丙氨酸转氨酶不同正常值上限的慢性HBV感染者肝组织病理改变分析

Liver histopathological changes in chronic HBV infection patients with alanine aminotransferase at different upper limits of normal value

目的分析丙氨酸转氨酶(ALT)不同正常值上限的慢性HBV感染者肝组织病理特征及影响因素。方法收集2014年1月至2020年12月宁波市镇海区中医医院和中国科学院大学宁波华美医院收治的667例住院接受肝穿刺活检的慢性HBV感染者(ALT<40 U/L且HBV DNA>30 IU/mL)的临床资料,将ALT分为Ⅰ组(男性<30 U/L,女性<19 U/L)、Ⅱ组(男性30~<35 U/L,女性19~<25 U/L)和Ⅲ组(男性35~<40 U/L,女性25~<40 U/L),同时根据肝脏炎症程度(G)和纤维化分期(S)将患者分为肝组织无明显损伤组(G且S<2组)和肝组织明显损伤组(G和/或S≥2组)。采用Ridit分析比较3组ALT的G/S构成比差异,采用Logistic回归分析影响肝组织发生明显肝损伤的危险因素,应用受试者工作特征曲线(ROC)及曲线下面积(AUC)寻找ALT的最佳诊断临界值。结果ALT三组间G和S的构成比差异均有统计学意义(χ^(2)=13.926和14.702,P<0.001)。G和/或S≥2组的构成比分别为26.05%(99/380)、32.03%(41/128)、46.54%(74/159),差异亦有统计学意义(χ^(2)=21.596,P<0.001)。Logistic多因素回归分析显示,影响肝组织损伤严重程度的保护因素为高白/球蛋白比值和PLT计数(OR=0.246和0.986,P<0.001),危险因素为肝组织HBcAg阴性、ALT和GGT水平升高(OR=3.797、1.053和1.013,P<0.001或<0.05)。ROC曲线显示男性患者肝组织明显损伤的ALT阈值为25.6 U/L;女性患者为25.5 U/L。结论ALT正常的慢性HBV感染者,随着ALT水平升高,肝组织病理损伤程度加重,临床上有必要降低判断明显肝组织病理损伤的ALT阈值。

Objective To investigate the pathological characteristics in chronic HBV infection patients with different upper limits of alanine aminotransferase(ALT)normal values and the influencing factors of liver tissue injury.Methods The clinical data of 667 chronic HBV infection patients with ALT<40 U/L and HBV DNA loads>30 IU/mL who received liver biopsy in Zhenhai District Hospital of Traditional Chinese Medicine and Hwa Mei Hospital from January 2014 to December 2020 were retrospectively analyzed.The enrolled patients were divided into ALTⅠgroup(<30 U/L for males,<19 U/L for females),ALTⅡgroup(≥30 U/L and<35 U/L for males,≥19 U/L and<25 U/L for females)and ALTⅢgroup(≥35 U/L and<40 U/L for males,≥25 U/L and<40 U/L for females).According to the degree of liver inflammation(G)and fibrosis stage(S),the enrolled patients were divided into non-significant damage group(G<2 and S<2)and significant damage group(≥G2 or/and≥S2).Ridit analysis was used to compare the G/S composition ratio among three ALT groups,Logistic regression was used to analyze the risk factors of liver injury,the receiver operating characteristic curve(ROC)and the area under the curve(AUC)were used to analyze the optimal diagnostic threshold of ALT.Results There were significant differences in the composition ratio of G and S among the three ALT groups(χ^(2)=13.926 and 14.702,both P<0.001).The constituent ratios of significant liver pathological damage in the three groups of ALT levels were 26.05%(99/380),32.03%(41/128)and 46.54%(74/159),respectively(χ^(2)=21.596,P<0.001).Multivariate logistic regression analysis showed that high white/globulin ratio and PLT counts(OR=0.246 and 0.986,both P<0.001)were the protective factors for liver tissue injury;while negative HBcAg staining and elevated ALT and GGT levels(OR=3.797,1.053 and 1.013,P<0.001 or<0.05)were the risk factors of liver injury.ROC curve demonstrated the ALT threshold of liver tissue damage in male and female patients were 25.6 U/L and 25.5 U/L.Conclusions In chronic HBV infection patients with normal ALT,with the increase of ALT level,the degree of liver tissue pathological damage may become more severe.The study demonstrates that it is necessary to lower the ALT threshold for protecting patients from liver tissue pathological damage.