Durability of Hepatitis B Surface Antigen Loss With Nucleotide Analogue and Peginterferon Therapy in Patients With Chronic Hepatitis B

Anna S Lok; Fabien Zoulim; Geoffrey Dusheiko; Henry L Y Chan; Maria Buti; Marc G Ghany; Anuj Gaggar; Jenny C Yang; George Wu; John F Flaherty; G Mani Subramanian; Stephen Locarnini; Patrick Marcellin

doi:10.1002/hep4.1436

Durability of Hepatitis B Surface Antigen Loss With Nucleotide Analogue and Peginterferon Therapy in Patients With Chronic Hepatitis B

Hepatol Commun. 2019 Oct 10;4(1):8-20. doi: 10.1002/hep4.1436. eCollection 2020 Jan.

Authors

Anna S Lok¹, Fabien Zoulim², Geoffrey Dusheiko³, Henry L Y Chan⁴, Maria Buti⁵, Marc G Ghany⁶, Anuj Gaggar⁷, Jenny C Yang⁷, George Wu⁷, John F Flaherty⁷, G Mani Subramanian⁷, Stephen Locarnini⁸, Patrick Marcellin⁹

Affiliations

¹ University of Michigan Ann Arbor MI.
² Hospices Civils de Lyon and INSERM Unit 1052 Lyon France.
³ Kings College Hospital University College London Medical School London United Kingdom.
⁴ Chinese University of Hong Kong Hong Kong S.A.R.
⁵ Vall d'Hebron Hospital Barcelona Spain.
⁶ National Institutes of Health Bethesda MD.
⁷ Gilead Sciences, Inc. Foster City CA.
⁸ Victorian Infectious Diseases Reference Laboratory Melbourne Australia.
⁹ Hôpital Beaujon Université de Paris Diderot Clichy France.

Abstract

In patients with chronic hepatitis B (CHB), loss of hepatitis B surface antigen (HBsAg) is considered a functional cure. However, HBsAg loss is uncommon with existing therapies, and predictive factors associated with HBsAg seroreversion are unknown. Using pooled data from three phase 3 clinical trials of patients with CHB treated with nucleos(t)ide analogue (NUC) monotherapy or peginterferon (Peg-IFN) ± NUC combination therapy, we conducted a retrospective analysis to characterize patients who achieved sustained HBsAg loss, the predictors of HBsAg seroreversion, and the impact of hepatitis B surface antibody (anti-HBs) seroconversion on durability of HBsAg loss. In these three international trials, 1,381 adults with CHB received either NUC monotherapy for up to 10 years or Peg-IFN-containing regimens for up to 1 year. A total of 55 patients had confirmed HBsAg loss, defined as two or more consecutive negative-qualitative HBsAg results, with a minimum of one repeat result after the end of treatment. Throughout a median of 96 (quartile [Q]1, Q3, 46, 135) weeks follow-up after HBsAg loss, HBsAg loss was durable in 82% (n = 45) of patients, with 10 patients experiencing HBsAg seroreversion. Anti-HBs seroconversion was observed during follow-up in 78% of patients who lost HBsAg and in 60% of those who subsequently seroreverted. In analyzing predictors of HBsAg seroreversion, study treatment was significant, yet anti-HBs seroconversion and treatment duration after initial HBsAg loss were not. Risk of HBsAg seroreversion was observed to be lower if HBsAg loss was sustained through the off-treatment week 24 visit (8/10 seroreversions occurred by posttreatment week 24). Conclusion: HBsAg loss after NUC or Peg-IFN-containing regimens was durable in 82% of patients with CHB. Anti-HBs seroconversion and treatment duration after initial HBsAg loss were not significantly associated with durability of HBsAg loss.