Pub Date : 2026-01-01Epub Date: 2025-10-17DOI: 10.1016/j.jhepr.2025.101645
Xiao-Dong Zhou , Sherlot Juan Song , Chloe Yitian Guo , Qin-Fen Chen , Grace Lai-Hung Wong , Ting-Ran Ye , George Boon Bee Goh , Yong Mong Bee , Li-You Lian , Terry Cheuk-Fung Yip , Jimmy Che-To Lai , Si-Yi Lei , Wen-Yue Liu , Ren Chenghan Fan , Cheng-Lv Hong , Giovanni Targher , Christopher D. Byrne , Guillemette Marot , Violeta Raverdy , Francois Pattou , Ming-Hua Zheng
<div><h3>Background & Aims</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous condition that presents varying risks for liver-related and cardiovascular complications. Clustering methods have identified distinct MASLD subtypes, yet their applicability to Asian populations remains unclear. This study aims to validate a MASLD clustering model using clinical variables from three Asian cohorts: Wenzhou Real-World (WRW), Hong Kong Clinical Data Analysis and Reporting System (CDARS), and SingHealth Diabetes Registry.</div></div><div><h3>Methods</h3><div>Clustering analysis was conducted based on age, BMI, hemoglobin A<sub>1c</sub>, alanine aminotransferase, LDL-cholesterol, and triglycerides. Outcomes included major adverse cardiovascular events (MACE), liver-related events (LRE), and new-onset type 2 diabetes (T2DM). They were analyzed using Cox regression risk models and Kaplan–Meier analyses to assess risk and incident events across MASLD clusters.</div></div><div><h3>Results</h3><div>Across the three cohorts, distinct risk patterns emerged for MACE, LRE, and T2DM among various MASLD clusters. For MACE, the cardiometabolic cluster exhibited the highest risk in all cohorts: WRW (hazard ratio [HR] 1.315, <em>p</em> <0.001), Hong Kong CDARS (HR 1.559, <em>p</em> <0.001), and SingHealth Diabetes Registry (HR 1.262, <em>p</em> <0.001). For LRE, the liver-specific cluster showed the highest risk in the WRW (HR 1.578, <em>p</em> = 0.002) and SingHealth Diabetes Registry cohorts (HR 2.403, <em>p</em> <0.001). In contrast, in the Hong Kong CDARS cohort, both the cardiometabolic (HR 1.818, <em>p</em> <0.001) and liver-specific clusters (HR 1.557, <em>p</em> <0.001) exhibited similarly increased risks. For T2DM, the cardiometabolic cluster showed the highest risk in the WRW (HR 3.418, <em>p</em> <0.001) and Hong Kong CDARS cohorts (HR 2.761, <em>p</em> <0.001).</div></div><div><h3>Conclusions</h3><div>The proposed MASLD clustering model is applicable to Asian populations, facilitating personalized treatment and optimizing outcomes.</div></div><div><h3>Impact and implications</h3><div>This study provides scientific justification for applying a validated clustering model to metabolic dysfunction-associated steatotic liver disease (MASLD), demonstrating that patient subgroups identified by data-driven methods carry distinct risks for cardiovascular and liver-related outcomes. These findings are important for clinicians, researchers, and policymakers as they highlight that MASLD is not a uniform disease but rather comprises heterogeneous subgroups with differing prognoses. In practice, this work supports subgroup-based strategies to personalize treatment, improve risk stratification, and optimize the allocation of healthcare resources. The results also offer a foundation for future research into targeted therapeutic interventions while acknowledging the need for further validation in diverse pop
背景和目的代谢功能障碍相关脂肪变性肝病（MASLD）是一种异质性疾病，呈现出肝脏相关和心血管并发症的不同风险。聚类方法已经确定了不同的MASLD亚型，但它们对亚洲人群的适用性仍不清楚。本研究旨在利用三个亚洲队列的临床变量验证MASLD聚类模型：温州真实世界（WRW）、香港临床数据分析和报告系统（CDARS）和SingHealth糖尿病登记处。方法根据年龄、BMI、糖化血红蛋白、丙氨酸转氨酶、低密度脂蛋白胆固醇、甘油三酯进行聚类分析。结果包括主要不良心血管事件（MACE）、肝脏相关事件（LRE）和新发2型糖尿病（T2DM）。使用Cox回归风险模型和Kaplan-Meier分析来评估MASLD集群的风险和事件事件。结果在三个队列中，不同的MASLD集群中出现了不同的MACE、LRE和T2DM风险模式。对于MACE，心脏代谢组在所有队列中表现出最高的风险：WRW（风险比[HR] 1.315, p <0.001）， Hong Kong CDARS（风险比[HR] 1.559, p <0.001）和SingHealth Diabetes Registry（风险比[HR] 1.262, p <0.001）。对于LRE，肝脏特异性群集在WRW （HR 1.578, p = 0.002）和SingHealth Diabetes Registry队列（HR 2.403, p <0.001）中显示出最高的风险。相比之下，在香港CDARS队列中，心脏代谢（HR 1.818, p <0.001）和肝脏特异性聚集（HR 1.557, p <0.001）均表现出类似的风险增加。对于T2DM，心脏代谢组在WRW组（HR 3.418, p <0.001）和香港CDARS组（HR 2.761, p <0.001）的风险最高。结论MASLD聚类模型适用于亚洲人群，有利于个性化治疗和优化治疗效果。影响和意义本研究为将有效的聚类模型应用于代谢功能障碍相关脂肪变性肝病（MASLD）提供了科学依据，表明通过数据驱动方法确定的患者亚组具有心血管和肝脏相关结局的不同风险。这些发现对临床医生、研究人员和政策制定者很重要，因为它们强调了MASLD不是一种统一的疾病，而是由预后不同的异质亚群组成。在实践中，这项工作支持基于亚组的策略来个性化治疗，改善风险分层，优化医疗资源分配。该结果也为未来的针对性治疗干预研究提供了基础，同时承认需要在不同人群中进一步验证。
{"title":"Validation of a data-driven clustering model for MASLD: Evidence from three large-scale Asian cohorts","authors":"Xiao-Dong Zhou , Sherlot Juan Song , Chloe Yitian Guo , Qin-Fen Chen , Grace Lai-Hung Wong , Ting-Ran Ye , George Boon Bee Goh , Yong Mong Bee , Li-You Lian , Terry Cheuk-Fung Yip , Jimmy Che-To Lai , Si-Yi Lei , Wen-Yue Liu , Ren Chenghan Fan , Cheng-Lv Hong , Giovanni Targher , Christopher D. Byrne , Guillemette Marot , Violeta Raverdy , Francois Pattou , Ming-Hua Zheng","doi":"10.1016/j.jhepr.2025.101645","DOIUrl":"10.1016/j.jhepr.2025.101645","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous condition that presents varying risks for liver-related and cardiovascular complications. Clustering methods have identified distinct MASLD subtypes, yet their applicability to Asian populations remains unclear. This study aims to validate a MASLD clustering model using clinical variables from three Asian cohorts: Wenzhou Real-World (WRW), Hong Kong Clinical Data Analysis and Reporting System (CDARS), and SingHealth Diabetes Registry.</div></div><div><h3>Methods</h3><div>Clustering analysis was conducted based on age, BMI, hemoglobin A<sub>1c</sub>, alanine aminotransferase, LDL-cholesterol, and triglycerides. Outcomes included major adverse cardiovascular events (MACE), liver-related events (LRE), and new-onset type 2 diabetes (T2DM). They were analyzed using Cox regression risk models and Kaplan–Meier analyses to assess risk and incident events across MASLD clusters.</div></div><div><h3>Results</h3><div>Across the three cohorts, distinct risk patterns emerged for MACE, LRE, and T2DM among various MASLD clusters. For MACE, the cardiometabolic cluster exhibited the highest risk in all cohorts: WRW (hazard ratio [HR] 1.315, <em>p</em> <0.001), Hong Kong CDARS (HR 1.559, <em>p</em> <0.001), and SingHealth Diabetes Registry (HR 1.262, <em>p</em> <0.001). For LRE, the liver-specific cluster showed the highest risk in the WRW (HR 1.578, <em>p</em> = 0.002) and SingHealth Diabetes Registry cohorts (HR 2.403, <em>p</em> <0.001). In contrast, in the Hong Kong CDARS cohort, both the cardiometabolic (HR 1.818, <em>p</em> <0.001) and liver-specific clusters (HR 1.557, <em>p</em> <0.001) exhibited similarly increased risks. For T2DM, the cardiometabolic cluster showed the highest risk in the WRW (HR 3.418, <em>p</em> <0.001) and Hong Kong CDARS cohorts (HR 2.761, <em>p</em> <0.001).</div></div><div><h3>Conclusions</h3><div>The proposed MASLD clustering model is applicable to Asian populations, facilitating personalized treatment and optimizing outcomes.</div></div><div><h3>Impact and implications</h3><div>This study provides scientific justification for applying a validated clustering model to metabolic dysfunction-associated steatotic liver disease (MASLD), demonstrating that patient subgroups identified by data-driven methods carry distinct risks for cardiovascular and liver-related outcomes. These findings are important for clinicians, researchers, and policymakers as they highlight that MASLD is not a uniform disease but rather comprises heterogeneous subgroups with differing prognoses. In practice, this work supports subgroup-based strategies to personalize treatment, improve risk stratification, and optimize the allocation of healthcare resources. The results also offer a foundation for future research into targeted therapeutic interventions while acknowledging the need for further validation in diverse pop","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 1","pages":"Article 101645"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682288","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 : 2026-01-01Epub Date: 2025-11-04DOI: 10.1016/j.jhepr.2025.101635
Sabrina Welland , Ann-Kristin Zöller , Ilektra A. Mavroeidi , Aurelie Tomczak , Christian Müller , Dong Yawen , Danmei Zhang , Felix Keil , Maria Pangerl , Taotao Zhou , Hossein Taghizadeh , Sebastian Lange , Maximilian N. Kinzler , Kataryna Shmanko , Maryam Barsch , Carolin Zimpel , Angela Djanani , Henning Schulze-Bergkamen , Julius Keyl , Florian Lüke , Arndt Vogel
<div><h3>Background & Aims</h3><div>Biliary tract cancers (BTC) are aggressive malignancies with limited treatment options. Owing to the high frequency of actionable genomic alterations (GA) and the availability of targeted therapies, molecular testing has become increasingly important; however, its clinical implementation remains inconsistent. This study aimed to evaluate real-world molecular testing practices, characterize the BTC molecular landscape, and assess the prognostic and predictive relevance of selected GA.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed genomic and clinical data from 1,521 patients treated at 18 centers in Germany and Austria. A side-by-side comparison of clinical grade reports generated on two different sequencing platforms was performed for 90 patients.</div></div><div><h3>Results</h3><div>Twenty-four different NGS panels were used across 18 centers. A comparative analysis highlighted the significant variability in reports used to inform therapeutic decisions in clinical practice. Although there were substantial differences in the number of GA covered, the broader panels identified a similar number of actionable GA, indicating that key therapeutic targets are sufficiently represented. Integration with clinical data suggested that certain GA, such as <em>HER2</em> amplifications (3%)<em>, BRAF</em><sup><em>V600E</em></sup> mutations (2%), and <em>FGFR2</em> alterations (14%), may have prognostic significance beyond their predictive value. Patients with actionable alterations (610, 40%) that were treated accordingly (n = 204, 13%) had prolonged overall survival (31.8 months <em>vs.</em> 22.8 months, <em>p</em> <0.01).</div></div><div><h3>Conclusion</h3><div>Standardized biomarker testing is crucial for effective integration of targeted therapies in the management of BTC. Our findings reinforce the value of targeted treatments and underscore the predictive and prognostic significance of selected GA.</div></div><div><h3>Impact and implications</h3><div>Genomic profiling is recommended in patients with biliary tract cancers (BTC) but lacks harmonization across platforms and centers. By retrospectively analyzing genomic and clinical information from 1,521 patients with BTC diagnosed and treated at 18 centers in Germany and Austria, we provide real-world insights into the implementation of molecular profiling in BTC, highlighting variability in next generation sequencing-based testing and its impact on the detection of genomic alterations. Standardized molecular testing strategies will be key to enable the integration of more consistent and comparable genomic datasets across studies. Further, by elucidating the prognostic relevance of individual genomic alterations, our insights carry significant implications for interpreting single-arm clinical trials within genomically stratified patient cohorts and underscore the importance of randomized studies to delineate the benefit of targeted therapies.</d
{"title":"Clinical practice and implications of biomarker testing in biliary tract cancer: An observational study","authors":"Sabrina Welland , Ann-Kristin Zöller , Ilektra A. Mavroeidi , Aurelie Tomczak , Christian Müller , Dong Yawen , Danmei Zhang , Felix Keil , Maria Pangerl , Taotao Zhou , Hossein Taghizadeh , Sebastian Lange , Maximilian N. Kinzler , Kataryna Shmanko , Maryam Barsch , Carolin Zimpel , Angela Djanani , Henning Schulze-Bergkamen , Julius Keyl , Florian Lüke , Arndt Vogel","doi":"10.1016/j.jhepr.2025.101635","DOIUrl":"10.1016/j.jhepr.2025.101635","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Biliary tract cancers (BTC) are aggressive malignancies with limited treatment options. Owing to the high frequency of actionable genomic alterations (GA) and the availability of targeted therapies, molecular testing has become increasingly important; however, its clinical implementation remains inconsistent. This study aimed to evaluate real-world molecular testing practices, characterize the BTC molecular landscape, and assess the prognostic and predictive relevance of selected GA.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed genomic and clinical data from 1,521 patients treated at 18 centers in Germany and Austria. A side-by-side comparison of clinical grade reports generated on two different sequencing platforms was performed for 90 patients.</div></div><div><h3>Results</h3><div>Twenty-four different NGS panels were used across 18 centers. A comparative analysis highlighted the significant variability in reports used to inform therapeutic decisions in clinical practice. Although there were substantial differences in the number of GA covered, the broader panels identified a similar number of actionable GA, indicating that key therapeutic targets are sufficiently represented. Integration with clinical data suggested that certain GA, such as <em>HER2</em> amplifications (3%)<em>, BRAF</em><sup><em>V600E</em></sup> mutations (2%), and <em>FGFR2</em> alterations (14%), may have prognostic significance beyond their predictive value. Patients with actionable alterations (610, 40%) that were treated accordingly (n = 204, 13%) had prolonged overall survival (31.8 months <em>vs.</em> 22.8 months, <em>p</em> <0.01).</div></div><div><h3>Conclusion</h3><div>Standardized biomarker testing is crucial for effective integration of targeted therapies in the management of BTC. Our findings reinforce the value of targeted treatments and underscore the predictive and prognostic significance of selected GA.</div></div><div><h3>Impact and implications</h3><div>Genomic profiling is recommended in patients with biliary tract cancers (BTC) but lacks harmonization across platforms and centers. By retrospectively analyzing genomic and clinical information from 1,521 patients with BTC diagnosed and treated at 18 centers in Germany and Austria, we provide real-world insights into the implementation of molecular profiling in BTC, highlighting variability in next generation sequencing-based testing and its impact on the detection of genomic alterations. Standardized molecular testing strategies will be key to enable the integration of more consistent and comparable genomic datasets across studies. Further, by elucidating the prognostic relevance of individual genomic alterations, our insights carry significant implications for interpreting single-arm clinical trials within genomically stratified patient cohorts and underscore the importance of randomized studies to delineate the benefit of targeted therapies.</d","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 1","pages":"Article 101635"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682308","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}
Under-dilated transjugular intrahepatic portosystemic shunts (U-TIPS) has been proposed to reduce the risk of overt hepatic encephalopathy (OHE) while effectively treating portal hypertension (PH) complications. In this study we assessed how end-procedural porto-caval pressure gradient (PCPG), obtained in sedated patients, and endoprosthesis dilation affect the risk of OHE after TIPS.
Methods
Consecutive patients with cirrhosis receiving TIPS for refractory ascites or recurrent PH-related bleeding were enrolled. OHE within 1-year was analyzed using a competing risk model, accounting for death and liver transplantation. Adequate hemodynamic response (AHR) was defined as post-TIPS PCPG <12 mmHg or reduction ≥60% in refractory ascites, and <12 mmHg or reduction ≥50% in PH-related bleeding. PCPG values outside of the above criteria were considered as inadequate response. U-TIPS was defined as endoprosthesis dilation ≤7 mm, as opposed to standard TIPS (S-TIPS).
Results
Among 408 patients enrolled, 50% received U-TIPS, 63% achieved AHR, and 46% had a PCPG <10 mmHg. One-year cumulative incidence of OHE was 33% and 50% in U-TIPS and S-TIPS, respectively (p <0.001). In the univariable analysis, both AHR and PCPG <10 mmHg, and S-TIPS were associated with higher cumulative incidence of OHE. In a model comprising age, previous history of OHE, TIPS indication, liver disease severity and endoprosthesis dilation, only S-TIPS along with older age, previous history of OHE and Child-Pugh class B and C, were statistically significantly associated with OHE.
Subgroup analysis stratified by U-TIPS vs. S-TIPS confirmed that AHR and PCPG <10 mmHg were not associated with OHE within either TIPS group.
Conclusions
The magnitude of the shunt emerges as an independent key determinant of post-TIPS OHE.
Impact and implications
TIPS carries a significant risk of overt hepatic encephalopathy. Low portosystemic pressure gradient and larger shunt diameter have been reported to increase the risk of overt hepatic encephalopathy. The TIPS dilation diameter represents an independent key determinant of post-TIPS overt hepatic encephalopathy. Thus, TIPS under-dilation reduces overt hepatic encephalopathy occurrence while effectively controlling portal hypertension complications even without meeting established hemodynamic targets.
{"title":"Shunt magnitude is a key determinant of overt hepatic encephalopathy in patients undergoing TIPS","authors":"Davide Roccarina , Dario Saltini , Marco Senzolo , Silvia Nardelli , Martina Rosi , Valentina Adotti , Marcello Bianchini , Lara Biribin , Stefania Gioia , Cristian Caporali , Lucia Ragozzino , Tomas Guasconi , Margherita Falcini , Federico Casari , Antonio Piscopo , Francesco Pindozzi , Stefano Gitto , Silvia Aspite , Gianmarco Falcone , Angelica Ingravallo , Francesco Vizzutti","doi":"10.1016/j.jhepr.2025.101676","DOIUrl":"10.1016/j.jhepr.2025.101676","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Under-dilated transjugular intrahepatic portosystemic shunts (U-TIPS) has been proposed to reduce the risk of overt hepatic encephalopathy (OHE) while effectively treating portal hypertension (PH) complications. In this study we assessed how end-procedural porto-caval pressure gradient (PCPG), obtained in sedated patients, and endoprosthesis dilation affect the risk of OHE after TIPS.</div></div><div><h3>Methods</h3><div>Consecutive patients with cirrhosis receiving TIPS for refractory ascites or recurrent PH-related bleeding were enrolled. OHE within 1-year was analyzed using a competing risk model, accounting for death and liver transplantation. Adequate hemodynamic response (AHR) was defined as post-TIPS PCPG <12 mmHg or reduction ≥60% in refractory ascites, and <12 mmHg or reduction ≥50% in PH-related bleeding. PCPG values outside of the above criteria were considered as inadequate response. U-TIPS was defined as endoprosthesis dilation ≤7 mm, as opposed to standard TIPS (S-TIPS).</div></div><div><h3>Results</h3><div>Among 408 patients enrolled, 50% received U-TIPS, 63% achieved AHR, and 46% had a PCPG <10 mmHg. One-year cumulative incidence of OHE was 33% and 50% in U-TIPS and S-TIPS, respectively (<em>p</em> <0.001). In the univariable analysis, both AHR and PCPG <10 mmHg, and S-TIPS were associated with higher cumulative incidence of OHE. In a model comprising age, previous history of OHE, TIPS indication, liver disease severity and endoprosthesis dilation, only S-TIPS along with older age, previous history of OHE and Child-Pugh class B and C, were statistically significantly associated with OHE.</div><div>Subgroup analysis stratified by U-TIPS <em>vs.</em> S-TIPS confirmed that AHR and PCPG <10 mmHg were not associated with OHE within either TIPS group.</div></div><div><h3>Conclusions</h3><div>The magnitude of the shunt emerges as an independent key determinant of post-TIPS OHE.</div></div><div><h3>Impact and implications</h3><div>TIPS carries a significant risk of overt hepatic encephalopathy. Low portosystemic pressure gradient and larger shunt diameter have been reported to increase the risk of overt hepatic encephalopathy. The TIPS dilation diameter represents an independent key determinant of post-TIPS overt hepatic encephalopathy. Thus, TIPS under-dilation reduces overt hepatic encephalopathy occurrence while effectively controlling portal hypertension complications even without meeting established hemodynamic targets.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 1","pages":"Article 101676"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786927","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 : 2026-01-01Epub Date: 2025-10-17DOI: 10.1016/j.jhepr.2025.101646
Youxin Wang , Ruiqiu Chen , Shi Yan Lee , Eunice X.X. Tan , Mark Muthiah , Zhou Yu , Margaret L.P. Teng , Jazleen Leo , Cheng Han Ng , Ashok Choudhury , Daniel Q. Huang
Background & Aims
Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) are rising causes of liver-related morbidity and mortality worldwide. The burden among women of childbearing age (15–49 years) is not well defined. We quantified global and regional trends from 2010 to 2021 and projected prevalence through 2035.
Methods
Prevalence, incident cases, and disability-adjusted life-years (DALYs) among women of childbearing age were estimated using the Global Burden of Disease 2021 framework. Temporal trends were evaluated using Joinpoint regression to estimate annual percent change. Inequality was assessed using the slope and concentration indices, and prevalence was projected using Bayesian age–period–cohort models.
Results
Between 2010 and 2021, global MASLD prevalence rose by 13.8%, reaching 15,759 per 100,000 population in 2021. The highest burden was observed in the Eastern Mediterranean region (24,530 per 100,000 population), with the most pronounced increases seen in high sociodemographic index countries (+20.0%) and the Western Pacific region (+21.9%). Conversely, ALD prevalence declined by 6.8% to 11.0 per 100,000 population, with notable declines in Europe (-15.5%) but modest increases in the Western Pacific (+10.5%) and Eastern Mediterranean (+3.7%). The burden of both MASLD and ALD rose steadily with age and peaked among women aged 45–49 years. Despite a higher prevalence, MASLD contributed modest DALY rates (20.4 per 100,000 population), whereas ALD, although less prevalent, imposed a greater burden (29.1 per 100,000 population). By 2035, MASLD prevalence is projected to reach 17,393 per 100,000 population (+10.4%), and ALD prevalence is projected to reach 11.5 per 100,000 population (+4.5%).
Conclusions
MASLD is rapidly increasing among women of childbearing age, with marked regional and socioeconomic disparities, whereas the burden of ALD appears to be in decline.
Impact and implications
Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) among women of childbearing age are often overlooked despite significant maternal and intergenerational health consequences. Our analysis shows a rising prevalence of MASLD and a modest decline in ALD, with marked regional and socioeconomic disparities, and projects continued MASLD growth through 2035. These findings are important for clinicians, researchers, and policymakers, given the associated maternal, neonatal, and intergenerational risks. Integrating metabolic and reproductive health services alongside equitable policy interventions may help mitigate these concerning trends.
{"title":"Rising burden of steatotic liver disease in women of childbearing age and projections to 2035","authors":"Youxin Wang , Ruiqiu Chen , Shi Yan Lee , Eunice X.X. Tan , Mark Muthiah , Zhou Yu , Margaret L.P. Teng , Jazleen Leo , Cheng Han Ng , Ashok Choudhury , Daniel Q. Huang","doi":"10.1016/j.jhepr.2025.101646","DOIUrl":"10.1016/j.jhepr.2025.101646","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) are rising causes of liver-related morbidity and mortality worldwide. The burden among women of childbearing age (15–49 years) is not well defined. We quantified global and regional trends from 2010 to 2021 and projected prevalence through 2035.</div></div><div><h3>Methods</h3><div>Prevalence, incident cases, and disability-adjusted life-years (DALYs) among women of childbearing age were estimated using the Global Burden of Disease 2021 framework. Temporal trends were evaluated using Joinpoint regression to estimate annual percent change. Inequality was assessed using the slope and concentration indices, and prevalence was projected using Bayesian age–period–cohort models.</div></div><div><h3>Results</h3><div>Between 2010 and 2021, global MASLD prevalence rose by 13.8%, reaching 15,759 per 100,000 population in 2021. The highest burden was observed in the Eastern Mediterranean region (24,530 per 100,000 population), with the most pronounced increases seen in high sociodemographic index countries (+20.0%) and the Western Pacific region (+21.9%). Conversely, ALD prevalence declined by 6.8% to 11.0 per 100,000 population, with notable declines in Europe (-15.5%) but modest increases in the Western Pacific (+10.5%) and Eastern Mediterranean (+3.7%). The burden of both MASLD and ALD rose steadily with age and peaked among women aged 45–49 years. Despite a higher prevalence, MASLD contributed modest DALY rates (20.4 per 100,000 population), whereas ALD, although less prevalent, imposed a greater burden (29.1 per 100,000 population). By 2035, MASLD prevalence is projected to reach 17,393 per 100,000 population (+10.4%), and ALD prevalence is projected to reach 11.5 per 100,000 population (+4.5%).</div></div><div><h3>Conclusions</h3><div>MASLD is rapidly increasing among women of childbearing age, with marked regional and socioeconomic disparities, whereas the burden of ALD appears to be in decline.</div></div><div><h3>Impact and implications</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) among women of childbearing age are often overlooked despite significant maternal and intergenerational health consequences. Our analysis shows a rising prevalence of MASLD and a modest decline in ALD, with marked regional and socioeconomic disparities, and projects continued MASLD growth through 2035. These findings are important for clinicians, researchers, and policymakers, given the associated maternal, neonatal, and intergenerational risks. Integrating metabolic and reproductive health services alongside equitable policy interventions may help mitigate these concerning trends.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 1","pages":"Article 101646"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682289","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 : 2026-01-01Epub Date: 2025-10-09DOI: 10.1016/j.jhepr.2025.101623
Kristoffer Kjærgaard , Jeppe Mygind Yeoman , Peter Lykke Eriksen , Anne Catrine Daugaard Mikkelsen , Emilie Eifer Møller , Ann-Sophie Frees Wietz , Andressa de Zawadzki , Lars Christian Gormsen , Sara Heebøll , Hendrik Vilstrup , Karen Louise Thomsen
Background & Aims
Binge drinking is a common pattern of alcohol intake often considered particularly harmful. However, its immediate effects on the development of hepatic steatosis and early alcohol-related liver injury are not well established. This study aimed to investigate the acute effects of binge drinking on the liver and its reversibility in healthy individuals.
Methods
Healthy adults were studied in a real-world setting before, the day after, and 10 days after attending a 3-day festival. The participants were alcohol abstinent 1 week prior to the first visit and between the last two visits. Each visit included liver MRI-proton density fat fraction and elastography, and blood tests. Alcohol and food intake were self-reported during the festival, and blood alcohol concentration was measured once daily.
Results
Fifteen participants (9 male, 6 female) aged 36 ± 5 years with a BMI of 23.2 ± 2.7 kg/m2 completed the study. They consumed 186 ± 56 g of alcohol per day resulting in a 2.5-fold increase in hepatic fat fraction from 1.9% (IQR 1.6%-2.5%) to 4.6% (IQR 2.4%-5.7%), p <0.0001. Six participants (40%) developed steatosis; compared to those without steatosis, they had higher baseline BMI, triglycerides and glucagon, and lower free fatty acids, while there was no difference in alcohol or energy consumption. Binge drinking also increased liver stiffness and triglycerides, while LDL-cholesterol decreased. After 10 days of abstinence, all outcome measures were normalised.
Conclusions
Three days of recreational binge drinking increased liver fat content and stiffness in most participants. This early consequence of excessive alcohol intake was resolved after 10 days of abstinence, suggesting that the acute hepatic effects of binge drinking are readily reversible if followed by short-term abstinence.
Impact and implications
Binge drinking is considered a high-risk pattern of alcohol intake associated with various health hazards, yet its immediate effects on the liver are not well understood. This study provides direct real-world evidence that one episode of binge drinking (3 days) can acutely induce hepatic steatosis in healthy individuals, particularly those with subclinical metabolic dysfunction. Importantly, all consequences of binge drinking were normalised following 10 days of alcohol abstinence. These findings offer timely insight into the health risks of recreational binge drinking and contribute knowledge with potential implications for public health messaging and recommendations, clinical guidance, and alcohol policies.
背景和目的酗酒是一种常见的酒精摄入模式，通常被认为是特别有害的。然而，它对肝脂肪变性和早期酒精相关肝损伤的直接影响尚未得到很好的证实。本研究旨在探讨酗酒对健康个体肝脏的急性影响及其可逆性。方法在现实环境中对健康成人参加为期3天的节日活动前、后1天和后10天进行研究。参与者在第一次访问前1周和最后两次访问之间戒酒。每次访问包括肝脏mri质子密度脂肪分数和弹性成像，以及血液检查。在节日期间，酒精和食物摄入量是自我报告的，血液酒精浓度每天测量一次。结果15名参与者（男9名，女6名）完成研究，年龄36±5岁，BMI为23.2±2.7 kg/m2。他们每天摄入186±56克酒精，导致肝脏脂肪含量从1.9% （IQR 1.6%-2.5%）增加2.5倍至4.6% (IQR 2.4%-5.7%), p <0.0001。6名参与者（40%）发生脂肪变性；与没有脂肪变性的人相比，他们的基线BMI、甘油三酯和胰高血糖素更高，游离脂肪酸更低，而酒精和能量消耗没有差异。酗酒还会增加肝脏硬度和甘油三酯，同时降低低密度脂蛋白胆固醇。禁欲10天后，所有结果指标归一化。结论3天的娱乐性狂饮增加了大多数参与者的肝脏脂肪含量和硬度。过量饮酒的早期后果在戒酒10天后就消失了，这表明，如果在短期戒酒后，酗酒对肝脏的急性影响很容易逆转。影响和启示酗酒被认为是一种高风险的酒精摄入模式，与各种健康危害有关，但其对肝脏的直接影响尚不清楚。这项研究提供了直接的现实证据，证明一次狂饮（3天）可以急性诱导健康个体的肝脂肪变性，特别是那些有亚临床代谢功能障碍的人。重要的是，在戒酒10天后，酗酒的所有后果都恢复正常。这些发现及时地揭示了娱乐性狂饮的健康风险，并为公共卫生信息和建议、临床指导和酒精政策提供了潜在的启示。
{"title":"Binge drinking acutely induces hepatic steatosis which is readily reversible: A real-world observational study in healthy adults","authors":"Kristoffer Kjærgaard , Jeppe Mygind Yeoman , Peter Lykke Eriksen , Anne Catrine Daugaard Mikkelsen , Emilie Eifer Møller , Ann-Sophie Frees Wietz , Andressa de Zawadzki , Lars Christian Gormsen , Sara Heebøll , Hendrik Vilstrup , Karen Louise Thomsen","doi":"10.1016/j.jhepr.2025.101623","DOIUrl":"10.1016/j.jhepr.2025.101623","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Binge drinking is a common pattern of alcohol intake often considered particularly harmful. However, its immediate effects on the development of hepatic steatosis and early alcohol-related liver injury are not well established. This study aimed to investigate the acute effects of binge drinking on the liver and its reversibility in healthy individuals.</div></div><div><h3>Methods</h3><div>Healthy adults were studied in a real-world setting before, the day after, and 10 days after attending a 3-day festival. The participants were alcohol abstinent 1 week prior to the first visit and between the last two visits. Each visit included liver MRI-proton density fat fraction and elastography, and blood tests. Alcohol and food intake were self-reported during the festival, and blood alcohol concentration was measured once daily.</div></div><div><h3>Results</h3><div>Fifteen participants (9 male, 6 female) aged 36 ± 5 years with a BMI of 23.2 ± 2.7 kg/m<sup>2</sup> completed the study. They consumed 186 ± 56 g of alcohol per day resulting in a 2.5-fold increase in hepatic fat fraction from 1.9% (IQR 1.6%-2.5%) to 4.6% (IQR 2.4%-5.7%), <em>p</em> <0.0001. Six participants (40%) developed steatosis; compared to those without steatosis, they had higher baseline BMI, triglycerides and glucagon, and lower free fatty acids, while there was no difference in alcohol or energy consumption. Binge drinking also increased liver stiffness and triglycerides, while LDL-cholesterol decreased. After 10 days of abstinence, all outcome measures were normalised.</div></div><div><h3>Conclusions</h3><div>Three days of recreational binge drinking increased liver fat content and stiffness in most participants. This early consequence of excessive alcohol intake was resolved after 10 days of abstinence, suggesting that the acute hepatic effects of binge drinking are readily reversible if followed by short-term abstinence.</div></div><div><h3>Impact and implications</h3><div>Binge drinking is considered a high-risk pattern of alcohol intake associated with various health hazards, yet its immediate effects on the liver are not well understood. This study provides direct real-world evidence that one episode of binge drinking (3 days) can acutely induce hepatic steatosis in healthy individuals, particularly those with subclinical metabolic dysfunction. Importantly, all consequences of binge drinking were normalised following 10 days of alcohol abstinence. These findings offer timely insight into the health risks of recreational binge drinking and contribute knowledge with potential implications for public health messaging and recommendations, clinical guidance, and alcohol policies.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 1","pages":"Article 101623"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594694","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 : 2026-01-01Epub Date: 2025-10-09DOI: 10.1016/j.jhepr.2025.101613
Erman Akkus , Antonella Cammarota , Laura Izquierdo-Sanchez , Jesus M. Banales , Alejandro Forner , Ana Lleo , Rocio I.R. Macias , Angela Lamarca , Mohamed Bouattour
<div><h3>Background & Aims</h3><div>Early-onset gastrointestinal cancers represent a growing global health concern. Among these, early-onset biliary tract cancer (EO-BTC) remains relatively understudied. In this systematic review, we synthesize current evidence for EO-BTC.</div></div><div><h3>Methods</h3><div>A comprehensive systematic literature search was performed across multiple databases. Original studies investigating epidemiology, risk factors, clinical presentation, pathological and/or molecular features, treatment, and prognosis of EO-BTC were included and synthesized. Meta-analyses were performed using the Mantel–Haenszel and generic inverse variance methods with random-effects models.</div></div><div><h3>Results</h3><div>In total, 32 studies were included. EO-BTC incidence varied by anatomical subtype, with a notable increase in early-onset intrahepatic cholangiocarcinoma. Disparities in ethnicity and socioeconomic status were apparent between younger and older patients. Clinically, the disease was often diagnosed at a more advanced stage in younger patients (for stage IV, odds ratio [OR], 1.31; 95% CI, 1.19–1.43; <em>p</em> <0.001; <em>I</em><sup><em>2</em></sup>, 62%) and was associated with a higher prevalence of intrahepatic cholangiocarcinoma (OR, 1.41; 95% CI, 1.23–1.61; <em>p</em> <0.001; <em>I</em><sup><em>2</em></sup>, 49%). <em>FGFR2</em> fusions were significantly more common in early-onset cases (OR, 2.81; 95% CI, 2.31–3.64; <em>p</em> <0.001; <em>I</em><sup><em>2</em></sup>, 0%). Younger patients had fewer comorbidities and more frequently received curative-intent local and systemic therapies (surgery: OR, 1.38; 95% CI, 1.22–1.57; <em>p</em> <0.001; <em>I</em><sup><em>2</em></sup>, 85%). Prognostic data were heterogeneous; however, pooled analysis suggested a trend to improved OS in patients with early-onset disease (unadjusted hazard ratio [HR], 0.84; 95% CI, 0.75–0.93; <em>p</em> = 0.001; <em>I</em><sup><em>2</em></sup>, 81%); adjusted HR, 0.78; 95% CI, 0.66–0.94; <em>p</em> = 0.007; <em>I</em><sup><em>2</em></sup>, 91%).</div></div><div><h3>Conclusions</h3><div>EO-BTC represents a clinically and molecularly distinct subset within biliary tract cancers, with emerging epidemiological patterns, a higher prevalence of actionable molecular alterations, and differences in treatment allocation. Further prospective and age-stratified studies are needed to guide age-adapted detection and therapeutic strategies.</div></div><div><h3>PROSPERO ID</h3><div>CRD420251039039.</div></div><div><h3>Impact and implications</h3><div>This systematic review highlights that EO-BTC exhibits different epidemiological and molecular patterns compared with later-onset disease, including a higher prevalence of intrahepatic subtypes and greater frequency of targetable alterations, such as <em>FGFR2</em> fusions. These findings underscore the importance of incorporating routine molecular profiling and the integration of stratified manag
{"title":"Epidemiology, clinical, molecular features, and prognosis of early-onset biliary tract cancer: A systematic review and meta-analysis","authors":"Erman Akkus , Antonella Cammarota , Laura Izquierdo-Sanchez , Jesus M. Banales , Alejandro Forner , Ana Lleo , Rocio I.R. Macias , Angela Lamarca , Mohamed Bouattour","doi":"10.1016/j.jhepr.2025.101613","DOIUrl":"10.1016/j.jhepr.2025.101613","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Early-onset gastrointestinal cancers represent a growing global health concern. Among these, early-onset biliary tract cancer (EO-BTC) remains relatively understudied. In this systematic review, we synthesize current evidence for EO-BTC.</div></div><div><h3>Methods</h3><div>A comprehensive systematic literature search was performed across multiple databases. Original studies investigating epidemiology, risk factors, clinical presentation, pathological and/or molecular features, treatment, and prognosis of EO-BTC were included and synthesized. Meta-analyses were performed using the Mantel–Haenszel and generic inverse variance methods with random-effects models.</div></div><div><h3>Results</h3><div>In total, 32 studies were included. EO-BTC incidence varied by anatomical subtype, with a notable increase in early-onset intrahepatic cholangiocarcinoma. Disparities in ethnicity and socioeconomic status were apparent between younger and older patients. Clinically, the disease was often diagnosed at a more advanced stage in younger patients (for stage IV, odds ratio [OR], 1.31; 95% CI, 1.19–1.43; <em>p</em> <0.001; <em>I</em><sup><em>2</em></sup>, 62%) and was associated with a higher prevalence of intrahepatic cholangiocarcinoma (OR, 1.41; 95% CI, 1.23–1.61; <em>p</em> <0.001; <em>I</em><sup><em>2</em></sup>, 49%). <em>FGFR2</em> fusions were significantly more common in early-onset cases (OR, 2.81; 95% CI, 2.31–3.64; <em>p</em> <0.001; <em>I</em><sup><em>2</em></sup>, 0%). Younger patients had fewer comorbidities and more frequently received curative-intent local and systemic therapies (surgery: OR, 1.38; 95% CI, 1.22–1.57; <em>p</em> <0.001; <em>I</em><sup><em>2</em></sup>, 85%). Prognostic data were heterogeneous; however, pooled analysis suggested a trend to improved OS in patients with early-onset disease (unadjusted hazard ratio [HR], 0.84; 95% CI, 0.75–0.93; <em>p</em> = 0.001; <em>I</em><sup><em>2</em></sup>, 81%); adjusted HR, 0.78; 95% CI, 0.66–0.94; <em>p</em> = 0.007; <em>I</em><sup><em>2</em></sup>, 91%).</div></div><div><h3>Conclusions</h3><div>EO-BTC represents a clinically and molecularly distinct subset within biliary tract cancers, with emerging epidemiological patterns, a higher prevalence of actionable molecular alterations, and differences in treatment allocation. Further prospective and age-stratified studies are needed to guide age-adapted detection and therapeutic strategies.</div></div><div><h3>PROSPERO ID</h3><div>CRD420251039039.</div></div><div><h3>Impact and implications</h3><div>This systematic review highlights that EO-BTC exhibits different epidemiological and molecular patterns compared with later-onset disease, including a higher prevalence of intrahepatic subtypes and greater frequency of targetable alterations, such as <em>FGFR2</em> fusions. These findings underscore the importance of incorporating routine molecular profiling and the integration of stratified manag","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 1","pages":"Article 101613"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682307","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 : 2026-01-01Epub Date: 2025-10-17DOI: 10.1016/j.jhepr.2025.101643
Lisa Sandmann , Mathias Jachs , Tammo L. Tergast , Lukas Hartl , Birgit Bremer , Martin A. Kabelitz , Michael Schwarz , Julius F.M. Egge , Lorenz Balcar , Benedikt Silvester Hofer , Christine S. Falk , Albert Friedrich Stättermayer , Markus Cornberg , Michael Trauner , Katja Deterding , Mattias Mandorfer , Heiner Wedemeyer , Thomas Reiberger , Benjamin Maasoumy
<div><h3>Background & Aims</h3><div>Portal hypertension (PH) drives decompensation in patients with advanced chronic liver disease. Effects of antiviral treatment with bulevirtide (BLV) and achievement of suggested treatment endpoints on PH in patients with chronic hepatitis D (CHD) are unknown.</div></div><div><h3>Methods</h3><div>BLV-treated CHD patients with PH were prospectively enrolled in this observational, multicenter study. Hepatic venous pressure gradient (HVPG) was measured before (BL) and after ≥12 months of BLV treatment (M12). HVPG response (≥10% decline) rates were compared between virological (VR), biochemical (BR), and combined (CR) responders <em>vs.</em> non-responders as defined in the BLV phase III studies. Associated changes in biomarkers of bacterial translocation, (dys)angiogenesis/endothelial dysfunction, and systemic inflammation (SI) were investigated.</div></div><div><h3>Results</h3><div>Of 34 patients receiving BL HVPG measurement, 20 patients with paired HVPG measurement and a BL clinically significant portal hypertension (CSPH) (≥10 mmHg HVPG) prevalence of 85% were included. At M12, HVPG significantly decreased in patients with CR (n = 12; 15.5 [IQR 10.5–21.8] to 12 [IQR 7.3–15.8] mmHg; <em>p</em> <0.001), VR (n = 14; 14.5 [IQR 10–21.3] to 12 [IQR 7.8–16.5] mmHg, <em>p</em> = 0.003), and BR (n = 16; 12.5 [IQR 10–20.5] to 10.5 [IQR 8–15] mmHg, <em>p</em> = 0.002); but not in non-responders. All patients with CSPH with CR (n = 10/10) and most of VR (83%, n = 10/12) and BR (85%, n = 11/13) achieved HVPG response, but no BLV non-responder. CSPH resolved in three of 17 (17.6%) patients. Markers of bacterial translocation (sCD163; <em>p</em> = 0.001), (dys)angiogenesis/endothelial dysfunction (Ang2; <em>p</em> = 0.001) and SI (IFNγ, IL-1RA, sCD25/IL-2Rα, CCL3/MIP-1alpha, HGF; all <em>p</em> <0.05) decreased in responders but not in non-responders.</div></div><div><h3>Conclusions</h3><div>Significant HVPG decreases accompanied by improvement of bacterial translocation, (dys)angiogenesis/endothelial dysfunction and SI are observed in patients with CHD achieving BLV response. These findings provide evidence for the validity and clinical relevance of the currently recommended on-treatment response criteria.</div></div><div><h3>Clinical trials registration</h3><div>This study is registered at <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT04863703).</div></div><div><h3>Impact and implications</h3><div>Portal hypertension is the main mechanism driving clinical deterioration in patients with compensated advanced chronic liver disease, for which patients with chronic hepatitis D (CHD) are at particularly high risk. This study demonstrates that in patients with CHD with portal hypertension, achieving response to antiviral treatment with bulevirtide decreases the hepatic venous pressure gradient (HVPG). Importantly, a clinical meaningful reduction in HVPG was observed only in treatment responder
背景：在晚期慢性肝病患者中，运动性高血压（PH）会导致代偿失调。布来韦肽（BLV）抗病毒治疗对慢性丁型肝炎（CHD）患者PH的影响和建议治疗终点的实现尚不清楚。方法采用blv治疗的冠心病合并PH患者前瞻性纳入这项观察性多中心研究。在BLV治疗前（BL）和治疗后≥12个月（M12）测量肝静脉压梯度（HVPG）。比较BLV III期研究中定义的病毒学（VR）、生化（BR）和联合（CR）应答者与无应答者之间的HVPG应答率（下降≥10%）。研究了细菌易位、血管生成/内皮功能障碍和全身性炎症（SI）等生物标志物的相关变化。结果34例接受BL HVPG测量的患者中，20例同时进行HVPG配对测量且BL临床显著门脉高压（CSPH） （HVPG≥10 mmHg）患病率为85%。在M12时，CR （n = 12; 15.5 [IQR 10.5 - 21.8]至12 [IQR 7.3-15.8] mmHg; p <0.001）、VR （n = 14; 14.5 [IQR 10-21.3]至12 [IQR 7.8-16.5] mmHg, p = 0.003）和BR （n = 16; 12.5 [IQR 10-20.5]至10.5 [IQR 8-15] mmHg, p = 0.002）患者的HVPG显著降低；但对无反应者则不然。所有伴有CR （n = 10/10）、大部分VR （83%, n = 10/12）和BR （85%, n = 11/13）的CSPH患者均达到HVPG应答，但无BLV无应答者。17例患者中3例（17.6%）CSPH消退。细菌易位（sCD163, p = 0.001）、血管生成/内皮功能障碍（Ang2, p = 0.001）和SI （IFNγ、IL-1RA、sCD25/IL-2Rα、CCL3/ mip -1 α、HGF，均p <；0.05）在应答者中下降，而在无应答者中没有下降。结论在达到BLV应答的冠心病患者中，HVPG显著降低，同时细菌易位、血管生成/内皮功能障碍和SI改善。这些发现为目前推荐的治疗反应标准的有效性和临床相关性提供了证据。临床试验注册本研究已在ClinicalTrials.gov注册（NCT04863703）。影响和意义运动高血压是代偿性晚期慢性肝病患者临床恶化的主要机制，其中慢性丁型肝炎（CHD）患者的风险特别高。本研究表明，在伴有门脉高压的冠心病患者中，布来韦肽抗病毒治疗获得应答可降低肝静脉压梯度（HVPG）。重要的是，HVPG的临床意义降低仅在临床试验中使用的终点定义的治疗应答者中观察到，特别是在所有达到联合应答的患者中。重要病理生理机制的生物标志物也得到了改进。对抗病毒治疗有反应的冠心病患者HVPG下降的临床意义的发现加强了建议的治疗反应标准的临床意义，支持BLV反应的疾病改善作用，可能转化为冠心病患者发病率和死亡率的降低。
{"title":"Treatment response to bulevirtide is linked to amelioration of portal hypertension in patients with chronic hepatitis D","authors":"Lisa Sandmann , Mathias Jachs , Tammo L. Tergast , Lukas Hartl , Birgit Bremer , Martin A. Kabelitz , Michael Schwarz , Julius F.M. Egge , Lorenz Balcar , Benedikt Silvester Hofer , Christine S. Falk , Albert Friedrich Stättermayer , Markus Cornberg , Michael Trauner , Katja Deterding , Mattias Mandorfer , Heiner Wedemeyer , Thomas Reiberger , Benjamin Maasoumy","doi":"10.1016/j.jhepr.2025.101643","DOIUrl":"10.1016/j.jhepr.2025.101643","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Portal hypertension (PH) drives decompensation in patients with advanced chronic liver disease. Effects of antiviral treatment with bulevirtide (BLV) and achievement of suggested treatment endpoints on PH in patients with chronic hepatitis D (CHD) are unknown.</div></div><div><h3>Methods</h3><div>BLV-treated CHD patients with PH were prospectively enrolled in this observational, multicenter study. Hepatic venous pressure gradient (HVPG) was measured before (BL) and after ≥12 months of BLV treatment (M12). HVPG response (≥10% decline) rates were compared between virological (VR), biochemical (BR), and combined (CR) responders <em>vs.</em> non-responders as defined in the BLV phase III studies. Associated changes in biomarkers of bacterial translocation, (dys)angiogenesis/endothelial dysfunction, and systemic inflammation (SI) were investigated.</div></div><div><h3>Results</h3><div>Of 34 patients receiving BL HVPG measurement, 20 patients with paired HVPG measurement and a BL clinically significant portal hypertension (CSPH) (≥10 mmHg HVPG) prevalence of 85% were included. At M12, HVPG significantly decreased in patients with CR (n = 12; 15.5 [IQR 10.5–21.8] to 12 [IQR 7.3–15.8] mmHg; <em>p</em> <0.001), VR (n = 14; 14.5 [IQR 10–21.3] to 12 [IQR 7.8–16.5] mmHg, <em>p</em> = 0.003), and BR (n = 16; 12.5 [IQR 10–20.5] to 10.5 [IQR 8–15] mmHg, <em>p</em> = 0.002); but not in non-responders. All patients with CSPH with CR (n = 10/10) and most of VR (83%, n = 10/12) and BR (85%, n = 11/13) achieved HVPG response, but no BLV non-responder. CSPH resolved in three of 17 (17.6%) patients. Markers of bacterial translocation (sCD163; <em>p</em> = 0.001), (dys)angiogenesis/endothelial dysfunction (Ang2; <em>p</em> = 0.001) and SI (IFNγ, IL-1RA, sCD25/IL-2Rα, CCL3/MIP-1alpha, HGF; all <em>p</em> <0.05) decreased in responders but not in non-responders.</div></div><div><h3>Conclusions</h3><div>Significant HVPG decreases accompanied by improvement of bacterial translocation, (dys)angiogenesis/endothelial dysfunction and SI are observed in patients with CHD achieving BLV response. These findings provide evidence for the validity and clinical relevance of the currently recommended on-treatment response criteria.</div></div><div><h3>Clinical trials registration</h3><div>This study is registered at <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT04863703).</div></div><div><h3>Impact and implications</h3><div>Portal hypertension is the main mechanism driving clinical deterioration in patients with compensated advanced chronic liver disease, for which patients with chronic hepatitis D (CHD) are at particularly high risk. This study demonstrates that in patients with CHD with portal hypertension, achieving response to antiviral treatment with bulevirtide decreases the hepatic venous pressure gradient (HVPG). Importantly, a clinical meaningful reduction in HVPG was observed only in treatment responder","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 1","pages":"Article 101643"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682351","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 : 2026-01-01Epub Date: 2025-11-25DOI: 10.1016/j.jhepr.2025.101648
Maja Thiele
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