{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T21:45:51Z","timestamp":1769291151266,"version":"3.49.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K07390"],"award-info":[{"award-number":["23K07390"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Virol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Patients with chronic hepatitis B (CHB) are at risk of developing hepatocellular carcinoma (HCC) during treatment with nucleos(t)ide analogs (NAs). Several factors, including abnormal ALT levels during NA treatment, are associated with HCC risk; however, the mechanisms of ALT abnormalities remain unknown. Here, deletions in the preS1\/2 region of the hepatitis B virus (HBV) genome were evaluated in the context of persistent ALT abnormalities after NA treatment. Out of the 198 patients with CHB who had been treated with NAs, 40 who had been treated with entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate as the first-line therapy and from whom serum samples had been collected before NA treatment were selected for analysis of the infecting virus. Total DNA was extracted from the samples and subjected to nested PCR to detect deletions in the preS1\/2 region of the HBV genome. Patients for whom deletions were found in \u2265\u200940% of the amplicons were classified as the \"high-del\" group, and the others were the \"low-del\" group. The preS1\/2 region was amplified from 39 (97.5%) of the 40 samples, and a deletion was found in 19 of these patients (48.7%). The cumulative incidence of HCC was found to be significantly higher in the high-del group than in the low-del group (25% vs. 7% at 2 years,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.021). The high-del group also had significantly higher ALT levels than the low-del group after 1 year of NA treatment (35 vs. 26 U\/L,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.020). In summary, patients with CHB with frequent preS1\/2 deletions showed higher ALT levels after NA treatment and a higher risk of developing HCC.\n                  <\/jats:p>","DOI":"10.1007\/s00705-025-06480-6","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T11:43:43Z","timestamp":1766058223000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between deletions in the preS1\/2 region of the hepatitis B virus genome and persistently abnormal ALT levels in patients with chronic hepatitis B treated with nucleos(t)ide analogs"],"prefix":"10.1007","volume":"171","author":[{"given":"Yurina","family":"Sato","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kotaro","family":"Doi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1171-7835","authenticated-orcid":false,"given":"Jun","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Ninomiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mio","family":"Tsuruoka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosuke","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masazumi","family":"Onuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoko","family":"Sawahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keishi","family":"Ouchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kengo","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Niitsuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Masamune","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"6480_CR1","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1016\/S0140-6736(22)01468-4","volume":"401","author":"WJ Jeng","year":"2023","unstructured":"Jeng WJ, Papatheodoridis GV, Lok ASF (2023) Hepatitis B. Lancet 401:1039\u20131052. https:\/\/doi.org\/10.1016\/S0140-6736(22)01468-4","journal-title":"Lancet"},{"key":"6480_CR2","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1016\/S2468-1253(23)00197-8","volume":"8","author":"C Polaris Observatory","year":"2023","unstructured":"Polaris Observatory C (2023) Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study. Lancet Gastroenterol Hepatol 8:879\u2013907. https:\/\/doi.org\/10.1016\/S2468-1253(23)00197-8","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"6480_CR3","doi-asserted-by":"publisher","unstructured":"Danpanichkul P, Duangsonk K, Chen VL, Saokhieo P, Dejvajara D, Sukphutanan B, Aboona MB, Lopimpisuth C, Pang Y, Ibrahim AF, Fallon MB, Huang DQ, Kim D, Singal AG, Yang JD, Aqel BA, Terrault NA, Wijarnpreecha K (2025) Global burden of HBV-related liver disease: Primary liver cancer due to chronic HBV infection increased in over one-third of countries globally from 2000 to 2021. Hepatology. https:\/\/doi.org\/10.1097\/HEP.0000000000001260","DOI":"10.1097\/HEP.0000000000001260"},{"key":"6480_CR4","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3892\/br.2020.1396","volume":"14","author":"J Inoue","year":"2021","unstructured":"Inoue J, Akahane T, Kobayashi T, Obara N, Umetsu T, Kakazu E, Ninomiya M, Iwata T, Sano A, Tsuruoka M, Sato K, Masamune A (2021) Switching to tenofovir disoproxil fumarate in entecavir-treated chronic hepatitis B patients: A pilot randomized controlled study. Biomed Rep 14:20. https:\/\/doi.org\/10.3892\/br.2020.1396","journal-title":"Biomed Rep"},{"key":"6480_CR5","doi-asserted-by":"publisher","first-page":"e30630","DOI":"10.1097\/MD.0000000000030630","volume":"101","author":"K Sato","year":"2022","unstructured":"Sato K, Inoue J, Akahane T, Kobayashi T, Sato S, Kisara N, Ninomiya M, Iwata T, Sano A, Tsuruoka M, Onuki M, Masamune A (2022) Switching to tenofovir alafenamide versus continued therapy in chronic hepatitis B patients who were treated with entecavir: A prospective, multicenter, randomized controlled study. Med (Baltim) 101:e30630. https:\/\/doi.org\/10.1097\/MD.0000000000030630","journal-title":"Med (Baltim)"},{"key":"6480_CR6","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1620\/tjem.2022.J084","volume":"258","author":"K Sato","year":"2022","unstructured":"Sato K, Inoue J, Akahane T, Kobayashi T, Takai S, Nakamura T, Sato T, Kimura O, Ninomiya M, Iwata T, Sano A, Tsuruoka M, Onuki M, Sawahashi S, Niitsuma H, Masamune A (2022) Switching to Tenofovir Alafenamide Fumarate in Chronic Hepatitis B Patients Who Had Detectable HBV DNA during Treatment with Entecavir. Tohoku J Exp Med 258:277\u2013285. https:\/\/doi.org\/10.1620\/tjem.2022.J084","journal-title":"Tohoku J Exp Med"},{"key":"6480_CR7","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1136\/gutjnl-2024-332182","volume":"73","author":"R Fan","year":"2024","unstructured":"Fan R, Zhao S, Niu J, Ma H, Xie Q, Yang S, Xie J, Dou X, Shang J, Rao H, Xia Q, Liu Y, Yang Y, Gao H, Sun A, Liang X, Yin X, Jiang Y, Yu Y, Sun J, Naoumov NV, Hou J, Chronic Hepatitis BSC (2024) High accuracy model for HBsAg loss based on longitudinal trajectories of serum qHBsAg throughout long-term antiviral therapy. Gut 73:1725\u20131736. https:\/\/doi.org\/10.1136\/gutjnl-2024-332182","journal-title":"Gut"},{"key":"6480_CR8","doi-asserted-by":"publisher","first-page":"605","DOI":"10.3350\/cmh.2022.0342","volume":"29","author":"CL Lin","year":"2023","unstructured":"Lin CL, Kao JH (2023) Development of hepatocellular carcinoma in treated and untreated patients with chronic hepatitis B virus infection. Clin Mol Hepatol 29:605\u2013622. https:\/\/doi.org\/10.3350\/cmh.2022.0342","journal-title":"Clin Mol Hepatol"},{"key":"6480_CR9","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.14218\/JCTH.2023.00087","volume":"11","author":"X Hao","year":"2023","unstructured":"Hao X, Fan R, Zeng HM, Hou JL (2023) Hepatocellular Carcinoma Risk Scores from Modeling to Real Clinical Practice in Areas Highly Endemic for Hepatitis B Infection. J Clin Transl Hepatol 11:1508\u20131519. https:\/\/doi.org\/10.14218\/JCTH.2023.00087","journal-title":"J Clin Transl Hepatol"},{"key":"6480_CR10","doi-asserted-by":"publisher","first-page":"2354","DOI":"10.3390\/jcm11092354","volume":"11","author":"J Inoue","year":"2022","unstructured":"Inoue J, Kobayashi T, Akahane T, Kimura O, Sato K, Ninomiya M, Iwata T, Takai S, Kisara N, Sato T, Nagasaki F, Miura M, Nakamura T, Umetsu T, Sano A, Tsuruoka M, Onuki M, Niitsuma H, Masamune A, Therme Study G (2022) Non-Achievement of Alanine Aminotransferase Normalization Associated with the Risk of Hepatocellular Carcinoma during Nucleos(t)ide Analogue Therapies: A Multicenter Retrospective Study. J Clin Med 11:2354. https:\/\/doi.org\/10.3390\/jcm11092354","journal-title":"J Clin Med"},{"key":"6480_CR11","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1111\/hepr.13957","volume":"54","author":"J Inoue","year":"2024","unstructured":"Inoue J, Akahane T, Kobayashi T, Kimura O, Sato K, Ninomiya M, Iwata T, Takai S, Kisara N, Sato T, Nagasaki F, Miura M, Nakamura T, Umetsu T, Sano A, Tsuruoka M, Onuki M, Sawahashi S, Niitsuma H, Masamune A, Group TS (2024) Usefulness of the Fibrosis-4 index and alanine aminotransferase at 1 year of nucleos(t)ide analog treatment for prediction of hepatocellular carcinoma in chronic hepatitis B patients. Hepatol Res 54:131\u2013141. https:\/\/doi.org\/10.1111\/hepr.13957","journal-title":"Hepatol Res"},{"key":"6480_CR12","doi-asserted-by":"publisher","first-page":"e70021","DOI":"10.1111\/jvh.70021","volume":"32","author":"J Inoue","year":"2025","unstructured":"Inoue J, Minami S, Abe K, Kida M, Haga H, Iino C, Numao H, Kuroda H, Ninomiya M, Tsuruoka M, Sato K, Onuki M, Sawahashi S, Ouchi K, Watanabe K, Akahane T, Kobayashi T, Ohira H, Ueno Y, Masamune A (2025) Validation Study of Scores Predicting Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Treated With Nucleos(t)ide Analogues. J Viral Hepat 32:e70021. https:\/\/doi.org\/10.1111\/jvh.70021","journal-title":"J Viral Hepat"},{"key":"6480_CR13","doi-asserted-by":"publisher","first-page":"406","DOI":"10.14309\/ajg.0000000000000490","volume":"115","author":"J Choi","year":"2020","unstructured":"Choi J, Kim GA, Han S, Lim YS (2020) Earlier Alanine Aminotransferase Normalization During Antiviral Treatment Is Independently Associated With Lower Risk of Hepatocellular Carcinoma in Chronic Hepatitis B. Am J Gastroenterol 115:406\u2013414. https:\/\/doi.org\/10.14309\/ajg.0000000000000490","journal-title":"Am J Gastroenterol"},{"key":"6480_CR14","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.3390\/jcm10091840","volume":"10","author":"S Kim","year":"2021","unstructured":"Kim S, Lee Y, Bang SM, Bak H, Yim SY, Lee YS, Yoo YJ, Jung YK, Kim JH, Seo YS, Yim HJ, Um SH, Byun KS, Yeon JE (2021) Early Normalization of Alanine Aminotransferase during Antiviral Therapy Reduces Risk of Hepatocellular Carcinoma in HBV Patients. J Clin Med 10:1840. https:\/\/doi.org\/10.3390\/jcm10091840","journal-title":"J Clin Med"},{"key":"6480_CR15","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.3390\/v13061124","volume":"13","author":"J Inoue","year":"2021","unstructured":"Inoue J, Sato K, Ninomiya M, Masamune A (2021) Envelope Proteins of Hepatitis B Virus: Molecular Biology and Involvement in Carcinogenesis. Viruses 13:1124. https:\/\/doi.org\/10.3390\/v13061124","journal-title":"Viruses"},{"key":"6480_CR16","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1111\/j.1478-3231.2012.02826.x","volume":"32","author":"JH Kao","year":"2012","unstructured":"Kao JH, Liu CJ, Jow GM, Chen PJ, Chen DS, Chen BF (2012) Fine mapping of hepatitis B virus pre-S deletion and its association with hepatocellular carcinoma. Liver Int 32:1373\u20131381. https:\/\/doi.org\/10.1111\/j.1478-3231.2012.02826.x","journal-title":"Liver Int"},{"key":"6480_CR17","doi-asserted-by":"publisher","first-page":"e0212559","DOI":"10.1371\/journal.pone.0212559","volume":"14","author":"Y Suzuki","year":"2019","unstructured":"Suzuki Y, Maekawa S, Komatsu N, Sato M, Tatsumi A, Miura M, Matsuda S, Muraoka M, Nakakuki N, Amemiya F, Takano S, Fukasawa M, Nakayama Y, Yamaguchi T, Inoue T, Sato T, Sakamoto M, Yamashita A, Moriishi K, Enomoto N (2019) HBV preS deletion mapping using deep sequencing demonstrates a unique association with viral markers. PLoS ONE 14:e0212559. https:\/\/doi.org\/10.1371\/journal.pone.0212559","journal-title":"PLoS ONE"},{"key":"6480_CR18","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/s12072-018-9858-x","volume":"12","author":"F Li","year":"2018","unstructured":"Li F, Li X, Yan T, Liu Y, Cheng Y, Xu Z, Shao Q, Liao H, Huang P, Li J, Chen GF, Xu D (2018) The preS deletion of hepatitis B virus (HBV) is associated with liver fibrosis progression in patients with chronic HBV infection. Hepatol Int 12:107\u2013117. https:\/\/doi.org\/10.1007\/s12072-018-9858-x","journal-title":"Hepatol Int"},{"key":"6480_CR19","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1002\/hep.31789","volume":"74","author":"YJ Liang","year":"2021","unstructured":"Liang YJ, Teng W, Chen CL, Sun CP, Teng RD, Huang YH, Liang KH, Chen YW, Lin CC, Su CW, Tao MH, Wu JC (2021) Clinical Implications of HBV PreS\/S Mutations and the Effects of PreS2 Deletion on Mitochondria, Liver Fibrosis, and Cancer Development. Hepatology 74:641\u2013655. https:\/\/doi.org\/10.1002\/hep.31789","journal-title":"Hepatology"},{"key":"6480_CR20","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1002\/path.4850","volume":"241","author":"YC Teng","year":"2017","unstructured":"Teng YC, Neo JC, Wu JC, Chen YF, Kao CH, Tsai TF (2017) Expression of a hepatitis B virus pre-S2 deletion mutant in the liver results in hepatomegaly and hepatocellular carcinoma in mice. J Pathol 241:463\u2013474. https:\/\/doi.org\/10.1002\/path.4850","journal-title":"J Pathol"},{"key":"6480_CR21","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1002\/hep.21669","volume":"46","author":"A Vallet-Pichard","year":"2007","unstructured":"Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, Fontaine H, Pol S (2007) FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology 46:32\u201336. https:\/\/doi.org\/10.1002\/hep.21669","journal-title":"Hepatology"},{"key":"6480_CR22","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/s0168-1702(97)00068-3","volume":"50","author":"HG Lee","year":"1997","unstructured":"Lee HG, Lim JS, Lee KY, Choi YK, Choe IS, Chung TW, Kim K (1997) Peptide-specific CTL induction in HBV-seropositive PBMC by stimulation with peptides in vitro: novel epitopes identified from chronic carriers. Virus Res 50:185\u2013194. https:\/\/doi.org\/10.1016\/s0168-1702(97)00068-3","journal-title":"Virus Res"},{"key":"6480_CR23","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/jvh.13402","volume":"28","author":"CDK Wungu","year":"2021","unstructured":"Wungu CDK, Ariyanto FC, Prabowo GI, Soetjipto S, Handajani R (2021) Meta-analysis: Association between hepatitis B virus preS mutation and hepatocellular carcinoma risk. J Viral Hepat 28:61\u201371. https:\/\/doi.org\/10.1111\/jvh.13402","journal-title":"J Viral Hepat"},{"key":"6480_CR24","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1093\/infdis\/jiaa739","volume":"224","author":"J Li","year":"2021","unstructured":"Li J, Yang HI, Yeh ML, Le MH, Le AK, Yeo YH, Dai CY, Barnett S, Zhang JQ, Huang JF, Trinh HN, Wong C, Wong C, Hoang JK, Cheung R, Yu ML, Nguyen MH (2021) Association Between Fatty Liver and Cirrhosis, Hepatocellular Carcinoma, and Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B. J Infect Dis 224:294\u2013302. https:\/\/doi.org\/10.1093\/infdis\/jiaa739","journal-title":"J Infect Dis"},{"key":"6480_CR25","doi-asserted-by":"publisher","first-page":"705","DOI":"10.3350\/cmh.2023.0004","volume":"29","author":"YJ Wong","year":"2023","unstructured":"Wong YJ, Nguyen VH, Yang HI, Li J, Le MH, Wu WJ, Han NX, Fong KY, Chen E, Wong C, Rui F, Xu X, Xue Q, Hu XY, Leow WQ, Goh GB, Cheung R, Wong G, Wong VW, Yu MW, Nguyen MH (2023) Impact of fatty liver on long-term outcomes in chronic hepatitis B: a systematic review and matched analysis of individual patient data meta-analysis. Clin Mol Hepatol 29:705\u2013720. https:\/\/doi.org\/10.3350\/cmh.2023.0004","journal-title":"Clin Mol Hepatol"},{"key":"6480_CR26","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1002\/hep.32792","volume":"77","author":"X Mao","year":"2023","unstructured":"Mao X, Cheung KS, Peng C, Mak LY, Cheng HM, Fung J, Peleg N, Leung HH, Kumar R, Lee JH, Shlomai A, Yuen MF, Seto WK (2023) Steatosis, HBV-related HCC, cirrhosis, and HBsAg seroclearance: A systematic review and meta-analysis. Hepatology 77:1735\u20131745. https:\/\/doi.org\/10.1002\/hep.32792","journal-title":"Hepatology"},{"key":"6480_CR27","doi-asserted-by":"publisher","first-page":"2571","DOI":"10.1007\/s10620-014-3180-9","volume":"59","author":"MM Wang","year":"2014","unstructured":"Wang MM, Wang GS, Shen F, Chen GY, Pan Q, Fan JG (2014) Hepatic steatosis is highly prevalent in hepatitis B patients and negatively associated with virological factors. Dig Dis Sci 59:2571\u20132579. https:\/\/doi.org\/10.1007\/s10620-014-3180-9","journal-title":"Dig Dis Sci"},{"key":"6480_CR28","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.jhep.2014.04.041","volume":"61","author":"T Pollicino","year":"2014","unstructured":"Pollicino T, Cacciola I, Saffioti F, Raimondo G (2014) Hepatitis B virus PreS\/S gene variants: pathobiology and clinical implications. J Hepatol 61:408\u2013417. https:\/\/doi.org\/10.1016\/j.jhep.2014.04.041","journal-title":"J Hepatol"},{"key":"6480_CR29","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1093\/infdis\/jiae353","volume":"231","author":"Y Nakaya","year":"2025","unstructured":"Nakaya Y, Onomura D, Hoshi Y, Yamagata T, Morita H, Okamoto H, Murata K (2025) Establishment of a Hepatitis B Virus Reporter System Harboring an HiBiT-Tag in the PreS2 Region. J Infect Dis 231:204\u2013213. https:\/\/doi.org\/10.1093\/infdis\/jiae353","journal-title":"J Infect Dis"},{"key":"6480_CR30","doi-asserted-by":"publisher","unstructured":"Wu Y, Ding Y, Shen C (2022) A systematic review of t cell epitopes defined from the proteome of Hepatitis B virus. Vaccines (Basel) 10. https:\/\/doi.org\/10.3390\/vaccines10020257","DOI":"10.3390\/vaccines10020257"},{"key":"6480_CR31","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.virusres.2017.06.028","volume":"238","author":"B Malve","year":"2017","unstructured":"Malve B, Eschlimann M, Galgey S, Fenaux H, Zoulim F, Goehringer F, Rabaud C, May T, Jeulin H, Schvoerer E (2017) Impact of deletions and mutations in Hepatitis B virus envelope proteins on serological profile and clinical evolution. Virus Res 238:141\u2013147. https:\/\/doi.org\/10.1016\/j.virusres.2017.06.028","journal-title":"Virus Res"},{"key":"6480_CR32","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1111\/hepr.14169","volume":"55","author":"K Sato","year":"2025","unstructured":"Sato K, Inoue J, Akahane T, Kobayashi T, Ninomiya M, Sano A, Tsuruoka M, Onuki M, Sawahashi S, Ouchi K, Doi K, Watanabe K, Niitsuma H, Masamune A (2025) Comparison of hepatitis B virus genotype B and C patients in Japan in terms of family history and maternal age at birth. Hepatol Res 55:773\u2013779. https:\/\/doi.org\/10.1111\/hepr.14169","journal-title":"Hepatol Res"},{"key":"6480_CR33","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1038\/s41575-020-0296-6","volume":"17","author":"PA Revill","year":"2020","unstructured":"Revill PA, Tu T, Netter HJ, Yuen LKW, Locarnini SA, Littlejohn M (2020) The evolution and clinical impact of hepatitis B virus genome diversity. Nat Rev Gastroenterol Hepatol 17:618\u2013634. https:\/\/doi.org\/10.1038\/s41575-020-0296-6","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"6480_CR34","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1093\/infdis\/jiq096","volume":"203","author":"P Yeung","year":"2011","unstructured":"Yeung P, Wong DK, Lai CL, Fung J, Seto WK, Yuen MF (2011) Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in chronic hepatitis B. J Infect Dis 203:646\u2013654. https:\/\/doi.org\/10.1093\/infdis\/jiq096","journal-title":"J Infect Dis"},{"key":"6480_CR35","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1111\/hepr.13398","volume":"49","author":"J Inoue","year":"2019","unstructured":"Inoue J, Akahane T, Nakayama H, Kimura O, Kobayashi T, Kisara N, Sato T, Morosawa T, Izuma M, Kakazu E, Ninomiya M, Iwata T, Takai S, Nakamura T, Sano A, Niitsuma H, Masamune A, Group TS (2019) Comparison of hepatitis B virus genotypes B and C among chronically hepatitis B virus-infected patients who received nucleos(t)ide analogs: A multicenter retrospective study. Hepatol Res 49:1263\u20131274. https:\/\/doi.org\/10.1111\/hepr.13398","journal-title":"Hepatol Res"},{"key":"6480_CR36","doi-asserted-by":"publisher","first-page":"e801","DOI":"10.1093\/cid\/ciac383","volume":"76","author":"N Chow","year":"2023","unstructured":"Chow N, Wong D, Lai CL, Mak LY, Fung J, Ma HT, Lei MW, Seto WK, Yuen MF (2023) Effect of Antiviral Treatment on Hepatitis B Virus Integration and Hepatocyte Clonal Expansion. Clin Infect Dis 76:e801\u2013e809. https:\/\/doi.org\/10.1093\/cid\/ciac383","journal-title":"Clin Infect Dis"}],"container-title":["Archives of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00705-025-06480-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00705-025-06480-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00705-025-06480-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T09:10:49Z","timestamp":1769245849000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00705-025-06480-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["6480"],"URL":"https:\/\/doi.org\/10.1007\/s00705-025-06480-6","relation":{},"ISSN":["0304-8608","1432-8798"],"issn-type":[{"value":"0304-8608","type":"print"},{"value":"1432-8798","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]},"assertion":[{"value":"6 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was approved by the medical ethics committee of Tohoku University (approval numbers 2016-1-280, 2020-1-1106, and 2024-1-012).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"27"}}