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Nucleos(t)ide Therapy and Long-Term Outcomes

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Hepatitis B Virus and Liver Disease

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Abstract

The goal of therapy for chronic hepatitis B is to decrease the risk of liver-related complications, including progression to cirrhosis, decompensated cirrhosis, hepatocellular carcinoma and death. Given that complete elimination of hepatitis B virus (HBV) from the host is not possible with currently available treatment owing to the persistence of covalently closed circular DNA and viral genome integration into host chromosomes inside hepatocyte, the primary target for treatment should be to suppress HBV replication and reduce serum HBV DNA at the lowest possible levels to achieve the goals. Currently, several approved nucleos(t)ide analogs (NUC) are available for treating chronic hepatitis B (CHB) in most countries: L-nucleosides (lamivudine and telbivudine); deoxyguanosine analog (entecavir); and acyclic nucleotide phosphonates (adefovir dipivoxil and tenofovir). These NUCs act primarily by inhibiting the reverse transcription of the pre-genomic HBV RNA to the first strand of HBV DNA. Most of the clinical practice guidelines recommend entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide as preferred first-line monotherapies due to their superior efficacy and high barrier to resistance over comparable drugs. NUCs are administered orally and have favorable safety profiles over the course of several years. Many data have consistently shown that long-term suppression of HBV DNA replication by NUCs leads to the improvement in hepatic inflammation and fibrosis, hepatic function, and survival of the patients, and reduction in the risk of hepatocellular carcinoma (HCC). However, it is still highly controversial regarding when is the optimal time to initiate the NUC treatment in the patients with CHB and which NUC is the best option to further reduce HCC risk.

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    Jonggi Choi & Young-Suk Lim

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    Jia-Horng Kao

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Choi, J., Lim, YS. (2021). Nucleos(t)ide Therapy and Long-Term Outcomes. In: Kao, JH. (eds) Hepatitis B Virus and Liver Disease. Springer, Singapore. https://doi.org/10.1007/978-981-16-3615-8_13

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