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New therapeutic options for persistent low-level viremia in patients with chronic hepatitis B virus infection: Increase of entecavir dosage
Guo-Qing Yin 1 , Jun Li 2 , Bei Zhong 3 , Yong-Fong Yang 4 , Mao-Rong Wang 5
Affiliations
Affiliations
1
Department of Infectious Diseases, Nanjing Zhong-Da Hospital, Southeast University School of Medicine, Nanjing 210009, Jiangsu Province, China. [email protected].
2
Department of Infectious Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
3
The Sixth Affiliated Hospital, Guangzhou Medical University/Qingyuan People's Hospital, Qingyuan 511518, Guangdong Province, China.
4
Department of Liver Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China.
5
Department of Infectious Diseases and Liver Disease Center, The Affiliated Nanjing Jinling Hospital, Nanjing University, Nanjing 210002, Jiangsu Province, China.
PMID: 33716446 PMCID: PMC7934007 DOI: 10.3748/wjg.v27.i8.666
Abstract
Chronic hepatitis B virus (HBV) infection (CHB) is a public health concern worldwide. Current therapies utilizing nucleos(t)ide analogs (NA) have not resulted in a complete cure for CHB. Furthermore, patients on long-term NA treatment often develop low-level viremia (LLV). Persistent LLV, in addition to causing the progression of liver disease or hepatocellular carcinoma, may shed light on the current plight of NA therapy. Here, we review the literature on LLV, NA treatment, and various doses of entecavir to find a strategy for improving the efficacy of this antiviral agent. For LLV patients, three therapeutic options are available, switching to another antiviral monotherapy, interferon-α switching therapy, and continuing monotherapy. In real-world clinical practice, entecavir overdose has been used in antiviral therapy for CHB patients with NA refractory and persistent LLV, which encouraged us to conduct further in-depth literature survey on dosage and duration related entecavir studies. The studies of pharmacodynamics and pharmacokinetics show that entecavir has the maximal selected index for safety, and has great potential in inhibiting HBV replication, in all of the NAs. In the particular section of the drug approval package published by the United States Food and Drug Administration, entecavir doses 2.5-20 mg/d do not increase adverse events, and entecavir doses higher than 1.0 mg/d might improve the antiviral efficacy. The literature survey led us to two suggestions: (1) Increasing entecavir dose to 1.0 mg/d for the treatment of NA naïve patients with HBV DNA >2 × 106 IU/mL is feasible and would provide better prognosis; and (2) Further research is needed to assess the long-term toxic effects of higher entecavir doses (2.5 and 5.0 mg/d), which may prove beneficial in treating patients with prior NA treatment, partial virological response, or LLV state.
Keywords: Chronic hepatitis B virus infection; Dose; Efficacy; Entecavir; Low-level viremia; Therapeutic options.
©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved. |
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发表于 2021-3-16 20:00