Predictive value of serum HBV RNA on relapse in patients with chronic hepatitis B after withdrawal of antiviral therapy: a meta-analysis

Abstract

Abstract: Objective To investigate the predictive value of serum hepatitis B virus (HBV) RNA on relapse in patients with chronic hepatitis B (CHB) after withdrawal of antiviral therapy, and to screen a new biomarker for safely drug withdrawl.Methods PubMed, Embase, Web of science, Cochrane library and https://clinicaltrials.gov/ were used to search for relevant English articles published from 2016-2020. Manual searching was also conducted. The articles were screened according to the inclusion and exclusion criteria. Data extraction and quality assessment were also performed in the involved articles. Revman 5.3 software was used for meta-analysis.Results Compared with HBV RNA-negative patients, serum HBV RNA-positive patients had a higher risk of clinical relapse after drug withdrawal (RR=2.98, 95%CI=1.55~5.72, P=0.001).Conclusion Serum HBV RNA is an important assistant biomarker for predicting clinical relapse after drug withdrawal in patients with CHB. And the predicting value of serum HBV RNA on HBV recurrence after drug withdrawl deserves further investigation.

Key words: Chronic hepatitis B, Serum hepatits B virus RNA, Pregenomic RNA, Meta-analysis

ZHANG Qi, WANG Yu-yan, QIN Bo. Predictive value of serum HBV RNA on relapse in patients with chronic hepatitis B after withdrawal of antiviral therapy: a meta-analysis[J]. Chinese Hepatolgy, 2022, 27(6): 647-651.

References

[1] WHO. Global hepatitis report 2017. Geneva. (2019-04-04) [cited 2021.09.04]. Available from: https://www.who.int/hepatitis/publications/global hepatitis report 2017/en/.
[2] Nassal M. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut, 2015, 64(12):1972-1984.
[3] Mak LY, Seto WK, Fung J, et al. Novel developments of hepatitis B: treatment goals, agents and monitoring tools. Expert Rev Clin Pharmacol, 2019, 12(2):109-120.
[4] Chinese Society of Infectious Disease Chinese Society of Hepatology; Chinese Medical Association. The expert consensus on clinical cure (functional cure) of chronic hepatitis B. Zhonghua Gan Zang Bing Za Zhi, 2019, 27(8):594-603.
[5] European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol, 2017, 67(2):370-398.
[6] Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology, 2018, 67(4):1560-1599.
[7] Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. The guidelines of prevention and treatment for chronic hepatitis B (2019 version). Zhonghua Gan Zang Bing Za Zhi, 2019, 27(12):938-961.
[8] Liu S, Zhou B, Valdes JD, et al. Serum Hepatitis B Virus RNA: A New Potential Biomarker for Chronic Hepatitis B Virus Infection. Hepatology, 2019, 69(4):1816-1827.
[9] Bai L, Zhang X, Kozlowski M, et al. Extracellular Hepatitis B Virus RNAs Are Heterogeneous in Length and Circulate as Capsid-Antibody Complexes in Addition to Virions in Chronic Hepatitis B Patients. J Virol, 2018, 92(24):e00798-18.
[10] Prakash K, Rydell GE, Larsson SB, et al. High serum levels of pregenomic RNA reflect frequently failing reverse transcription in hepatitis B virus particles. Virol J, 2018, 15(1):86.
[11] Jansen L, Kootstra NA, van Dort KA, et al. Hepatitis B Virus Pregenomic RNA Is Present in Virions in Plasma and Is Associated With a Response to Pegylated Interferon Alfa-2a and Nucleos(t)ide Analogues. J Infect Dis, 2016, 213(2):224-232.
[12] Giersch K, Allweiss L, Volz T, et al. Serum HBV pgRNA as a clinical marker for cccDNA activity. J Hepatol, 2017, 66(2):460-462.
[13] Huang H, Wang J, Li W, et al. Serum HBV DNA plus RNA shows superiority in reflecting the activity of intrahepatic cccDNA in treatment-naÏve HBV-infected individuals. J Clin Virol, 2018, 99-100:71-78.
[14] Gao Y, LiY, Meng Q, et al. Serum Hepatitis B Virus DNA, RNA, and HBsAg: Which Correlated Better with Intrahepatic Covalently Closed Circular DNA before and after Nucleos(t)ide Analogue Treatment? J Clinical Microb, 2017, 55(10): 2972-2982.
[15] Wang J, Shen T, Huang X, et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound. J Hepatol, 2016, 65(4):700-710.
[16] Carey I, Gersch J, Wang B, et al. Pregenomic HBV RNA and Hepatitis B Core-Related Antigen Predict Outcomes in Hepatitis B e Antigen-Negative Chronic Hepatitis B Patients Suppressed on Nucleos(T)ide Analogue Therapy. Hepatology, 2020, 72(1):42-57.
[17] Fan R, Zhou B, Xu M, et al. Association Between Negative Results From Tests for HBV DNA and RNA and Durability of Response After Discontinuation of Nucles(t)ide Analogue Therapy. Clin Gastroenterol Hepatol, 2020, 18(3):719-727.e7.
[18] Alawad A, Gara N, Ball E, et al. The Role of HBV RNA Levels As a Predictor of Withdrawal Flares after Stopping Nucleoside Analogues in Patients with Chronic Hepatitis B. Hepatology (Baltimore, Md), 2018, 68:1228A-A.
[19] Wang J, Chen X, wu Y, et al. Serum HBV RNA is a potential predictor of hepatitis B surface antigen reversion. Hepatol Commull, 2018, 2(10): 1168-1171.
[20] Seto WK, Liu KS, Mak LY, et al. Role of serum HBV RNA and hepatitis B surface antigen levels in identifying Asian patients with chronic hepatitis B suitable for entecavir cessation. Gut, 2021, 70(4):775-783.
[21] Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9):603-605.