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[慢性乙型肝炎低病毒血症治疗患者的人口统计学特征及相关影响因素:一项单中心回顾性横断面研究]

[Demographic characteristics and associated influencing factors in treated patients with chronic hepatitis B with hypoviremia : a single-center retrospective cross-sectional study].

作者信息

Li T, Kong Y, Liu Y Y, Liu T F, Ma A D, Li L Q, Pei Z Y, Zhang L Y

机构信息

Department of Hepatology, Second Hospital, Lanzhou University, Lanzhou 730030, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2023 Jan 20;31(1):42-48. doi: 10.3760/cma.j.cn501113-20220121-00039.

Abstract

To investigate the demographic characteristics and clinical influencing factors which associates with the occurrence probability of persistent or intermittent hypoviremia (LLV) in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs). A single-center retrospective analysis was performed on patients with CHB who received outpatient NAs therapy for≥48 ± 2 weeks. According to the serum hepatitis B virus (HBV) DNA load at 48±2 weeks treatment, the study groups were divided into LLV (HBV DNA < 20 IU/ml and < 2 000 IU/ml) and MVR group (sustained virological response, HBV DNA < 20 IU/ml). Demographic characteristics and clinical data at the start of NAs treatment (considered as baseline) were retrospectively collected for both patient groups. The differences in the reduction of HBV DNA load during treatment was compared between the two groups. Correlation and multivariate analysis were further conducted to analyze the associated factors influencing the LLV occurrence. Statistical analysis was performed using the independent samples t-test, c2 test, Spearman analysis, multivariate logistic regression analysis, or area under the receiver operating characteristic curve. A total of 509 cases were enrolled, with 189 and 320 in the LLV and MVR groups, respectively. Compared to patients with MVR group at baseline: (1) the demographics characteristics of patients showed that LLV group was younger in age (39.1 years, = 0.027), had a stronger family history (60.3%, = 0.001), 61.9% received ETV treatment, and higher proportion of compensated cirrhosis (20.6%, = 0.025) at baseline; (2) the serum virological characteristics of patients showed that LLV group had higher HBV DNA load, qHBsAg level, qHBeAg level, HBeAg positive rate, and the proportion of genotype C HBV infection but decreased HBV DNA during treatment ( < 0.001) at baseline; (3) the biochemical characteristics of patients showed that LLV group had lower serum ALT levels ( = 0.007) at baseline; (4) the noninvasive fibrosis markers of patients showed that LLV group were characterized by high aspartate aminotransferase platelet ratio index (APRI) ( = 0.02) and FIB-4 ( = 0.027) at baseline. HBV DNA, qHBsAg and qHBeAg were positively correlated with LLV occurrence ( = 0.559, 0.344, 0.435, respectively), while age and HBV DNA reduction were negatively correlated ( = -0.098, -0.876, respectively). Logistic regression analysis showed that ETV treatment history, high HBV DNA load at baseline, high qHBsAg level, high qHBeAg level, HBeAg positive, low ALT and HBV DNA level were independent risk factors for patients with CHB who developed LLV with NAs treatment. Multivariate prediction model had a good predictive value for LLV occurrence [AUC 0.922 (95%: 0.897 ~ 0.946)]. In this study, 37.1% of CHB patients treated with first-line NAs has LLV. The formation of LLV is influenced by various factors. HBeAg positivity, genotype C HBV infection, high baseline HBV DNA load, high qHBsAg level, high qHBeAg level, high APRI or FIB-4 value, low baseline ALT level, reduced HBV DNA during treatment, concomitant family history, metabolic liver disease history, and age < 40 years old are potential risk factors for developing LLV in patients with CHB during the therapeutic process.

摘要

为研究接受核苷(酸)类似物(NAs)治疗的慢性乙型肝炎(CHB)患者中,与持续或间歇性低病毒血症(LLV)发生概率相关的人口统计学特征和临床影响因素。对接受门诊NAs治疗≥48±2周的CHB患者进行单中心回顾性分析。根据治疗48±2周时的血清乙型肝炎病毒(HBV)DNA载量,将研究组分为LLV组(HBV DNA<20 IU/ml且<2000 IU/ml)和MVR组(持续病毒学应答,HBV DNA<20 IU/ml)。回顾性收集两组患者开始NAs治疗时(视为基线)的人口统计学特征和临床资料。比较两组治疗期间HBV DNA载量下降的差异。进一步进行相关性和多因素分析,以分析影响LLV发生的相关因素。采用独立样本t检验、c2检验、Spearman分析、多因素logistic回归分析或受试者工作特征曲线下面积进行统计分析。共纳入509例患者,LLV组和MVR组分别有189例和320例。与基线时MVR组患者相比:(1)患者的人口统计学特征显示,LLV组年龄较小(39.1岁,P = 0.027),家族史更强(60.3%,P = 0.001),61.9%接受ETV治疗,基线时代偿期肝硬化比例更高(20.6%,P = 0.025);(2)患者的血清病毒学特征显示,LLV组基线时HBV DNA载量、qHBsAg水平、qHBeAg水平、HBeAg阳性率及基因型C HBV感染比例更高,但治疗期间HBV DNA下降(P<0.001);(3)患者生化特征显示,LLV组基线时血清ALT水平较低(P = 0.007);(4)患者的无创纤维化标志物显示,LLV组基线时天冬氨酸转氨酶血小板比值指数(APRI)(P = 0.02)和FIB-4(P = 0.027)较高。HBV DNA、qHBsAg和qHBeAg与LLV发生呈正相关(分别为P = 0.559、0.344、0.435),而年龄和HBV DNA下降呈负相关(分别为P = -0.098、-0.876)。logistic回归分析显示,ETV治疗史、基线时高HBV DNA载量、高qHBsAg水平、高qHBeAg水平、HBeAg阳性、低ALT及HBV DNA水平是CHB患者接受NAs治疗发生LLV的独立危险因素。多因素预测模型对LLV发生具有良好的预测价值[AUC 0.922(95%:0.897~0.946)]。本研究中,一线NAs治疗的CHB患者有37.1%发生LLV。LLV的形成受多种因素影响。HBeAg阳性、基因型C HBV感染、基线高HBV DNA载量、高qHBsAg水平、高qHBeAg水平、高APRI或FIB-4值、基线低ALT水平、治疗期间HBV DNA下降、伴有家族史、代谢性肝病病史及年龄<40岁是CHB患者治疗过程中发生LLV的潜在危险因素。

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