血清 HBV RNA 可预测核苷（酸）类似物治疗慢性乙型肝炎患者的 HBeAg 清除和血清学转换。

Serum HBV RNA predicts HBeAg clearance and seroconversion in patients with chronic hepatitis B treated with nucleos(t)ide analogues.

机构信息

Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.

Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment & Research, Beijing YouAn Hospital, Capital Medical University, Beijing, China.

出版信息

J Viral Hepat. 2022 Jun;29(6):420-431. doi: 10.1111/jvh.13671. Epub 2022 Mar 17.

DOI:10.1111/jvh.13671

PMID:35274400

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9311425/

Abstract

This study evaluated the predictive value of serum HBV DNA, HBV RNA, HBcrAg, HBsAg, intrahepatic HBV DNA and cccDNA for HBeAg clearance and seroconversion during long-term treatment with nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB). A single centre, prospective cohort of CHB patients was used for this study. Serum HBV RNA levels were retrospectively measured at baseline, 6, 12, 24, 36, 48, 60, 72 and 84 months post-NAs treatment. Serum HBsAg and HBcrAg levels were quantified at baseline, month 6, 60 and 72. Histological samples from liver biopsy at baseline and month 60 were analysed for intrahepatic HBV DNA and cccDNA. Eighty-three HBeAg-positive patients were enrolled with a median follow-up time of 108 months (range 18-138 months). Of them, 53 (63.86%) patients achieved HBeAg clearance, and 37 (44.58%) achieved HBeAg seroconversion. Cox multivariate analysis showed that only baseline HBV RNA was independently associated with HBeAg clearance and seroconversion (<5.45 log copies/mL, HR = 5.06, 95% CI: 1.87-13.71, p = .001; HR = 3.38, 95% CI: 1.28-8.91, p = .01). The independent association with HBeAg clearance and seroconversion remained for HBV RNA levels at month 6 (<4.72 log copies/mL, HR = 4.16, 95% CI: 1.61-10.72, p = .003; HR = 6.52, 95% CI: 1.85-22.94, p = .003) and month 12 (<4.08 log copies/mL, HR = 3.68, 95% CI: 1.96-6.90, p < .001; HR = 2.79, 95% CI: 1.31-5.94, p = .008). The AUCs of baseline HBV RNA for predicting the HBeAg clearance (0.83, 95% CI: 0.70-0.96, 0.83, 95% CI: 0.70-0.96 and 0.82, 95% CI: 0.69-0.95 respectively) and seroconversion (0.89, 95% CI: 0.77-1.00; 0.81, 95% CI: 0.66-0.95 and 0.84, 95% CI: 0.71-0.98 respectively) at month 36, 60 and 84 were higher than those of HBV DNA, HBsAg and HBcrAg. In conclusion, lower serum HBV RNA at baseline, month 6 and 12 post-NAs treatment could predict HBeAg clearance and seroconversion during long-term NAs treatment.

摘要

本研究评估了血清 HBV DNA、HBV RNA、HBcrAg、HBsAg、肝内 HBV DNA 和 cccDNA 对慢性乙型肝炎（CHB）患者长期核苷（酸）类似物（NA）治疗期间 HBeAg 清除和血清学转换的预测价值。该研究采用单中心前瞻性队列研究，纳入了 83 例 HBeAg 阳性患者，中位随访时间为 108 个月（18-138 个月）。其中，53 例（63.86%）患者实现了 HBeAg 清除，37 例（44.58%）患者实现了 HBeAg 血清学转换。多因素 Cox 分析显示，只有基线 HBV RNA 与 HBeAg 清除和血清学转换独立相关（<5.45log 拷贝/ml，HR=5.06，95%CI：1.87-13.71，p=0.001；HR=3.38，95%CI：1.28-8.91，p=0.01）。HBV RNA 水平在 6 个月（<4.72log 拷贝/ml，HR=4.16，95%CI：1.61-10.72，p=0.003；HR=6.52，95%CI：1.85-22.94，p=0.003）和 12 个月（<4.08log 拷贝/ml，HR=3.68，95%CI：1.96-6.90，p<0.001；HR=2.79，95%CI：1.31-5.94，p=0.008）时与 HBeAg 清除和血清学转换的独立相关仍然存在。基线 HBV RNA 预测 HBeAg 清除的 AUC 值分别为 0.83（95%CI：0.70-0.96）、0.83（95%CI：0.70-0.96）和 0.82（95%CI：0.69-0.95），预测 HBeAg 血清学转换的 AUC 值分别为 0.89（95%CI：0.77-1.00）、0.81（95%CI：0.66-0.95）和 0.84（95%CI：0.71-0.98），均高于 HBV DNA、HBsAg 和 HBcrAg。总之，NA 治疗前、6 个月和 12 个月时血清 HBV RNA 水平较低可预测长期 NAs 治疗期间的 HBeAg 清除和血清学转换。