JHEP Reports最新文献

{"title":"Loss of Cdkn1a protects against MASLD alone or with alcohol intake by preserving lipid homeostasis","authors":"Arantza Lamas-Paz , Alejandro Hionides-Gutiérrez , Feifei Guo , Gonzalo Jorquera , Laura Morán-Blanco , Raquel Benedé-Ubieto , Mariana Mesquita , Olga Estévez-Vázquez , Kang Zheng , Marina Mazariegos , Elena Vázquez-Ogando , Elena Blázquez-López , Iris Asensio , Beste Mutlu , Beatriz Gomez-Santos , María Isabel Peligros , Javier Vaquero , Rafael Bañares , Teresa C. Delgado , María Luz Martínez-Chantar , Francisco Javier Cubero","doi":"10.1016/j.jhepr.2024.101230","DOIUrl":"10.1016/j.jhepr.2024.101230","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Expression of P21, encoded by the <em>CDKN1A</em> gene, has been associated with fibrosis progression in steatotic liver disease (SLD); however, the underlying mechanisms remain unknown. In the present study, we investigated the function of CDKN1A in SLD.</div></div><div><h3>Methods</h3><div><em>CDKN1A</em> expression levels were evaluated in different patient cohorts with SLD, fibrosis, and advanced chronic liver disease (ACLD). <em>Cdkn1a</em><sup>-/-</sup> and <em>Cdkn1a</em><sup>+/+</sup> mice were fed with either a Western diet (WD), a Lieber-DeCarli (LdC) diet plus multiple EtOH (ethanol) binges, or a DuAL diet (metabolic dysfunction-associated fatty liver disease and alcohol-related liver). Primary hepatocytes were isolated and functional assays performed.</div></div><div><h3>Results</h3><div>A significant increase in <em>CDKN1A</em> expression was observed in patients with steatohepatitis and fibrosis (with a positive correlation with both NAFLD Activity Score and fibrosis staging scores), cirrhosis and ACLD. <em>Cdkn1a</em><sup>+/+</sup> mice, fed a DuAL diet exhibited liver injury and cell death increased reactive oxygen species (ROS), and markers of senescence (γH2AX, β-GAL, <em>Cdkn1a/p53</em>) contributing to steatosis and inflammation. In contrast, <em>Cdkn1a</em><sup>-/-</sup> mutant mice showed a significant decrease in senescence-associated markers as well as in markers of liver injury, hepatic steatosis and an increase in fatty acid oxidation and reduction in free fatty acid uptake as well as <em>de novo</em> lipogenesis. Mechanistically, activation of the AMPK-SIRT3 was observed in <em>Cdkn1a</em>-deleted animals.</div></div><div><h3>Conclusions</h3><div><em>Cdkn1a</em> deletion protected against preclinical SLD by promoting fatty acid oxidation and preventing free fatty acid uptake and <em>de novo</em> lipogenesis via the AMPK-SIRT3 axis. <em>CDKN1A</em> expression was found to be directly correlated with increased severity of NAFLD Activity Score and fibrosis in patients with SLD. CDKN1A could be a potential theragnostic target for the treatment of metabolic dysregulation in patients with SLD, with and without alcohol consumption.</div></div><div><h3>Impact and implications:</h3><div>Expression of p21, encoded by the <em>CDKN1A</em> gene, has been associated with fibrosis progression in steatotic liver disease (SLD), but the molecular mechanisms remain elusive. Interestingly, in this study we found that <em>Cdkn1a</em> deletion protected against preclinical SLD by promoting fatty acid oxidation and preventing free fatty acid uptake and <em>de novo</em> lipogenesis, via the AMPK-SIRT3 axis. Translationally, <em>Cdkn1a</em> expression was found to be directly correlated with increased severity of NAFLD Activity Score (NAS) and fibrosis in SLD patients, and therefore, CDKN1A might be used potential theragnostic target for the treatment of metabolically induced SLD, with and without alcohol","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 1","pages":"Article 101230"},"PeriodicalIF":9.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases","authors":"Enrique García-Nieto ,&nbsp;Juan Carlos Rodriguez-Duque ,&nbsp;Coral Rivas-Rivas ,&nbsp;Paula Iruzubieta ,&nbsp;María José Garcia ,&nbsp;Laura Rasines ,&nbsp;Ana Alvarez-Cancelo ,&nbsp;Agustín García-Blanco ,&nbsp;José Ignacio Fortea ,&nbsp;Angela Puente ,&nbsp;Beatriz Castro ,&nbsp;Maria Luisa Cagigal ,&nbsp;Javier Rueda-Gotor ,&nbsp;Ricardo Blanco ,&nbsp;Montserrat Rivero ,&nbsp;Susana Armesto ,&nbsp;Marcos Antonio González-López ,&nbsp;Anna Esteve Codina ,&nbsp;Marta Gut ,&nbsp;Jose Pedro Vaque ,&nbsp;María Teresa Arias-Loste","doi":"10.1016/j.jhepr.2024.101167","DOIUrl":"10.1016/j.jhepr.2024.101167","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Growing evidence suggests an increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in the context of immune-mediated inflammatory diseases (IMIDs). We aimed to clinically and mechanistically characterize steatotic liver disease (SLD) in a prospective cohort of patients with IMID compared to controls.</div></div><div><h3>Methods</h3><div>Cross-sectional, case-control study including a subset of patients with IMID. Controls from the general population were age-, sex-, type 2 diabetes-, and BMI-matched at a 1:2 ratio. SLD was established using controlled attenuation parameter. Liver biopsies were obtained when significant liver fibrosis was suspected. Total RNA was extracted from freshly frozen cases and analyzed by RNA-seq. Differential gene expression was performed with ‘limma-voom’. Gene set-enrichment analysis was performed using the fgsea R package with a preranked “limma t-statistic” gene list.</div></div><div><h3>Results</h3><div>A total of 1,456 patients with IMID and 2,945 controls were included. Advanced SLD (liver stiffness measurement ≥9.7 kPa) (13.46% <em>vs.</em> 3.79%; <em>p &lt;</em>0.001) and advanced MASLD (12.8% <em>vs</em>. 2.8%; <em>p &lt;</em>0.001) prevalence were significantly higher among patients with IMID than controls. In multivariate analysis, concomitant IMID was an independent, and the strongest, predictor of advanced SLD (adjusted odds ratio 3.318; 95% CI 2.225-4.947; <em>p</em> &lt;0.001). Transcriptomic data was obtained in 109 patients and showed 87 significant genes differentially expressed between IMID-MASLD and control-MASLD. IMID-MASLD cases displayed an enriched expression of genes implicated in pro-tumoral activities or the control of the cell cycle concomitant with a negative expression of genes related to metabolism.</div></div><div><h3>Conclusions</h3><div>The prevalence of advanced SLD and MASLD is disproportionately elevated in IMID cohorts. Our findings suggest that IMIDs may catalyze a distinct MASLD pathway, divergent from classical metabolic routes, highlighting the need for tailored clinical management strategies.</div></div><div><h3>Impact and implications</h3><div>The prevalence of steatotic liver disease with advanced fibrosis is increased in patients with immune-mediated inflammatory diseases, independent of classic metabolic risk factors or high-risk alcohol consumption. Transcriptomic analysis revealed a unique gene expression signature associated with cellular activities that are compatible with a liver condition leading to an accelerated and aggressive form of steatotic liver disease. Our findings underscore the importance of heightened screening for advanced liver disease risk across various medical disciplines overseeing patients with immune-mediated inflammatory diseases.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 10","pages":"Article 101167"},"PeriodicalIF":9.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copyright and information","authors":"","doi":"10.1016/S2589-5559(24)00243-X","DOIUrl":"10.1016/S2589-5559(24)00243-X","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 10","pages":"Article 101239"},"PeriodicalIF":9.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MASLD-related HCC: Multicenter study comparing patients with and without cirrhosis","authors":"Carole Vitellius ,&nbsp;Elvire Desjonqueres ,&nbsp;Marie Lequoy ,&nbsp;Giuliana Amaddeo ,&nbsp;Isabelle Fouchard ,&nbsp;Gisele N’Kontchou ,&nbsp;Clemence M. Canivet ,&nbsp;Marianne Ziol ,&nbsp;Hélène Regnault ,&nbsp;Adrien Lannes ,&nbsp;Frederic Oberti ,&nbsp;Jerome Boursier ,&nbsp;Nathalie Ganne-Carrie","doi":"10.1016/j.jhepr.2024.101160","DOIUrl":"10.1016/j.jhepr.2024.101160","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Despite its growing incidence, hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) in non-cirrhotic livers remains poorly characterized. We compared the characteristics, management, survival, and trends of MASLD-related HCC in patients with or without underlying cirrhosis in a large multicenter cohort.</div></div><div><h3>Methods</h3><div>A total of 354 cases of MASLD-related HCC presented at the liver tumor meetings of four French university hospitals between 2007 and 2018 were included in the study. Data were extracted from the meetings’ databases and from the French Birth and Death Registry.</div></div><div><h3>Results</h3><div>Of HCC cases, 35% occurred in the absence of cirrhosis. HCC was diagnosed through screening in 60% of patients with cirrhosis, and incidentally in 72% of patients without it. Patients without cirrhosis were older, had a greater tumor burden, but also better liver function than patients with cirrhosis. Patients without cirrhosis showed better overall survival than those with cirrhosis (<em>p =</em> 0.043). However, cirrhosis was not independently associated with overall survival, the independent predictors were age, liver function, tumor burden and BCLC classification. Patients without cirrhosis underwent surgery more frequently than patients with cirrhosis (41% <em>vs.</em> 11%, <em>p &lt;</em>0.001), even in cases where the largest tumors were ≥5 cm (42% <em>vs.</em> 14%, <em>p =</em> 0.002) or there were four or more lesions (19% <em>vs.</em> 2%, <em>p =</em> 0.024). Among the patients (with/without cirrhosis) who underwent surgery, survival was not significantly different. The cirrhosis/no cirrhosis ratio remained stable over the study period.</div></div><div><h3>Conclusions</h3><div>In MASLD-related HCC, patients without cirrhosis account for 35% of cases and have poor prognostic factors (higher age and larger tumors) but also better liver function, resulting in more aggressive management of advanced tumors and better survival compared to patients with cirrhosis.</div></div><div><h3>Impact and implications:</h3><div>The incidence of hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) is projected to increase by 47% to 130% by year 2030 with one-third of cases occurring in non-cirrhotic livers, making them inaccessible to screening and therefore more likely to be diagnosed at an advanced stage. Our study shows that survival in patients with MASLD-related HCC depends on age, tumor burden and underlying liver function and the preserved liver function of these non-cirrhotic patients allows them to be managed surgically. A better understanding of the pathophysiological processes driving HCC occurrence in patients with non-cirrhotic MASLD will help guide the screening and early management of these patients.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 10","pages":"Article 101160"},"PeriodicalIF":9.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Board page","authors":"","doi":"10.1016/S2589-5559(24)00241-6","DOIUrl":"10.1016/S2589-5559(24)00241-6","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 10","pages":"Article 101237"},"PeriodicalIF":9.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142420007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent varices in cured patients: Understanding the role of hepatic venous pressure gradient","authors":"Pol Olivas ,&nbsp;Alexandre Soler-Perromat ,&nbsp;Luis Tellez ,&nbsp;José Antonio Carrión ,&nbsp;Edilmar Alvarado-Tapias ,&nbsp;José Ferrusquía-Acosta ,&nbsp;Sabela Lens ,&nbsp;Antonio Guerrero ,&nbsp;Ángeles Falgà ,&nbsp;Pamela Vizcarra ,&nbsp;Lara Orts ,&nbsp;Valeria Perez-Campuzano ,&nbsp;Sarah Shalaby ,&nbsp;Sonia Torres ,&nbsp;Anna Baiges ,&nbsp;Fanny Turon ,&nbsp;Juan Carlos García-Pagán ,&nbsp;Ángeles García-Criado ,&nbsp;Virginia Hernández-Gea","doi":"10.1016/j.jhepr.2024.101170","DOIUrl":"10.1016/j.jhepr.2024.101170","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Etiologic factor removal (ER) drives recompensation and improves portal hypertension in cirrhosis. Esophageal varices (EV) and portosystemic shunts (PSS) have been found in patients despite hepatic venous pressure gradient (HVPG) dropping below 10 mmHg after ER, questioning HVPG accuracy in reflecting true portal pressure in the setting of ER. We aim to evaluate the correlation of HVPG with direct portal pressure (DPP) in patients with persistence of EV after ER despite HVPG &lt;10 mmHg.</div></div><div><h3>Methods</h3><div>This is a bicentric ‘proof of concept’ study evaluating HVPG and ultrasound-guided percutaneous DPP in patients with HCV or alcohol-related cirrhosis with persistent varices and HVPG &lt;10 mmHg after at least 5 years of ER.</div></div><div><h3>Results</h3><div>Seven patients with HCV and three with alcohol-related cirrhosis with persistent varices and HVPG &lt;10 mmHg after at least 5 years of ER were included. At evaluation, all patients had a patent portal vein and were compensated. The median platelet count was 129.5 (IQR 95–145) × 10⁹/ml, and the median liver stiffness measurement was 16.15 (IQR 14.4–22.3) kPa. In five patients, EV remained the same size (two large and three small), and five downsized to small after ER. Wedge hepatic vein pressure (median 19 [IQR 16.5–20] mmHg) and portal pressure (median 18 [IQR 15–19.5] mmHg) had an excellent correlation (R = 0.93, <em>p</em> &lt;0.0001). Portal pressure gradient (PPG) confirmed the absence of clinically significant portal hypertension as identified by HVPG across all the patients.</div></div><div><h3>Conclusions</h3><div>HVPG accurately reflects PPG in the context of HCV and alcohol-related cirrhosis regression. After ER, EV may persist despite HVPG &lt;10 mmHg. The benefit of prophylaxis in patients with EV and HVPG &lt;10 mmHg is unknown. Future studies with clinical endpoints are needed to validate our findings.</div></div><div><h3>Impact and implications:</h3><div>Despite a favorable evolution after the removal of the etiologic factor, varices persist in some patients, and there is a lack of concise guidelines for the evaluation and management of portal hypertension in this population. Our research underscores the persistence of varices in the absence of clinically significant portal hypertension and significantly demonstrates the accuracy of hepatic venous pressure gradient (HVPG) in reflecting portal vein pressure in this specific patient group. These findings emphasize the crucial role of HVPG in the assessment of portal hypertension after etiologic factor removal and lay the groundwork for further investigation into clinical outcomes and the necessity of non-selective beta-blockers in individuals with persistent varices after the removal of etiologic factor.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 10","pages":"Article 101170"},"PeriodicalIF":9.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141853167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered fatty acid metabolism rewires cholangiocarcinoma stemness features","authors":"Giulia Lori ,&nbsp;Mirella Pastore ,&nbsp;Nadia Navari ,&nbsp;Benedetta Piombanti ,&nbsp;Richell Booijink ,&nbsp;Elisabetta Rovida ,&nbsp;Ignazia Tusa ,&nbsp;Monika Lewinska ,&nbsp;Jesper B. Andersen ,&nbsp;Tiziano Lottini ,&nbsp;Annarosa Arcangeli ,&nbsp;Maria Letizia Taddei ,&nbsp;Erica Pranzini ,&nbsp;Caterina Mancini ,&nbsp;Cecilia Anceschi ,&nbsp;Stefania Madiai ,&nbsp;Elena Sacco ,&nbsp;Stefano Rota ,&nbsp;Adriana Trapani ,&nbsp;Gennaro Agrimi ,&nbsp;Chiara Raggi","doi":"10.1016/j.jhepr.2024.101182","DOIUrl":"10.1016/j.jhepr.2024.101182","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Among the reprogrammed metabolic pathways described in cancer stem cells, aberrant lipid metabolism has recently drawn increasing attention. Our study explored the contribution of fatty acids (FA) in the regulation of stem-like features in intrahepatic cholangiocarcinoma (iCCA).</div></div><div><h3>Methods</h3><div>We previously identified a functional stem-like subset in human iCCA by using a three-dimensional sphere (SPH) model in comparison to parental cells grown as monolayers (MON). In this study, quantification of intracellular free FA and lipidomic analysis (triacylglycerol [TAG] composition, <em>de novo</em> synthesis products) was performed by Liquid chromatography–mass spectrometry (LC–MS); quadrupole time-of-flight liquid chromatography/mass spectrometry (Q-TOF LC/MS), respectively, in both SPH and MON cultures.</div></div><div><h3>Results</h3><div>Stem-like SPH showed a superior content of free FA (citric, palmitic, stearic, and oleic acids) and unsaturated TAG. Molecularly, SPH showed upregulation of key metabolic enzymes involved in <em>de novo</em> FA biosynthesis (AceCS1, ACLY, ACAC, FASN, ACSL1) and the mTOR signalling pathway. In patients with iCCA (n = 68), tissue expression of <em>FASN</em>, a key gene involved in FA synthesis, correlated with 5-year overall survival. Interference with FASN activity in SPH cells through both specific gene silencing (siRNA) or pharmacological inhibition (orlistat) decreased sphere-forming ability and expression of stem-like markers. In a murine xenograft model obtained by injection of iCCA-SPH cells, FASN inhibition by orlistat or injection of <em>FASN</em>-silenced cells significantly reduced tumour growth and expression of stem-like genes.</div></div><div><h3>Conclusion</h3><div>Altered FA metabolism contributes to the maintenance of a stem-like phenotype in iCCA. FASN inhibition may represent a new approach to interfere with the progression of this deadly disease.</div></div><div><h3>Impact and implications</h3><div>Recent evidence indicates that metabolic disorders correlate with an increased susceptibility to intrahepatic cholangiocarcinoma (iCCA). Our investigation emphasises the pivotal involvement of lipid metabolism in the tumour stem cell biology of iCCA, facilitated by the upregulation of crucial enzymes and the mTOR signalling pathway. From a clinical perspective, this underscores the dual role of FASN as both a prognostic indicator and a therapeutic target, suggesting that FASN inhibitors could enhance patient outcomes by diminishing stemness and tumour aggressiveness. These findings pave the way for novel therapeutic strategies for iCCA and shed light on its relationship with metabolic disorders such as diabetes, obesity, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 10","pages":"Article 101182"},"PeriodicalIF":9.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALT levels, alcohol use, and metabolic risk factors have prognostic relevance for liver-related outcomes in the general population","authors":"Ville Männistö ,&nbsp;Veikko Salomaa ,&nbsp;Antti Jula ,&nbsp;Annamari Lundqvist ,&nbsp;Satu Männistö ,&nbsp;Markus Perola ,&nbsp;Fredrik Åberg","doi":"10.1016/j.jhepr.2024.101172","DOIUrl":"10.1016/j.jhepr.2024.101172","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;A new nomenclature and subclassification for steatotic liver disease (SLD) was recently introduced. We validated the prognostic value of SLD subclasses in a Finnish population-based cohort and explored the impact of metabolic risk factors and alcohol consumption on liver-related outcomes and death.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The study included 23,910 individuals (47% men, mean age 50.5 ± 14.0 years, BMI 27.0 ± 4.7 kg/m&lt;sup&gt;2&lt;/sup&gt;) from the FINRISK and Health 2000 health examination surveys with healthcare registry linkage for severe liver-related outcomes and deaths. SLD was identified by alanine aminotransferase (ALT) levels &gt;20 U/L in women and &gt;30 U/L in men (primary analysis) or fatty liver index (FLI) ≥60 (sensitivity analysis).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The prevalence of ALT-defined SLD was 43% (n = 10,380), with subclass rates of 34.5% for metabolic dysfunction-associated steatotic liver disease (MASLD), 4.2% for coexistent MASLD and alcohol-related liver disease (ALD) (i.e., MetALD), and 1.8% for ALD. During a median 13.3-year follow-up, we observed 129 liver-related events. MetALD and ALD increased the age- and sex-adjusted liver-related outcome risk by fourfold (HR 3.83, 95% CI 2.51–5.84, &lt;em&gt;p&lt;/em&gt; &lt;0.001) and eightfold (HR 7.90, 95% CI 5.16–12.30, &lt;em&gt;p&lt;/em&gt; &lt;0.001), respectively, compared with patients with MASLD. ALD was also associated with the highest risk for non-liver mortality. Metabolic risk factors were present in 93% and 96% of individuals with ALT-defined SLD and ALD, respectively. Alcohol use amplified the risk of liver-related outcomes in individuals with MASLD. Sensitivity analyses by the FLI were similar.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;SLD is a significant public health concern. Nearly all ALD cases exhibit metabolic risk factors. Among ALT-defined SLD subclasses, ALD presents the highest risk for both liver-related and non-liver-related outcomes. Alcohol use increases the risk of liver-related outcomes in individuals with MASLD.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;This study provides important information for physicians, researchers, and patients, demonstrating that the new classification of steatotic liver disease (SLD) has prognostic relevance at the population level. Evaluating the SLD subclass for a patient helps in understanding the magnitude of the risk for liver- and non-liver-related outcomes. In particular, the risks are highest in those with alcohol-related liver disease (ALD), but also increased in individuals with coexisting metabolic dysfunction-associated steatotic liver disease (MASLD) and ALD (MetALD) when compared with those with MASLD. However, alcohol use increased the risk of liver-related outcomes also in individuals with MASLD, highlighting the importance of evaluating alcohol use in every patient with SLD. Nearly all individuals with ALD have metabolic risk factors, and it is important to treat the","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 10","pages":"Article 101172"},"PeriodicalIF":9.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141851645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges in the diagnosis and management of AIH-PBC syndrome","authors":"Alessio Gerussi ,&nbsp;Pietro Invernizzi ,&nbsp;Marco Carbone","doi":"10.1016/j.jhepr.2024.101224","DOIUrl":"10.1016/j.jhepr.2024.101224","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 1","pages":"Article 101224"},"PeriodicalIF":9.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world experience with long-term albumin in patients with cirrhosis and ascites","authors":"Enrico Pompili ,&nbsp;Giacomo Zaccherini ,&nbsp;Salvatore Piano ,&nbsp;Pierluigi Toniutto ,&nbsp;Antonio Lombardo ,&nbsp;Stefania Gioia ,&nbsp;Giulia Iannone ,&nbsp;Clara De Venuto ,&nbsp;Marta Tonon ,&nbsp;Roberta Gagliardi ,&nbsp;Maurizio Baldassarre ,&nbsp;Greta Tedesco ,&nbsp;Giorgio Bedogni ,&nbsp;Marco Domenicali ,&nbsp;Vito Di Marco ,&nbsp;Silvia Nardelli ,&nbsp;Vincenza Calvaruso ,&nbsp;Davide Bitetto ,&nbsp;Paolo Angeli ,&nbsp;Paolo Caraceni","doi":"10.1016/j.jhepr.2024.101221","DOIUrl":"10.1016/j.jhepr.2024.101221","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Long-term albumin (LTA) is currently standard of care for patients with decompensated cirrhosis in many Italian hepatology centres. In this real-life study, we aimed to describe patient, logistical and treatment-related characteristics in daily clinical practice and to identify predictors of response.</div></div><div><h3>Methods</h3><div>We performed a multicentre, retrospective, observational study in patients with cirrhosis and ascites receiving LTA between 01/2016 and 02/2022 and followed until death, TIPS (transjugular intrahepatic portosystemic shunt) placement, transplantation or 02/2023.</div></div><div><h3>Results</h3><div>A total of 312 patients, the majority with alcohol-related cirrhosis, were included. At baseline, median Child-Pugh, MELD, and MELD-Na were 8, 15, and 18, respectively. Ascites was grade 2 in 55% of patients, grade 3 in 35% and refractory in 27%, while 47% had received large volume paracentesis in the previous 6 months. Median LTA was 10 months with a median dose of 40 g/week. Ascites resolved to grade 0-1 in 34% of patients within the first 3 months and 56% by the end of treatment. Predictors of ascites resolution were age (<em>p =</em> 0.007), baseline grade of ascites (<em>p =</em> 0.007), no paracentesis in the previous 6 months (<em>p =</em> 0.001), aetiological treatment in the past 12 months or during LTA (<em>p =</em> 0.005), weekly albumin dose (<em>p =</em> 0.014) and serum albumin concentration of 40 g/L after 1 month of treatment (<em>p =</em> 0.017). Of the 83 patients with refractory ascites at inclusion, 26% had grade 0/1 ascites at the last observation. No severe albumin-related side-effects were reported and only 1% discontinued for logistical reasons.</div></div><div><h3>Conclusions</h3><div>LTA is feasible as an outpatient treatment for the management of ascites. In the current study, ascites resolved in more than half of patients receiving LTA on top of diuretics, including in some with refractory ascites. Predictors of response to LTA provide useful information for tailoring treatment.</div></div><div><h3>Impact and implications:</h3><div>The ANSWER randomised-controlled trial has shown that long-term albumin treatment (LTA) is an effective approach for the management of patients with cirrhosis and ascites. This observational study provides novel information on target patients, modalities and length of treatment, predictors of ascites resolution, stopping criteria, and clinical trajectories of patients on treatment. LTA is a feasible option in the daily clinical practice for the management of ascites when given on top of diuretics. Rather than an alternative therapy, LTA should be integrated with the other treatment options already available for patients with difficult-to-treat ascites. The predictive factors of response identified in the present study can help physicians to individualise LTA and optimise the decision-making process.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"6 12","pages":"Article 101221"},"PeriodicalIF":9.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}