Josh Bilson, Theresa J Hydes, Declan McDonnell, Ryan M Buchanan, Eleonora Scorletti, Alessandro Mantovani, Giovanni Targher, Christopher D Byrne
{"title":"Impact of Metabolic Syndrome Traits on Kidney Disease Risk in Individuals with MASLD: A UK Biobank Study.","authors":"Josh Bilson, Theresa J Hydes, Declan McDonnell, Ryan M Buchanan, Eleonora Scorletti, Alessandro Mantovani, Giovanni Targher, Christopher D Byrne","doi":"10.1111/liv.16159","DOIUrl":"https://doi.org/10.1111/liv.16159","url":null,"abstract":"<p><strong>Background and aims: </strong>The impact of metabolic syndrome (MetS) traits on chronic kidney disease (CKD) risk in metabolic dysfunction-associated steatotic liver disease (MASLD) is unknown. We investigated the impact of type and number of MetS traits and liver fibrosis on prevalent CKD and incident end-stage renal disease (ESRD) risk in SLD.</p><p><strong>Methods: </strong>234 488 UK Biobank participants' were analysed. Hepatic steatosis index (> 36 for SLD, < 30 for no SLD) and MRI-proton density fat fraction (≥ 5.56%) were used to identify SLD. MetS traits were identified using MASLD criteria. Advanced fibrosis (FIB-4 score > 2.67) was determined using FIB-4 scores. eGFR < 60 mL/min/1.73 m<sup>2</sup> or albuminuria > 3 mg/mmol identified prevalent CKD. A validated algorithm identified incident ESRD. Binary logistic and Cox regressions were used to test associations with prevalent CKD ([adjusted odds ratios (ORs)]) and incident ESRD (adjusted hazard ratios [HRs]) respectively.</p><p><strong>Results: </strong>102 410 participants (41.2%) had SLD. 64.4% had MetS. 1.3% had FIB-4 score > 2.67. With SLD and only one MetS trait, hypertension (OR 1.35, 95% CI 1.35-1.72) or type 2 diabetes (T2D) (OR 1.89, 95% CI 1.06-3.38) increased risk of prevalent CKD. MetS (≥ 3 traits) increased prevalent CKD risk (OR 1.94, 95% CI 1.75-2.15), which was further increased by advanced liver fibrosis (OR 4.29, 95% CI 3.36-5.47). CKD prevalence increased with increasing MetS traits. Over 13.6 years (median follow-up), MetS was associated with increased risk of developing ESRD (HR 1.70, 95% CI 1.19-2.43).</p><p><strong>Conclusions: </strong>In MASLD, hypertension, and T2D, number of MetS traits and liver fibrosis increased risk of prevalent CKD and presence of MetS increased the risk of incident ESRD.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644393","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}
Alejandro Hionides-Gutierrez, Naroa Goikoetxea-Usandizaga, Carlos Sanz-García, María L Martínez-Chantar, Francisco Javier Cubero
{"title":"Novel Emerging Mechanisms in Acetaminophen (APAP) Hepatotoxicity.","authors":"Alejandro Hionides-Gutierrez, Naroa Goikoetxea-Usandizaga, Carlos Sanz-García, María L Martínez-Chantar, Francisco Javier Cubero","doi":"10.1111/liv.16167","DOIUrl":"https://doi.org/10.1111/liv.16167","url":null,"abstract":"<p><strong>Background: </strong>Drug-induced liver injury represents a critical public health issue, marked by unpredictable and potentially severe adverse reactions to medications, herbal products or dietary supplements.</p><p><strong>Aims: </strong>Acetaminophen is notably a leading cause of hepatotoxicity, impacting over one million individuals worldwide.</p><p><strong>Materials & methods: </strong>Extensive research has elucidated the intricate mechanisms driving APAP-induced liver injury, emphasising the significant roles of endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction and cell death.</p><p><strong>Results: </strong>These insights pave the way for innovative therapeutic strategies, including the use of magnesium, bile acids, microbiota modulation and mesenchymal stem cells.</p><p><strong>Discussion & conclusion: </strong>This review explores into these pathological mechanisms, proposing viable therapeutic interventions for patients suffering from APAP-induced liver injury.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644395","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}
Yuya Seko, Huapeng Lin, Vincent Wai-Sun Wong, Takeshi Okanoue
{"title":"Impact of PNPLA3 in Lean Individuals and in Cryptogenic Steatotic Liver Disease.","authors":"Yuya Seko, Huapeng Lin, Vincent Wai-Sun Wong, Takeshi Okanoue","doi":"10.1111/liv.16164","DOIUrl":"https://doi.org/10.1111/liv.16164","url":null,"abstract":"<p><strong>Background: </strong>Although metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with obesity, around 20% of individuals with hepatic steatosis may nonetheless have normal body mass index, a condition often referred to as lean nonalcoholic fatty liver disease (NAFLD). Under the new nomenclature and definition of MASLD, lean NAFLD can be further divided into lean MASLD (when there is one or more cardiometabolic risk factors) and cryptogenic steatotic liver disease (when there is no cardiometabolic risk factor).</p><p><strong>Results: </strong>Current studies suggest that the at-risk PNPLA3 rs738409 variant is more common among individuals with lean NAFLD than their overweight and obese counterparts. However, even in this group, cardiometabolic risk factors are often required for the development of hepatic steatosis and liver injury. In the general population, PNPLA3 gene polymorphism is associated with an increased risk of MASLD, more severe liver histology (i.e., the presence of steatohepatitis and fibrosis) and future development of hepatocellular carcinoma and cirrhotic complications. Emerging data also suggest that individuals carrying the PNPLA3 GG genotype might have a greater reduction in hepatic steatosis and liver enzymes with lifestyle intervention and metabolic treatments, such as glucagon-like peptide-1 receptor agonists.</p><p><strong>Conclusion: </strong>Studies have not specifically examined the impact of PNPLA3 in lean individuals.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623303","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}
José Sánchez, Sheila González, Paloma Lluch, María Pilar Ballester
{"title":"Reply to: Recompensation After TIPS for Patients With Advanced Cirrhosis: A New Way to Reverse the Outcomes?","authors":"José Sánchez, Sheila González, Paloma Lluch, María Pilar Ballester","doi":"10.1111/liv.16166","DOIUrl":"https://doi.org/10.1111/liv.16166","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623307","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":"Letter to Editor: 'Recompensation After TIPS Reduces the Incidence of Hepatocellular Carcinoma and Increases Survival in Patients With Cirrhosis'.","authors":"Xian-Hai Hu, Fan-Yu An, You-Jian Xu","doi":"10.1111/liv.16144","DOIUrl":"https://doi.org/10.1111/liv.16144","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623304","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}
Carine Nicolas, Quentin Domas, Stanislas Pol, Edouard Bardou-Jacquet, Véronique Loustaud-Ratti, Sophie Métivier, Tarik Asselah, Dominique Thabut, Marc Bourlière, Philippe Mathurin, Juliette Foucher, Dominique Larrey, Anne Varaut, Laurent Alric, François Bailly, Léon Muti, Benjamin Buchard, Armando Abergel
{"title":"Direct Antivirals Can Achieve a Cure in All Patients With Chronic Hepatitis C due to Genotype 5: A French Multicentre Study.","authors":"Carine Nicolas, Quentin Domas, Stanislas Pol, Edouard Bardou-Jacquet, Véronique Loustaud-Ratti, Sophie Métivier, Tarik Asselah, Dominique Thabut, Marc Bourlière, Philippe Mathurin, Juliette Foucher, Dominique Larrey, Anne Varaut, Laurent Alric, François Bailly, Léon Muti, Benjamin Buchard, Armando Abergel","doi":"10.1111/liv.16158","DOIUrl":"https://doi.org/10.1111/liv.16158","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis C virus genotype 5 (HCV-GT-5) is found mainly in South Africa. In our area in central France, the prevalence of HCV-GT-5 is 14%.</p><p><strong>Methods and results: </strong>Here we evaluated sustained virological response at week 12 post-treatment (SVR12) in 147 HCV-GT-5 patients from 14 French university hospitals (2014-2021) treated with direct-acting antivirals (DAA) in real-life. Patients had mainly received sofosbuvir/ledipasvir ± ribavirin, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir. Overall SVR12 was 98% (144/147). Two patients experienced relapse: one was successfully retreated with the same DAAs (sofosbuvir/ledipasvir) plus ribavirin, and the other refused further DAA treatment. One patient with virological failure (sofosbuvir/velpatasvir) had received a second treatment (sofosbuvir/velpatasvir/voxilaprevir) and progressed to cure.</p><p><strong>Conclusions: </strong>HCV-GT-5 patients treated with a DAA regimen had a 99% SVR12 in intention-to-treat (including initial therapy and retreatment) and 100% SVR12 per protocol. Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir show very good efficacy in real-world HCV-GT-5 patients.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623293","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}
Felix Piecha, Beatrice-Victoria Jahn, Johannes Köntopf, Anja Koop, Ann-Kathrin Ozga, Amirah Al-Jawazneh, Aenne Harberts, Christoph Riedel, Peter Buggisch, Daniel Benten, Peter Hübener, Gerhard Adam, Samuel Huber, Ansgar W Lohse, Peter Bannas, Johannes Kluwe
{"title":"Recompensation of Liver Cirrhosis by TIPS Reduces Epithelial Cell Death Markers, Translating Into Improved Clinical Outcome.","authors":"Felix Piecha, Beatrice-Victoria Jahn, Johannes Köntopf, Anja Koop, Ann-Kathrin Ozga, Amirah Al-Jawazneh, Aenne Harberts, Christoph Riedel, Peter Buggisch, Daniel Benten, Peter Hübener, Gerhard Adam, Samuel Huber, Ansgar W Lohse, Peter Bannas, Johannes Kluwe","doi":"10.1111/liv.16156","DOIUrl":"https://doi.org/10.1111/liv.16156","url":null,"abstract":"<p><strong>Background and aims: </strong>Portal hypertension is the main pathophysiological driver of decompensation in patients with liver cirrhosis. Epithelial cell death markers, m30 and m65, correlate with hepatic injury and predict outcomes across various stages of liver disease. We aim (i) to evaluate whether portal hypertension itself contributes to liver outcome-relevant epithelial injury, and (ii) to analyse the capacity of m30/m65 to predict outcome in patients receiving a transjugular intrahepatic portosystemic shunt (TIPS) for refractory ascites.</p><p><strong>Methods: </strong>Sixty-six patients undergoing TIPS placement for refractory ascites and 20 patients with compensated cirrhosis as controls were prospectively enrolled in this monocentric cohort study. Epithelial cell death markers were analysed pre-TIPS, as well as 1-3 and 6-9 months post-TIPS. The capacity of baseline levels of m30/m65 in predicting six-month transplant-free survival rates was analysed by multivariable Cox proportional hazards regression.</p><p><strong>Results: </strong>Levels of m30 and m65 were higher in patients with decompensated cirrhosis (pre-TIPS) compared with compensated cirrhosis (controls). Following correction of portal hypertension by TIPS and recompensation, both markers decreased over time, reaching levels comparable to patients with compensated cirrhosis. On multivariable analysis, pre-TIPS baseline levels of m30 and m65 were not predictive for six-month survival.</p><p><strong>Conclusion: </strong>Correction of portal hypertension via TIPS reduces levels of epithelial cell death markers, indicating that portal hypertension is a driver of outcome-relevant, hepatic cell death in patients with decompensated cirrhosis. Baseline m30/m65 values do not affect six-month survival rates, which suggests that TIPS placement overcomes the unfavourable spontaneous prognosis otherwise indicated by elevated baseline m30/65 levels.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623306","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":"Response to: Impact of GLP-1RA on Adverse Liver Outcomes Among Patients With Alcohol-Associated Liver Disease and Type 2 Diabetes.","authors":"Zayed Rashid, Mujtaba Khalil, Timothy M Pawlik","doi":"10.1111/liv.16161","DOIUrl":"https://doi.org/10.1111/liv.16161","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623308","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":"Exploring the potential of large language models in identifying metabolic dysfunction-associated steatotic liver disease: A comparative study of non-invasive tests and artificial intelligence-generated responses.","authors":"Wanying Wu, Yuhu Guo, Qi Li, Congzhuo Jia","doi":"10.1111/liv.16112","DOIUrl":"https://doi.org/10.1111/liv.16112","url":null,"abstract":"<p><strong>Background and aims: </strong>This study sought to assess the capabilities of large language models (LLMs) in identifying clinically significant metabolic dysfunction-associated steatotic liver disease (MASLD).</p><p><strong>Methods: </strong>We included individuals from NHANES 2017-2018. The validity and reliability of MASLD diagnosis by GPT-3.5 and GPT-4 were quantitatively examined and compared with those of the Fatty Liver Index (FLI) and United States FLI (USFLI). A receiver operating characteristic curve was conducted to assess the accuracy of MASLD diagnosis via different scoring systems. Additionally, GPT-4V's potential in clinical diagnosis using ultrasound images from MASLD patients was evaluated to provide assessments of LLM capabilities in both textual and visual data interpretation.</p><p><strong>Results: </strong>GPT-4 demonstrated comparable performance in MASLD diagnosis to FLI and USFLI with the AUROC values of .831 (95% CI .796-.867), .817 (95% CI .797-.837) and .827 (95% CI .807-.848), respectively. GPT-4 exhibited a trend of enhanced accuracy, clinical relevance and efficiency compared to GPT-3.5 based on clinician evaluation. Additionally, Pearson's r values between GPT-4 and FLI, as well as USFLI, were .718 and .695, respectively, indicating robust and moderate correlations. Moreover, GPT-4V showed potential in understanding characteristics from hepatic ultrasound imaging but exhibited limited interpretive accuracy in diagnosing MASLD compared to skilled radiologists.</p><p><strong>Conclusions: </strong>GPT-4 achieved performance comparable to traditional risk scores in diagnosing MASLD and exhibited improved convenience, versatility and the capacity to offer user-friendly outputs. The integration of GPT-4V highlights the capacities of LLMs in handling both textual and visual medical data, reinforcing their expansive utility in healthcare practice.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623294","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}