A significant number of patients with hepatitis B virus (HBV) infection who discontinue nucleotide analog use after an extended treatment period experience a grade 3 or higher laboratory abnormality, according to results published in The Lancet Gastroenterology & Hepatology. The results also indicated that some people who are negative for hepatitis B e antigen (HBeAg) can achieve a low-replicative state.
This study included data on participants from 2 completed randomized controlled studies: GS-US-174-0102 (ClinicalTrials.gov identifier: NCT00117676) and GS-US-174-0103 (ClinicalTrials.gov identifier: NCT00116805). In both studies, participants who had completed ≥8 years of nucleotide analog treatment, were positive for hepatitis B surface antigen (HBsAg) with HBV DNA concentration of <29 IU/mL, and were unwilling/unable to continue treatment were required to participate in a 24-week treatment-free follow-up (TFFU) phase.
This study includes data on participants in the TFFU phase. Participants were assessed at baseline and every 4 weeks for changes in qualitative serum HBsAg, HBV DNA, and alanine aminotransferase (ALT) concentrations.
A total of 124 participants started the TFFU phase, but 44% (n=54) did not complete 24 weeks of follow-up.
During the TFFU phase, 26% (n=32) of participants reported an adverse event (AE), with 4% (n=5) reporting serious AEs. The serious AEs included elevated ALT concentrations in 2 participants, hepatic flare in 2 participants, and increased lipase level in 1 participant.
The researchers found that 31% (n=38) of participants had grade 3 or higher laboratory abnormalities, most of which were ALT elevations (n=36).
Of 106 participants who were negative for HBeAg in the TFFU phase, 59% (n=63) completed 24 weeks of follow-up. The researchers observed HBsAg loss in 5% (n=5) of the HBeAg participants. In addition, 35% (n=37) had both HBV DNA concentrations of <2000 IU/mL and ALT concentrations less than the upper limit of normal at week 24.
Of 18 participants who were positive for HBeAg who entered the TFFU phase, 7 (n=39%) completed 24 weeks of follow-up. Of these, none had HBsAg loss or HBV DNA <2000 IU/mL; 1 participant had an ALT less than the upper limit of normal at week 24.
“More data are required to predict which patients might benefit from [nucleotide analog withdrawal], and alternative cure strategies might be needed before finite therapeutic options become a reality for more patients with chronic hepatitis B,” wrote the researchers.
Disclosures: This study was sponsored by Gilead Sciences, Inc. The sponsor collected the data, monitored the study conduct, and performed the statistical analyses. Multiple authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.
Buti M, Wong DK, Gane E, et al. Safety and efficacy of stopping tenofovir disoproxil fumarate in patients with chronic hepatitis B following at least 8 years of therapy: a prespecified follow-up analysis of two randomised trials. Lancet Gastroenterol Hepatol. 2019;4(4):296-304.