血清HBV pgRNA、HBcrAg动态变化对停用NAs治疗的慢性乙型肝炎患者临床和病毒学复发的评估

摘要/Abstract

摘要： 目的观察血清标志物乙型肝炎病毒前基因RNA(HBV pgRNA)、乙型肝炎核心相关抗原(HBcrAg)动态变化评估慢性乙型肝炎(CHB)患者停用核苷(酸)类似物(NAs)治疗的临床和病毒学复发价值。方法 2020年7月—2021年7月公安县人民医院收治的65例CHB患者,所有患者均达到停用NAs治疗的标准,并在停药后对患者至少进行半年以上的随访。对血清HBV pgRNA、HBcrAg水平、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆红素(TBil)等进行检测。结果有HBV感染家族史患者的复发率(70.4%)高于无HBV感染家族史的患者(30.8%),血清HBV pgRNA水平≥4.06 log₁₀拷贝/mL的患者复发率(79.2%)比<4.06 log₁₀拷贝/mL的患者复发率高(41.5%),血清HBcrAg水平≥3.4 log₁₀ U/L的患者复发率(76.9%)比<3.4 log₁₀ U/L患者的复发率(41.0%)高,乙型肝炎e抗原(HBeAg)消失时间发生在12个月内的患者的复发率(46.0%)低于发生在12~24个月、≥24个月的患者(88.9%、83.3%),HBeAg血清学转换时间发生在12个月内的患者的复发率(46.0%)低于发生在12~24个月、≥24个月的患者(88.9%、83.3%),停药时乙型肝炎表面抗原(HBsAg)＜150 ng/mL的患者的复发率(26.3%)低于≥150 ng/mL的患者(67.4%)(P<0.05)。HBV感染家族史、HBeAg血清学转换时间、HBeAg消失时间、停药时HBsAg水平、血清HBV pgRNA水平、血清HBcrAg水平均为停用NAs治疗的CHB患者临床和病毒学复发的影响因素(P<0.05);HBV感染家族史、HBeAg血清学转换时间、停药时HBsAg水平、血清HBV pgRNA水平、血清HBcrAg水平均为停用NAs治疗的CHB患者临床和病毒学复发的危险因素(P<0.05)。结论停用NAs治疗的CHB患者临床和病毒学复发的危险因素在于HBeAg血清学转换时间、HBV感染家族史、停药时HBsAg水平、血清HBV pgRNA水平、血清HBcrAg水平,临床应据此采取相应的措施,定期对HBsAg水平、血清HBV pgRNA水平、血清HBcrAg水平予以监测,以降低CHB患者的复发率。

关键词: 慢性乙型肝炎, 乙型肝炎病毒前基因RNA, 乙型肝炎核心相关抗原, 临床复发, 病毒学复发

Abstract: Objective To observe the value of dynamic changes of serum markers such as hepatitis B virus pregene RNA (HBV pgRNA) and hepatitis B core associated antigen (HBcrAg) in the evaluation of the clinical and virological recurrence in chronic hepatitis B (CHB) patients after discontinuing nucleoside (acid) analogues (NAs) treatment. Methods Between July 2020 and July 2021, sixty-five patients with CHB were admitted to our hospital. All patients met the criteria for discontinuation of NAs therapy, and were followed up for at least half a year after discontinuation. Serum levels of HBV pgRNA, HBcrAg, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (TBil) were detected. Results Patients with a family history of HBV infection (70.4%) had a higher recurrence rate than those without (30.8%). Patients with serum HBV pgRNA levels ≥ 4.06 log₁₀copies/mL (79.2%) had a higher recurrence rate than patients with<4.06 log₁₀copies/mL (41.5%). Patients with serum HBcrAg levels ≥ 3.4 log₁₀ U/L (76.9%) had a higher recurrence rate than patients with<3.4 log₁₀ U/L (41.0%), The recurrence rate (46.0%) of patients with hepatitis B E antigen (HBeAg) disappearance within 12 months was lower than that of patients with HBeAg disappearance within 12 to 24 months (88.9%, 83.3%), and the recurrence rate (46.0%) of patients with serological HBeAg conversion within 12 months was lower than that of patients with HBeAg disappearance within 12 to 24 months (88.9%, 83.3%), The recurrence rate of patients with hepatitis B B surface antigen (HBsAg)<150 ng/mL (26.3%) was lower than that of patients with HBsAg≥ 150 ng/mL (67.4%) (P<0.05). HBeAg serological conversion time, family history of HBV infection, HBeAg disappearance time, HBsAg level, serum HBV pgRNA level and serum HBcrAg level at the time of drug withdrawal were all influential factors for clinical and virologic recurrence in CHB patients who stopped NAs treatment (P<0.05). HBeAg serological conversion time, family history of HBV infection, HBsAg level at drug withdrawal, serum HBV pgRNA level, and serum HBcrAg level were all risk factors for clinical and virologic recurrence in CHB patients who stopped NAs treatment (P<0.05). Conclusion The risk factors for clinical and virological recurrence in CHB patients who have stopped NAs therapy are HBeAg serological conversion time, family history of HBV infection, HBsAg level, serum HBV pgRNA level and serum HBcrAg level at the time of drug withdrawal. Clinical measures should be taken accordingly. The HBsAg level, serum HBV pgRNA level and serum HBcrAg level should be monitored regularly to reduce the recurrence rate of CHB patients.

Key words: Chronic hepatitis B, Hepatitis B virus pregene RNA, Hepatitis B core-associated antigen, Clinical recurrence, Virological relapse

鲁石, 张志红, 欧阳慧, 贺宇. 血清HBV pgRNA、HBcrAg动态变化对停用NAs治疗的慢性乙型肝炎患者临床和病毒学复发的评估[J]. 肝脏, 2025, 30(2): 175-179.

LU Shi, ZHANG Zhi-hong, OUYANG Hui, HE Yu. Dynamic changes of serum HBV pgRNA and HBcrAg in patients with chronic hepatitis B after discontinuation of NAs therapy: assessment of clinical and virology relapse[J]. Chinese Hepatolgy, 2025, 30(2): 175-179.

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