0.001)and TG(OR=12.334,95%CI:3.973~38.286,P<0.001)were the risk factors for hepatic steatosis occurrence in children with CHB.MAFLD(OR=4.104,95%CI:1.703~9.889,P=0.002),liver inflammation(OR=3.557,95%CI:1.553~8.144,P=0.003),andγ-glutamyl transferase(OR=1.019,95%CI:1.001 to 1.038,P=0.038)were independent risk factors for significant hepatic fibrosis in children with CH.Conclusion MAFLD occurrence is related to metabolic factors in children with CHB.Additionally,the combination of MAFLD may promote liver fibrosis progression in CHB patients.