Responses are durable for up to 5 years after completion of peginterferon alfa-2a treatment in hepatitis B e antigen-positive patients W.-L. Chuang 1 | J. Jia 2 | H. L. Y. Chan 3 | K.-H. Han 4 | T. Tanwandee 5 | D. Tan 6 | X. Chen 2 | E. Gane 7 | T. Piratvisuth 8 | L. Chen 9 | Q. Xie 9 | J. J.-Y. Sung 3 | D. Messinger 10 | C. Wat 11 | G. Bakalos 12 | Y. F. Liaw 13 1 Kaohsiung, Taiwan 2 Beijing, China 3 Hong Kong SAR, China 4 Seoul, Korea 5 Bangkok, Thailand 6 Changsha, China 7 Grafton, New Zealand 8 Hat-Yai, Thailand 9 Shanghai, China 10 Mannheim, Germany 11 Welwyn Garden City, UK 12 Basel, Switzerland 13 Taipei, Taiwan Correspondence Prof. Y. F. Liaw, Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan. Email: liveryfl@gmail.com Funding information F. Hoffmann-La Roche Summary Background: In the large randomised NEPTUNE study, peginterferon alfa-2a 180 lg/wk for 48 weeks produced higher hepatitis B e antigen (HBeAg) serocon- version rates 24 weeks post-treatment (36%) than a lower dose (90 lg/wk) and/or shorter duration (24 weeks) (range 14%-26%). Aim: To determine seroconversion rates 5 years after completion of treatment in NEPTUNE. Methods: HBeAg-positive patients who completed 24 weeks’ follow-up in NEP- TUNE (with peginterferon alfa-2a 90 lg/wk 9 24 weeks [group 1]; 180 lg/ wk 9 24 weeks [2]; 90 lg/wk 9 48 weeks [3] or 180 lg/wk 9 48 weeks [4]) were followed up. Results: Three hundred and eighty three of the 544 patients in the original study were enrolled in the long-term follow-up study. Many patients (196 overall; more in groups 1-3 than 4) received nucleos(t)ide analogues or immunomodulators during follow-up, and more patients had missing data at year 5 in groups 2 and 4 (48 weeks, 50/112) than in groups 1 and 3 (24 weeks, 23/103), which confounds the planned per-protocol analysis. HBeAg seroconversion rates in groups 1, 2, 3 and 4 at year 5 were 47.5%, 50.7%, 52.2% and 67.1%, respectively, (odds ratio for group 4 versus 1-3: 2.02; 95% CI 1.21, 3.38), using multiple imputation methods for missing measurements. Conclusion: Seroconversion rates are durable for up to 5 years after completion of peginterferon alfa-2a therapy and, consistent with NEPTUNE, the results suggest that the licensed regimen (180 lg 9 48 weeks) is more efficacious for HBeAg-posi- tive patients than a lower dose and/or shorter treatment duration. The Handling Editor for this article was Professor Roy Pounder, and it was accepted for publication after full peer-review. The authors’ complete affiliations are listed in Appendix 1. Received: 15 December 2017 | First decision: 10 January 2018 | Accepted: 12 February 2018 DOI: 10.1111/apt.14595 1306 | © 2018 John Wiley & Sons Ltd wileyonlinelibrary.com/journal/apt Aliment Pharmacol Ther. 2018;47:1306–1316.