Risk Factors Related to Low-level Viraemia in Chronic Hepatitis B Patients Receiving Entecavir Treatment

Overview

Journal Front Cell Infect Microbiol

Specialties Cell Biology
Infectious Diseases
Microbiology

Date 2024 Aug 22

PMID 39170987

Authors

Zhong-Bin Li

Dan-Dan Chen

Yun-Fei Jia

Qing-Juan He

Li Cui

Feng-Xia Du

Yao-Jie Kang

Xin Feng

Mengwen He

Xue-Yuan Jin

Jing Chen

Yudong Wang

Dong Ji

George Lau

Shu-Gao Wu

Affiliations

Soon will be listed here.

Abstract

Background: About 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent low-grade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV.

Methods: In this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed.

Results: Totally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, < 0.001), HBV DNA ≥ 6.0 Log IU/mL (OR = 1.370, 95% CI: 1.054-1.780, = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, = 0.002), and PLT < 100×10/L (OR = 1.450, 95% CI: 1.094-1.922, = 0.010) at baseline were related to the development of LLV.

Conclusions: High HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment.

References

Li J, Dong X, Cao L, Zhang Z, Zhao W, Shang Q . Factors associated with persistent positive in HBV DNA level in patients with chronic Hepatitis B receiving entecavir treatment. Front Cell Infect Microbiol. 2023; 13:1151899. PMC: 10311917. DOI: 10.3389/fcimb.2023.1151899. View

Wong G, Wong V, Chan H, Tse P, Wong J, Chim A . Undetectable HBV DNA at month 12 of entecavir treatment predicts maintained viral suppression and HBeAg-seroconversion in chronic hepatitis B patients at 3 years. Aliment Pharmacol Ther. 2012; 35(11):1326-35. DOI: 10.1111/j.1365-2036.2012.05098.x. View

Li Z, Li L, Niu X, Chen S, Fu Y, Wang C . Switching from entecavir to tenofovir alafenamide for chronic hepatitis B patients with low-level viraemia. Liver Int. 2021; 41(6):1254-1264. DOI: 10.1111/liv.14786. View

Zhang Q, Cai D, Hu P, Ren H . Low-level viremia in nucleoside analog-treated chronic hepatitis B patients. Chin Med J (Engl). 2021; 134(23):2810-2817. PMC: 8668013. DOI: 10.1097/CM9.0000000000001793. View

. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016; 64(6):1388-402. DOI: 10.1016/j.jhep.2015.11.004. View

. EASL Clinical Practice Guidelines: Drug-induced liver injury. J Hepatol. 2019; 70(6):1222-1261. DOI: 10.1016/j.jhep.2019.02.014. View

Kim M, Kim S, Kim B, Park J, Kim D, Ahn S . Increased risk of hepatocellular carcinoma in chronic hepatitis B patients with transient elastography-defined subclinical cirrhosis. Hepatology. 2015; 61(6):1851-9. DOI: 10.1002/hep.27735. View

Kim T, Sinn D, Kang W, Gwak G, Paik Y, Choi M . Hepatitis B virus DNA levels and overall survival in hepatitis B-related hepatocellular carcinoma patients with low-level viremia. J Gastroenterol Hepatol. 2019; 34(11):2028-2035. DOI: 10.1111/jgh.14750. View

Huang D, Li X, Le M, Le A, Yeo Y, Trinh H . Natural History and Hepatocellular Carcinoma Risk in Untreated Chronic Hepatitis B Patients With Indeterminate Phase. Clin Gastroenterol Hepatol. 2021; 20(8):1803-1812.e5. DOI: 10.1016/j.cgh.2021.01.019. View

10.

Hou J, Zhao W, Lee C, Hann H, Peng C, Tanwandee T . Outcomes of Long-term Treatment of Chronic HBV Infection With Entecavir or Other Agents From a Randomized Trial in 24 Countries. Clin Gastroenterol Hepatol. 2019; 18(2):457-467.e21. DOI: 10.1016/j.cgh.2019.07.010. View

11.

Chen H, Fu J, Li L, Wang X, Pan X . Risk factors of low-level viremia in chronic hepatitis B patients receiving Entecavir monotherapy: a retrospective cohort study. J Gastroenterol Hepatol. 2023; 39(1):180-184. DOI: 10.1111/jgh.16357. View

12.

Yuen M, Seto W, Fung J, Wong D, Yuen J, Lai C . Three years of continuous entecavir therapy in treatment-naïve chronic hepatitis B patients: VIRAL suppression, viral resistance, and clinical safety. Am J Gastroenterol. 2011; 106(7):1264-71. DOI: 10.1038/ajg.2011.45. View

13.

Ji D, Chen Y, Bi J, Shang Q, Liu H, Wang J . Entecavir plus Biejia-Ruangan compound reduces the risk of hepatocellular carcinoma in Chinese patients with chronic hepatitis B. J Hepatol. 2022; 77(6):1515-1524. DOI: 10.1016/j.jhep.2022.07.018. View

14.

Sun Y, Wu X, Zhou J, Meng T, Wang B, Chen S . Persistent Low Level of Hepatitis B Virus Promotes Fibrosis Progression During Therapy. Clin Gastroenterol Hepatol. 2020; 18(11):2582-2591.e6. DOI: 10.1016/j.cgh.2020.03.001. View

15.

. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2011; 35 Suppl 1:S64-71. PMC: 3632174. DOI: 10.2337/dc12-s064. View

16.

Wang W, Jia R, Jin X, Li X, Zhou S, Zhang X . Serum cytokine change profile associated with HBsAg loss during combination therapy with PEG-IFN-α in NAs-suppressed chronic hepatitis B patients. Front Immunol. 2023; 14:1121778. PMC: 9899895. DOI: 10.3389/fimmu.2023.1121778. View

17.

Kim H, Cho Y, Jeon W, Kim B . Clinical characteristics of patients with chronic hepatitis B who developed genotypic resistance to entecavir: Real-life experience. Clin Mol Hepatol. 2017; 23(4):323-330. PMC: 5760008. DOI: 10.3350/cmh.2017.0005. View

18.

Uchida Y, Nakao M, Tsuji S, Uemura H, Kouyama J, Naiki K . Significance of switching of the nucleos(t)ide analog used to treat Japanese patients with chronic hepatitis B virus infection from entecavir to tenofovir alafenamide fumarate. J Med Virol. 2019; 92(3):329-338. DOI: 10.1002/jmv.25644. View

19.

Verbiest M, Brakema E, van der Kleij R, Sheals K, Allistone G, Williams S . National guidelines for smoking cessation in primary care: a literature review and evidence analysis. NPJ Prim Care Respir Med. 2017; 27(1):2. PMC: 5434788. DOI: 10.1038/s41533-016-0004-8. View

20.

Lok A, Trinh H, Carosi G, Akarca U, Gadano A, Habersetzer F . Efficacy of entecavir with or without tenofovir disoproxil fumarate for nucleos(t)ide-naïve patients with chronic hepatitis B. Gastroenterology. 2012; 143(3):619-628.e1. DOI: 10.1053/j.gastro.2012.05.037. View