丙氨酸转氨酶低于2倍正常值上限的慢性乙型肝炎患者的肝脏病理学特征及其影响因素

Hepatic pathological characteristics and factors influencing alanine transaminase value below twice the upper limit of normal in patients with chronic hepatitis B

目的分析丙氨酸转氨酶(ALT)低于2倍正常值上限(ULN)的慢性乙型肝炎(CHB)患者的肝脏病理学特征及其影响因素,探讨启动抗病毒治疗ALT阈值的优化策略。方法回顾性收集2010年1月—2019年12月行肝穿刺活体组织学检查的CHB初治患者及其临床资料。利用多元回归模型探讨ALT水平和显著肝组织学改变(≥G2/S2)的风险。采用受试者操作特征曲线评价不同模型诊断肝组织炎症≥G2或纤维化≥S2的价值。结果共纳入447例符合要求的CHB患者,中位数年龄为38.0岁,72.9%为男性。ALT水平在正常范围时,分别有66.9%和53.0%的患者存在显著的肝脏炎症(≥G2)和纤维化(≥S2);ALT为1~2×ULN时,肝脏炎症≥G2和纤维化≥S2的比例上升为81.2%和60.0%。调整混杂因素后,发现较高的ALT水平(>29 U/L)与显著的肝脏炎症(OR:2.30,95%置信区间:1.11~4.77)以及纤维化(OR:1.84,95%置信区间:1.10~3.09)有关。引入γ-谷氨酰转移酶-血小板比值(GPR)后,不同ALT治疗阈值标准下的CHB患者出现≥G2/S2的比例显著降低,尤其是对肝纤维化≥S2的误判可以得到显著的改善(33.5%~57.5%)。结论无论ALT正常或在2×ULN以内,均有超过半数的CHB患者存在明显的炎症及纤维化。GPR可以显著改善不同ALT治疗阈值对CHB患者病情的准确判断。

Objective To analyze the hepatic pathological characteristics and factors influencing an alanine transaminase value below twice the upper limit of normal in patients with chronic hepatitis B(CHB)and further explore the optimal ALT threshold strategy for initiating antiviral therapy.Methods Clinical data of treatment-naïve CHB patients who underwent liver biopsies from January 2010 to December 2019 were retrospectively collected.Multiple regression models were used to explore the ALT levels and significant risk of hepatic histological changes(≥G2/S2).Receiver operating characteristic curve was used to evaluate the value of different models in diagnosing liver tissue inflammation≥G2 or fibrosis≥S2.Results A total of 447 eligible CHB patients,with a median age of 38.0 years and 72.9%males,were included.During ALT normalization,there was significant liver inflammation(≥G2)and fibrosis(≥S2)in 66.9%and 53.0%of patients,respectively.With an ALT rise of 1-2×ULN,the proportions of liver inflammation≥G2 and fibrosis≥S2 were 81.2%and 60.0%,respectively.After adjusting for confounding factors,higher ALT levels(>29 U/L)were found to be associated with significant liver inflammation(OR:2.30,95%CI:1.11~4.77)and fibrosis(OR:1.84,95%CI:1.10~3.09).After the measurement of glutamyltransferase-platelet ratio(GPR),the proportion of CHB patients with≥G2/S2 was significantly reduced under different treatment thresholds of ALT standards,and in particular,the erroneous evaluation of liver fibrosis≥S2 was significantly improved(33.5%to 57.5%).Conclusion More than half of CHB patients have a normal ALT or one within 2×ULN,regardless of whether or not there is apparent inflammation and fibrosis.GPR can significantly improve the precise assessment of different conditions of treatment thresholds for the ALT value in CHB patients.