Effectiveness of tenofovir alafenamide for chronic hepatitis B patients with a poor response to the previously used nucleos(t)ide analogs.

Abstract

BACKGROUND:

Few studies have demonstrated the potency of tenofovir alafenamide (TAF) in patients with poor response to other nucleos(t)ide analogs (NAs).

METHODS:

We conducted a retrospective study comprising consecutive 40 patients exhibiting a poor response to other NAs, who subsequently received TAF-containing regimens. The primary outcome was the prevalence of virological response (VR) at each time and maintained virological response (MVR) under TAF-containing regimens until week 96.

RESULTS:

In the entire cohort, the prevalence of MVR was 71.1% (27/38). Further, poor tenofovir disoproxil fumarate (TDF) response was significantly associated with a lower prevalence of MVR (p = 0.014). In TDF-naïve patients, the prevalence of MVR was 92.3% (12/13) and 62.5% (5/8) in patients with lamivudine resistance (LAM-r) and entecavir resistance (ETV-r), respectively. Further, viral load and HBeAg status at baseline were associated with a lower prevalence of MVR (p = 0.013). Among the seven patients with prior TDF exposure, 2 patients achieved MVR. Among them, one patient with development of viral breakthrough during TDF/LAM achieved MVR after switching to TAF/ETV. In contrast, one of the five patients with non-MVR had three substitutions (rtS106C, rtD134N/S, and rtL269I) of quadruple mutations in addition to ETV-r. Other patients with rtA181T + rtN236T also could not achieve MVR.

CONCLUSION:

TAF exhibited high antiviral potency in patients with LAM-r and ETV-r. However, TAF potency was associated with previous TDF response, viral load, and HBeAg status at baseline. Additionally, a quadruple mutation may impact tenofovir resistance; however, further studies are needed to verify this.

• Authors: Daiki Yamashige, Tetsuya Hosaka, Fumitaka Suzuki, Shunichiro Fujiyama, Yusuke Kawamura, Hitomi Sezaki, Norio Akuta, Masahiro Kobayashi, Yoshiyuki Suzuki, Satoshi Saitoh, Yasuji Arase, Kenji Ikeda, Mariko Kobayashi, Hiromitsu Kumada
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 56 Issue 11 Pg. 1008-1021 (11 2021) ISSN: 1435-5922 [Electronic] Japan
• PMID: 34596753 (Publication Type: Journal Article, Observational Study)
• Copyright: © 2021. Japanese Society of Gastroenterology.

Chemical References

• Nucleosides
• Tenofovir

Topics

• Aged
• Cohort Studies
• Female
• Hepatitis B, Chronic (drug therapy)
• Humans
• Male
• Microbial Sensitivity Tests (methods, statistics & numerical data)
• Middle Aged
• Nucleosides (therapeutic use)
• Retrospective Studies
• Tenofovir (administration & dosage, pharmacology)
• Treatment Outcome