JHEP Reports最新文献

{"title":"First-line chemotherapy with selective internal radiation therapy for intrahepatic cholangiocarcinoma: The French ACABi GERCOR PRONOBIL cohort","authors":"Nicolas Adamus , Julien Edeline , Julie Henriques , Nadim Fares , Thierry Lecomte , Anthony Turpin , Dewi Vernerey , Mathilde Vincens , Brice Chanez , David Tougeron , Christophe Tournigand , Eric Assenat , Matthieu Delaye , Sylvain Manfredi , Olivier Bouché , Nicolas Williet , Angelique Vienot , Lorraine Blaise , Léo Mas , Cindy Neuzillet , Gaël S. Roth","doi":"10.1016/j.jhepr.2024.101279","DOIUrl":"10.1016/j.jhepr.2024.101279","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Selective internal radiation therapy (SIRT) is a promising option for liver-only unresectable intrahepatic cholangiocarcinoma (iCCA). The Real-SIRTCCA study retrospectively assessed the benefit of adding SIRT to chemotherapy in this setting within the French nationwide observational cohort ACABi-GERCOR-PRONOBIL.</div></div><div><h3>Methods</h3><div>Inclusion criteria were advanced iCCA with limited or no extrahepatic disease, treated with first-line gemcitabine plus platinum chemotherapy +/- concurrent SIRT. All patients treated with chemotherapy and concurrent SIRT were included. To ensure groups’ similarity, a rigorous selection was applied to the chemo-only group, with exclusion of patients with liver involvement >50% and extrahepatic metastases. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response rate (ORR) and tumor resection rate. Propensity score and inverse probability of treatment weighting (IPTW) propensity approaches were used to address confounding factors between groups.</div></div><div><h3>Results</h3><div>Between July 2007 and December 2023, 277 patients met the Real-SIRTCCA inclusion criteria, with 88 in the chemo-SIRT group and 189 in chemo-only group. Chemo-SIRT was associated with longer PFS (median = 10.8 <em>vs.</em> 5.5 months, hazard ratio [HR] 0.54, 95% CI 0.41-0.71, <em>p <</em>0.0001), a trend for longer OS (median = 22.5 <em>vs.</em> 15.1 months, HR 0.76, 95% CI 0.57-1.01), higher ORR (58.3% <em>vs.</em> 28.5%, odds ratio [OR] 3.51, 95% CI 2.03-6.09, <em>p <</em>0.0001), and resection rate (18.7% <em>vs</em>. 8.8%, <em>p</em> = 0.0279) compared to chemo-alone. After IPTW, the superiority of chemo-SIRT was confirmed with better PFS (HR 0.55, 95% CI 0.45-0.66, <em>p <</em>0,0001), OS (HR 0.70, 95% CI 0.58-0.85, <em>p</em> = 0.0004), ORR (OR 3.17, 95% CI 2.18-4.49, <em>p <</em>0.0001) and resection rate (OR 2.94, 95% CI 1.71-5.03, <em>p <</em>0.0001).</div></div><div><h3>Conclusions</h3><div>Adding SIRT to first-line chemotherapy significantly improved survival outcomes, ORR, and secondary tumor resection rates in locally advanced iCCA. Prospective randomized data are needed to confirm these results.</div></div><div><h3>Impact and implications:</h3><div>Herein, we report the results of the Real-SIRTCCA study, comparing the efficacy of the gemcitabine-platinum systemic first-line chemotherapy with or without selective internal radiation therapy (SIRT) in 277 patients with locally advanced intrahepatic cholangiocarcinoma within the cohort ACABi-PRONOBIL. An improvement of progression-free survival, overall survival, tumor response and secondary surgical resection rate was observed in favor of chemo-SIRT, before adjustment and after inverse probability of treatment weighting propensity score analyses. Even though prospective randomized data would be needed to confirm these findings, we believe that ","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101279"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080189","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":"Understanding virologic heterogeneity in chronic hepatitis B treatment","authors":"Renqi Luo , Xue Ran , Ruihan Sun","doi":"10.1016/j.jhepr.2024.101249","DOIUrl":"10.1016/j.jhepr.2024.101249","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101249"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058801","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":"Sex differences in murine MASH induced by a fructose-palmitate-cholesterol-enriched diet","authors":"Lakshmi Arivazhagan , Sofie Delbare , Robin A. Wilson , Michaele B. Manigrasso , Boyan Zhou , Henry H. Ruiz , Kaamashri Mangar , Ryoko Higa , Emily Brown , Huilin Li , Michael J. Garabedian , Ravichandran Ramasamy , Kathryn J. Moore , Edward A. Fisher , Neil D. Theise , Ann Marie Schmidt","doi":"10.1016/j.jhepr.2024.101222","DOIUrl":"10.1016/j.jhepr.2024.101222","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Metabolic syndrome-associated steatotic liver disease (MASLD) and metabolic syndrome-associated steatohepatitis (MASH) have global prevalence rates exceeding 25% and 3-6%, respectively. The introduction of high-fructose corn syrup to the diet in the 1970s has been linked to metabolic and hepatic disturbances. Despite these associations, the potential for sex-dependent responses resulting from fructose-containing diets on MASLD/MASH has not been addressed.</div></div><div><h3>Methods</h3><div>Female and male C57BL/6J mice were fed a fructose-palmitate-cholesterol (FPC)-NASH diet <em>vs.</em> standard chow for 16 weeks (n = 40 mice). At sacrifice, plasma and liver were retrieved, the latter for single-nucleus RNA sequencing. Publicly available data sets of human male and female MASH liver were probed.</div></div><div><h3>Results</h3><div>The FPC-NASH diet-induced metabolic dysfunction in both female and male mice, with females exhibiting more severe hepatic steatosis (<em>p =</em> 0.0262), inflammation (<em>p =</em> 0.0206), and fibrosis (<em>p <</em>0.0001). Single-nucleus RNA sequencing revealed distinct sex-specific transcriptional profiles in hepatocytes and stellate cells responding to the FPC-NASH diet compared to the standard chow. In female mice, compared to males, pathways associated with lipid and metabolic processes in hepatocytes and cell-cell communication and adhesion in stellate cells were enriched. Metabolic flux analyses demonstrated reduced bile acid metabolism in female mice and human hepatocytes in FPC-NASH and MASH conditions, respectively, compared to their male counterparts.</div></div><div><h3>Conclusions</h3><div>Molecular profiling of hepatocytes and stellate cells in FPC-NASH diet-fed mice revealed significant sex differences mirrored in human MASH. The identification of intrinsic, within-sex, diet-dependent disparities underscores the critical need to include both male and female individuals in MAFLD/MASH studies and clinical trials.</div></div><div><h3>Impact and implications:</h3><div>Despite the importance of metabolic dysfunction-associated steatohepatitis (MASH) in impairment of human health, the potential for and mechanisms of sex-dependent responses have yet to be well-studied, particularly with respect to the possible influence of high-fructose corn syrup additives to the diet, which has been linked to metabolic and hepatic disturbances. In a mouse model of fructose supplementation to a NASH diet, female mice displayed significantly higher MASH scores (steatosis, inflammation and fibrosis) compared to male mice. Single-nucleus RNA sequencing of livers revealed intrinsic, diet-dependent molecular disparities within sex, which were exaggerated when comparing female <em>vs.</em> male mice fed the fructose-containing NASH diet; many of these findings were recapitulated in human female <em>vs.</em> male patients with MASH. These results highlight potential mechanistic explana","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101222"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170898","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":"Reply to: “Understanding virologic heterogeneity in chronic hepatitis B treatment”","authors":"Philippa C. Matthews , Tingyan Wang , Eleanor Barnes , the Health Informatics Collaborative for Viral Hepatitis","doi":"10.1016/j.jhepr.2024.101280","DOIUrl":"10.1016/j.jhepr.2024.101280","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101280"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046258","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":"Risk of hepatocellular carcinoma in Asian patients with primary biliary cholangitis: A nationwide and hospital cohort study","authors":"Jihye Lim ,&nbsp;Ye-Jee Kim ,&nbsp;Sehee Kim ,&nbsp;Jonggi Choi","doi":"10.1016/j.jhepr.2024.101251","DOIUrl":"10.1016/j.jhepr.2024.101251","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Large-scale studies on the association between primary biliary cholangitis (PBC) and hepatocellular carcinoma (HCC) in Asians are scarce. This study aimed to evaluate the incidence of HCC and its risk factors in a nationwide cohort.</div></div><div><h3>Methods</h3><div>The data of 4,882 patients with PBC and 38,603 matched controls were extracted from the Korean National Health Insurance Service (2007–2020) and analyzed. The incidence of HCC and its risk factors in patients with PBC were assessed and compared with those in the matched controls. The results were validated in a multicenter hospital cohort of 862 patients with PBC, recruited from Asan Medical Center (n = 815) and Yeouido St. Mary’s Hospital (n = 47) in Korea.</div></div><div><h3>Results</h3><div>In total, 105 patients with PBC developed HCC over the median follow-up period of 5.42 years, yielding an incidence rate of 3.7/1,000 person-years (PYs), which was significantly higher than that in the controls (0.5/1,000 PYs; adjusted hazard ratio: 9.07; 95% CI: 6.71–12.27). PBC, older age, male sex, diabetes, and smoking were identified as significant risk factors for HCC. Twenty-three of the 862 patients with PBC developed HCC in the multicenter hospital cohort, yielding an incidence of 4.0/1,000 PYs (95% CI: 2.4–5.7). Older age (subdistribution hazard ratio [SHR]: 1.05, 95% CI: 1.00–1.10), male sex (SHR: 3.00, 95% CI: 1.11–8.13), current alcohol consumption (SHR: 3.70, 95% CI: 1.08–12.59), and cirrhosis (SHR: 5.17, 95% CI: 2.07–12.93) were identified as risk factors in the hospital cohort.</div></div><div><h3>Conclusions</h3><div>Patients with PBC were at a significantly higher risk of developing HCC. Older age and male sex were consistent risk factors in both cohorts.</div></div><div><h3>Impact and implications:</h3><div>Notable heterogeneity has been observed among different studies in terms of the incidence of hepatocellular carcinoma (HCC) in patients with primary biliary cholangitis (PBC). Large-scale studies on the association between PBC and HCC in Asians are scarce. In our nationwide cohort study, patients with PBC exhibited a significantly heightened risk of developing HCC and mortality than the age- and sex-matched controls. Individuals with PBC had a 9.1-fold higher risk of developing HCC than their matched counterparts, with an incidence rate of 3.7/1,000 person-years. Older age, male sex, smoking, and diabetes were identified as prominent risk factors for HCC in patients with PBC in the nationwide cohort. Older age, male sex, and alcohol consumption were identified as the factors significantly contributing to the elevated risk of HCC in patients with PBC in validation multicenter hospital cohort.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101251"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005511","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(25)00020-5","DOIUrl":"10.1016/S2589-5559(25)00020-5","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101344"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143229972","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":"Metabolomic liquid biopsy dynamics predict early-stage HCC and actionable candidates of human hepatocarcinogenesis","authors":"Kornelius Schulze ,&nbsp;Tim Daniel Rose ,&nbsp;Lorenz Adlung ,&nbsp;Manuela Peschka ,&nbsp;Francesca Pagani ,&nbsp;Joao Gorgulho ,&nbsp;Thorben W. Fründt ,&nbsp;Ismail Labgaa ,&nbsp;Philipp K. Haber ,&nbsp;Carolin Zimpel ,&nbsp;Darko Castven ,&nbsp;Arndt Weinmann ,&nbsp;Teresa Garzia-Lezana ,&nbsp;Moritz Waldmann ,&nbsp;Thomas Renné ,&nbsp;Hannah Voß ,&nbsp;Manuela Moritz ,&nbsp;Dorian Orlikowski ,&nbsp;Hartmut Schlüter ,&nbsp;Jan Baumbach ,&nbsp;Johann von Felden","doi":"10.1016/j.jhepr.2025.101340","DOIUrl":"10.1016/j.jhepr.2025.101340","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;Actionable candidates of hepatocarcinogenesis remain elusive, and tools for early detection are suboptimal. Our aim was to demonstrate that serum metabolome profiles reflect the initiation of hepatocellular carcinoma (HCC) and enable the identification of biomarkers for early HCC detection and actionable candidates for chemoprevention.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This global cohort study included 654 patients and 801 biospecimens. Following serum metabolome profiling across the spectrum of hepatocarcinogenesis, we conducted a phase II biomarker case–control study for early HCC detection. Findings were independently validated through &lt;em&gt;in silico&lt;/em&gt; analysis, mRNA sequencing, and proteome profiling of primary HCC and non-tumoral tissue, and &lt;em&gt;in vitro&lt;/em&gt; experiments.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Aspartic acid, glutamic acid, taurine, and hypoxanthine were differentially abundant in the serum across chronic liver disease, cirrhosis, initial HCC, and progressed HCC, independent of sex, age, and etiology. In a phase II biomarker case–control study, a blood-based metabolite signature yielded an AUC of 94% to discriminate between patients with early-stage HCC and controls with cirrhosis, including independent validation. Unsupervised biclustering (MoSBi), lipid network analysis (LINEX&lt;sup&gt;2&lt;/sup&gt;), and pathway enrichment analysis confirmed alterations in amino acid-, lipid-, and nucleotide-related pathways. In tumor tissue, these pathways were significantly deregulated regarding gene and protein expression in two independent datasets, including actionable targets RRM2, GMPS, BCAT1, PYCR2, and NEU1. &lt;em&gt;In vitro&lt;/em&gt; knockdown confirmed a functional role in proliferation and migration, as exemplified for PYCR2.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;These findings demonstrate that serum metabolome profiling indicates deregulated metabolites and pathways during hepatocarcinogenesis. Our liquid biopsy approach accurately detects early-stage HCC outperforming currently recommended surveillance tools and facilitates identification of actionable candidates for chemoprevention.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;Deregulated cellular metabolism is a hallmark of cancer. In smaller studies, circulating metabolite profiles have been associated with HCC, although mainly in the context of fatty liver disease. Translation strategies for primary prevention or early detection are lacking. In this global study, we present an unsupervised landscape of the altered serum metabolome profile during hepatocarcinogenesis, independent of age, sex, and etiology. We provide a blood-based metabolite signature that accurately identifies early-stage HCC in a phase II biomarker study including independent validation. Further RRM2, GMPS, BCAT1, PYCR2, and NEU1 are identified in tumor tissue as actionable candidates for prevention. Our data provide the rationale for clinical trials testing liquid biops","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 5","pages":"Article 101340"},"PeriodicalIF":9.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving epidemiology of HCC in Spain","authors":"Margarita Sala ,&nbsp;Sonia Pascual ,&nbsp;Maria Rosa Rota Roca ,&nbsp;Ana María Matilla ,&nbsp;Marta Campos ,&nbsp;Manuel Delgado ,&nbsp;María Teresa Ferrer ,&nbsp;José Luís Montero ,&nbsp;Jesús Manuel González-Santiago ,&nbsp;Antonio Guerrero ,&nbsp;Carles Aracil ,&nbsp;Carlos Rodríguez-Lope ,&nbsp;Marta Romero-Gutiérrez ,&nbsp;Miguel Sogbe ,&nbsp;Sergio Vázquez-Rodríguez ,&nbsp;Javier Fuentes Olmo ,&nbsp;Beatriz Mínguez ,&nbsp;Luís Cortés-García ,&nbsp;Nicolau Vallejo-Senra ,&nbsp;Paloma Rendón Unceta ,&nbsp;María Varela","doi":"10.1016/j.jhepr.2025.101336","DOIUrl":"10.1016/j.jhepr.2025.101336","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>The epidemiological landscape of hepatocellular carcinoma (HCC) in Europe is evolving. This study aims to provide an updated description of the current epidemiology of liver cancer in Spain.</div></div><div><h3>Methods</h3><div>This multicenter prospective study collected demographic and clinical data on primary liver cancer between October 2022 and January 2023. We conducted descriptive and comparative analyses with data collected in 2008 and 2014.</div></div><div><h3>Results</h3><div>Of the 767 cases of primary liver cancer collected from 52 centers, 91% were diagnosed as HCC. The majority of patients were male (83.3%), average age 68 years, 80.7% had cirrhosis. The primary causes were alcohol (29.9% alone, 55% combined with other etiologies), liver disease related to metabolic syndrome (LDrMS, 23%) and hepatitis C (17.3%). Treatments included ablation (15.7%), systemic therapy (14.7%), and chemoembolization (14.6%). Data from 29 centers (n = 1,351) across three registries revealed a significant increase in LDrMS (from 4.9% to 24%) and HCC in non-cirrhotic livers (from 4.2% to 7.9%). Meanwhile, hepatitis C decreased sharply (from 43% to 17.5%). Alcohol-related cases remained stable. There was a slight increase in male patients and hypertension, diabetes, and obesity. Patients with cirrhosis diagnosed outside of screening programs presented with larger tumors and more advanced disease. This led to fewer evaluations for curative treatments.</div></div><div><h3>Conclusions</h3><div>Alcohol accounts for 30% of HCC cases and is the main etiology. The registry shows a decrease in hepatitis C-related HCC, an increase in LDrMS and HCC in non-cirrhotic livers. Surveillance was implemented in ∼80% of the recommended population. There is a need for improved screening and prevention strategies, particularly for alcohol abuse and LDrMS, to enhance HCC management.</div></div><div><h3>Impact and implications</h3><div>Our study showcases the involvement of numerous reference centers across Spain and examines over 1,300 patients to track the changing epidemiology of hepatocellular carcinoma (HCC) over 14 years. In patients with known liver cirrhosis, more than 80% of HCC diagnoses were made through screening leading to early-stage identification and curative treatment opportunities. Notably, there has been a shift in HCC etiology within the registries from hepatitis C to liver disease related to metabolic syndrome, with an increase in cases without cirrhosis. Findings indicate a need for the prevention and early detection of HCC, particularly focusing on alcohol and liver disease related to metabolic syndrome, along with greater involvement of health authorities, to improve the participation of at-risk patients in screening programs.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 5","pages":"Article 101336"},"PeriodicalIF":9.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792695","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":"Serum proteomics of adults with acute liver failure provides mechanistic insights and attractive prognostic biomarkers","authors":"Katharina Remih ,&nbsp;Franziska-Maria Hufnagel ,&nbsp;Anna Sophie Karl ,&nbsp;Valerie Durkalski-Mauldin ,&nbsp;William Martens Lee ,&nbsp;Constantine J. Karvellas ,&nbsp;Zemin Su ,&nbsp;Jody A. Rule ,&nbsp;Petra Tomanová ,&nbsp;Laura Krieg ,&nbsp;Isabel Karkossa ,&nbsp;Kristin Schubert ,&nbsp;Martin von Bergen ,&nbsp;Frank Tacke ,&nbsp;Sonja Luckhardt ,&nbsp;Nicole Ziegler ,&nbsp;Aimo Kannt ,&nbsp;Bastian Engel ,&nbsp;Richard Taubert ,&nbsp;Robert John Fontana ,&nbsp;Pavel Strnad","doi":"10.1016/j.jhepr.2025.101338","DOIUrl":"10.1016/j.jhepr.2025.101338","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;Acute liver failure (ALF) is defined as rapid onset coagulopathy and encephalopathy in patients without a prior history of liver disease. We performed untargeted and targeted serum proteomics to delineate processes occurring in adult patients with ALF and to identify potential biomarkers.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Sera of 319 adult patients with ALF (∼50% acetaminophen [APAP]-related cases) were randomly selected from admission samples of the multicenter USA Acute Liver Failure Study Group consortium and subdivided into discovery/validation cohorts. They were analyzed using untargeted proteomics with mass spectroscopy and a serum cytokine profiling and compared with 30 healthy controls. The primary clinical outcome was 21-day transplant-free survival. Single-cell RNAseq data mapped biomarkers to cells of origin; functional enrichment analysis provided mechanistic insights. Novel prognostic scores were compared with the model for end-stage liver disease and ALFSG prognostic index scores.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In the discovery cohort, 117 proteins differed between patients with ALF and healthy controls. There were 167 proteins associated with APAP-related ALF, with the majority being hepatocyte-derived. Three hepatocellular proteins (ALDOB, CAT, and PIGR) robustly and reproducibly discriminated APAP from non-APAP cases (AUROCs ∼0.9). In the discovery cohort, 37 proteins were related to 21-day outcome. The key processes associated with survival were acute-phase response and hepatocyte nuclear factor 1α signaling. SERPINA1 and LRG1 were the best individual discriminators of 21-day transplant-free survival in both cohorts. Two models of blood-based proteomic biomarkers outperformed the model for end-stage liver disease and ALFSG prognostic index and were reproduced in the validation cohort (AUROCs 0.83-0.86) for 21-day transplant-free survival.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Proteomics and cytokine profiling identified new, reproducible biomarkers associated with APAP etiology and 21-day outcome. These biomarkers may improve prognostication and understanding of the etiopathogenesis of ALF but need to be independently validated.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;Acute liver failure (ALF) is a sudden, and severe condition associated with high fatality. More sensitive and specific prognostic scores are urgently needed to facilitate decision-making regarding liver transplantation in patients with ALF. Our proteomic analysis uncovered marked differences between acetaminophen and non-acetaminophen-related ALF. The identification of routinely measurable biomarkers that are associated with 21-day transplant-free survival and the derivation of novel prognostic scores may facilitate clinical management as well as decisions for/against liver transplantation. Further studies are needed to quantify less abundant proteins. Although we used two cohorts, our findings still ","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 5","pages":"Article 101338"},"PeriodicalIF":9.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759980","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":"Protective value of ischemia-free liver transplantation on post-transplant acute kidney injury","authors":"Qiang Zhao ,&nbsp;Jinbo Huang ,&nbsp;Meiting Qin ,&nbsp;Yunhua Tang ,&nbsp;Zhiying Liu ,&nbsp;Yefu Li ,&nbsp;Zhiyong Guo ,&nbsp;Jia Dan ,&nbsp;Yu Nie ,&nbsp;Xiaoshun He","doi":"10.1016/j.jhepr.2025.101339","DOIUrl":"10.1016/j.jhepr.2025.101339","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Ischemia-free liver transplantation (IFLT) completely avoids ischemia–reperfusion injury (IRI), thus potentially reducing acute kidney injury (AKI) after liver transplantation (LT). Therefore, this study investigated whether IFLT has a protective effect against AKI after LT.</div></div><div><h3>Methods</h3><div>In total, 862 patients who had undergone LT between 2017 to 2022 were divided into an ischemia-free liver transplantation group (IFLT group) and conventional liver transplantation group (CLT group) based on the surgical methods used. Propensity score matching (PSM) was used for post hoc randomization in the 1:1 matching between the groups. Post-transplant kidney function, graft function, and patient survival were compared between the groups. Multivariate logistic regression analysis was used to identify the risk factors of AKI after LT.</div></div><div><h3>Results</h3><div>Overall, 745 out of 862 patients were finally enrolled, of whom 98 underwent IFLT. PSM created 94 pairs of patients. IFLT resulted in a significant reduction in Stage-3 AKI (3.2% <em>vs.</em> 16.0%, <em>p</em> = 0.003), severe AKI (SAKI) (13.8% <em>vs.</em> 25.5%, <em>p</em> = 0.044), and renal replacement therapy (RRT) ratio (3.2% <em>vs.</em> 12.8%, <em>p</em> = 0.015) compared with the CLT group. The early allograft dysfunction (EAD) incidence of the IFLT group significantly decreased (8.5% <em>vs.</em> 44.7%, <em>p</em> &lt;0.001). Livers from the extended criteria donation (ECD) were received in 49 patients who underwent IFLT and 46 patients who underwent CLT. Compared with the ECD-CLT group, the Stage-3 AKI and SAKI incidence in the ECD-IFLT group were both decreased (<em>p &lt;</em>0.05). Multivariate logistic regression analysis further confirmed that both using IFLT and avoiding ECD were protective factors for post-transplant Stage-3 AKI.</div></div><div><h3>Conclusions</h3><div>IFLT significantly reduces the incidence of post-transplant SCKI, Stage-3 AKI, and RRT. Importantly, this protective effect is also present in patients receiving ECD livers.</div></div><div><h3>Impact and implications</h3><div>Ischemia-free liver transplantation significantly reduces the incidence of severe acute kidney injury, Stage-3 acute kidney injury and renal replacement therapy after liver transplantation. Importantly, this protective effect is also present in patients receiving extended criteria donation livers.</div></div><div><h3>Clinical trial number</h3><div><span><span>ChiCTR2400081755</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 4","pages":"Article 101339"},"PeriodicalIF":9.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696635","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}