ISSN: 1859 - 2872
Correlation between plasma HBV-RNA and HBcrAg levels in chronic Hepatitis B patients treated with Tenofovir disoproxil fumarate
Main Article Content
Keywords
Chronic hepatits B, HBV-RNA, HBV-DNA, HBcrAg
Abstract
Objective: To evaluate the correlation between plasma HBV-RNA and HBcrAg levels in CHB patients receiving tenofovir disoproxil fumarate. Subject and method: Fifty-six CHB patients undergoing NA therapy were enrolled. Plasma HBV-RNA levels were quantified using real-time RT-PCR (limit of detection [LOD]: 2 log₁₀ copies/mL), and HBcrAg levels were measured by chemiluminescent enzyme immunoassay (LOD: 3 log₁₀ U/mL). Statistical analyses were performed using MedCalc version 23.1.5. Result: Plasma HBV-RNA and HBcrAg levels were significantly higher in HBeAg-positive patients compared with HBeAg-negative ones (median 3.74 vs. 2.83 log₁₀ copies/mL; 6.95 vs. 3.28 log₁₀ U/mL; p<0.05). A moderate positive correlation was observed between HBV-RNA and HBcrAg (rs = 0.71; p<0.0001), which was stronger among patients with HBeAg positivity (rs = 0,71 vs. 0,54), high HBsAg levels (≥ 1000U/mL) (rs = 0,74 vs. 0,68), or undetectable plasma HBV-DNA (rs = 0,73 vs. 0,67). Conclusion: Plasma HBV-RNA and HBcrAg are valuable biomarkers for assessing viral transcriptional activity, particularly in patients with undetectable HBV-DNA, and hold potential as routine indicators for treatment monitoring and management of chronic hepatitis B.
Article Details
References
1. Kranidioti H, Manolakopoulos S, Khakoo SI (2015) Outcome after discontinuation of nucleot (s) ide analogues in chronic hepatitis B: relapse rate and associated factors. Annals of gastroenterology: quarterly publication of the Hellenic Society of Gastroenterology 28(2): 173.
2. Huang ZH, Lu GY, Qiu LX, et al (2022) Risk of hepatocellular carcinoma in antiviral treatment-naïve chronic hepatitis B patients treated with entecavir or tenofovir disoproxil fumarate: A network meta-analysis. BMC cancer 22(1): 287.
3. Sheena BS, Hiebert L, Han H et al (2022) Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet Gastroenterology & Hepatology 7(9): 796-829.
4. Alberts CJ, Clifford GM, Georges D et al Worldwide prevalence of hepatitis B virus and hepatitis C virus among patients with cirrhosis at country, region, and global levels: A systematic review. The Lancet Gastroenterology & Hepatology.
5. Lampertico P, Agarwal K, Berg T et al (2017) EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. Journal of hepatology 67(2): 370-398.
6. Viganò M, Puoti M, Lampertico P (2016) Nucleos (t) ide Analogue Based Therapy and Management of Patients. Hepatitis B Virus in Human Diseases. Springer: 339-359.
7. Xia Y, Guo H (2020) Hepatitis B virus cccDNA: Formation, regulation and therapeutic potential. Antiviral research 180: 104824.
8. Jeng WJ, Sheen IS, Chen YC et al (2013) Off‐therapy durability of response to entecavir therapy in hepatitis B e antigen‐negative chronic hepatitis B patients. Hepatology 58(6): 1888-1896.
9. Qiu Yw, Huang Lh, Yang W et al (2016) Hepatitis B surface antigen quantification at hepatitis B e antigen seroconversion predicts virological relapse after the cessation of entecavir treatment in hepatitis B e antigen-positive patients. International Journal of Infectious Diseases 43: 43-48.
10. Zhao L, Chen F, Quitt , et al (2021) Hepatitis B virus envelope proteins can serve as therapeutic targets embedded in the host cell plasma membrane. Cellular Microbiology 23(12): 13399.
11. Adraneda C, Tan YC, Yeo EJ, Kew GS, Khakpoor A, Lim SG (2022) A critique and systematic review of the clinical utility of hepatitis B core-related antigen. Journal of Hepatology. 2022;
12. Nguyen UD, Le Do Q, Vu QAN et al (2023) Selective detection of HBV pre-genomic RNA in chronic hepatitis B patients using a novel RT-PCR assay. Clinical and Experimental Medicine 2023: 1-9.
13. Thompson AJ, Jackson K, Bonanzinga S et al (2023) Baseline serum HBV RNA is associated with the risk of hepatitis flare after stopping nucleoside analog therapy in HBeAg-negative participants. Hepatology Communications. 7(8).
14. Đặng Thị Bích, Vũ Thị Thu Hương, Nguyễn Thị Vân Hà, và cộng sự (2025) Sự thay đổi nồng độ HBcrAg trong quá trình điều trị viêm gan B mạn tính bằng thuốc nucleot(s)ide và mối tương quan với các dấu ấn sinh học. Tạp chí Y học Việt Nam 549(1)doi:10.51298/vmj.v549i1.13538.
15. Phạm Thị Thùy, Nguyễn Thị Vân Hồng (2023) Khảo sát sự thay đổi của HBcrAg trên bệnh nhân viêm gan B mạn trước và sau điều trị tenofovir disoproxil fumarate 300mg. Tạp chí Y học Việt Nam 521(1). doi:10.51298/vmj.v521i1.3994
16. Mak L-Y, Wong D, Kuchta A et al (2022) Hepatitis B virus pre-genomic RNA and hepatitis B core-related antigen reductions at week 4 predict favourable hepatitis B surface antigen response upon long-term nucleos (t) ide analogue in chronic hepatitis B. Clinical and Molecular Hepatology 29(1): 146.
17. Chen EQ, Wang ML, Tao YC et al (2019) Serum HB crAg is better than HBV RNA and HB sAg in reflecting intrahepatic covalently closed circular DNA. Journal of viral hepatitis 26(5): 586-595.
18. Mak LY, Cloherty G, Wong DKH et al (2021) HBV RNA profiles in patients with chronic hepatitis B under different disease phases and antiviral therapy. Hepatology 73(6): 2167-2179.
19. Liao H, Liu Y, Li X et al (2019) Monitoring of serum HBV RNA, HBcrAg, HBsAg and anti-HBc levels in patients during long-term nucleoside/nucleotide analogue therapy. Antiviral therapy 24(2): 105-115.
20. Wang C-R, Liu X-q, Shen W et al (2024) Profiles of HBcrAg and pgRNA in pregnant women with chronic HBV under different disease phases and antiviral prophylaxis. Oxford University Press US 2024:ofae241.
21. Lai X, OuYang W, Li S et al (2024) Predictive role of early treatment dynamics of HBV RNA and HBcrAg for HBeAg seroconversion in children with chronic hepatitis B. Journal of Medical Virology 96(5): 29670.
2. Huang ZH, Lu GY, Qiu LX, et al (2022) Risk of hepatocellular carcinoma in antiviral treatment-naïve chronic hepatitis B patients treated with entecavir or tenofovir disoproxil fumarate: A network meta-analysis. BMC cancer 22(1): 287.
3. Sheena BS, Hiebert L, Han H et al (2022) Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet Gastroenterology & Hepatology 7(9): 796-829.
4. Alberts CJ, Clifford GM, Georges D et al Worldwide prevalence of hepatitis B virus and hepatitis C virus among patients with cirrhosis at country, region, and global levels: A systematic review. The Lancet Gastroenterology & Hepatology.
5. Lampertico P, Agarwal K, Berg T et al (2017) EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. Journal of hepatology 67(2): 370-398.
6. Viganò M, Puoti M, Lampertico P (2016) Nucleos (t) ide Analogue Based Therapy and Management of Patients. Hepatitis B Virus in Human Diseases. Springer: 339-359.
7. Xia Y, Guo H (2020) Hepatitis B virus cccDNA: Formation, regulation and therapeutic potential. Antiviral research 180: 104824.
8. Jeng WJ, Sheen IS, Chen YC et al (2013) Off‐therapy durability of response to entecavir therapy in hepatitis B e antigen‐negative chronic hepatitis B patients. Hepatology 58(6): 1888-1896.
9. Qiu Yw, Huang Lh, Yang W et al (2016) Hepatitis B surface antigen quantification at hepatitis B e antigen seroconversion predicts virological relapse after the cessation of entecavir treatment in hepatitis B e antigen-positive patients. International Journal of Infectious Diseases 43: 43-48.
10. Zhao L, Chen F, Quitt , et al (2021) Hepatitis B virus envelope proteins can serve as therapeutic targets embedded in the host cell plasma membrane. Cellular Microbiology 23(12): 13399.
11. Adraneda C, Tan YC, Yeo EJ, Kew GS, Khakpoor A, Lim SG (2022) A critique and systematic review of the clinical utility of hepatitis B core-related antigen. Journal of Hepatology. 2022;
12. Nguyen UD, Le Do Q, Vu QAN et al (2023) Selective detection of HBV pre-genomic RNA in chronic hepatitis B patients using a novel RT-PCR assay. Clinical and Experimental Medicine 2023: 1-9.
13. Thompson AJ, Jackson K, Bonanzinga S et al (2023) Baseline serum HBV RNA is associated with the risk of hepatitis flare after stopping nucleoside analog therapy in HBeAg-negative participants. Hepatology Communications. 7(8).
14. Đặng Thị Bích, Vũ Thị Thu Hương, Nguyễn Thị Vân Hà, và cộng sự (2025) Sự thay đổi nồng độ HBcrAg trong quá trình điều trị viêm gan B mạn tính bằng thuốc nucleot(s)ide và mối tương quan với các dấu ấn sinh học. Tạp chí Y học Việt Nam 549(1)doi:10.51298/vmj.v549i1.13538.
15. Phạm Thị Thùy, Nguyễn Thị Vân Hồng (2023) Khảo sát sự thay đổi của HBcrAg trên bệnh nhân viêm gan B mạn trước và sau điều trị tenofovir disoproxil fumarate 300mg. Tạp chí Y học Việt Nam 521(1). doi:10.51298/vmj.v521i1.3994
16. Mak L-Y, Wong D, Kuchta A et al (2022) Hepatitis B virus pre-genomic RNA and hepatitis B core-related antigen reductions at week 4 predict favourable hepatitis B surface antigen response upon long-term nucleos (t) ide analogue in chronic hepatitis B. Clinical and Molecular Hepatology 29(1): 146.
17. Chen EQ, Wang ML, Tao YC et al (2019) Serum HB crAg is better than HBV RNA and HB sAg in reflecting intrahepatic covalently closed circular DNA. Journal of viral hepatitis 26(5): 586-595.
18. Mak LY, Cloherty G, Wong DKH et al (2021) HBV RNA profiles in patients with chronic hepatitis B under different disease phases and antiviral therapy. Hepatology 73(6): 2167-2179.
19. Liao H, Liu Y, Li X et al (2019) Monitoring of serum HBV RNA, HBcrAg, HBsAg and anti-HBc levels in patients during long-term nucleoside/nucleotide analogue therapy. Antiviral therapy 24(2): 105-115.
20. Wang C-R, Liu X-q, Shen W et al (2024) Profiles of HBcrAg and pgRNA in pregnant women with chronic HBV under different disease phases and antiviral prophylaxis. Oxford University Press US 2024:ofae241.
21. Lai X, OuYang W, Li S et al (2024) Predictive role of early treatment dynamics of HBV RNA and HBcrAg for HBeAg seroconversion in children with chronic hepatitis B. Journal of Medical Virology 96(5): 29670.
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Published
Mar 12, 2026
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How to Cite
ỨngN. Đình, HoàngN. H., & ThọH. H. (2026). Correlation between plasma HBV-RNA and HBcrAg levels in chronic Hepatitis B patients treated with Tenofovir disoproxil fumarate. Tạp Chí Y Dược lâm sàng 108, 21(2). https://doi.org/10.52389/ydls.v21i2.2957