The informative value of noninvasive tools for assessment of liver fibrosis in chronic hepatitis B patients under antiviral treatment with nucleoside and nucleotide analogues

Thi-Hanh Nguyen, Liudmila Y. Ilchenko, Lubov Melnikova, K. Kyuregyan, I. Gordeychuk
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Abstract

Background: Antiviral therapy (AVT) with nucleoside and nucleotide analogues (NAs) for chronic hepatitis B (CHB) is aimed at prevention of the development and progression of fibrosis, liver cirrhosis, and hepatocellular carcinoma. Therefore, monitoring of changes in liver fibrosis over time with noninvasive tests is a necessary prerequisite for the assessment of treatment efficacy. However, there are very few studies on changes of transient elastometry (TE) over time, the calculated indices APRI and FIB-4 under AVT in patients with CHB. Aim: To assess changes in noninvasive tests (TE, APRI, FIB-4) over time and to identify factors influencing the fibrosis severity in CHB patients treated with NAs. Materials and methods: This retrospective study was performed in 42 CHB patients, in whom noninvasive methods (TE, APRI and FIB-4) were used before and during NA-based AVT. The patients were divided into two groups: those with a significant reduction in liver density (SRLD, at least by 25% from their baseline TE) and those without a significant reduction ( 25%). Results: Virological response was achieved in 38/42 patients after NA-based AVT (mean duration, 21 months). TE values decreased significantly in the patients with severe fibrosis/cirrhosis (F3/F4) (from 14.2 to 8.3 kPa, p = 0.001), with minimal/moderate fibrosis (F1/F2) (from 5.9 to 5.1 kPa, p = 0.009), and in HBeAg-negative patients (from 6.9 to 5.2 kPa, p 0.001). The F3/F4, F1/F2, HBeAg-positive and HBeAg-negative patients demonstrated a significant reduction in APRI and FIB-4 indices (all p 0.05). Higher baseline TE values were independently associated with SRLD (odds ratio 1.324; 95% confidence interval (CI) 1.0291.702; p = 0.029). Baseline TE, APRI, and FIB-4 values positively correlated with their values on treatment (all p 0.05). The AUROC values of APRI and FIB-4 reduction as SRLD predictors were 0.632 (95% CI 0.4570.807; p = 0.160) and 0.578 (95% CI 0.3910.764; p = 0.408), respectively. Conclusion: NA-based AVT promoted the regression of fibrosis in CHB patients. A high baseline TE value was identified as an independent SRLD predictor. At the same time, despite moderate positive correlations between TE, APRI and FIB-4 parameters, the calculated indexes APRI and FIB-4 cannot be used to predict SRLD. The decrease in liver tissue density by at least 25% correlated only with TE parameters, which makes it possible to recommend TE for monitoring liver fibrosis in CHB patients treated with NA.
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在接受核苷和核苷酸类似物抗病毒治疗的慢性乙型肝炎患者中,无创工具评估肝纤维化的信息价值
背景:核苷和核苷酸类似物(NAs)抗病毒治疗(AVT)用于慢性乙型肝炎(CHB),旨在预防纤维化、肝硬化和肝细胞癌的发生和进展。因此,通过无创检查监测肝纤维化随时间的变化是评估治疗效果的必要前提。然而,关于慢性乙型肝炎患者AVT下瞬时弹性测量(TE)随时间变化、计算指标APRI和FIB-4的研究很少。目的:评估非侵入性检查(TE、APRI、FIB-4)随时间的变化,并确定影响NAs治疗的CHB患者纤维化严重程度的因素。材料和方法:本回顾性研究在42例CHB患者中进行,在na基AVT之前和期间使用无创方法(TE, APRI和FIB-4)。患者被分为两组:肝密度显著降低(SRLD,至少比基线TE降低25%)和无显著降低(25%)的患者。结果:42例患者中有38例在na基AVT治疗后获得病毒学应答(平均持续时间21个月)。TE值在严重纤维化/肝硬化(F3/F4)患者(从14.2降至8.3 kPa, p = 0.001)、轻度/中度纤维化(F1/F2)患者(从5.9降至5.1 kPa, p = 0.009)和hbeg阴性患者(从6.9降至5.2 kPa, p = 0.001)中显著降低。F3/F4、F1/F2、hbeag阳性和hbeag阴性患者APRI和FIB-4指数均显著降低(p均0.05)。较高的基线TE值与SRLD独立相关(优势比1.324;95%置信区间(CI) 1.0291.702;P = 0.029)。基线TE、APRI和FIB-4值与其治疗时的值呈正相关(均p 0.05)。APRI和FIB-4降低作为SRLD预测因子的AUROC值为0.632 (95% CI 0.4570.807;p = 0.160)和0.578 (95% CI 0.3910.764;P = 0.408)。结论:基于na的AVT可促进CHB患者纤维化的消退。高基线TE值被确定为独立的SRLD预测因子。同时,尽管TE、APRI和FIB-4参数之间存在适度的正相关,但计算得到的指标APRI和FIB-4不能用于预测SRLD。肝组织密度下降至少25%仅与TE参数相关,这使得推荐TE监测接受NA治疗的CHB患者的肝纤维化成为可能。
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