{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T19:15:22Z","timestamp":1773342922661,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,24]],"date-time":"2024-03-24T00:00:00Z","timestamp":1711238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gilead Sciences, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Currently, there are insufficient data to recommend the treatment of patients with hepatitis B e antigen (HBeAg)-negative chronic infection who have normal ALT and low HBV DNA, since the prognosis is generally regarded as favorable. The aim of this pilot study was to determine whether the use of tenofovir disoproxil fumarate (TDF) 300 mg\/day for 3 years was able to achieve functional cure (HBsAg loss) and HBsAg seroconversion in HBeAb-positive individuals. Methods: Fifty patients not on antiviral therapy (40% men, mean age 48.9 \u00b1 10.9 years, 84% Asians) with minimal fibrosis were enrolled. Results: TDF reduced HBV DNA significantly to undetectable levels after 6 months. Overall, 48.3% of inactive carriers (baseline HBV DNA &lt; 2000 IU\/mL) remained HBV DNA negative 6 months after treatment withdrawal, which was significantly higher than the 5.6% in those who were not inactive carriers (baseline HBV DNA \u2265 2000 IU\/mL) (p = 0.003). The HBsAg levels did not drop throughout the study period with no difference between inactive carriers versus those who were not. Five inactive carriers achieved functional cure, but none of these were amongst those who were not inactive carriers. No renal dysfunction or ALT flare on treatment withdrawal was observed. Conclusions: TDF could potentially be used to induce functional cure in patients who are inactive carriers with normal ALT, low HBV DNA and without advanced fibrosis.<\/jats:p>","DOI":"10.3390\/jcm13071864","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T12:32:36Z","timestamp":1711369956000},"page":"1864","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Use of Tenofovir Disoproxil Fumarate in the Management of eAg-Negative Chronic Hepatitis B Infection"],"prefix":"10.3390","volume":"13","author":[{"given":"Nishita","family":"Jagarlamudi","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON M5G2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Reyes","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON M5G2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Fung","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON M5G2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florence","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON M5G2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,24]]},"reference":[{"key":"ref_1","unstructured":"WHO (2023, December 09). Hepatitis B, Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-b."},{"key":"ref_2","unstructured":"(2023, December 09). Available online: https:\/\/www150.statcan.gc.ca\/n1\/daily-quotidien\/221026\/dq221026a-eng.htm."},{"key":"ref_3","unstructured":"(2023, December 09). Available online: https:\/\/www.canada.ca\/en\/public-health\/services\/publications\/diseases-conditions\/report-hepatitis-b-c-canada-2018.html."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/S0140-6736(22)01468-4","article-title":"Hepatitis B","volume":"401","author":"Jeng","year":"2023","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/hep.28156","article-title":"AASLD guidelines for treatment of chronic hepatitis B","volume":"63","author":"Terrault","year":"2016","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection","volume":"67","author":"Lampertico","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12072-015-9675-4","article-title":"Asian-Pacific clinical practice guidelines on the management of hepatitis B: A 2015 update","volume":"10","author":"Sarin","year":"2016","journal-title":"Hepatol. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e50","DOI":"10.1097\/MCG.0b013e3182a9a2e1","article-title":"Predictors of significant fibrosis in chronic hepatitis B patients with low viremia","volume":"48","author":"Abdo","year":"2014","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1007\/s12072-021-10137-2","article-title":"Chronic hepatitis B: The demise of the \u2018inactive carrier\u2019 phase","volume":"15","author":"Koffas","year":"2021","journal-title":"Hepatol. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0140-6736(15)61276-4","article-title":"Discrimination against people with hepatitis B in China","volume":"386","author":"Kan","year":"2015","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/S0140-6736(11)61460-8","article-title":"Discrimination against hepatitis B carriers in China","volume":"378","author":"Yang","year":"2011","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1002\/hep4.1875","article-title":"Aiming for functional cure with established and novel therapies for chronic hepatitis B","volume":"6","author":"Choi","year":"2022","journal-title":"Hepatol. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1002\/hep.29800","article-title":"Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance","volume":"67","author":"Terrault","year":"2018","journal-title":"Hepatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1002\/hep.22878","article-title":"Long-term outcome of hepatitis B e antigen-negative hepatitis B surface antigen carriers in relation to changes of alanine aminotransferase levels over time","volume":"49","author":"Tai","year":"2009","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1053\/jhep.2001.27834","article-title":"Hepatitis B e antigen-negative chronic hepatitis B","volume":"34","author":"Hadziyannis","year":"2001","journal-title":"Hepatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/j.1365-2893.2011.01450.x","article-title":"Serial HBV DNA levels in patients with persistently normal transaminase over 10 years following spontaneous HBeAg seroconversion","volume":"19","author":"Chen","year":"2012","journal-title":"J. Viral Hepat."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1053\/j.gastro.2008.02.075","article-title":"Virological and histological features of chronic hepatitis b virus infected asymptomatic patients with persistently normal ALT","volume":"134","author":"Kumar","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s12072-007-9002-9","article-title":"Spontaneous relapse of hepatitis in inactive HBsAg carriers","volume":"1","author":"Chu","year":"2007","journal-title":"Hepatol. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1053\/j.gastro.2007.08.039","article-title":"Predictive factors for reactivation of hepatitis B following hepatitis B e antigen seroconversion in chronic hepatitis B","volume":"133","author":"Chu","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"156","DOI":"10.3138\/canlivj.2018-0008","article-title":"Management of Hepatitis B Virus Infection: 2018 Guidelines from the Canadian Association for the Study of the Liver and Association of Medical Microbiology and Infectious Disease Canada","volume":"1","author":"Coffin","year":"2018","journal-title":"Can. Liver J."},{"key":"ref_21","first-page":"1425","article-title":"Guidelines for the prevention and treatment of chronic hepatitis B (version 2022)","volume":"11","author":"You","year":"2023","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1111\/apt.14613","article-title":"Anti-viral therapy can be delayed or avoided in a significant proportion of HBeAg-negative Caucasian patients in the Grey Zone","volume":"47","author":"Bonacci","year":"2018","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1007\/s12072-021-10263-x","article-title":"Risk scores to predict HCC and the benefits of antiviral therapy for CHB patients in gray zone of treatment guidelines","volume":"15","author":"Teng","year":"2021","journal-title":"Hepatol. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1002\/hep.21612","article-title":"HBsAg seroclearance in asymptomatic carriers of high endemic areas: Appreciably high rates during a long-term follow-up","volume":"45","author":"Chu","year":"2007","journal-title":"Hepatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.cgh.2020.05.041","article-title":"Association between seroclearance of hepatitis B surface antigen and long-term clinical outcomes of patients with chronic hepatitis B virus infection: Systematic review and meta-analysis","volume":"19","author":"Anderson","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/ofid\/ofaa208","article-title":"Short-term peginterferon-Induced high functional cure rate in inactive chronic hepatitis B virus carriers with low surface antigen levels","volume":"7","author":"Zeng","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1002\/hep.29213","article-title":"A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha","volume":"66","author":"Cao","year":"2017","journal-title":"Hepatology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/S2468-1253(17)30083-3","article-title":"Peg-interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: A randomised controlled, open-label trial","volume":"2","author":"Jansen","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1111\/liv.14155","article-title":"Ten-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B virus infection","volume":"39","author":"Marcellin","year":"2019","journal-title":"Liver Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e9756","DOI":"10.1097\/MD.0000000000009756","article-title":"Effect of tenofovir on renal function in patients with chronic hepatitis B","volume":"97","author":"Jung","year":"2018","journal-title":"Medicine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1111\/jgh.13294","article-title":"Three-year efficacy and safety of tenofovir in nucleos(t)ide analog-na\u00efve and nucleos(t)ide analog-experienced chronic hepatitis B patients","volume":"31","author":"Wang","year":"2016","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jhep.2016.08.008","article-title":"Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)\/TDF in lamivudine resistant hepatitis B: A 5-year randomised study","volume":"66","author":"Fung","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1002\/jmv.25433","article-title":"Antiviral therapy and the development of osteopenia\/osteoporosis among Asians with chronic hepatitis B","volume":"91","author":"Wei","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"486","DOI":"10.14309\/ajg.0000000000002468","article-title":"Long-term treatment with tenofovir alafenamide for chronic hepatitis B results in high rates of viral suppression and favorable renal and bone safety","volume":"119","author":"Chan","year":"2023","journal-title":"Am. J. Gastroenterol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.jhep.2022.01.007","article-title":"Probability of HBsAg loss after nucleo(s)tide analogue withdrawal depends on HBV genotype and viral antigen levels","volume":"76","author":"Sonneveld","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1136\/gutjnl-2019-318981","article-title":"Limited sustained response after stopping nucleos(t)ide analogues in patients with chronic hepatitis B: Results from a randomised controlled trial (Toronto STOP study)","volume":"68","author":"Liem","year":"2019","journal-title":"Gut"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.jhep.2017.07.012","article-title":"Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients\u2014Finite study","volume":"67","author":"Berg","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.cld.2023.05.009","article-title":"Test all for hepatitis B virus: Link to care and treatment if quantitative DNA positive, vaccinate if susceptible","volume":"27","author":"Roma","year":"2023","journal-title":"Clin. Liver Dis."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/7\/1864\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:17:47Z","timestamp":1760105867000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/7\/1864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,24]]},"references-count":38,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["jcm13071864"],"URL":"https:\/\/doi.org\/10.3390\/jcm13071864","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,24]]}}}