Journal of Hepatology最新文献

{"title":"Real-world effectiveness and safety of bulevirtide monotherapy for up to 96 weeks in patients with HDV-related cirrhosis","authors":"Elisabetta Degasperi, Maria Paola Anolli, Mathias Jachs, Thomas Reiberger, Victor De Ledinghen, Sophie Metivier, Gianpiero D’Offizi, Francesco di Maria, Christoph Schramm, Hartmut Schmidt, Caroline Zöllner, Frank Tacke, Christopher Dietz-Fricke, Heiner Wedemeyer, Margarita Papatheodoridi, George Papatheodoridis, Ivana Carey, Kosh Agarwal, Florian Van Bömmel, Maurizia R. Brunetto, Pietro Lampertico","doi":"10.1016/j.jhep.2024.12.044","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.12.044","url":null,"abstract":"<h3>Background and aims</h3>Bulevirtide (BLV) 2 mg/day is EMA approved for treatment of compensated chronic hepatitis due to Delta virus (HDV) infection, however real-life data in large cohorts of patients with cirrhosis are lacking.<h3>Methods</h3>Consecutive HDV-infected patients with cirrhosis starting BLV 2 mg/day since September 2019 were included in a European retrospective multicenter real-life study (SAVE-D). Patient characteristics before and during BLV treatment were collected. Virological, biochemical, combined responses, adverse events and liver-related events (HCC, decompensation, liver transplant) were assessed.<h3>Results</h3>244 patients with HDV-related cirrhosis receiving BLV monotherapy for a median of 92 (IQR 71-96) weeks were included: at BLV start, median (IQR) age was 49 (40-58) years, 61% men, ALT 80 (55-130) U/L, liver stiffness measurement (LSM) 18.3 (13.0-26.3) kPa, platelets 94 (67-145) x 10³/mm³, 54% with esophageal varices, 95% Child Pugh score A, 10% HIV-coinfected, 92% on NUC, median HDV RNA 5.4 (4.1-6.5) Log₁₀ IU/mL, HBsAg 3.8 (3.4-4.1) Log₁₀ IU/mL. At weeks (W)48 and 96, virological, biochemical and combined responses were observed in 65% and 79%, 61% and 64%, 44% and 54% of patients, respectively. AST, GGT, albumin, IgG and LSM values significantly improved throughout treatment. Serum bile acid levels increased in most patients, only 10% patients reported mild and transient pruritus, independently of bile acid levels. The W96 cumulative risk of de-novo HCC and decompensation was 3.0% (95% CI 2-6%) and 2.8% (95% CI 1-5%), respectively. Thirteen (5%) patients underwent liver transplantation (n=11 for HCC, n=2 for decompensation).<h3>Conclusion</h3>BLV 2 mg/day monotherapy up to 96 weeks was safe and effective in patients with HDV-related cirrhosis. Virological and clinical responses increased over time. Liver-related complications were few.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"14 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936335","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}

{"title":"TGM2-mediated histone serotonylation promotes HCC progression via MYC signalling pathway","authors":"Renshun Dong, Tianci Wang, Wei Dong, Haoquan Zhang, Yani Li, Ran Tao, Qiumeng Liu, Huifang Liang, Xiaoping Chen, Bixiang Zhang, Xuewu Zhang","doi":"10.1016/j.jhep.2024.12.038","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.12.038","url":null,"abstract":"<h3>Background &amp; Aims</h3>Hepatocellular carcinoma (HCC) is an aggressive malignancy with few effective treatment options. H3Q5ser, a serotonin-based histone modification mediated by transglutaminase 2 (TGM2), affects diverse biological processes, such as neurodevelopment. The role of TGM2-mediated H3Q5ser in HCC progression remains unclear. This study investigated the role of TGM2 in promoting HCC progression and evaluated its potential as a therapeutic target for HCC treatment.<h3>Methods</h3>Adeno-associated virus (AAV)-mediated liver-specific overexpression models of <em>Tgm2</em> or <em>H3.3</em> were adopted to validate the effects of H3Q5ser on HCC progression. CUT&amp;Tag and RNA sequencing was employed to investigate the underlying mechanisms. HCC organoids, subcutaneous xenograft models, and hydrodynamic tail vein injection models were used to evaluate the treatment efficiency of TGM2 inhibitors.<h3>Results</h3>TMG2 expression positively correlated with higher AFP levels, poor differentiation, and a later BCLC stage. <em>Tgm2</em> deficiency or H3Q5ser inhibition notably inhibited HCC progression. CUT&amp;Tag and RNA sequencing analyses revealed that downregulated genes were enriched in the MYC pathway following treatment with the TGM2 inhibitors. Furthermore, transcriptional intermediary factor 1 β mediated the recruitment of TGM2 to MYC, facilitating H3Q5ser modifications on MYC target genes. Finally, targeting the transglutaminase activity of TGM2 significantly suppressed HCC progression and showed synergy with sorafenib treatment in preclinical models. TGM2 inhibitors did not cause significant myelosuppression or tissue damage.<h3>Conclusions</h3>TGM2 serves as a prognostic biomarker and targeting its transglutaminase activity may be an effective strategy for inhibiting HCC progression.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"73 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935152","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}

{"title":"Spliced exon9 ADRM1 promotes liver oncogenicity via selective degradation of tumor suppressor FBXW7","authors":"Yanmei Sun, Mingjing Xu, Ho Lee Wan, Xiaofan Ding, Alissa M. Wong, Dandan Pu, Kelvin K. Ng, Nathalie Wong","doi":"10.1016/j.jhep.2024.12.037","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.12.037","url":null,"abstract":"<h3>Background &amp; Aims</h3>The ubiquitin receptor ADRM1/Rpn13 governs the specificity of eukaryotic protein degradation. By SMRT sequencing, we first discovered a novel spliced variant of ADRM1 with a skipped exon 9, termed ADRM1-ΔEx9, in human hepatocellular carcinoma (HCC). This study aimed to elucidate this novel ubiquitin receptor's underlying biology and clinical implications in HCC.<h3>Methods</h3>The role of ADRM1-ΔEx9 in early liver carcinogenesis was studied using human liver-derived non-tumoral organoids and a murine model with hydrodynamic <em>in vivo</em> transfection. ADRM1-ΔEx9 biology in HCC and its potential as a biomarker for predicting Olaparib response were investigated using patient-derived tumor organoids and xenograft models. The underlying mechanism was delineated using the Proteome Profiler Human Ubiquitin Array.<h3>Results</h3>ADRM1-ΔEx9, not its full-length counterpart, conferred human liver organoids with pro-survival advantages and a more profound tumor formation in a hydrodynamic transfected murine model. Functional knockdown resulted in spontaneous apoptosis in cell lines and patient-derived organoids, highlighting a pivotal role for ADRM1-ΔEx9 in HCC oncogenicity. Mechanistically, the shortened C-terminus of ADRM1-ΔEx9 signified a specific deubiquitinase partner BAP1 and navigated proteasome specificity. The new exon 8-10 fusion in ADRM1-ΔEx9 created a <em>de novo</em> binding to tumor suppressor protein FBXW7, resulting in its selective proteasome-mediated degradation. The loss of FBXW7 protein in ADRM1-ΔEx9 expressing tumors underscores their sensitivity to PARP inhibitor Olaparib. Notably, findings on ADRM1-ΔEx9 in primary HCC tumors denote its overexpression in a subgroup of patients with inferior survival and a window of therapeutic opportunity through its synthetic lethality association with Olaparib.<h3>Conclusion</h3>ADRM1-ΔEx9 redirects ubiquitin proteasome specificity to degrade the tumor suppressor protein FBXW7 selectively. This promotes HCC tumor formation and provides a synthetic lethal link for PARPi therapy.<h3>Impact and implications</h3>Reduced tumor suppressor protein FBXW7 expression is pivotal in HCC pathogenesis and other liver diseases. However, the regulatory mechanism governing FBXW7 protein expression remains elusive. Herein, we unveil a non-canonical spliced isoform of the ubiquitin receptor ADRM1 that selectively degrades FBXW7 protein, thereby promoting the premalignant transformation of hepatic cells and conferring growth advantages to HCC tumors. Furthermore, our results demonstrate that ADRM1-ΔEx9-expressing HCC tumors exhibited sensitivity to Olaparib in a dose-dependent manner, implicating the potential use of Olaparib in targeting ADRM1-ΔEx9-driven HCC growth.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"48 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935150","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}

{"title":"Why weight loss is only half the battle: the epigenetic memory of adipose tissue","authors":"Valerie Chew","doi":"10.1016/j.jhep.2024.12.011","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.12.011","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Context</h2>Obesity is a major driver of chronic diseases, including type 2 diabetes, cardiovascular disease, and metabolic dysfunction-associated steatotic liver disease (MASLD), posing significant public health challenges¹. While weight loss (WL) through dietary, pharmacological, or surgical interventions offers metabolic improvements, sustaining these benefits is notoriously difficult due to the phenomenon of \"yo-yo\" or oscillatory weight rebound effect2, 3. Early studies attributed this phenomenon to</section></section><section><section><h2>Objectives, Methods and Findings</h2>The study analysed subcutaneous AT (scAT) and omental AT (omAT) biopsies from 18 lean individuals (who have never had obesity) and 20 individuals with obesity (without diabetes) before (T0) and 2 yr after (T1) bariatric surgery (BaS) from three independent studies⁹. Only those who achieved at least a 25% reduction in body mass index post-BaS (the WL cohort) were included. Despite no major differences in the snRNA-seq cellular composition between T0 and T1, a significant number of differentially</section></section><section><section><h2>Significance of Findings</h2>Collectively, these results indicate that prior nutritional states leave a lasting epigenetic imprint on adipocytes, influencing their future response to feeding and contributing to rebound obesity. Epigenetic changes, including histone modifications and chromatin accessibility, were key drivers of these differences, emphasizing how prior metabolic states can influence adipocyte function and promote long-term obesity outcomes.Notably, while these obesogenic imprints appear stable in AT, similar</section></section><section><section><h2>Declaration of Competing Interest</h2>None</section></section><section><section><h2>Acknowledgement:</h2>This work was supported by the National Medical Research Council (NMRC), Singapore (reference number: CIRG22jul-0025, NMRC/OFLCG/003/2018) and National Research Foundation, Singapore (ref number: NRF-CRP26-2021-0005).</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"66 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929530","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}

{"title":"The use of immunotherapy pre-liver transplant","authors":"Laia Aceituno, Annabel Katherine Gravely, Grainne Mary O’Kane, Arndt Vogel, Gonzalo Sapisochin","doi":"10.1016/j.jhep.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.11.005","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Financial support</h2>The authors did not receive any financial support to produce this manuscript.</section></section><section><section><h2>Authors’ contributions</h2>Aceituno L: Created and developed the manuscript, including building the snapshot. Gravely A: Created and developed the manuscript, including building the snapshot. O’Kane GM: supervised the project and provided assistance with writing the manuscript and the snapshot. Vogel A: supervised the project and provided assistance with writing the manuscript and the snapshot. Sapisochin G: supervised the overall project, assistance with the development of the idea and provided assistance with writing</section></section><section><section><h2>Conflict of interest</h2>The authors of this study declare that they do not have any conflict of interest.Please refer to the accompanying ICMJE disclosure forms for further details.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"82 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924572","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}

{"title":"Host hepatocyte senescence determines the success of hepatocyte transplantation in a mouse model of liver injury","authors":"Victoria L. Gadd, Sofia Ferreira-Gonzalez, Tak Yung Man, Alastair M. Kilpatrick, Rhona E. Aird, Ian P. Smith, Daniel Rodrigo-Torres, Dominic Kurian, John M. Hallett, Candice Ashmore-Harris, Hannah Esser, Marisa F. Ferreira, Mark T. Macmillan, Wei-Yu Lu, Stuart J. Forbes","doi":"10.1016/j.jhep.2024.12.039","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.12.039","url":null,"abstract":"<h3>Background &amp; Aims</h3>Hepatocyte transplantation has shown promise for genetic diseases of the hepatocytes but to date has shown limited efficacy for non-genetic forms of severe liver injury. Limited cell engraftment and poor function of donor hepatocytes in recipient livers impacts the clinical utility of hepatocyte cell therapy. The mechanisms underpinning this are poorly understood. We explored this in a liver injury model, where predictable levels of injury and hepatocyte senescence was induced in <em>AhCreMdm2</em>^fl/fl mice through genetic excision of hepatocyte <em>Mdm2</em>.<h3>Methods</h3>Freshly isolated mouse, or human cryopreserved hepatocytes were delivered via intrasplenic injection into <em>AhCreMdm2</em>^fl/fl (immune competent and deficient strains) mice. Engraftment kinetics, donor cell engraftment and host liver function were assessed. Paired transcriptomic and proteomic analyses were performed on healthy vs senescent mouse hepatocytes.<h3>Results</h3>We found inhibition of host hepatocyte proliferation and liver injury is a requirement for donor hepatocyte engraftment and long-term repopulation, improving liver repair and function, but excessive senescence inhibited this process causing graft function decline due to transmission of senescence from host to donor cells. Paired proteomic and transcriptomic analysis of healthy vs senescent hepatocytes reveal a unique senescent signature associated with paracrine senescence. Modification of the host niche prior to transplantation with the senotherapeutic drug ABT737 improved donor cell proliferative capacity.<h3>Conclusions</h3>The host niche impacts the initial engraftment and long-term function of transplanted hepatocytes. Targeting paracrine senescence may be a way to improve donor hepatocyte function, optimise therapy and guide translation into the clinics.<h3>Impact and Implications</h3>Hepatocyte transplantation has shown promise for genetic diseases but has limited efficacy for acute and severe liver injury. Poor engraftment and functionality inhibit wide-spread clinical application. We show that host senescence provides a required non-competitive niche for donor hepatocytes to repopulate the recipient liver, but can paradoxically, negatively impact donor function. These findings demonstrate a requirement for a clear understanding of the host niche prior to cell transfusion. This has significant implications not only for hepatocellular therapies, but also when developing and optimising any pre-clinical and clinical cell therapies.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"34 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917498","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}

{"title":"Hepatitis B virus spliced 1 RNA, a key factor for viral expression.","authors":"Pierre Bablon, Céline Goy, Hoan Nguyen Dang, Jules Sotty, Patrick Soussan","doi":"10.1016/j.jhep.2024.04.033","DOIUrl":"10.1016/j.jhep.2024.04.033","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":"e39-e41"},"PeriodicalIF":26.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908862","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}

{"title":"Neuropilin-1 is a novel host factor modulating the entry of hepatitis B virus.","authors":"Haibo Yu, Jihua Ren, Haijun Deng, Linfeng Li, Zhenzhen Zhang, Shengtao Cheng, Zufeng Guo, Ailong Huang, Yongjun Dang, Kunling Song, Daiqing Wu, Xinyan Yao, Yiping Qin, Zhen Yang, Kexin Xu, Xin He, Juan Chen","doi":"10.1016/j.jhep.2024.06.032","DOIUrl":"10.1016/j.jhep.2024.06.032","url":null,"abstract":"<p><strong>Background & aims: </strong>Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for HBV. However, hepatocytes expressing NTCP exhibit varying susceptibilities to HBV infection. This study aimed to investigate whether other host factors modulate the process of HBV infection.</p><p><strong>Methods: </strong>Liver biopsy samples obtained from children with hepatitis B were used for single-cell sequencing and susceptibility analysis. Primary human hepatocytes, HepG2-NTCP cells, and human liver chimeric mice were used to analyze the effect of candidate host factors on HBV infection.</p><p><strong>Results: </strong>Single-cell sequencing and susceptibility analysis revealed a positive correlation between neuropilin-1 (NRP1) expression and HBV infection. In the HBV-infected cell model, NRP1 overexpression before HBV inoculation significantly enhanced viral attachment and internalization, and promoted viral infection in the presence of NTCP. Mechanistic studies indicated that NRP1 formed a complex with LHBs (large hepatitis B surface proteins) and NTCP. The NRP1 b domain mediated its interaction with conserved arginine residues at positions 88 and 92 in the preS1 domain of LHBs. This NRP1-preS1 interaction subsequently promoted the binding of preS1 to NTCP, facilitating viral infection. Moreover, disruption of the NRP1-preS1 interaction by the NRP1 antagonist EG00229 significantly attenuated the binding affinity between NTCP and preS1, thereby inhibiting HBV infection both in vitro and in vivo.</p><p><strong>Conclusions: </strong>Our findings indicate that NRP1 is a novel host factor for HBV infection, which interacts with preS1 and NTCP to modulate HBV entry into hepatocytes.</p><p><strong>Impact and implications: </strong>HBV infection is a global public health problem, but the understanding of the early infection process of HBV remains limited. Through single-cell sequencing, we identified a novel host factor, NRP1, which modulates HBV entry by interacting with HBV preS1 and NTCP. Moreover, antagonists targeting NRP1 can inhibit HBV infection both in vitro and in vivo. This study could further advance our comprehension of the early infection process of HBV.</p>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":"37-50"},"PeriodicalIF":26.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498211","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}

{"title":"Patient-reported outcomes in chronic hepatitis delta: An exploratory analysis of the phase III MYR301 trial of bulevirtide.","authors":"Maria Buti, Heiner Wedemeyer, Soo Aleman, Vladimir Chulanov, Viacheslav Morozov, Olga Sagalova, Tatiana Stepanova, Robert G Gish, Andrew Lloyd, Ankita M Kaushik, Vithika Suri, Dmitry Manuilov, Anu O Osinusi, John F Flaherty, Pietro Lampertico","doi":"10.1016/j.jhep.2024.06.031","DOIUrl":"10.1016/j.jhep.2024.06.031","url":null,"abstract":"<p><strong>Background & aims: </strong>Once-daily treatment of chronic hepatitis delta (CHD) with bulevirtide is well tolerated and associated with significant reductions in HDV RNA in the blood and in biochemical liver disease activity. This study explored the effects of 48-week bulevirtide treatment on health-related quality of life (HRQoL) in patients with CHD.</p><p><strong>Methods: </strong>In an open-label, randomised, phase III trial, 150 patients with CHD and compensated liver disease were stratified by cirrhosis status and randomised 1:1:1 to no treatment (control), bulevirtide 2 mg/day, or bulevirtide 10 mg/day for 48 weeks. HRQoL was evaluated by the following patient-reported outcome instruments at baseline, 24 weeks, and 48 weeks: EQ-5D-3L, Hepatitis Quality of Life Questionnaire, and Fatigue Severity Scale.</p><p><strong>Results: </strong>Patient characteristics and HRQoL scores were balanced at baseline between the treatment (2 mg, n = 49; 10 mg, n = 50) and control (n = 51) groups. Patients receiving 2 mg bulevirtide reported significant improvements compared with controls on the Hepatitis Quality of Life Questionnaire domains of role physical, hepatitis-specific limitations, and hepatitis-specific health distress. Numerically higher scores for general health, hepatitis-specific limitations, and hepatitis-specific health distress domains were reported by patients with cirrhosis who received bulevirtide vs. controls. Fatigue Severity Scale scores remained stable across treatment groups throughout. At week 48, patients in the 2 mg group showed greater mean improvement from baseline in health status compared with controls on the EQ-5D-3L visual analogue scale.</p><p><strong>Conclusion: </strong>Patient-reported outcomes indicate that 48-week treatment with bulevirtide monotherapy may improve aspects of HRQoL in patients with CHD.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov Identifier, NCT03852719.</p><p><strong>Impact and implications: </strong>Bulevirtide 2 mg is the only approved treatment for patients with chronic hepatitis delta (CHD) in the EU. Patients with CHD have worse quality of life scores than those with chronic hepatitis B. Bulevirtide treatment for 48 weeks reduced HDV RNA and alanine aminotransferase levels and was well tolerated among patients with CHD. For the first time, this study shows that patients who received bulevirtide therapy for 48 weeks reported improvements in physical and hepatitis-related quality of life domains compared with those who did not receive therapy (control group).</p>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":"28-36"},"PeriodicalIF":26.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620132","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}

{"title":"Pre-transplant immune checkpoint inhibitor use: The intersection between medicine, surgery and pharmacy.","authors":"David M Salerno, Tara Shertel, Robert S Brown","doi":"10.1016/j.jhep.2024.07.022","DOIUrl":"10.1016/j.jhep.2024.07.022","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":"e62-e63"},"PeriodicalIF":26.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792599","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}