Abstract | BACKGROUND: Effective and well tolerated nucleos(t)ide analogue treatment exists for patients with chronic hepatitis B, although treatment is generally anticipated to be life-long, with concomitant costs and treatment-related side-effects. We aimed to characterise the outcomes of patients with persistent viral suppression who discontinued nucleotide analogue use after extended treatment. METHODS: The primary objective of this prespecified analysis was to evaluate the safety of stopping long-term tenofovir disoproxil fumarate therapy in patients enrolled in two (completed) randomised controlled studies, GS-US-174-0102 (ClinicalTrials.gov, number NCT00117676) and GS-US-174-0103 (ClinicalTrials.gov, number NCT00116805). In those studies, patients who had completed 8 years or more of nucleotide analogue treatment, were hepatitis B surface antigen ( HBsAg)-positive with hepatitis B virus (HBV) DNA concentration of less than 29 IU/mL, and were unwilling or unable to continue therapy were required by protocol to enter a 24-week treatment-free follow-up (TFFU) phase. We present data for patients in the TFFU phase who were assessed at baseline and monitored every 4 weeks for changes in qualitative serum HBsAg, HBV DNA, and alanine aminotransferase (ALT) concentrations in addition to standard safety assessments. FINDINGS: Of 124 patients who entered the TFFU phase, 54 (44%) patients did not complete 24 weeks of follow-up (median 12 weeks; IQR 0-20). Overall, 32 (26%) patients reported an adverse event. Serious adverse events occurred in five (4%) patients, including elevated ALT concentrations in two patients, hepatic flare in two patients, and increased lipase in one patient. 38 (31%) of patients had grade 3 or higher laboratory abnormalities, the majority of which were ALT elevations (36 patients). Of the 106 hepatitis B e antigen ( HBeAg)-negative patients who entered the TFFU phase, 63 (59%) were followed for 24 weeks. HBsAg loss was observed in five (5%) of the 106 HBeAg-negative patients who entered the TFFU phase, and 37 (35%) had both HBV DNA concentrations of less than 2000 IU/mL and ALT concentrations less than the ULN at TFFU week 24. 18 HBeAg-positive patients entered the TFFU phase, of whom seven (39%) were followed up for 24 weeks. Of these seven patients, none had HBsAg loss or HBV DNA of less than 2000 IU/mL and one (14%) had an ALT less than the ULN at week 24. INTERPRETATION: Within 24 weeks of stopping 8 years or more of nucleotide analogue therapy almost a third of patients experienced a grade 3 or higher laboratory abnormality. Although few patients achieved HBsAg loss, a subgroup of HBeAg-negative patients can achieve a low-replicative state within a short duration of follow-up. FUNDING: Gilead Sciences, Inc.
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Authors | Maria Buti, David K Wong, Edward Gane, Robert Flisiak, Michael Manns, Kelly Kaita, Harry L A Janssen, Marjoleine Op den Brouw, Belinda Jump, Kathryn Kitrinos, Gerald Crans, John Flaherty, Anuj Gaggar, Patrick Marcellin |
Journal | The lancet. Gastroenterology & hepatology
(Lancet Gastroenterol Hepatol)
Vol. 4
Issue 4
Pg. 296-304
(04 2019)
ISSN: 2468-1253 [Electronic] Netherlands |
PMID | 30795958
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2019 Elsevier Ltd. All rights reserved. |
Chemical References |
- DNA, Viral
- Hepatitis B Surface Antigens
- Hepatitis B e Antigens
- Nucleotides
- Reverse Transcriptase Inhibitors
- Tenofovir
- Alanine Transaminase
- Lipase
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Topics |
- Adult
- Alanine Transaminase
(blood)
- DNA, Viral
(blood)
- Female
- Follow-Up Studies
- Hepatitis B Surface Antigens
(blood)
- Hepatitis B e Antigens
(blood)
- Hepatitis B virus
(genetics)
- Hepatitis B, Chronic
(drug therapy)
- Humans
- Lipase
(blood)
- Liver
(metabolism)
- Male
- Middle Aged
- Nucleotides
(agonists)
- Reverse Transcriptase Inhibitors
(therapeutic use)
- Symptom Flare Up
- Tenofovir
(therapeutic use)
- Withholding Treatment
(statistics & numerical data, trends)
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