JHEP Reports最新文献

{"title":"Transjugular diagnostic procedures in hepatology: Indications, techniques and interpretation","authors":"Dominik Bettinger ,&nbsp;Annalisa Berzigotti ,&nbsp;Mattias Mandorfer ,&nbsp;Cristina Ripoll ,&nbsp;Christian Labenz ,&nbsp;Eugen Zizer ,&nbsp;Tony Bruns ,&nbsp;Andrea De Gottardi ,&nbsp;Johannes Emrich ,&nbsp;Cornelius Engelmann ,&nbsp;Benjamin Maasoumy ,&nbsp;Arnulf Ferlitsch ,&nbsp;Valentin Fuhrmann ,&nbsp;Jan Hinrichs ,&nbsp;Christian Jansen ,&nbsp;Karoline Lackner ,&nbsp;Robert Matzberger ,&nbsp;Carsten Meyer ,&nbsp;Behrang Mozayani ,&nbsp;Michael Praktiknjo ,&nbsp;Matthias M. Dollinger","doi":"10.1016/j.jhepr.2025.101437","DOIUrl":"10.1016/j.jhepr.2025.101437","url":null,"abstract":"<div><div>Measurement of the hepatic venous pressure gradient (HVPG) and transjugular liver biopsy have emerged as important tools in clinical hepatology. Measurement of HVPG is considered the gold standard for detecting clinically significant portal hypertension, with an HVPG of ≥10 mmHg being the key prognostic threshold in patients with compensated advanced chronic liver disease (cACLD; compensated cirrhosis). A transjugular liver biopsy can be obtained within the same procedure and may be preferred over percutaneous liver biopsy in patients with coagulopathy, ascites and/or significant obesity. Endoscopic ultrasound-guided procedures are currently under investigation and require standardisation. This article summarises critical technical aspects of HVPG measurements and transjugular liver biopsy and provides a detailed overview of their current role in the context of emerging non-invasive tests and endoscopic approaches.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101437"},"PeriodicalIF":9.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517991","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":"Minimally invasive hepatectomy vs. thermoablation for single small (≤3 cm) hepatocellular carcinoma: A weighted real-life national comparison","authors":"Felice Giuliante ,&nbsp;Simone Famularo ,&nbsp;Sara Grasselli ,&nbsp;Angelo Sangiovanni ,&nbsp;Alessandro Vitale ,&nbsp;Giuseppe Cabibbo ,&nbsp;Andrea Lauterio ,&nbsp;Federica Cipriani ,&nbsp;Alice Saccomandi ,&nbsp;Marco Arru ,&nbsp;Elisa Pinto ,&nbsp;Maurizia Rossana Brunetto ,&nbsp;Maria Stella Franzè ,&nbsp;Camilla Graziosi ,&nbsp;Claudia Campani ,&nbsp;Fabio Marra ,&nbsp;Mariella Di Marco ,&nbsp;Mariarosaria Marseglia ,&nbsp;Valentina Santi ,&nbsp;Mario Capasso ,&nbsp;Francesca Notte","doi":"10.1016/j.jhepr.2025.101420","DOIUrl":"10.1016/j.jhepr.2025.101420","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;For patients with single small (≤3 cm) hepatocellular carcinoma ablation is the first-line treatment, although a high rate of recurrence has been reported. The aim was to compare videolaparoscopic liver resection (laparoscopic resection group) &lt;em&gt;vs.&lt;/em&gt; percutaneous thermoablation (ablation group) in terms of overall survival, recurrence-free survival and early recurrence in a real-life national scenario.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The study is a retrospective collection with subsequent survival analysis. Data were collected from two Italian HCC registries, ITA.LI.CA and HE.RC.O.LE.S. An inverse probability of treatment weighting analysis was performed to balance baseline differences between groups. The Kaplan–Meier method and double-robust Cox multivariable regression were run to estimate the survival and the risk of mortality and recurrence.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Between 2008 and 2022, 1,465 patients were enrolled. The laparoscopic resection group and ablation group consisted of 496 and 969 patients, respectively. At baseline, the ablation group had more advanced liver disease, with higher rates of cirrhosis (90.7% &lt;em&gt;vs.&lt;/em&gt; 77.3%, &lt;em&gt;p&lt;/em&gt; &lt;0.001) and Child-Pugh B status (18.4% &lt;em&gt;vs.&lt;/em&gt; 8.8%, &lt;em&gt;p&lt;/em&gt; &lt;0.001). After a median follow-up of 59 months and after weighting median overall survival was 60 months (95% CI 52–66) for the ablation group and 93 months (95% CI 75–110) for the laparoscopic resection group (hazard ratio [HR] 0.607, 95% CI 0.533–0.691, &lt;em&gt;p&lt;/em&gt; &lt;0.001). Median recurrence-free survival was 26 months (95% CI 23–29) for the ablation group and 39 months (95% CI 30–55) for the laparoscopic resection group (HR 0.736, 95% CI 0.659–0.822, &lt;em&gt;p&lt;/em&gt; = 0.0013). Laparoscopy was associated with a reduced risk of early recurrence (HR 0.747, 95% CI 0.655–0.853, &lt;em&gt;p&lt;/em&gt; = 0.011).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This study provides real-world evidence that for patients with single ≤3 cm HCC, videolaparoscopic liver resection offers superior long-term oncological outcomes compared with thermoablation. These findings support the preference for surgical treatment in this patient population.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;Percutaneous thermoablation is considered an appropriate alternative to liver resection for small (≤3 cm) single hepatocellular carcinoma because of not-inferior overall survival, although several authors reported increased recurrence risk. Whether videolaparoscopic liver resection could guarantee comparable survival but superior oncologic control of the disease is a matter of debate. This study comparing videolaparoscopy &lt;em&gt;vs.&lt;/em&gt; thermoablation in a large national cohort of 1,465 patients observed that the former guaranteed significant prolonged OS (93 months [95% CI 75–110] &lt;em&gt;vs.&lt;/em&gt; 60 months [95% CI 52–66] for the ablation group) and recurrence-free survival (26 months [95% CI 23–29] for ablatio","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101420"},"PeriodicalIF":9.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523145","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":"Phosphatidylethanol and ethyl glucuronide to categorize alcohol consumption in alcohol-related cirrhosis","authors":"Benedict T.K. Vanlerberghe ,&nbsp;Catalina Dumitrascu ,&nbsp;Nele Van den Eede ,&nbsp;Hugo Neels ,&nbsp;Hannah van Malenstein ,&nbsp;Tom J.G. Gevers ,&nbsp;Matthijs Kramer ,&nbsp;Lukas Van Melkebeke ,&nbsp;Ad A.M. Masclee ,&nbsp;Douwe de Boer ,&nbsp;Schalk van der Merwe ,&nbsp;Frederik Nevens ,&nbsp;Alexander L.N. van Nuijs ,&nbsp;Jef Verbeek","doi":"10.1016/j.jhepr.2025.101433","DOIUrl":"10.1016/j.jhepr.2025.101433","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Phosphatidylethanol (PEth) is an alcohol-use biomarker that could bridge the detection windows of urinary ethyl glucuronide (uEtG) and scalp hair ethyl glucuronide (hEtG), but has been rarely validated in patients with liver disease. Reported detection windows of these biomarkers also vary significantly, and available studies have focused solely on any alcohol use. Yet, categorizing patients with liver disease based on their level of alcohol use would be highly informative. Here, we assessed the diagnostic accuracy and optimal detection windows of whole-blood PEth, uEtG, hEtG, and the novel biomarker fingernail ethyl glucuronide (nEtG), for different levels of alcohol use in patients with alcohol-related cirrhosis.</div></div><div><h3>Methods</h3><div>Patients with alcohol-related cirrhosis were questioned on their alcohol use over the previous 3 months using the Alcohol Timeline Followback (n = 116). In addition, 1–7-day (uEtG), 1–5-week (PEth), and 3-month (hEtG and nEtG) detection windows were assessed for any, increased (women ≥2 units/day or men ≥3 units/day), or excessive alcohol use (women ≥5 units/day or men ≥6 units/day).</div></div><div><h3>Results</h3><div>uEtG, PEth, and hEtG had high diagnostic accuracies for any alcohol use at optimal detection windows of 3 days [area under the receiver operating characteristic curve (AUROC): 0.990 (95% confidence interval (CI): 0.975–1.000)], 3 weeks [AUROC: 0.986 (95% CI: 0.958–1.000)], and 3 months [AUROC: 0.925 (95% CI: 0.862–0.987)], respectively. They had high negative predictive values (&gt;92%) for increased and excessive use. nEtG showed promising results for assessing any alcohol use over the previous 3 months [AUROC: 0.962 (95% CI: 0.924–1.000)].</div></div><div><h3>Conclusions</h3><div>PEth and EtG have excellent and complementary diagnostic accuracies to detect any alcohol use and rule out increased alcohol use in patients with alcohol-related cirrhosis. nEtG provides an alternative for hEtG, but requires further validation.</div></div><div><h3>Impact and implications</h3><div>The correct identification and categorization of alcohol use is a major challenge in the treatment of patients with liver disease. Furthermore, given the new nomenclature toward steatotic liver disease, it has become essential to be able to categorize alcohol use into any, increased, or excessive use. The validation of PEth and urine, scalp hair, and nail EtG in patients with alcohol-related liver disease provides us with reliable options to overcome these issues in both clinical care and pharmacological trials on steatotic liver disease.</div></div><div><h3>Clinical Trials registration</h3><div>The study is registered at <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT04363424).</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101433"},"PeriodicalIF":9.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516898","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":"CD4 T cells and B cell help – when exhausted cells can still function","authors":"Jill Weisser,&nbsp;Tobias Boettler","doi":"10.1016/j.jhepr.2025.101435","DOIUrl":"10.1016/j.jhepr.2025.101435","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101435"},"PeriodicalIF":9.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270184","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":"Patient-derived organoids inform pharmacogenomic vulnerabilities in liver cancer","authors":"Alissa Michelle Wong ,&nbsp;Hao Huang ,&nbsp;Aikha Melissa Wong ,&nbsp;Howard Ho Wai Leung ,&nbsp;Winnie Wing Yan Cheung ,&nbsp;Yin Kau Lam ,&nbsp;Xiaofan Ding ,&nbsp;Luyao Zhang ,&nbsp;Clarice Chu ,&nbsp;Yue Liu ,&nbsp;Cecilia Ka Wing Chan ,&nbsp;Anthony Wing Hung Chan ,&nbsp;Kelvin Kwok Chai Ng ,&nbsp;Xin Wang ,&nbsp;Stephen Lam Chan ,&nbsp;Nathalie Wong","doi":"10.1016/j.jhepr.2025.101426","DOIUrl":"10.1016/j.jhepr.2025.101426","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Patient-derived tumor organoids (PDTOs) are a reliable model for preclinical and translational studies. Despite positive retrospective correlations with patient response, challenges such as culture success, cost, standardization, and time constraints hinder their clinical utility in precision medicine. Here, we optimize PDTO establishment using growth factor-reduced media (GF-) to mitigate these challenges and (1) identify somatic variant indicators that can improve the therapeutic index of existing FDA-approved drugs against hepatocellular carcinoma (HCC), (2) elucidate synthetic lethal candidates against undruggable HCC driver mutations, and (3) assess the feasibility of PDTOs in personalized therapy.</div></div><div><h3>Methods</h3><div>We successfully established a panel of 23 PDTOs from patients with HCC undergoing curative hepatectomy using a protocol primarily based on growth factor-reduced medium. PDTOs were subjected to comprehensive analyses, including the identification of hallmark mutations, assessment of genomic heterogeneity, transcriptomic profiling, and histological characterization. A 100-drug repurposing screen was conducted on the PDTOs and organoids derived from adjacent non-tumoral and normal livers to explore tumor-specific drug responses. Pharmacogenomic analysis using elastic net was performed (cut-off <em>p</em> &lt;0.05) and synthetic lethality links were subject to experimental validation. The clinical relevance of PDTOs in personalized therapy were investigated through two case studies.</div></div><div><h3>Results</h3><div>Our results reveal that GF-derived PDTOs mimic histology and genetic heterogeneity of HCC. Pharmacogenomic analysis showed that the majority of tested FDA-approved drugs were not associated with HCC driver mutations (&lt;5%). In addition, non-canonical signaling from <em>CTNNB1</em> mutations were associated with ceritinib sensitivity (<em>p</em> &lt;0.0001) via polypharmacological targeting of RPS6KA3. The PDTO case study showed clear benefit to patient survival by aiding clinical management.</div></div><div><h3>Conclusions</h3><div>Our findings underscore the utility of PDTOs established from minimal GF media in many facets of precision oncology advancements.</div></div><div><h3>Impact and implications</h3><div>Patient-derived tumor organoids are a reliable model for preclinical and translational studies. Despite positive retrospective correlations with patient response data, challenges such as culture success, cost, standardization, and time constraints hinder their clinical utility in guiding precision medicine. This study underscores the utility of patient-derived organoids established from growth factor-reduced media in many facets of precision oncology, showing for the first time in hepatocellular carcinoma, clear benefit to patient survival in a proof-of-concept case study.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101426"},"PeriodicalIF":9.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270182","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":"Safety, efficacy, and outcomes of invasive coronary angiography in liver transplant candidates","authors":"Carme Ginard ,&nbsp;Giulia Pagano ,&nbsp;Salvatore Brugaletta ,&nbsp;Annabel Blasi ,&nbsp;Marta Sánchez-Ric ,&nbsp;Ander Regueiro ,&nbsp;Roger Pujol ,&nbsp;Sergio Rodriguez-Tajes ,&nbsp;Pablo Ruiz ,&nbsp;Jordi Colmenero ,&nbsp;Gonzalo Crespo","doi":"10.1016/j.jhepr.2025.101428","DOIUrl":"10.1016/j.jhepr.2025.101428","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Invasive coronary angiography (ICA) with/without percutaneous coronary intervention (PCI) is recommended in liver transplant (LT) candidates at risk of silent coronary artery disease (CAD). The outcomes and safety of this approach have been scarcely analyzed in Europe.</div></div><div><h3>Methods</h3><div>This retrospective, single-center study included all patients assessed as LT candidates between July 2015 and December 2022. Outcomes before and after LT were compared between patients with and without ICA as part of pre-LT assessment. Findings and outcomes of ICA were recorded.</div></div><div><h3>Results</h3><div>A total of 912 patients were considered for LT, of whom 202 had an ICA. Patients with ICA more frequently presented contraindications for LT (<em>p</em> = 0.026). Severe (&gt;70%) CAD was found in 29/202 cases (14%), and PCI was performed in 18 (9%). All patients received drug-eluting stents, and the duration of dual antiplatelet therapy (DAPT) was 1 month in 80%. Eight patients (4%) presented complications, which were more frequent in patients who received PCI (22%). One patient died from acute-on-chronic liver failure after post-DAPT bleeding. In the 516 patients who underwent transplantation, the incidence of cardiovascular events (CVEs) increased with the burden of CAD, from 11% in patients without ICA indication to 43% in patients with PCI (<em>p</em> &lt;0.001), without differences in mortality (<em>p</em> = 0.529).</div></div><div><h3>Conclusions</h3><div>In a contemporary cohort of LT candidates, ICA was associated with a low incidence of complications, although some of these, related to DAPT, can be life-threatening. The burden of disease in ICA correlates with the incidence of post-LT CVEs, although this did not result in a higher mortality.</div></div><div><h3>Impact and implications</h3><div>Invasive coronary angiography (ICA) is performed in potential liver transplant (LT) candidates to identify severe coronary artery disease that may either be treated to permit LT or contraindicate LT if untreatable, but its safety and outcomes are not well defined. We show that ICA is associated with a low incidence of complications in LT candidates, although severe coronary artery disease requiring percutaneous treatment followed by dual antiplatelet therapy increased the risk of severe complications. In addition, ICA identifies patients with untreatable disease that can contraindicate LT. Finally, the higher the burden of disease on ICA, the higher the incidence of post-LT cardiovascular events, although this was not associated with increased post-LT mortality. These results support the use of ICA in LT candidates, although being aware of the potential risks is crucial for physicians and patients.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 7","pages":"Article 101428"},"PeriodicalIF":9.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270183","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":"Efficacy of atezolizumab plus bevacizumab for unresectable HCC: Systematic review and meta-analysis of real-world evidence","authors":"Giulia Francesca Manfredi ,&nbsp;Claudia Angela Maria Fulgenzi ,&nbsp;Ciro Celsa ,&nbsp;Bernardo Stefanini ,&nbsp;Antonio D'Alessio ,&nbsp;Matthias Pinter ,&nbsp;Bernhard Scheiner ,&nbsp;Nichola Awosika ,&nbsp;Leonardo Brunetti ,&nbsp;Pasquale Lombardi ,&nbsp;Charles Latchford ,&nbsp;Pei-Chang Lee ,&nbsp;Yi-Hsiang Huang ,&nbsp;Chun-Yen Lin ,&nbsp;Andrea Dalbeni ,&nbsp;Arndt Vogel ,&nbsp;Peter R. Galle ,&nbsp;Masatoshi Kudo ,&nbsp;Lorenza Rimassa ,&nbsp;Hong Jae Chon ,&nbsp;David J. Pinato","doi":"10.1016/j.jhepr.2025.101431","DOIUrl":"10.1016/j.jhepr.2025.101431","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Atezolizumab plus bevacizumab (A+B) is a standard-of-care treatment in unresectable hepatocellular carcinoma (uHCC). Verification of its effectiveness outside clinical trials is an area of unmet need, especially in estimating long-term survival outcomes.</div></div><div><h3>Methods</h3><div>We conducted a systematic review and meta-analysis of the MEDLINE, Embase, and Cochrane libraries to evaluate therapy outcomes in patients treated with frontline A+B for uHCC outside trials. Pooled estimates of overall survival (OS) and progression-free survival (PFS) at 6 and 12 months were calculated from individual patient-level data using random-effects analysis.</div></div><div><h3>Results</h3><div>Of 2,179 patients selected from 12 cohorts, 80.5% were male, median age was 66 years (IQR 61.6–73.0), 61.6% had advanced-stage hepatocellular carcinoma (HCC), and 83.6% were Child–Pugh (CP) class A. Pooled 6- and 12-month OS was 82% (95% CI: 76–86%; <em>I</em>² = 80%) and 65% (95% CI: 60–70%; <em>I</em>² = 66%). Median OS of patients with CP-A liver function was 20.9 months (95% CI: 15.7–20.9), consistent with IMbrave150 estimates (19.2 months, 95% CI: 17.0–23.7, <em>p</em> = 0.58). Pooled PFS at 6 and 12 months was 57% (95% CI: 53–61%; <em>I</em>² = 49%) and 35% (95% CI: 31–39%, <em>I</em>² = 60%). Among patients with longer follow-up, the OS (n = 1,783) and PFS (n = 959) rates were 52% (95% CI: 46–58; <em>I</em>² = 90%) and 26% (95% CI: 17–37; <em>I</em>² = 91%) at 18 months, respectively. At 24 months, OS (n = 1,556) rate was 39% (95% CI: 31–49; <em>I</em>² = 90%) and PFS (n = 732) rate was 25% (95% CI: 12–45; <em>I</em>² = 95%).</div></div><div><h3>Conclusions</h3><div>The effectiveness of A+B after registration mirrors its efficacy estimates from clinical trial datasets. Long-term survival at 24 months can be achieved in up to 39% of patients with uHCC treated with A+B in routine clinical practice.</div></div><div><h3>Impact and implications</h3><div>This study provides real-world evidence supporting the long-term efficacy of atezolizumab plus bevacizumab (A+B) for unresectable hepatocellular carcinoma, showing survival outcomes similar to those achieved in clinical trials. These findings are important for clinicians in supporting A+B as a frontline treatment, particularly for patients with Child–Pugh class A liver function. They also offer valuable insights for policymakers and researchers for optimising treatment strategies for unresectable hepatocellular carcinoma. However, results should be interpreted with caution because of potential variability in patient populations.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101431"},"PeriodicalIF":9.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517990","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":"Ability of soluble TREM2 and PRO-C3 as biomarkers to predict changes in MASLD activity","authors":"Charlotte Wilhelmina Wernberg ,&nbsp;Vineesh Indira Chandran ,&nbsp;Mette Munk Lauridsen ,&nbsp;Maria Kløjgaard Skytthe ,&nbsp;Camilla Dalby Hansen ,&nbsp;Johanne Kragh Hansen ,&nbsp;Lea Ladegaard Grønkjær ,&nbsp;Birgitte Gade Jacobsen ,&nbsp;Tina Di Caterino ,&nbsp;Sönke Detlefsen ,&nbsp;Maja Thiele ,&nbsp;Alejandro Mayorca Guiliani ,&nbsp;Ida Falk Villesen ,&nbsp;Diana Julie Leeming ,&nbsp;Morten Karsdal ,&nbsp;Jonas Heilskov Graversen ,&nbsp;Aleksander Krag","doi":"10.1016/j.jhepr.2025.101432","DOIUrl":"10.1016/j.jhepr.2025.101432","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;Diet and weight loss remain the primary treatment for most patients with metabolic dysfunction-associated fatty liver disease (MASLD), with one recent drug therapy approved for severe cases. However, a significant need remains for non-invasive tests (NITs) that can assist clinicians in evaluating treatment response. We aimed to explore the ability of several NITs to reflect a change of at least one point in histologic non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This study explores biomarkers reflecting treatment response in 173 patients from secondary care with type 2 diabetes or severe obesity, all of whom underwent repeated liver biopsies and blood samples. We measured soluble triggering receptor expressed on myeloid cells 2 (TREM2), collagen markers PRO-C3, PRO-C4, PRO-C6, PRO-C8, and PRO-C18L and liver stiffness measured by FibroScan, FAST-score, and homeostatic model assessment of insulin resistance (HOMA-IR). We studied biomarker changes and their capacity to reflect liver biopsy alterations in two distinct cohorts, using comparative paired analyses and multivariable logistic regression to evaluate the results.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Mean age was 52 years (±12), 38% male, 52% had NAS ≥3 at baseline (90/173), 70% had F0–F1 fibrosis, and 23% (39/173) had metabolic dysfunction-associated steatohepatitis. Significant differences were seen in sTREM2, PRO-C3, HOMA-IR, and FAST-score levels by NAS changes (worsened, no-change, improved) (&lt;em&gt;p&lt;/em&gt; = 0.0001). In multivariable analysis, sTREM2 + PRO-C3 and HOMA-IR predicted NAS improvement (AUROC &gt;0.75), with an odds ratio of 1.13 for each unit decrease (&lt;em&gt;p&lt;/em&gt; = 0.001, 95% CI 1.04–1.21). FIB-4 and non-alcoholic fatty liver disease fibrosis score (NFS) did not reflect NAS improvement (AUROC &lt;0.60, OR &lt;1.05, &lt;em&gt;p&lt;/em&gt; &gt;0.5).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;sTREM2, PRO-C3, and HOMA-IR indicate NAS improvement and warrant further investigation as surrogate markers for gauging intervention response.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;Non-invasive tests (NITs) will play a crucial role in monitoring treatment responses in metabolic dysfunction-associated steatotic liver disease, providing a viable alternative to liver biopsies. Our study investigates whether NITs reflect histological responses based on changes in the non-alcoholic fatty liver disease (NAFLD) activity score (NAS) in patients with type 2 diabetes mellitus or obesity. We used non-invasive markers, some corresponding to different biological aspects of disease severity. We found that reductions in certain NIT levels correlate well with NAS reduction and composite histological improvements (lobular inflammation and ballooning). Combining soluble triggering receptor expressed on myeloid cells 2, PRO-C3, or homeostatic model assessment of insulin resistance enhances the potential for monitorin","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101432"},"PeriodicalIF":9.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516900","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":"Deep learning can predict cardiovascular events from liver imaging","authors":"Gregory Patrick Veldhuizen ,&nbsp;Tim Lenz ,&nbsp;Didem Cifci ,&nbsp;Marko van Treeck ,&nbsp;Jan Clusmann ,&nbsp;Yazhou Chen ,&nbsp;Carolin V. Schneider ,&nbsp;Tom Luedde ,&nbsp;Peter W. de Leeuw ,&nbsp;Ali El-Armouche ,&nbsp;Daniel Truhn ,&nbsp;Jakob Nikolas Kather","doi":"10.1016/j.jhepr.2025.101427","DOIUrl":"10.1016/j.jhepr.2025.101427","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;Cardiovascular mortality remains the leading cause of death and a significant source of morbidity, with metabolic alterations being key etiological factors. As the main metabolic organ, the liver could predict prodromal changes associated with increased cardiovascular risk. However, quantifying this risk remains challenging. This study explores the use of transformer neural networks on liver magnetic resonance imaging (MRI) data to enhance cardiovascular risk prediction.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Using the extensive collection of liver MRIs in the UK Biobank, we developed a feature extractor with a vision transformer backbone trained in a self-supervised manner. This encoder was then used to predict cardiovascular outcomes from liver MRI scans. Unlike traditional methods, no manual feature selection was required, minimizing bias. Performance was assessed via fivefold cross validation, where predicted risk scores were compared against actual cardiovascular outcomes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The model was trained on 44,672 liver MRIs. In the fivefold cross-validation predicting major adverse cardiac events, the mean AUC was 0.70 with a 95% CI of 0.69–0.72 and &lt;em&gt;p&lt;/em&gt; &lt;0.001. The F-statistic from the one-way ANOVA comparing the Systematic Coronary Risk Evaluation 2 (SCORE2) values of the three prediction model score groups was 68.49 with &lt;em&gt;p&lt;/em&gt; &lt;0.001. The log-rank test comparing the survival of those with prediction model scores above and below 0.5 had a test statistic of 43 and &lt;em&gt;p&lt;/em&gt; &lt;0.001. The multivariate log-rank test comparing the survival of those in the four quartiles of prediction model scores had a test statistic of 61 and &lt;em&gt;p&lt;/em&gt; &lt;0.001.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Vision transformer-based models demonstrate promise as quantifiable biomarkers for cardiovascular risk assessment by capturing subtle metabolic and vascular information from liver MRI scans. These findings highlight their strong predictive performance and potential value in risk stratification. Further prospective studies and external validation will be required to establish their clinical utility.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;Our study demonstrates that deep learning applied to liver MRI can predict cardiovascular risk, highlighting the role of the liver as a metabolic indicator of early cardiovascular disease. These findings are significant for clinicians and researchers seeking non-invasive, imaging-based biomarkers for cardiovascular risk stratification, particularly in patients who might not yet exhibit overt symptoms. If validated in prospective studies, this approach could enhance current risk assessment models, allowing for earlier and more personalized interventions in high-risk individuals. However, further validation is necessary before clinical implementation, ensuring broad applicability and integration into existing prevention frameworks.","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101427"},"PeriodicalIF":9.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572228","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":"Single-cell analysis of mature hepatocytes reveals an IRF1-driven restriction of HDV infection","authors":"Frauke Lange ,&nbsp;Jonathan Garn ,&nbsp;Matthias Bruhn ,&nbsp;Thomas Pietschmann ,&nbsp;Arnaud Carpentier","doi":"10.1016/j.jhepr.2025.101429","DOIUrl":"10.1016/j.jhepr.2025.101429","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Stem cell-derived hepatocyte-like cells (HLCs) are an <em>in vitro</em> model of hepatocytes reproducing mature hepatic functions. However, heterogeneous or imperfect differentiation may limit their biological relevance. HLCs are susceptible to all primary hepatitis viruses, including HDV. Importantly, HLCs support limited HDV replication, at a significantly lower level than hepatoma cell lines.</div></div><div><h3>Methods</h3><div>We used single-cell RNA sequencing (scRNAseq) to analyse control and HDV-infected HLCs. We assessed maturation and heterogeneity of the HLCs population. We visualised viral genomic and antigenomic sequences abundance and innate immune response at the single-cell level. Further functional characterisation was performed in HLCs and hepatoma cell lines.</div></div><div><h3>Results</h3><div>HLCs form a population of hepatocytes exhibiting various levels of maturation, with a minor hybrid population of myofibroblast/hepatocyte cells associated with immature phenotype. Upon HDV inoculation, Interferon-Stimulated Genes expression was induced in infected cells, but not in bystander HLCs. Moreover, Interferon Regulatory Factor 1 (IRF1) was enriched in infected HLCs with undetectable levels of viral genome replication, suggesting it may restrict viral infection. Decreasing IRF1 expression in HLCs by 50% improved susceptibility to HDV infection by 10-fold (<em>p</em> &lt;0.01). Moreover, IRF1 overexpression in hepatoma cell lines restored physiological basal level of IRF1 effector antiviral genes and inhibited HDV infection (∼50% reduction after 7 days, <em>p</em> &lt;0.01). Importantly, in IRF1 expressing cells, cell division-mediated spread was inhibited and infection was significantly decreased after 2 weeks of culture (&gt;1.5 log decrease, <em>p</em> &lt;0.001).</div></div><div><h3>Conclusions</h3><div>scRNAseq of HLCs identified IRF1 as a potent restriction factor of HDV infection, through an antiviral mechanism blocking HDV infection at an early step of the viral cycle.</div></div><div><h3>Impact and implications</h3><div>We performed single-cell RNA sequencing of control and HDV-inoculated stem cell-derived hepatocytes, and characterised them in terms of hepatic differentiation, viral abundance and response to infection. We identified IRF1 as a constitutive cellular factor restricting HDV infection in mature hepatocytes, particularly targeting HDV in the cytoplasm. This work improves our understanding of mature cell culture models for HDV, needed to decipher its host–pathogens interactions. Identification of antiviral effector genes opens the way to the development of new host targeted antiviral strategies, particularly for targeting cell division-mediated spread that is not inhibited by currently used entry inhibitors (Hepcludex).</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 8","pages":"Article 101429"},"PeriodicalIF":9.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516899","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}