妊娠合并慢性乙型肝炎血清HBV pgRNA、PreS1抗原表达与肝内胆汁淤积症的相关性分析

Correlation of serum HBV pgRNA,PreS1 antigen expression and intrahepatic cholestasis in pregnant women with chronic hepatitis B

目的 探究妊娠合并慢性乙型肝炎病人血清乙型肝炎病毒(HBV)前基因组RNA(HBV pgRNA)、前S1抗原(PreS1Ag)水平变化及与妊娠期肝内胆汁淤积症(ICP)发生的相关性。方法 选取2017年6月至2020年6月在雅安市人民医院进行孕期检查的慢性乙型肝炎孕妇279例作为研究对象,根据入组病人是否患有ICP分为合并ICP组43例、未合并ICP组236例。比较两组病人血清中HBV pgRNA、PreS1 Ag水平,并分析两组血清HBV pgRNA、PreS1 Ag表达与HBV DNA表达水平相关性;比较两组病人妊娠结局,并分析合并ICP组病人血清HBV pgRNA表达水平及PreS1 Ag阳性表达率与妊娠结局的关系。受试者操作特征(ROC)曲线分析血清HBV pgRNA、PreS1 Ag光密度[D(λ)]值诊断慢性乙型肝炎孕妇合并ICP的效能。结果 合并ICP组慢性乙型肝炎病人血清HBV表面抗原(HbsAg)水平[(3.71±0.92)log IU/mL]、HBV e抗原(HbeAg)阳性率[65.12%(28/43)]、HBV DNA含量[(8.03±1.69)log copies/mL]、天冬氨酸转氨酶(AST)[(79.68±15.73)U/L]、丙氨酸转氨酶(ALT)[(72.08±16.95)U/L]、PreS1 Ag阳性表达率[88.37%(38/43)]、PreS1 Ag D(λ)值水平(1.24±0.25)及HBV pgRNA表达水平[(5.17±1.25)log copies/mL]明显高于未合并ICP组[(2.26±0.74)log IU/mL、24.15%(57/236)、(5.19±1.07)logcopies/mL、(23.01±12.47)U/L、(21.76±10.51)U/L、67.80%(160/236)、(0.92±0.23)、(3.02±0.98)logcopies/mL](P<0.05)。血清HBV pgRNA诊断慢性乙型肝炎孕妇合并ICP的曲线下面积(AUC)为0.89,灵敏度为81.40%,特异度为80.50%。PreS1 Ag D(λ)值诊断慢性乙型肝炎孕妇合并ICP的AUC为0.83,灵敏度为76.70%,特异度为79.20%。二者联合诊断的AUC为0.91,灵敏度为93.00%,特异度为78.40%。合并ICP组、未合并ICP组血清PreS1 Ag阳性的慢性乙型肝炎病人血清HBV DNA、HBV pgRNA表达水平均明显高于PreS1 Ag阴性表达病人(P<0.05)。合并ICP组、未合并ICP组血清HBV pgRNA、PreS1 Ag D(λ)值均与HBV DNA表达水平呈正相关(P<0.05)。合并ICP组产后出血、早产的发生率明显高于未合并ICP组(P<0.05)。发生不良妊娠结局的慢性乙型肝炎合并ICP病人血清PreS1 Ag阳性表达率、PreS1 Ag D(λ)值、HBV pgRNA表达水平均明显高于未发生不良妊娠结局病人(P<0.05)。结论 合并ICP的慢性乙型肝炎病人血清HBV pgRNA表达水平、PreS1 Ag阳性表达率及D(λ)值水平均明显升高,对ICP有一定诊断价值,且两者水平变化均与HBV DNA含量有关,并可能预示病人不良妊娠结局的发生。

Objective To investigate the changes of serum HBV pregenomic RNA(HBV pgRNA)and pre-S1 antigen(PreS1 Ag)lev-els in pregnant women with chronic hepatitis B and their correlation with intrahepatic cholestasis of pregnancy(ICP).Methods A total of 279 pregnant women with chronic hepatitis B who underwent pregnancy examination in Ya'an People's Hospital from June 2017 to June 2020 were selected as the research objects.According to whether the patients had ICP,they were assinged into ICP group(n=43)and non-ICP group(n=236).The levels of serum HBV pgRNA and PreS1 Ag were compared between the two groups,and the correla-tion between the expressions of HBV pgRNA and PreS1 Ag and the expression of HBV DNA was analyzed.The pregnancy outcomes were compared between the two groups,and the relationship between serum HBV pgRNA level,PreS1 Ag positive expression rate and pregnancy outcome in ICP group was analyzed.Receiver operating characteristic(ROC)curve analysis was made of serum HBV pgRNA,PreS1 Ag D(λ)value in the diagnosis of chronic hepatitis B pregnant women complicated with ICP.Results The level of se-rum HBV surface antigen(HBsAg)[(3.71±0.92)log IU/mL],positive rate of HBV e antigen(HBeAg)[65.12%(28/43)],content of HBV DNA[(8.03±1.69)log copies/mL],aspartate aminotransferase(AST)[(79.68±15.73)U/L],alanine aminotransferase(ALT)[(72.08±16.95)U/L],positive expression rate of PreS1 Ag[88.37%(38/43)],PreS1 Ag D(λ)value level(1.24±0.25)and expression level of HBV pgRNA[(5.17±1.25)log copies/mL]in the ICP group were significantly higher than those in the non-ICP group[(2.26±0.74)log IU/mL,24.15%(57/236),(5.19±1.07)log copies/mL,(23.01±12.47)U/L,(21.76±10.51)U/L,67.80%(160/236),(0.92±0.23),(3.02±0.98)log copies/mL](P<0.05).The area under the curve(AUC)of serum HBV pgRNA for the diagnosis of ICP in pregnant women with chronic hepatitis B was 0.89,the sensitivity was 81.40%,and the specificity was 80.50%.The AUC of PreS1 Ag D(λ)value in the diagnosis of chronic hepatitis B pregnant women complicated with ICP was 0.83,the sensitivity was 76.70%,and the specificity was 79.20%.The AUC of the combined diagnosis was 0.912,the sensitivity was 93.00%,and the specificity was 78.40%.The levels of serum HBV DNA and HBV pgRNA in patients with positive serum PreS1 Ag in ICP group and non-ICP group were significantly higher than those in pa-tients with negative PreS1 Ag(P<0.05).The serum HBV pgRNA and PreS1 Ag D(λ)value in the ICP group and the non-ICP group were positively correlated with the expression level of HBV DNA(P<0.05).The incidences of postpartum hemorrhage and premature birth in the ICP group were significantly higher than those in the non-ICP group(P<0.05).The positive expression rate of serum PreS1 Ag,PreS1 Ag D(λ)value and the expression level of HBV pgRNA in patients with adverse pregnancy outcomes were significantly higher than those in patients without adverse pregnancy outcomes(P<0.05).Conclusion The serum HBV pgRNA expression level,the posi-tive expression rate of PreS1 Ag and the D(λ)value of chronic hepatitis B pregnant women complicated with ICP are significantly in-creased,which have a certain diagnostic value for ICP,and the changes of the two levels are related to the content of HBV DNA,and may indicate poor pregnancy outcomes.