Liver International最新文献

{"title":"Hepatic-specific Pgc-1α ablation drives fibrosis in a MASH model","authors":"Maria Arconzo,&nbsp;Elena Piccinin,&nbsp;Emanuela Pasculli,&nbsp;Marica Cariello,&nbsp;Nicolas Loiseau,&nbsp;Justine Bertrand-Michel,&nbsp;Hervé Guillou,&nbsp;Maria L. Matrella,&nbsp;Gaetano Villani,&nbsp;Antonio Moschetta","doi":"10.1111/liv.16052","DOIUrl":"10.1111/liv.16052","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background &amp; Aims</h3>\u0000 \u0000 <p>Metabolic dysfunction-associated steatohepatitis (MASH) is a growing cause of chronic liver disease, characterized by fat accumulation, inflammation and fibrosis, which development depends on mitochondrial dysfunction and oxidative stress. Highly expressed in the liver during fasting, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) regulates mitochondrial and oxidative metabolism. Given the relevant role of mitochondrial function in MASH, we investigated the relationship between PGC-1α and steatohepatitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We measured the hepatic expression of Pgc-1α in both MASH patients and wild-type mice fed a western diet (WD) inducing steatosis and fibrosis. We then generated a pure C57BL6/J strain loss of function mouse model in which Pgc-1α is selectively deleted in the liver and we fed these mice with a WD supplemented with sugar water that accurately mimics human MASH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed that the hepatic expression of Pgc-1α is strongly reduced in MASH, in both humans and mice. Moreover, the hepatic ablation of Pgc-1α promotes a considerable reduction of the hepatic mitochondrial respiratory capacity, setting up a bioenergetic harmful environment for liver diseases. Indeed, the lack of Pgc-1α decreases mitochondrial function and increases inflammation, fibrosis and oxidative stress in the scenario of MASH. Intriguingly, this profibrotic phenotype is not linked with obesity, insulin resistance and lipid disbalance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In a MASH model the hepatic ablation of Pgc-1α drives fibrosis independently from lipid and glucose metabolism. These results add a novel mechanistic piece to the puzzle of the specific and crucial role of mitochondrial function in MASH development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752059","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":"Optimizing of a suitable protocol for isolating tissue-derived extracellular vesicles and profiling small RNA patterns in hepatocellular carcinoma","authors":"Wenjing Yang,&nbsp;Yu Liu,&nbsp;Jiyan Wang,&nbsp;Te Liu,&nbsp;Tongtong Tian,&nbsp;Tong Li,&nbsp;Lin Ding,&nbsp;Wei Chen,&nbsp;Hao Wang,&nbsp;Jie Zhu,&nbsp;Chunyan Zhang,&nbsp;Baishen Pan,&nbsp;Jian Zhou,&nbsp;Jia Fan,&nbsp;Beili Wang,&nbsp;XinRong Yang,&nbsp;Wei Guo","doi":"10.1111/liv.16011","DOIUrl":"10.1111/liv.16011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Extracellular vesicles (EVs) facilitate cell–cell interactions in the tumour microenvironment. However, standard and efficient methods to isolate tumour tissue-derived EVs are lacking, and their biological functions remain elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To determine the optimal method for isolating tissue-derived EVs, we compared the characterization and concentration of EVs obtained by three previously reported methods using transmission electron microscopy, nanoparticle tracking analysis, and nanoflow analysis (Nanoflow). Additionally, the differential content of small RNAs, especially tsRNAs, between hepatocellular carcinoma (HCC) and adjacent normal liver tissues (ANLTs)-derived EVs was identified using Arraystar small RNA microarray. The targets of miRNAs and tsRNAs were predicted, and downstream functional analysis was conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, non-negative matrix factorization and survival prediction analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A differential centrifugation-based protocol without cell cultivation (NC protocol) yielded higher EV particles and higher levels of CD9⁺ and CD63⁺ EVs compared with other isolation protocols. Interestingly, the NC protocol was also effective for isolating frozen tissue-derived EVs that were indistinguishable from fresh tissue. HCC tissues showed significantly higher EV numbers compared with ANLTs. Furthermore, we identified different types of small RNAs in HCC tissue-derived EVs, forming a unique multidimensional intercellular communication landscape that can differentiate between HCC and ANLTs. ROC analysis further showed that the combination of the top 10 upregulated small RNAs achieved better diagnostic performance (AUC = .950 [.895–1.000]). Importantly, most tsRNAs in HCC tissue-derived EVs were downregulated and mitochondria-derived, mainly involving in lipid-related metabolic reprogramming.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The NC protocol was optimal for isolating EVs from HCC, especially from frozen tissues. Our study emphasized the different roles of small-RNA in regulating the HCC ecosystem, providing insights into HCC progression and potential therapeutic targets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734582","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":"Unmet needs in autoimmune hepatitis: Results of the prospective multicentre European Reference Network Registry (R-LIVER)","authors":"Ida Schregel,&nbsp;Maria Papp,&nbsp;Nora Sipeki,&nbsp;Patricia J. Kovats,&nbsp;Richard Taubert,&nbsp;Bastian Engel,&nbsp;Alejandro Campos-Murguia,&nbsp;George N. Dalekos,&nbsp;Nikolaos Gatselis,&nbsp;Kalliopi Zachou,&nbsp;Piotr Milkiewicz,&nbsp;Maciej K. Janik,&nbsp;Joanna Raszeja-Wyszomirska,&nbsp;Henriette Ytting,&nbsp;Felix Braun,&nbsp;Christian Casar,&nbsp;Marcial Sebode,&nbsp;Ansgar W. Lohse,&nbsp;Christoph Schramm,&nbsp;the European Reference Network (ERN) RARE-LIVER","doi":"10.1111/liv.16035","DOIUrl":"10.1111/liv.16035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The European Reference Network on Hepatological Diseases (ERN RARE-LIVER) launched the prospective, multicentre, quality-controlled R-LIVER registry on rare liver diseases. The aim of this study was to assess the presentation and outcome of autoimmune hepatitis (AIH) after 1 year of treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were prospectively collected at the time of diagnosis and after 6 and 12 months follow-up. Complete biochemical response (CBR) was defined as normalization of alanine aminotransferase (ALT) and immunoglobulin G (IgG) serum levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 231 patients from six European centres were included in the analysis. After 6 months of treatment 50% (106/212), and after 12 months 63% (131/210) of patients reached CBR with only 27% (56/211) achieving a steroid-free CBR within the first year.</p>\u0000 \u0000 <p>Overall, 16 different treatment regimens were administered. Change of treatment, mostly due to intolerance, occurred in 30.4% within the first 6 months. In multivariate analysis, younger age at diagnosis (odds ratio [OR] = 1.03 [95% confidence interval (CI) 1.01–1.05]; <i>p</i> = .007), severe fibrosis (OR .38 [95% .16–.89], <i>p</i> = .026) and change of treatment within the first 6 months (OR .40 [95% CI .2–.86]; <i>p</i> = .018) were associated with a lesser chance of ALT normalization at 12 months follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The landscape of AIH treatment in Europe is highly heterogeneous, even between expert centres. The results from this first European multicentre prospective registry reveal several unmet needs, highlighted by the overall low rates of CBR and the frequent failure to withdraw corticosteroids.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734584","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":"Exploring the impact of gut microbiota on liver health in mice and patients with Wilson disease","authors":"Hao-Jie Zhong,&nbsp;Ai-Qun Liu,&nbsp;Dong-Ni Huang,&nbsp;Zhi-Hua Zhou,&nbsp;Shun-Peng Xu,&nbsp;Lei Wu,&nbsp;Xin-Ping Yang,&nbsp;Yangchao Chen,&nbsp;Ming-Fan Hong,&nbsp;Yong-Qiang Zhan","doi":"10.1111/liv.16046","DOIUrl":"10.1111/liv.16046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Distinctive gut microbial profiles have been observed between patients with Wilson disease (WD) and healthy individuals. Despite this, the exact relationship and influence of gut microbiota on the advancement of WD-related liver damage remain ambiguous. This research seeks to clarify the gut microbiota characteristics in both human patients and mouse models of WD, as well as their impact on liver injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Gut microbial features in healthy individuals, patients with WD, healthy mice and mice with early- and late-stage WD were analysed using 16S rRNA gene sequencing. Additionally, WD-afflicted mice underwent treatment with either an antibiotic cocktail (with normal saline as a control) or healthy microbiota (using disease microbiota as a control). The study assessed gut microbiota composition, hepatic transcriptome profiles, liver copper concentrations and hepatic pathological injuries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with hepatic WD and mice with WD-related liver injury displayed altered gut microbiota composition, notably with a significant reduction in <i>Lactobacillus</i> abundance. Additionally, the abundances of several gut genera, including <i>Lactobacillus</i>, <i>Veillonella</i> and <i>Eubacterium coprostanoligenes</i>, showed significant correlations with the severity of liver injury in patients with WD. In WD mice, antibiotic treatment or transplantation of healthy microbiota altered the gut microbial structure, increased <i>Lactobacillus</i> abundance and modified the hepatic transcriptional profile. These interventions resulted in reduced hepatic copper concentration and alleviation of WD-related liver injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Individuals and mice with pronounced WD-related liver injury exhibited shifts in gut microbial composition. Regulating gut microbiota through healthy microbiota transplantation emerges as a promising therapeutic approach for treating WD-related liver injury.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734581","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 changing landscape of alcohol consumption in the women","authors":"Chong-Chi Chiu,&nbsp;Che-Hong Chen,&nbsp;Si-Wai Vivian Chiu,&nbsp;Jaw-Town Lin","doi":"10.1111/liv.16021","DOIUrl":"10.1111/liv.16021","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734580","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 comments on ‘Changing landscape of alcohol-associated liver disease in younger individuals, women and ethnic minorities’","authors":"Juan P. Arab,&nbsp;Winston Dunn,&nbsp;Gene Im,&nbsp;Ashwani K. Singal","doi":"10.1111/liv.16038","DOIUrl":"10.1111/liv.16038","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734583","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":"Alcohol consumption and liver phenotype of individuals with alpha-1 antitrypsin deficiency","authors":"Malin Fromme,&nbsp;Carolin V. Schneider,&nbsp;Nurdan Guldiken,&nbsp;Samira Amzou,&nbsp;Yizhao Luo,&nbsp;Monica Pons,&nbsp;Joan Genesca,&nbsp;Marc Miravitlles,&nbsp;Katrine H. Thorhauge,&nbsp;Mattias Mandorfer,&nbsp;Johan Waern,&nbsp;Kai Markus Schneider,&nbsp;Jan Sperl,&nbsp;Sona Frankova,&nbsp;Marc Bartel,&nbsp;Holger Zimmer,&nbsp;Markus Zorn,&nbsp;Aleksander Krag,&nbsp;Alice Turner,&nbsp;Christian Trautwein,&nbsp;Pavel Strnad","doi":"10.1111/liv.16044","DOIUrl":"10.1111/liv.16044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Alpha-1 antitrypsin deficiency is an inherited disorder caused by alpha-1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver-related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Reported alcohol consumption was evaluated in two cohorts: (i) the community-based United Kingdom Biobank (17 145 Pi*MZ, 141 Pi*ZZ subjects, and 425 002 non-carriers [Pi*MM]); and (ii) the European Alpha1 liver consortium (561 Pi*ZZ individuals). Cohort (ii) included measurements of carbohydrate-deficient transferrin (CDT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In both cohorts, no/low alcohol intake was reported by &gt;80% of individuals, while harmful consumption was rare (~1%). Among Pi*MM and Pi*MZ individuals from cohort (i), moderate alcohol consumption resulted in a &lt;30% increased rate of elevated transaminases and ~50% increase in elevated gamma-glutamyl transferase values, while harmful alcohol intake led to an at least twofold increase in the abnormal levels. In Pi*ZZ individuals from both cohorts, moderate alcohol consumption had no marked impact on serum transaminase levels. Among Pi*ZZ subjects from cohort (ii) who reported no/low alcohol consumption, those with increased CDT levels more often had signs of advanced liver disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Pi*MZ/Pi*ZZ genotype does not seem to markedly aggravate the hepatic toxicity of moderate alcohol consumption. CDT values might be helpful to detect alcohol consumption in those with advanced fibrosis. More data are needed to evaluate the impact of harmful alcohol consumption.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731310","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":"Serum-free light chains as a dependable biomarker for stratifying patients with metabolic dysfunction-associated steatotic liver disease","authors":"Antonio Liguori,&nbsp;Francesca D'Ambrosio,&nbsp;Cecilia Napodano,&nbsp;Vanessa Gentili,&nbsp;Maria Cristina Giustiniani,&nbsp;Maurizio Pompili,&nbsp;Antonio Grieco,&nbsp;Gianludovico Rapaccini,&nbsp;Andrea Urbani,&nbsp;Antonio Gasbarrini,&nbsp;Umberto Basile,&nbsp;Luca Miele,&nbsp;FPG-UCSC PROMETEO Research Group","doi":"10.1111/liv.16036","DOIUrl":"10.1111/liv.16036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Adaptive immunity is gaining a significant role in progression of metabolic dysfunction-associated steatotic liver disease (MASLD). B-cell activity can be assessed by serum-free light chains (sFLCs) k and λ levels. The objective of the present investigation is to examine the utility of sFLCs as non-invasive biomarkers for the stratification of MASLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled a consecutive cohort from an outpatient liver unit. Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) was made with liver biopsy according to current guidelines. Compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) were defined according to Baveno VII criteria. sFLCs were measured by turbidimetry using an immunoassay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We evaluated 254 patients, 162/254 (63.8%) were male. Median age was 54 years old, and the median body mass index was 28.4 kg/m². A total of 157/254 (61.8%) subjects underwent liver biopsy: 88 had histological diagnosis of MASH, 89 were considered as simple metabolic dysfunction-associated steatotic liver (MASL) and 77/254 (30.3%) patients with compensated metabolic dysfunction-associated cirrhosis. By using Baveno VII criteria, 101/254 (39.7%) patients had cACLD; among them, 45/101 (44.5%) had CSPH. Patients with cACLD showed higher sFLC levels compared with patients without cACLD (<i>p</i> &lt; .01), and patients with CSPH showed higher sFLC levels than patients without CSPH (<i>p</i> &lt; .01). At multivariable analysis, sFLCs were associated with cACLD (<i>p</i> &lt; .05) independently from γ-globulins and other known dysmetabolic risk factors. κFLC was associated with CSPH (<i>p</i> &lt; .05) independently from γ-globulins and other known dysmetabolic risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>sFLCs could be a simple biomarker for stratification of cACLD in MASLD patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627044","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":"Ammonia and urea metabolism in acute liver failure: A multicentre cohort study","authors":"Filipe S. Cardoso,&nbsp;David Toapanta,&nbsp;Natalia Jimenez,&nbsp;Pedro Fidalgo,&nbsp;António Figueiredo,&nbsp;Miriam Valdivieso,&nbsp;Nuno Germano,&nbsp;Jody A. Rule,&nbsp;William M. Lee,&nbsp;Juan G. Abraldes,&nbsp;Enric Reverter,&nbsp;Constantine J. Karvellas","doi":"10.1111/liv.16043","DOIUrl":"10.1111/liv.16043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background &amp; Aims</h3>\u0000 \u0000 <p>Ammonia is metabolized into urea in the liver. In acute liver failure (ALF), ammonia has been associated with survival. However, urea variation has been poorly studied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Observational cohort including ALF patients from Curry Cabral Hospital (Lisbon, Portugal) and Clinic Hospital (Barcelona, Spain) between 10/2010 and 01/2023. The United States ALF Study Group cohort was used for external validation. Primary exposures were serum ammonia and urea on ICU admission. Primary endpoint was 30-day transplant-free survival (TFS). Secondary endpoint was explanted liver weight.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 191 ALF patients, median (IQR) age was 46 (32; 57) years and 85 (44.5%) were males. Overall, 86 (45.0%) patients were transplanted and 75 (39.3%) died. Among all ALF patients, following adjustment for age, sex, body weight, and aetiology, higher ammonia or lower urea was independently associated with higher INR on ICU admission (<i>p</i> &lt; .009). Among all ALF patients, following adjustment for sex, aetiology, and lactate, higher ammonia was independently associated with lower TFS (adjusted odds ratio (95% confidence interval [CI]) = 0.991 (0.985; 0.997); <i>p</i> = .004). This model predicted TFS with good discrimination (area under receiver operating curve [95% CI] = 0.78 [0.75; 0.82]) and reasonable calibration (<i>R</i>² of 0.43 and Brier score of 0.20) after external validation. Among transplanted patients, following adjustment for age, sex, actual body weight, and aetiology, higher ammonia (<i>p</i> = .024) or lower (<i>p</i> &lt; .001) urea was independently associated with lower explanted liver weight.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Among ALF patients, serum ammonia and urea were associated with ALF severity. A score incorporating serum ammonia predicted TFS reasonably well.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627042","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":"High disease burden and healthcare resource usage in patients with acute porphyria—A population-based analysis","authors":"Ulrich Stölzel,&nbsp;Bjoern Ambrosius,&nbsp;Sarah Brun,&nbsp;Frank Tacke","doi":"10.1111/liv.16037","DOIUrl":"10.1111/liv.16037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Acute porphyria is a chronic recurrent disease with late diagnosis, heterogeneous clinical presentations and potentially devastating complications. The study aimed at providing real-world evidence on the natural course of acute porphyria, patient characteristics, disease burden, and healthcare utilization before diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This observational study used anonymized claims data covering 8 365 867 persons from German statutory health insurance, spanning 6 years (2015–2020). Patients with at least one diagnosis of acute porphyria during the index period (2019–2020) were classified into three groups by attack frequency. These findings were compared with two age- and sex-adjusted reference groups: the general population and fibromyalgia patients. Prevalence over the index period was calculated for all porphyria patients and those with active acute porphyria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We revealed a prevalence of 79.8 per 1 000 000 for acute porphyria, with 12.9 per 1 000 000 being active cases. Acute porphyria patients, particularly with frequent attacks, demonstrated a higher comorbidity burden compared to the general population. Within the year before the recorded diagnosis, patients with acute porphyria required a median of 23.0 physician visits, significantly higher than the general population's 16.0. Additionally, 33.8% were hospitalized at least once during this period, a notably higher proportion than the general population (19.3%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study's findings, collected before the introduction of givosiran, as the first approved preventive therapy for acute porphyria in Europe, highlight the need for healthcare strategies and policies tailored to the complex needs of acute porphyria patients. The significant healthcare demands, heightened comorbidity burden, and increased healthcare system utilization emphasize the urgency of developing a comprehensive support infrastructure for these patients. Also, these acute porphyria real-world findings provide additional insights on disease characteristics in Germany.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627043","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}