Pub Date : 2026-01-15DOI: 10.1016/S0168-8278(25)02696-0
{"title":"Become an EASL member today and benefit from reduced fees to all EASL events!","authors":"","doi":"10.1016/S0168-8278(25)02696-0","DOIUrl":"10.1016/S0168-8278(25)02696-0","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"84 2","pages":"Page v"},"PeriodicalIF":33.0,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145963099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-15DOI: 10.1016/S0168-8278(25)02695-9
{"title":"Submit your late-breaker for EASL Congress 2026 from 16 - 31 March!","authors":"","doi":"10.1016/S0168-8278(25)02695-9","DOIUrl":"10.1016/S0168-8278(25)02695-9","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"84 2","pages":"Page iv"},"PeriodicalIF":33.0,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145963098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-15DOI: 10.1016/S0168-8278(25)02693-5
{"title":"Register for the EASL SLD Summit 2026, 26-28 February in Budapest!","authors":"","doi":"10.1016/S0168-8278(25)02693-5","DOIUrl":"10.1016/S0168-8278(25)02693-5","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"84 2","pages":"Page ii"},"PeriodicalIF":33.0,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145963096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-15DOI: 10.1016/S0168-8278(25)02701-1
{"title":"JHEP at a glance (February 2026)","authors":"","doi":"10.1016/S0168-8278(25)02701-1","DOIUrl":"10.1016/S0168-8278(25)02701-1","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"84 2","pages":"Pages e47-e58"},"PeriodicalIF":33.0,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/j.jhep.2025.12.025
Jerome Bouquet, Scott D. Speer, Alexander Koenig, Christine M. Livingston, Michael Savarese, Chi Lau, Elise Angelini, Nicholas Galwey, Phillip Yates, Lauren Maynard, Shihyun You, Jennifer Cremer, Melanie Paff, Dickens Theodore, Rob Elston, Jill Walker
<h3>Background and Aims</h3>Single nucleotide polymorphisms (SNPs) in the hepatitis B virus (HBV) genome may impact efficacy of novel drugs for chronic HBV infection. This analysis of the B-Clear study (NCT04449029) evaluated the frequency of baseline and treatment-emergent SNPs in the bepirovirsen binding site and association with virological response.<h3>Methods</h3>HBV sequencing was attempted on all baseline samples collected from B-Clear participants and select post-baseline samples from participants meeting pre-defined resistance monitoring criteria. Participants were categorized according to nucleos(t)ide analog (NA) treatment status and HBsAg response. SNPs were identified using next-generation sequencing and reported if the allelic frequency was ≥5%. Binding site SNPs effect on viral fitness and susceptibility to bepirovirsen was assessed <em>in vitro</em>.<h3>Results</h3>Baseline sequences were obtained for 40% (90/226) and 96% (219/229) of On-NA and Not-on-NA participants, respectively. Baseline SNPs were identified in 7% (22/309) of participants. These participants showed numerically smaller HBsAg reductions than those without SNPs, but 18% (4/22) achieved transient HBsAg loss. Post-baseline sequences were obtained for 22% (49/226) and 62% (143/229) of On-NA and Not-on-NA participants, respectively. Of 16 post-baseline SNPs, 8 were treatment-emergent. SNPs were detected at 12 of the 20 binding site positions, however only two SNPs had an allelic frequency >50% (C1589A [max 99%] and C1600T [max 99%]). Six SNPs showed sufficient viral fitness to be evaluated for susceptibility to bepirovirsen <em>in vitro</em>. C1589A demonstrated the largest reduction in susceptibility (4.1-fold) to bepirovirsen.<h3>Conclusions</h3>The majority of participants achieved >1 log HBsAg reductions, including transient HBsAg loss in some, though numerically smaller HBsAg reductions in participants with baseline SNPs require further investigation to better understand resistance mechanisms to bepirovirsen.<h3>Impacts and Implications</h3>HBV sequence polymorphisms can lead to antiviral resistance for the treatment of chronic HBV infection. Therefore, it is important for HCPs to understand the prevalence and development of bepirovirsen binding site SNPs and how their presence in patients with chronic HBV infection may impact the virological response to bepirovirsen treatment. The Phase 2b clinical study findings reported here show that the large majority (92%) of non-responders, partial responders or relapsers did not have bepirovirsen binding site SNPs. Those with bepirovirsen binding site SNPs (7% of participants) still achieved HBsAg reductions, indicating that there is no need at this stage to test for specific HBV variants when administering bepirovirsen, and that treatment resistance via a change in sequence complementarity may be minimal and likely multifactorial. Additional data from ongoing Phase 3 studies of bepirovirsen will provide additional
{"title":"Single nucleotide polymorphisms in the bepirovirsen binding site have limited impact on treatment response in chronic hepatitis B","authors":"Jerome Bouquet, Scott D. Speer, Alexander Koenig, Christine M. Livingston, Michael Savarese, Chi Lau, Elise Angelini, Nicholas Galwey, Phillip Yates, Lauren Maynard, Shihyun You, Jennifer Cremer, Melanie Paff, Dickens Theodore, Rob Elston, Jill Walker","doi":"10.1016/j.jhep.2025.12.025","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.12.025","url":null,"abstract":"<h3>Background and Aims</h3>Single nucleotide polymorphisms (SNPs) in the hepatitis B virus (HBV) genome may impact efficacy of novel drugs for chronic HBV infection. This analysis of the B-Clear study (NCT04449029) evaluated the frequency of baseline and treatment-emergent SNPs in the bepirovirsen binding site and association with virological response.<h3>Methods</h3>HBV sequencing was attempted on all baseline samples collected from B-Clear participants and select post-baseline samples from participants meeting pre-defined resistance monitoring criteria. Participants were categorized according to nucleos(t)ide analog (NA) treatment status and HBsAg response. SNPs were identified using next-generation sequencing and reported if the allelic frequency was ≥5%. Binding site SNPs effect on viral fitness and susceptibility to bepirovirsen was assessed <em>in vitro</em>.<h3>Results</h3>Baseline sequences were obtained for 40% (90/226) and 96% (219/229) of On-NA and Not-on-NA participants, respectively. Baseline SNPs were identified in 7% (22/309) of participants. These participants showed numerically smaller HBsAg reductions than those without SNPs, but 18% (4/22) achieved transient HBsAg loss. Post-baseline sequences were obtained for 22% (49/226) and 62% (143/229) of On-NA and Not-on-NA participants, respectively. Of 16 post-baseline SNPs, 8 were treatment-emergent. SNPs were detected at 12 of the 20 binding site positions, however only two SNPs had an allelic frequency >50% (C1589A [max 99%] and C1600T [max 99%]). Six SNPs showed sufficient viral fitness to be evaluated for susceptibility to bepirovirsen <em>in vitro</em>. C1589A demonstrated the largest reduction in susceptibility (4.1-fold) to bepirovirsen.<h3>Conclusions</h3>The majority of participants achieved >1 log HBsAg reductions, including transient HBsAg loss in some, though numerically smaller HBsAg reductions in participants with baseline SNPs require further investigation to better understand resistance mechanisms to bepirovirsen.<h3>Impacts and Implications</h3>HBV sequence polymorphisms can lead to antiviral resistance for the treatment of chronic HBV infection. Therefore, it is important for HCPs to understand the prevalence and development of bepirovirsen binding site SNPs and how their presence in patients with chronic HBV infection may impact the virological response to bepirovirsen treatment. The Phase 2b clinical study findings reported here show that the large majority (92%) of non-responders, partial responders or relapsers did not have bepirovirsen binding site SNPs. Those with bepirovirsen binding site SNPs (7% of participants) still achieved HBsAg reductions, indicating that there is no need at this stage to test for specific HBV variants when administering bepirovirsen, and that treatment resistance via a change in sequence complementarity may be minimal and likely multifactorial. Additional data from ongoing Phase 3 studies of bepirovirsen will provide additional ","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"83 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/j.jhep.2025.12.024
Liteng Lin, Rui Li, Kangshun Zhu
{"title":"Reply to: “Reassessing the L. reuteri / indole-3-lactic acid pathway in TACE-related liver injury”","authors":"Liteng Lin, Rui Li, Kangshun Zhu","doi":"10.1016/j.jhep.2025.12.024","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.12.024","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"265 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.jhep.2025.12.008
Panu K. Luukkonen
{"title":"Redox-dependent substrate use in hepatic gluconeogenesis shapes exercise performance","authors":"Panu K. Luukkonen","doi":"10.1016/j.jhep.2025.12.008","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.12.008","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"314 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.jhep.2025.12.014
Debbie L. Shawcross
{"title":"Standing on the shoulders of giants","authors":"Debbie L. Shawcross","doi":"10.1016/j.jhep.2025.12.014","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.12.014","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"17 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-10DOI: 10.1016/j.jhep.2025.12.002
George V. Papatheodoridis, Anna S.F. Lok
{"title":"In memoriam: Professor Stephanos J. Hadziyannis","authors":"George V. Papatheodoridis, Anna S.F. Lok","doi":"10.1016/j.jhep.2025.12.002","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.12.002","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"59 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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