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721例ALT正常的慢性乙型肝炎患者肝脏病理炎症和纤维化状况及其影响因素分析

[Analysis of hepatic pathological inflammation and fibrosis condition and its influencing factors in 721 patients with chronic hepatitis B with normal ALT].

作者信息

Ning H B, Jin H M, Li K, Peng Z, Shang J

机构信息

Department of Infectious Diseases, Henan Provincal People's Hospital, Zhengzhou University People's Hospital, Zhengzhou 450000, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2022 Jul 20;30(7):746-751. doi: 10.3760/cma.j.cn501113-20210624-00298.

Abstract

To analyze the hepatic pathological inflammation and fibrosis condition in order to explore the relationship with related clinical indicators in patients with chronic hepatitis B patients with normal alanine aminotransferase (ALT). 721 cases of chronic hepatitis B with normal ALT who were initially diagnosed in the Department of Infectious Diseases of Henan Provincial People's Hospital from August 2016 to December 2019 were retrospectively collected. Liver biopsy was performed in all patients. General data of patients such as gender, age, liver function indexes, blood routine indexes, HBsAg level, HBeAg status, HBV DNA level, spleen thickness and prothrombin time were collected. Univariate and multivariate analysis methods were used to determine the influencing factors of inflammation and fibrosis degree with liver biopsy. A receiver operating characteristic curve (ROC) was used to evaluate the established multi-factor prediction model. Alpha=0.05 was considered as a standard orientation of test. The average age of 721 cases with chronic hepatitis B was 36.1±9.7 years, and the male to female ratio was 1.28/1, with inflammation and fibrosis grade mainly concentrated in G1S1 (349 cases), G1S2 (132 cases), G2S2 (119 cases), and G2S1 (57 cases). Among them, there were 349 (48.4%) cases of G1S1, and 372 (51.6%) cases of G/S≥2. The main manifestations were mild to moderate inflammation and fibrosis, and only 64 (8.88%) cases had severe G/S≥3. HBsAg level (stratified with 4 log10 IU/ml as the boundary) analyzed in 721 cases were correlated with the relevant clinical indicators stratification and liver pathological inflammation and fibrosis, and the difference was statistically significant (inflammation grade, =6.182, =0.013; Fibrosis grade, =36.534, =0.001). Univariate analysis of the relevant clinical indicators that may influence the patient's liver pathological G/S ≥2 showed the patient's age, albumin, γ- glutamyltransferase (GGT), platelet, prothrombin time (PT), spleen thickness and HBsAg level were all statistically significant (<0.05), while multivariate analysis showed that age, GGT, PT, and spleen thickness had statistical differences (<0.05). The prediction model was established in accordance to multivariate analysis, and the area under the ROC curve was 0.642. Maximization of the sum of sensitivity and specificity as cut-off value of Logit =0.497, the diagnostic sensitivity, specificity, and Youden's index were 60.6%, 64.5%, and 0.252, respectively. More than half of patients with chronic hepatitis B with normal ALT have significant inflammation and fibrosis and require timely antiviral therapy. Age, GGT, PT and spleen thickness can help comprehensively evaluate the liver inflammation and fibrosis status among patients, but the lack of accurate prediction models suggests that more effective indicators that can help predict the inflammation and fibrosis status of such patients have yet to be discovered. Therefore, liver biopsy should still be actively performed in patients with normal ALT to confirm the diagnosis and timely treatment.

摘要

分析慢性乙型肝炎患者谷丙转氨酶(ALT)正常时的肝脏病理炎症和纤维化情况,以探讨其与相关临床指标的关系。回顾性收集2016年8月至2019年12月在河南省人民医院感染科初诊的721例ALT正常的慢性乙型肝炎患者。所有患者均行肝穿刺活检。收集患者的性别、年龄、肝功能指标、血常规指标、HBsAg水平、HBeAg状态、HBV DNA水平、脾脏厚度及凝血酶原时间等一般资料。采用单因素和多因素分析方法确定肝穿刺活检中炎症和纤维化程度的影响因素。采用受试者工作特征曲线(ROC)评估所建立的多因素预测模型。以α=0.05作为检验的标准水准。721例慢性乙型肝炎患者平均年龄为36.1±9.7岁,男女比例为1.28/1,炎症和纤维化分级主要集中在G1S1(349例)、G1S2(132例)、G2S(119例)和G2S1(57例)。其中,G1S1有349例(48.4%),G/S≥2有372例(51.6%)。主要表现为轻至中度炎症和纤维化,仅有64例(8.88%)G/S≥3为重度。对721例患者分析的HBsAg水平(以4 log10 IU/ml为界分层)与相关临床指标分层及肝脏病理炎症和纤维化相关,差异有统计学意义(炎症分级,χ²=6.182,P=0.013;纤维化分级,χ²=36.534,P=0.001)。对可能影响患者肝脏病理G/S≥2的相关临床指标进行单因素分析,结果显示患者年龄、白蛋白、γ-谷氨酰转移酶(GGT)、血小板、凝血酶原时间(PT)、脾脏厚度及HBsAg水平差异均有统计学意义(P<0.05),而多因素分析显示年龄、GGT、PT及脾脏厚度差异有统计学意义(P<0.05)。根据多因素分析建立预测模型,ROC曲线下面积为0.642。以敏感度和特异度之和最大化为截断值时Logit=0.497,诊断敏感度、特异度及约登指数分别为60.6%、64.5%和0.252。超过半数ALT正常的慢性乙型肝炎患者存在显著炎症和纤维化,需要及时抗病毒治疗。年龄、GGT、PT及脾脏厚度有助于综合评估患者肝脏炎症和纤维化状态,但缺乏准确的预测模型提示仍有待发现更有效的有助于预测此类患者炎症和纤维化状态的指标。因此,对于ALT正常的患者仍应积极行肝穿刺活检以明确诊断并及时治疗。

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