Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. With the widespread implementation of HBV vaccination and the availability of highly effective antiviral therapies, the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC has proportionally increased. Notably, up to 20%–30% of MASLD–related HCC cases develop in the absence of overt cirrhosis. Several genetic variants, primarily in genes related to lipid metabolism, play a key role in HCC development in individuals with MASLD and alcohol-related liver disease. Among these, the rs738409 C>G polymorphism (I148M) in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene is the strongest genetic factor predisposing to the entire spectrum of MASLD conditions, including cirrhosis and HCC. Importantly, combining PNPLA3 I148M with multiple genetic variants robustly associated with progressive liver disease (i.e., polygenic risk scores) improves risk stratification and prediction of HCC in at-risk individuals compared to the single variant alone. In this review, we will discuss the latest evidence on the epidemiology of HCC and the contribution of PNPLA3 and PNPLA3-based polygenic risk scores to the development of HCC in at-risk individuals.
{"title":"PNPLA3 I148M and Hepatocellular Carcinoma","authors":"Federica Tavaglione, Grazia Pennisi, Serena Pelusi","doi":"10.1111/liv.70051","DOIUrl":"https://doi.org/10.1111/liv.70051","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. With the widespread implementation of HBV vaccination and the availability of highly effective antiviral therapies, the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC has proportionally increased. Notably, up to 20%–30% of MASLD–related HCC cases develop in the absence of overt cirrhosis. Several genetic variants, primarily in genes related to lipid metabolism, play a key role in HCC development in individuals with MASLD and alcohol-related liver disease. Among these, the rs738409 C>G polymorphism (I148M) in the <i>patatin-like phospholipase domain-containing protein 3</i> (<i>PNPLA3</i>) gene is the strongest genetic factor predisposing to the entire spectrum of MASLD conditions, including cirrhosis and HCC. Importantly, combining <i>PNPLA3</i> I148M with multiple genetic variants robustly associated with progressive liver disease (i.e., polygenic risk scores) improves risk stratification and prediction of HCC in at-risk individuals compared to the single variant alone. In this review, we will discuss the latest evidence on the epidemiology of HCC and the contribution of <i>PNPLA3</i> and <i>PNPLA3</i>-based polygenic risk scores to the development of HCC in at-risk individuals.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yasmina Tashkent, Jocelyn M. Choo, Alyson Richard, Zhengyi Wang, Luis Calzadilla-Bertot, Egi Vasil, Sophie Miller, Steven L. Taylor, Kerry L. Ivey, Richard Woodman, Brendan Adler, Oyekoya T. Ayonrinde, John K. Olynyk, Lawrence J. Beilin, Trevor A. Mori, Alan J. Wigg, Kate R. Muller, Leon A. Adams, Geraint B. Rogers
Background and Aims
Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide. As SLD pathogenesis has been linked to gut microbiome alterations, we aimed to identify SLD-associated gut microbiome features early in SLD development by utilising a highly characterised cohort of community-dwelling younger adults.
Methods and Results
At age 27 years, 588 participants of the Raine Study Generation 2 underwent cross-sectional assessment. Hepatic steatosis was quantified using a validated magnetic resonance imaging (MRI) volumetric liver fat fraction (VLFF) equation (HepaFat). Of the 588 participants, 488 (83%) were classified as having ‘no SLD’ (VLFF ≤ 3.55%), 76 (12.9%) with ‘mild–moderate’ SLD (VLFF: 3.56%–13.4%) and 24 (4.10%) with ‘severe’ SLD (VLFF > 13.4%). Stool microbiome profiling identified an association between severe SLD and lower microbiota alpha diversity (observed features [p = 0.015], Pielou evenness [p = 0.001] and Shannon diversity [p = 0.002]) compared to no SLD. Faecal microbiota composition differed significantly between no SLD and both mild–moderate (p = 0.004) and severe SLD groups (p = 0.001). There was no significant difference in microbiota dispersion between SLD groups. Reduced relative abundance of short-chain fatty acid producing bacteria, and higher levels of proinflammatory bacterial taxa, were both significantly associated with severe SLD (q < 0.05).
Conclusions
SLD in younger adults is associated with reduced intestinal microbial diversity and a pattern of bacterial taxa depletion that is consistent with other chronic inflammatory conditions. Our characterisation of gut microbiome characteristics in early SLD development provides a potential basis for risk identification and reduction.
Trial Registration
The Raine Study is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617001599369)
{"title":"Steatotic Liver Disease in Younger Adults is Associated With Altered Gut Microbiology","authors":"Yasmina Tashkent, Jocelyn M. Choo, Alyson Richard, Zhengyi Wang, Luis Calzadilla-Bertot, Egi Vasil, Sophie Miller, Steven L. Taylor, Kerry L. Ivey, Richard Woodman, Brendan Adler, Oyekoya T. Ayonrinde, John K. Olynyk, Lawrence J. Beilin, Trevor A. Mori, Alan J. Wigg, Kate R. Muller, Leon A. Adams, Geraint B. Rogers","doi":"10.1111/liv.70032","DOIUrl":"https://doi.org/10.1111/liv.70032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide. As SLD pathogenesis has been linked to gut microbiome alterations, we aimed to identify SLD-associated gut microbiome features early in SLD development by utilising a highly characterised cohort of community-dwelling younger adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>At age 27 years, 588 participants of the Raine Study Generation 2 underwent cross-sectional assessment. Hepatic steatosis was quantified using a validated magnetic resonance imaging (MRI) volumetric liver fat fraction (VLFF) equation (HepaFat). Of the 588 participants, 488 (83%) were classified as having ‘no SLD’ (VLFF ≤ 3.55%), 76 (12.9%) with ‘mild–moderate’ SLD (VLFF: 3.56%–13.4%) and 24 (4.10%) with ‘severe’ SLD (VLFF > 13.4%). Stool microbiome profiling identified an association between severe SLD and lower microbiota alpha diversity (observed features [<i>p</i> = 0.015], Pielou evenness [<i>p</i> = 0.001] and Shannon diversity [<i>p</i> = 0.002]) compared to no SLD. Faecal microbiota composition differed significantly between no SLD and both mild–moderate (<i>p</i> = 0.004) and severe SLD groups (<i>p</i> = 0.001). There was no significant difference in microbiota dispersion between SLD groups. Reduced relative abundance of short-chain fatty acid producing bacteria, and higher levels of proinflammatory bacterial taxa, were both significantly associated with severe SLD (<i>q</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SLD in younger adults is associated with reduced intestinal microbial diversity and a pattern of bacterial taxa depletion that is consistent with other chronic inflammatory conditions. Our characterisation of gut microbiome characteristics in early SLD development provides a potential basis for risk identification and reduction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The Raine Study is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617001599369)</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lesley A. Patmore, Kirsi van Eekhout, Özgür M. Koc, Robert J. de Knegt, Harry L. A. Janssen, Willem P. Brouwer, Matthijs Kramer, Pieter Honkoop, Joep de Bruijne, Greet J. Boland, Douwe F. Postma, Hans Blokzijl, Robert A. de Man, R. Bart Takkenberg, Milan J. Sonneveld
Background and Aims
Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of liver-related events in patients with chronic hepatitis B (CHB), possibly by accelerating fibrosis progression. Therefore, we studied the influence of MASLD on liver stiffness measurement (LSM) kinetics in CHB patients.
Methods
We conducted a multicenter retrospective cohort study of CHB patients with at least two LSM with FibroScan. We studied the absolute change in LSM and the change in LSM stage from the first LSM to the most recent LSM among CHB patients with MASLD compared to patients without MASLD.
Results
We analysed 1055 CHB patients; 259 (28.0%) had MASLD. Patients with MASLD had a higher first and last LSM (6.1 vs. 5.2 kPa and 5.6 vs. 4.7 kPa, p < 0.001), were significantly less likely to achieve a decrease in LSM stage (52.8% vs. 74% p < 0.001) and were more likely to experience an increase in LSM stage (19.3% vs. 13.6%, p = 0.035) during follow-up. 417 (39.5%) patients initiated antiviral therapy (AVT) which was associated with a decline in LSM (p < 0.001). However, patients with MASLD who were treated were less likely to decrease in LSM stage (52.4% vs. 77.0%, p < 0.001) and were more likely to experience an increase in LSM stage (23.5% vs. 12.8%, p = 0.021) despite AVT.
Conclusion
Presence of MASLD was independently associated with higher LSM in untreated CHB patients and with less decline in LSM after initiation of AVT. Furthermore, CHB patients with MASLD were more likely to experience an increase in LSM despite AVT.
{"title":"The Association Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Change in Liver Stiffness in Patients With Chronic Hepatitis B","authors":"Lesley A. Patmore, Kirsi van Eekhout, Özgür M. Koc, Robert J. de Knegt, Harry L. A. Janssen, Willem P. Brouwer, Matthijs Kramer, Pieter Honkoop, Joep de Bruijne, Greet J. Boland, Douwe F. Postma, Hans Blokzijl, Robert A. de Man, R. Bart Takkenberg, Milan J. Sonneveld","doi":"10.1111/liv.70042","DOIUrl":"https://doi.org/10.1111/liv.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of liver-related events in patients with chronic hepatitis B (CHB), possibly by accelerating fibrosis progression. Therefore, we studied the influence of MASLD on liver stiffness measurement (LSM) kinetics in CHB patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a multicenter retrospective cohort study of CHB patients with at least two LSM with FibroScan. We studied the absolute change in LSM and the change in LSM stage from the first LSM to the most recent LSM among CHB patients with MASLD compared to patients without MASLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We analysed 1055 CHB patients; 259 (28.0%) had MASLD. Patients with MASLD had a higher first and last LSM (6.1 vs. 5.2 kPa and 5.6 vs. 4.7 kPa, <i>p</i> < 0.001), were significantly less likely to achieve a decrease in LSM stage (52.8% vs. 74% <i>p</i> < 0.001) and were more likely to experience an increase in LSM stage (19.3% vs. 13.6%, <i>p</i> = 0.035) during follow-up. 417 (39.5%) patients initiated antiviral therapy (AVT) which was associated with a decline in LSM (<i>p</i> < 0.001). However, patients with MASLD who were treated were less likely to decrease in LSM stage (52.4% vs. 77.0%, <i>p</i> < 0.001) and were more likely to experience an increase in LSM stage (23.5% vs. 12.8%, <i>p</i> = 0.021) despite AVT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Presence of MASLD was independently associated with higher LSM in untreated CHB patients and with less decline in LSM after initiation of AVT. Furthermore, CHB patients with MASLD were more likely to experience an increase in LSM despite AVT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tianying Zheng, Yajing Zhu, Hanyu Jiang, Chongtu Yang, Yuxiang Ye, Mustafa R. Bashir, Chenhui Li, Liling Long, Shishi Luo, Bin Song, Yinan Chen, Yidi Chen
Background & Aims
Microvascular invasion (MVI) is associated with poor prognosis in hepatocellular carcinoma (HCC). Topology may improve the predictive performance and interpretability of deep learning (DL). We aimed to develop and externally validate an MRI-based topology DL model for preoperative prediction of MVI.
Methods
This dual-centre retrospective study included consecutive surgically treated HCC patients from two tertiary care hospitals. Automatic liver and tumour segmentations were performed with DL methods. A pure convolutional neural network (CNN) model, a topology-CNN (TopoCNN) model and a topology-CNN-clinical (TopoCNN+Clinic) model were developed and externally validated. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). Cox regression analyses were conducted to identify risk factors for recurrence-free survival within 2 years (early RFS) and overall survival (OS).
Results
In total, 589 patients were included (292 [49.6%] with pathologically confirmed MVI). The AUCs of the TopoCNN and TopoCNN+Clinic models were 0.890 and 0.895 for the internal test dataset and 0.871 and 0.879 for the external test dataset, respectively. For tumours ≤ 3.0 cm, the AUCs of the TopoCNN and TopoCNN+Clinic models were 0.879 and 0.929 for the internal test dataset, and 0.763 and 0.758 for the external test dataset. The TopoCNN-derived MVI prediction probability was an independent risk factor for early RFS (hazard ratio 6.64) and OS (hazard ratio 13.33).
Conclusions
The MRI topological DL model based on automatic liver and tumour segmentation could accurately predict MVI and effectively stratify postoperative early RFS and OS, which may assist in personalised treatment decision-making.
{"title":"MRI-Based Topology Deep Learning Model for Noninvasive Prediction of Microvascular Invasion and Assisting Prognostic Stratification in HCC","authors":"Tianying Zheng, Yajing Zhu, Hanyu Jiang, Chongtu Yang, Yuxiang Ye, Mustafa R. Bashir, Chenhui Li, Liling Long, Shishi Luo, Bin Song, Yinan Chen, Yidi Chen","doi":"10.1111/liv.16205","DOIUrl":"https://doi.org/10.1111/liv.16205","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background & Aims</h3>\u0000 \u0000 <p>Microvascular invasion (MVI) is associated with poor prognosis in hepatocellular carcinoma (HCC). Topology may improve the predictive performance and interpretability of deep learning (DL). We aimed to develop and externally validate an MRI-based topology DL model for preoperative prediction of MVI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This dual-centre retrospective study included consecutive surgically treated HCC patients from two tertiary care hospitals. Automatic liver and tumour segmentations were performed with DL methods. A pure convolutional neural network (CNN) model, a topology-CNN (TopoCNN) model and a topology-CNN-clinical (TopoCNN+Clinic) model were developed and externally validated. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). Cox regression analyses were conducted to identify risk factors for recurrence-free survival within 2 years (early RFS) and overall survival (OS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 589 patients were included (292 [49.6%] with pathologically confirmed MVI). The AUCs of the TopoCNN and TopoCNN+Clinic models were 0.890 and 0.895 for the internal test dataset and 0.871 and 0.879 for the external test dataset, respectively. For tumours ≤ 3.0 cm, the AUCs of the TopoCNN and TopoCNN+Clinic models were 0.879 and 0.929 for the internal test dataset, and 0.763 and 0.758 for the external test dataset. The TopoCNN-derived MVI prediction probability was an independent risk factor for early RFS (hazard ratio 6.64) and OS (hazard ratio 13.33).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The MRI topological DL model based on automatic liver and tumour segmentation could accurately predict MVI and effectively stratify postoperative early RFS and OS, which may assist in personalised treatment decision-making.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"AI-Driven MRI for Microvascular Invasion Prediction in HCC: A Reply to the Interpretable and Open AI Models HCC","authors":"Yidi Chen, Tianying Zheng, Yinan Chen, Bin Song","doi":"10.1111/liv.70013","DOIUrl":"https://doi.org/10.1111/liv.70013","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stephen A. Harrison, Patrick Mayo, Todd Hobbs, Caroline Zhao, Carlos Canizares, Robert Foster, Michael P. McRae, Steve M. Helmke, Gregory T. Everson
Background and Aims
Rencofilstat inhibits cyclophilin to reduce hepatic inflammation and fibrosis, which, in turn, could improve liver function and reduce portal-systemic shunting. Since HepQuant quantifies liver function and portal-systemic shunting, it was used to measure the hepatic effects of rencofilstat treatment of MASH with advanced fibrosis.
Methods
Seventy subjects with suspected ≥ F3 MASH, defined from liver biopsy or AGILE 3+ ≥ 0.53, were randomised to rencofilstat 75 mg/d (n = 24), 150 mg/d (n = 23) or 225 mg/d (n = 23), and tested by HepQuant at baseline, 60 and 120 days. The DuO version included oral dosing of d4-cholate and two blood samples (20 and 60 min). DuO's disease severity index (DSI) and portal-systemic shunting fraction (SHUNT%) were evaluated for changes from baseline at 60 and 120 days of rencofilstat treatment.
Results
Across all subjects, there was a significant decrease in SHUNT% both at Day 60 (−1.67%, p = 0.0156) and Day 120 (−1.55%, p = 0.0441). In the 225 mg rencofilstat arm, 56% of subjects (10/18) were responders by Day 120 (p = 0.0549), and their DSIs improved with a mean change of −1.61 (p = 0.0190). Across all treatment arms, subjects with DSI > 18.3 at baseline had the greatest improvement with treatment (ΔDSI = −2.59, p = 0.0053).
Conclusion
Although further studies are warranted, the decreases in DSI and SHUNT% suggest that rencofilstat 225 mg/d improves hepatic function and portal-systemic shunting. HepQuant DuO is simple to administer, well-tolerated and a useful tool for detecting the hepatic effects of treatment.
Trial Registration
The study was registered at ClinicalTrials.gov, NCT05461105
{"title":"Rencofilstat Treatment Improves Liver Function in MASH With Advanced Fibrosis as Quantified by HepQuant DuO","authors":"Stephen A. Harrison, Patrick Mayo, Todd Hobbs, Caroline Zhao, Carlos Canizares, Robert Foster, Michael P. McRae, Steve M. Helmke, Gregory T. Everson","doi":"10.1111/liv.70036","DOIUrl":"https://doi.org/10.1111/liv.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Rencofilstat inhibits cyclophilin to reduce hepatic inflammation and fibrosis, which, in turn, could improve liver function and reduce portal-systemic shunting. Since HepQuant quantifies liver function and portal-systemic shunting, it was used to measure the hepatic effects of rencofilstat treatment of MASH with advanced fibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Seventy subjects with suspected ≥ F3 MASH, defined from liver biopsy or AGILE 3+ ≥ 0.53, were randomised to rencofilstat 75 mg/d (<i>n</i> = 24), 150 mg/d (<i>n</i> = 23) or 225 mg/d (<i>n</i> = 23), and tested by HepQuant at baseline, 60 and 120 days. The DuO version included oral dosing of d4-cholate and two blood samples (20 and 60 min). DuO's disease severity index (DSI) and portal-systemic shunting fraction (SHUNT%) were evaluated for changes from baseline at 60 and 120 days of rencofilstat treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Across all subjects, there was a significant decrease in SHUNT% both at Day 60 (−1.67%, <i>p</i> = 0.0156) and Day 120 (−1.55%, <i>p</i> = 0.0441). In the 225 mg rencofilstat arm, 56% of subjects (10/18) were responders by Day 120 (<i>p</i> = 0.0549), and their DSIs improved with a mean change of −1.61 (<i>p</i> = 0.0190). Across all treatment arms, subjects with DSI > 18.3 at baseline had the greatest improvement with treatment (ΔDSI = −2.59, <i>p</i> = 0.0053).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although further studies are warranted, the decreases in DSI and SHUNT% suggest that rencofilstat 225 mg/d improves hepatic function and portal-systemic shunting. HepQuant DuO is simple to administer, well-tolerated and a useful tool for detecting the hepatic effects of treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The study was registered at ClinicalTrials.gov, NCT05461105</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Commentary on ‘Safety of Anticoagulation When Undergoing Endoscopic Variceal Ligation: A Systematic Review and Meta-Analysis’","authors":"Zhenwei Wang, Ying Zhu, Liangliang Chen","doi":"10.1111/liv.70021","DOIUrl":"https://doi.org/10.1111/liv.70021","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug-induced liver injury (DILI) is a complex and potentially severe adverse reaction to drugs, herbal products or dietary supplements. DILI can mimic other liver diseases clinical presentation, and currently lacks specific diagnostic biomarkers, which hinders its diagnosis. In some cases, DILI may progress to acute liver failure. Given its public health risk, novel methodologies to enhance the understanding of DILI are crucial. Recently, the increasing availability of larger datasets has highlighted artificial intelligence (AI) as a powerful tool to construct complex models. In this review, we summarise the evidence about the use of AI in DILI research, explaining fundamental AI concepts and its subfields. We present findings from AI-based approaches in DILI investigations for risk stratification, prognostic evaluation and causality assessment and discuss the adoption of natural language processing (NLP) and large language models (LLM) in the clinical setting. Finally, we explore future perspectives and challenges in utilising AI for DILI research.
{"title":"Artificial Intelligence: An Emerging Tool for Studying Drug-Induced Liver Injury","authors":"Hao Niu, Ismael Alvarez-Alvarez, Minjun Chen","doi":"10.1111/liv.70038","DOIUrl":"https://doi.org/10.1111/liv.70038","url":null,"abstract":"<p>Drug-induced liver injury (DILI) is a complex and potentially severe adverse reaction to drugs, herbal products or dietary supplements. DILI can mimic other liver diseases clinical presentation, and currently lacks specific diagnostic biomarkers, which hinders its diagnosis. In some cases, DILI may progress to acute liver failure. Given its public health risk, novel methodologies to enhance the understanding of DILI are crucial. Recently, the increasing availability of larger datasets has highlighted artificial intelligence (AI) as a powerful tool to construct complex models. In this review, we summarise the evidence about the use of AI in DILI research, explaining fundamental AI concepts and its subfields. We present findings from AI-based approaches in DILI investigations for risk stratification, prognostic evaluation and causality assessment and discuss the adoption of natural language processing (NLP) and large language models (LLM) in the clinical setting. Finally, we explore future perspectives and challenges in utilising AI for DILI research.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Author's Reply: Commentary on Safety of Anticoagulation When Undergoing Endoscopic Variceal Ligation","authors":"Jing Hong Loo, Joo Wei Ethan Quek, Yu Jun Wong","doi":"10.1111/liv.70034","DOIUrl":"https://doi.org/10.1111/liv.70034","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 3","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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