The predictive value of serum HBV-LP combined with HBV RNA for recurrence after discontinuation of long-acting interferon in the treatment of chronic hepatitis B

Abstract

Abstract: Objective To analyze the predictive value of serum hepatitis B virus large protein (HBV-LP) combined with hepatitis B virus ribonucleic acid (HBV RNA) for recurrence after discontinuation of long-acting interferon in the treatment of chronic hepatitis B (CHB). Methods A total of 70 CHB patients who received long-acting interferon treatment in our hospital from January 2022 to December 2023 were selected and divided into the recurrence group (n=19) and the non-recurrence group (n=51) according to the recurrence situation after drug withdrawal. All included patients were tested for serum level of the HBV-LP and HBV RNA on the day after drug withdrawal. General data, related biochemical indicators, and the level of the HBV-LP and HBV RNA of each group were analyzed and compared. The predictive value of serum HBV-LP combined with HBV RNA for recurrence after drug withdrawal in CHB patients were evaluated by the receiver operator characteristics (ROC) curve. The related factors affecting recurrence after drug withdrawal in CHB patients were investigated by multivariate logistic regression analysis. Results The proportion of alcohol consumption history in the recurrence group was higher than that in the non-recurrence group (52.63% vs. 21.57%), and the difference was statistically significant (P<0.05). In the recurrence group, the serum ALT was (89.55±23.42) U/L, AST was (72.35±20.65) U/L, AFP was (30.11±10.23) μg/L, HBsAg was (8.10±1.67) lg IU/mL, and HBcrAg was (7.09±1.55) lg IU/mL, HBV DNA (4.24±0.88) lg IU/mL, HBV-LP (41.41±9.55) μg/L, HBV RNA (4.65±1.01) lg copies /mL, higher than the non-recurrence group [(31.34±10.55) U/L, (27.45±9.10) U/L, (21.52±6.56) μg/L, (5.10±1.09) lg IU/mL, (5.07±1.08) lg IU/mL, (2.11±0.43) lg IU/mL, (18.67±4.39) μg/L, (1.98±0.40) lg copies /mL], and the difference was statistically significant (P<0.05). ROC curve analysis showed that the area under the curve (AUC) of serum HBV-LP, HBV RNA, and their combination for predicting recurrence after drug withdrawal in CHB patients were 0.840, 0.852, and 0.901, respectively. ALT≥55.87 U/L (OR=2.421), HBcrAg≥6.33 lg IU/mL (OR=2.787), HBV DNA≥2.88 lg IU/mL (OR=1.900), HBV-LP ≥ 30.56 μg/L (OR=2.239), and HBV RNA ≥ 3.09 lg copies/mL (OR=3.557) were all risk factors for recurrence after drug withdrawal in CHB patients (P<0.05). Conclusion Abnormal elevation of serum HBV-LP and HBV RNA are closely related to recurrence after drug withdrawal in CHB patients treated with long-acting interferon, and both can effectively predict recurrence after drug withdrawal. Moreover, their combination has a higher predictive value.

Key words: Chronic hepatitis B, Hepatitis B virus large protein, Hepatitis B virus ribonucleic acid, Recurrence, Predictive value

CHEN Chong, ZHANG Min-min. The predictive value of serum HBV-LP combined with HBV RNA for recurrence after discontinuation of long-acting interferon in the treatment of chronic hepatitis B[J]. Chinese Hepatolgy, 2025, 30(11): 1515-1520.

References

[1] Shen Y, Wu S D, Chen Y, et al. Alterations in gut microbiome and metabolomics in chronic hepatitis B infection-associated liver disease and their impact on peripheral immune response[J]. Gut Microbes,2023,15(1):2155018.
[2] Guan G, Zhang T, Ning J, et al. Higher TP53BP2 expression is associated with HBsAg loss in peginterferon-α-treated patients with chronic hepatitis B[J]. J Hepatol,2024,80(1):41-52.
[3] 安萍,卞丽. 长效干扰素对HBeAg阳性CHB患者肝功能指标及QLS-CHB评分的影响[J]. 中国现代药物应用,2023,17(15):94-97.
[4] 谭敏. 长效IFN治疗慢性乙肝获临床治愈后维持应答的影响因素[D]. 长沙:中南大学,2023.
[5] 潘家莉,罗皓,张霞霞,等. 血清乙型肝炎病毒前基因组RNA在慢性乙型肝炎患者长期抗病毒治疗中的变化特点[J]. 中华肝脏病杂志,2024,32(1):16-21.
[6] 林海霞,刘颖,林璐,等. 慢性乙型肝炎患者血清HBV-LP、PreS1、HMGB1水平与HBV-DNA水平的相关性[J]. 中国民康医学,2022,34(19):105-107.
[7] 吴宝灵,徐龙,余海滨,等. 血清HBsAg、HBV RNA水平对慢性乙型肝炎患者核苷(酸)类药物治疗停药预测的价值[J]. 实用临床医学,2023,32(5):1-4.
[8] 中华医学会感染病学分会,中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J/CD]. 中国肝脏病杂志(电子版),2019,11(4):527.
[9] 周芳,王永平,欧阳宇. HBV pgRNA联合HBcrAg对慢性乙型肝炎患者停药后复发的预测价值[J]. 中国肝脏病杂志(电子版),2024,16(2):42-47.
[10] 张诗琬,陈星,刘娇,等. 慢性乙型肝炎患者停用核苷(酸)类似物后循环血清中HBV pgRNA、HBcrAg表达水平与复发的相关性分析[J]. 临床肝胆病杂志, 2023, 39 (01): 56-62.
[11] 单姗,贾继东. 中国慢性乙型肝炎治疗的进展与挑战[J]. 临床肝胆病杂志,2025, 41(2): 205-209.
[12] 苗亮,贾春辉,陈寒冬,等. 恩替卡韦治疗慢性乙型肝炎获得病毒学应答后肝纤维化逆转影响因素研究[J]. 临床军医杂志,2024,52(2):176-179.
[13] 王燕腾,李红,李贝贝,等. 长效干扰素治疗慢性乙型肝炎病毒感染者的疗效分析[J]. 山西医药杂志, 2023,52(8):563-569.
[14] 吴倩君,吴迪,韩梅芳. 预测慢性乙型肝炎停药后复发的血清学标志物研究进展[J]. 医学综述, 2023, 29(14):2794-2800.
[15] 刘爱云,于欣,马苏琳. Pre-S1 Ag、Pre-S2 Ag及HBV-LP在乙肝病毒检测中的性能比较[J]. 菏泽医学专科学校学报, 2020, 32 (02): 23-25+31.
[16] 王世全,朱康宁,张琦. 慢性乙肝患者血清HBV-LP和Pre S1-Ag与病毒复制状态的相关性[J]. 江苏预防医学,2021,32(2):157-159,166.
[17] 蒋石艳,左丽,陈美利,等. 血清HBV-LP联合PRKRA对HBV相关原发性肝癌术后复发风险的预测价值[J]. 青岛大学学报(医学版),2024,60(3):407-411.
[18] 李艳芳,杨雪梅,罗萍,等. 乙型病毒性肝炎患者血清HBV-LP与HBV-DNA水平表达的相关性及临床意义[J]. 现代生物医学进展,2020,020(2):353-356,369.
[19] 王庆果,石文斐,乔楠. Pre-S1Ag、Pre-S2Ag及HBV-LP在乙肝病毒检测中的性能[J]. 滨州医学院学报,2023,46(3):193-196.
[20] 生卡玛丽娅·依里哈木. HBV-RNA、HBcrAg检测在CHB患者抗病毒治疗中的意义[D]. 新疆:新疆医科大学,2024.
[21] 孙华宝,李美琦,赖启南,等. 血清HBV RNA定量检测在慢性乙肝患者抗病毒治疗中临床研究[J]. 实验与检验医学,2022,40(3):306-309.
[22] Wu L, Yang Z, Zheng M. Biogenesis of serum HBV RNA and clinical phenomena of serum HBV RNA in chronic hepatitis B patients before and after receiving nucleos(t)ide analogues therapy[J]. J Viral Hepat,2024,31(5):255-265.
[23] Mak L Y, Huang Q, Wong D K, et al. Residual HBV DNA and pgRNA viraemia is associated with hepatocellular carcinoma in chronic hepatitis B patients on antiviral therapy[J]. J Gastroenterol, 2021,56(5):479-488.
[24] Testoni B, Scholtès C, Plissonnier M L, et al. Quantification of circulating HBV RNA expressed from intrahepatic cccDNA in untreated and NUC treated patients with chronic hepatitis B[J]. Gut, 2024, 73(4):659-667.
[25] Wang Y, Liu Y, Liao H, et al. Serum HBV DNA plus RNA reflecting cccDNA level before and during NAs treatment in HBeAg positive CHB patients[J]. Int J Med Sci, 2022,19(5):858-866.