End-stage liver disease represents a critical hepatic condition with high mortality, for which liver transplantation remains the only effective treatment. However, the scarcity of suitable donors results in numerous patients dying while awaiting transplantation. Novel strategies, including cell therapies and technologies mimicking liver organogenesis, offer promising alternatives for treating end-stage liver disease by potentially providing new sources of liver grafts. Recently, significant progress has been made in this field, including stem cell transplantation, hepatocyte transplantation, in vitro liver tissue generation, and liver replacement technologies. Several clinical studies have demonstrated that stem cell transplantation and hepatocyte transplantation can prolong patient survival and serve as a bridge to liver transplantation. Furthermore, in vitro liver tissue generation technologies, such as liver organoids and three-dimensional bioprinting, can generate hepatic tissues with sophisticated structures and functions, making them promising transplantation materials. Notably, liver replacement technologies hold considerable potential for producing biologically functional and transplantable liver grafts. In this review, we discuss the fundamental principles and recent advancements in cell therapies and liver organogenesis technologies while also addressing the challenges and future prospects in this rapidly evolving field.
{"title":"Cell therapies and liver organogenesis technologies: Promising strategies for end-stage liver disease.","authors":"Shaoyang Qin, Xiaochen Bo, Hongyuan Liu, Zhishuo Zhang, Zhicong Zhao, Qiang Xia","doi":"10.1097/HEP.0000000000001321","DOIUrl":"10.1097/HEP.0000000000001321","url":null,"abstract":"<p><p>End-stage liver disease represents a critical hepatic condition with high mortality, for which liver transplantation remains the only effective treatment. However, the scarcity of suitable donors results in numerous patients dying while awaiting transplantation. Novel strategies, including cell therapies and technologies mimicking liver organogenesis, offer promising alternatives for treating end-stage liver disease by potentially providing new sources of liver grafts. Recently, significant progress has been made in this field, including stem cell transplantation, hepatocyte transplantation, in vitro liver tissue generation, and liver replacement technologies. Several clinical studies have demonstrated that stem cell transplantation and hepatocyte transplantation can prolong patient survival and serve as a bridge to liver transplantation. Furthermore, in vitro liver tissue generation technologies, such as liver organoids and three-dimensional bioprinting, can generate hepatic tissues with sophisticated structures and functions, making them promising transplantation materials. Notably, liver replacement technologies hold considerable potential for producing biologically functional and transplantable liver grafts. In this review, we discuss the fundamental principles and recent advancements in cell therapies and liver organogenesis technologies while also addressing the challenges and future prospects in this rapidly evolving field.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1567-1586"},"PeriodicalIF":18.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770815","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 : 2026-11-01Epub Date: 2026-04-29DOI: 10.1097/HEP.0000000000001779
Armando Andres Roca Suarez, Barbara Testoni, Fabien Zoulim
{"title":"B-BEST: Profiling the intrahepatic HBV reservoir at single-cell resolution.","authors":"Armando Andres Roca Suarez, Barbara Testoni, Fabien Zoulim","doi":"10.1097/HEP.0000000000001779","DOIUrl":"10.1097/HEP.0000000000001779","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1267-1269"},"PeriodicalIF":18.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758262","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 : 2026-11-01Epub Date: 2026-09-24DOI: 10.1097/HEP.0000000000001826
Zobair M Younossi, Leyla de Avila, Salvatore Petta, Hannes Hagström, Seung Up Kim, Atsushi Nakajima, Javier Crespo, Laurent Castera, Naim Alkhouri, Ming-Hua Zheng, Sombat Treeprasertsuk, Prooksa Ananchuensook, Shalimar, Emmanuel Tsochatzis, Shenoy Kotacherry Trivikrama, Leena Kondarappassery Balakumaran, Jian-Gao Fan, Stuart K Roberts, Khalid Alswat, Vincent Wai-Sun Wong, Yusuf Yilmaz, Winston Dunn, Sven Francque, Ahmed Cordie, Ming-Lung Yu, Mattias Ekstedt, George Boon-Bee Goh, Claudia P Oliveira, Mario Guimaraes Pessoa, Wah Kheong Chan, Marlen Ivon Castellanos Fernandez, Ajay Duseja, Juan Pablo Arab, George Papatheodoridis, Giada Sebastiani, Cristiane Villela-Nogueira, Roberta D'Ambrosio, Pietro Lampertico, Khalid Alnaamani, A G Holleboom, Arun Valsan, Arathi Venu, Mohamed El-Kassas, Grazia Pennisi, Ying Shang, Wen-Yue Liu, Hye Won Lee, Takashi Kobayashi, Satoru Kakizaki, Cyrielle Caussy, Brian Pearlman, Paula Iruzubieta, Rida Nadeem, Felice Cinque, Antonia Neonaki, Mirko Zoncapé, Rui-Xu Yang, Sherlot Juan Song, Nicholas Dunn, Zouhir Gadi, Ming-Lun Yeh, Kevin Kim-Jun, Sanjiv Mahadeva, Licet Gonzalez Fabian, Ahmed Almohsen, Nathalie Leite, Nicola Pugliese, Johan Vessby, Chencheng Xie, Narendra Singh Choudhary, Ethan Friend, Maria Poca, Takumi Kawaguchi, Francesco Paolo Russo, Adrian Gadano, Luis Antonio Diaz, Ashwani K Singal, Berenice Segrestin, Nadege Gunn, Didac Mauricio, Marco Arrese, Anna Fracanzani, Rosa Lombardi, Brian Lam, Andrei Racila, Saleh A Alqahtani, Maria Stepanova
{"title":"Erratum: Global performance of non-invasive tests in MASLD: Insights from the G-MASLD study.","authors":"Zobair M Younossi, Leyla de Avila, Salvatore Petta, Hannes Hagström, Seung Up Kim, Atsushi Nakajima, Javier Crespo, Laurent Castera, Naim Alkhouri, Ming-Hua Zheng, Sombat Treeprasertsuk, Prooksa Ananchuensook, Shalimar, Emmanuel Tsochatzis, Shenoy Kotacherry Trivikrama, Leena Kondarappassery Balakumaran, Jian-Gao Fan, Stuart K Roberts, Khalid Alswat, Vincent Wai-Sun Wong, Yusuf Yilmaz, Winston Dunn, Sven Francque, Ahmed Cordie, Ming-Lung Yu, Mattias Ekstedt, George Boon-Bee Goh, Claudia P Oliveira, Mario Guimaraes Pessoa, Wah Kheong Chan, Marlen Ivon Castellanos Fernandez, Ajay Duseja, Juan Pablo Arab, George Papatheodoridis, Giada Sebastiani, Cristiane Villela-Nogueira, Roberta D'Ambrosio, Pietro Lampertico, Khalid Alnaamani, A G Holleboom, Arun Valsan, Arathi Venu, Mohamed El-Kassas, Grazia Pennisi, Ying Shang, Wen-Yue Liu, Hye Won Lee, Takashi Kobayashi, Satoru Kakizaki, Cyrielle Caussy, Brian Pearlman, Paula Iruzubieta, Rida Nadeem, Felice Cinque, Antonia Neonaki, Mirko Zoncapé, Rui-Xu Yang, Sherlot Juan Song, Nicholas Dunn, Zouhir Gadi, Ming-Lun Yeh, Kevin Kim-Jun, Sanjiv Mahadeva, Licet Gonzalez Fabian, Ahmed Almohsen, Nathalie Leite, Nicola Pugliese, Johan Vessby, Chencheng Xie, Narendra Singh Choudhary, Ethan Friend, Maria Poca, Takumi Kawaguchi, Francesco Paolo Russo, Adrian Gadano, Luis Antonio Diaz, Ashwani K Singal, Berenice Segrestin, Nadege Gunn, Didac Mauricio, Marco Arrese, Anna Fracanzani, Rosa Lombardi, Brian Lam, Andrei Racila, Saleh A Alqahtani, Maria Stepanova","doi":"10.1097/HEP.0000000000001826","DOIUrl":"10.1097/HEP.0000000000001826","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E70-E71"},"PeriodicalIF":18.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035877","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 : 2026-11-01Epub Date: 2026-02-06DOI: 10.1097/HEP.0000000000001712
Claudia Wing-Kwan Wu, Rashid N Lui
{"title":"Unraveling the immunogenetic architecture of cholangiocarcinoma.","authors":"Claudia Wing-Kwan Wu, Rashid N Lui","doi":"10.1097/HEP.0000000000001712","DOIUrl":"10.1097/HEP.0000000000001712","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1262-1263"},"PeriodicalIF":18.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140422","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 : 2026-11-01Epub Date: 2026-05-06DOI: 10.1097/HEP.0000000000001780
Vania Cari, María I Perez, Ignacio Tellez, Francisco Idalsoaga, Arun Valsan, Gowripriya Nair, Kriti Soni, S Fisher Rhoads, Jorge Arnold, Maria Ayala-Valverde, Carolina Ramirez-Cadiz, Prasun K Jalal, Mohamad A Ibrahim, Mohamed A Elfeki, Juan P Roblero, Daniela Simian, Jose A Velarde-Ruiz Velasco, Jacqueline Cordova, Fátima Higuera-de-la-Tijera, Rita Silva, Cristina M Rocha, Roberta C Araujo, Guilherme M Fontani, Gustavo H Pereira, Fernando Bessone, Mario Tanno, Ayelen Kisch, Manuel Mendizabal, Sebastian Marciano, Gonzalo Gomez-Perdiguero, Pedro Montes, Patricia Guerra Salazar, Geraldine Ramos, Kristina R Chacko, Lubomir Skladaný, Rakhi Maiwall, Douglas Simonetto, Arun J Sanyal, Vijay H Shah, Ashwani K Singal, Winston Dunn, Patrick S Kamath, Rohit Loomba, Marco Arrese, Ramon Bataller, Luis A Díaz, Juan Pablo Arab
Background and aims: Although the role of cardiometabolic risk factors (CMRFs) has been characterized in steatotic liver disease, their role in the severity of alcohol-associated hepatitis (AH) remains unclear. We aimed to evaluate the impact of CMRFs on mortality.
Approach and results: Multinational prospective cohort study (2015-2024) including hospitalized patients with AH across 32 centers in 14 countries. Diagnosis of AH was made using the National Institute on Alcohol Abuse and Alcoholism criteria. Analyses included adjusted competing-risk models by age, sex, ethnicity, history of cirrhosis, CMRF, corticosteroid use, MELD, and acute-on-chronic liver failure grade, with liver transplantation as a competing risk. Nine hundred thirty-six participants were included; the mean age was 48±11.2 years, and 88.9% were male. At least 1 CMRF was present in 46.6%; median body mass index was 24.2 kg/m 2 [IQR: 22.8-28.2], prevalence of diabetes 17.6%, hypertension 16.5%, and dyslipidemia 5.8%. Median MELD was 24.4 (19.3-31.4), 86.7% had severe AH, and 180-day survival was 72.9%. Survival did not differ by CMRF status (log-rank p =0.453). In adjusted competing-risk models, higher age (subdistribution hazard ratio [sHR] 1.03; 95% CI: 1.01-1.04), greater alcohol intake (per g/day; sHR: 1.001; 95% CI: 1.000-1.002), MELD (sHR: 1.04; 95% CI: 1.01-1.06), and acute-on-chronic liver failure grade 2-3 (sHR: 2.34 and 4.34) predicted mortality. However, no individual CMRF independently increased mortality. A prespecified nonlinear body mass index analysis showed modestly lower mortality between 25 and 40 kg/m², with a higher risk above 40 kg/m².
Conclusions: Among patients with severe AH, metabolic dysfunction was not associated with increased mortality. Although a higher body mass index was associated with slightly lower mortality in AH, this may reflect better nutritional status rather than a true protective effect.
{"title":"Exploring the interaction between metabolic dysfunction and alcohol-associated hepatitis: A global study.","authors":"Vania Cari, María I Perez, Ignacio Tellez, Francisco Idalsoaga, Arun Valsan, Gowripriya Nair, Kriti Soni, S Fisher Rhoads, Jorge Arnold, Maria Ayala-Valverde, Carolina Ramirez-Cadiz, Prasun K Jalal, Mohamad A Ibrahim, Mohamed A Elfeki, Juan P Roblero, Daniela Simian, Jose A Velarde-Ruiz Velasco, Jacqueline Cordova, Fátima Higuera-de-la-Tijera, Rita Silva, Cristina M Rocha, Roberta C Araujo, Guilherme M Fontani, Gustavo H Pereira, Fernando Bessone, Mario Tanno, Ayelen Kisch, Manuel Mendizabal, Sebastian Marciano, Gonzalo Gomez-Perdiguero, Pedro Montes, Patricia Guerra Salazar, Geraldine Ramos, Kristina R Chacko, Lubomir Skladaný, Rakhi Maiwall, Douglas Simonetto, Arun J Sanyal, Vijay H Shah, Ashwani K Singal, Winston Dunn, Patrick S Kamath, Rohit Loomba, Marco Arrese, Ramon Bataller, Luis A Díaz, Juan Pablo Arab","doi":"10.1097/HEP.0000000000001780","DOIUrl":"10.1097/HEP.0000000000001780","url":null,"abstract":"<p><strong>Background and aims: </strong>Although the role of cardiometabolic risk factors (CMRFs) has been characterized in steatotic liver disease, their role in the severity of alcohol-associated hepatitis (AH) remains unclear. We aimed to evaluate the impact of CMRFs on mortality.</p><p><strong>Approach and results: </strong>Multinational prospective cohort study (2015-2024) including hospitalized patients with AH across 32 centers in 14 countries. Diagnosis of AH was made using the National Institute on Alcohol Abuse and Alcoholism criteria. Analyses included adjusted competing-risk models by age, sex, ethnicity, history of cirrhosis, CMRF, corticosteroid use, MELD, and acute-on-chronic liver failure grade, with liver transplantation as a competing risk. Nine hundred thirty-six participants were included; the mean age was 48±11.2 years, and 88.9% were male. At least 1 CMRF was present in 46.6%; median body mass index was 24.2 kg/m 2 [IQR: 22.8-28.2], prevalence of diabetes 17.6%, hypertension 16.5%, and dyslipidemia 5.8%. Median MELD was 24.4 (19.3-31.4), 86.7% had severe AH, and 180-day survival was 72.9%. Survival did not differ by CMRF status (log-rank p =0.453). In adjusted competing-risk models, higher age (subdistribution hazard ratio [sHR] 1.03; 95% CI: 1.01-1.04), greater alcohol intake (per g/day; sHR: 1.001; 95% CI: 1.000-1.002), MELD (sHR: 1.04; 95% CI: 1.01-1.06), and acute-on-chronic liver failure grade 2-3 (sHR: 2.34 and 4.34) predicted mortality. However, no individual CMRF independently increased mortality. A prespecified nonlinear body mass index analysis showed modestly lower mortality between 25 and 40 kg/m², with a higher risk above 40 kg/m².</p><p><strong>Conclusions: </strong>Among patients with severe AH, metabolic dysfunction was not associated with increased mortality. Although a higher body mass index was associated with slightly lower mortality in AH, this may reflect better nutritional status rather than a true protective effect.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1503-1513"},"PeriodicalIF":18.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831425","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 : 2026-10-16DOI: 10.1097/hep.0000000000001851
Prowpanga Udompap
{"title":"A gentler squeeze: A first signal from OCE-205, a selective V1a mixed agonist–antagonist for hepatorenal syndrome–acute kidney injury","authors":"Prowpanga Udompap","doi":"10.1097/hep.0000000000001851","DOIUrl":"https://doi.org/10.1097/hep.0000000000001851","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"14 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187891","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 : 2026-10-16DOI: 10.1097/hep.0000000000001853
Enis H. Ozmert
{"title":"Present but not prescient: Cardiometabolic risk factors in alcohol-associated hepatitis","authors":"Enis H. Ozmert","doi":"10.1097/hep.0000000000001853","DOIUrl":"https://doi.org/10.1097/hep.0000000000001853","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"13 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187888","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 : 2026-10-16DOI: 10.1097/hep.0000000000001820
Kevin Houston, Juan Pablo Arab
{"title":"Rethinking albumin after paracentesis: It’s not just about the volume","authors":"Kevin Houston, Juan Pablo Arab","doi":"10.1097/hep.0000000000001820","DOIUrl":"https://doi.org/10.1097/hep.0000000000001820","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"68 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187887","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 : 2026-10-16DOI: 10.1097/hep.0000000000001852
Hanna Erickson
{"title":"Turning down the ammonia dial: Phase 2a evidence for YAQ007 in cirrhosis","authors":"Hanna Erickson","doi":"10.1097/hep.0000000000001852","DOIUrl":"https://doi.org/10.1097/hep.0000000000001852","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"20 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187889","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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