JHEP Reports最新文献

{"title":"Associations between fruit and vegetable consumption and HCC occurrence in patients with liver cirrhosis","authors":"Florian Manneville ,&nbsp;Zineb Zouakia ,&nbsp;Séverine Donneger ,&nbsp;Leopold K. Fezeu ,&nbsp;Alice Bellicha ,&nbsp;Pierre Nahon ,&nbsp;Mathilde Touvier ,&nbsp;Nathalie Ganne-Carrié ,&nbsp;Chantal Julia","doi":"10.1016/j.jhepr.2025.101355","DOIUrl":"10.1016/j.jhepr.2025.101355","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Prospective studies are needed to increase knowledge of fruit and vegetable consumption effects on hepatocellular carcinoma (HCC) risk. This study aimed to investigate the association between fruit and vegetable consumption and incident HCC in French patients with liver cirrhosis.</div></div><div><h3>Methods</h3><div>This study used data from a French prospective observational cohort nested in two national prospective cohorts of patients with histologically proven compensated alcohol-related or viral liver cirrhosis. Fruit and vegetable consumption was assessed by a trained dietitian using semi-quantitative food-frequency questionnaire validated in French and analyzed as binary exposure according to predefined thresholds (≥ 240 g/day for fruit or vegetables and ≥ 400 g/day for fruit and vegetables combined). Incident HCC was primary outcome. Propensity scores were used in Poisson regression models.</div></div><div><h3>Results</h3><div>Among 179 patients analyzed, 20 HCC were diagnosed during follow-up (median 7.3 [Q1-Q3: 4.1-8.0] years). A significant association was observed between HCC incidence and vegetable consumption ≥ 240 g/day (adjusted RR 0.35, 95%CI [0.13; 0.98], p = 0,04), but not with consumption of fruit and vegetable ≥ 400 g/day (RR 0.49, 95%CI [0.18; 1.32], p =0,16), nor with fruit consumption ≥ 240 g/day (RR= 0.80, 95% CI [0.28; 2.31], p=0.68).</div></div><div><h3>Conclusions</h3><div>This longitudinal study documented insufficient fruit and/or vegetable consumption in 42.5% of patients with liver cirrhosis and a 65% reduction of HCC incidence in those with vegetable consumption ≥ 240 g/day. Reproduction of results in a larger sample are necessary to explore the potential of fruit and vegetables as protective factors in HCC.</div></div><div><h3>Impact and implications</h3><div>The association between fruit and vegetable consumption and the risk of hepatocellular carcinoma (HCC) is poorly documented in the population of cirrhotic patients, while such knowledge is crucial for adapting HCC prevention messages. Our study shows 57.5% of patients with liver cirrhosis reported consuming fruit and/or vegetables at or above the French and WHO threshold of 400g/day, with a higher proportion of patients consuming at least 240g/day of vegetable compared with those consuming at least 240g/day of fruit (47.5% versus 38.6%). The results suggest that consuming at least 240g/day of vegetables reduces the risk of HCC by 65% in patients with liver cirrhosis.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 5","pages":"Article 101355"},"PeriodicalIF":9.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792620","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":"Liver fibrosis progression analyzed with AI predicts renal decline","authors":"Dan-Qin Sun ,&nbsp;Jia-Qi Shen ,&nbsp;Xiao-Fei Tong ,&nbsp;Ya-Yun Ren ,&nbsp;Hai-Yang Yuan ,&nbsp;Yang-Yang Li ,&nbsp;Xin-Lei Wang ,&nbsp;Sui-Dan Chen ,&nbsp;Pei-Wu Zhu ,&nbsp;Xiao-Dong Wang ,&nbsp;Christopher D. Byrne ,&nbsp;Giovanni Targher ,&nbsp;Lai Wei ,&nbsp;Vincent W.S. Wong ,&nbsp;Dean Tai ,&nbsp;Arun J. Sanyal ,&nbsp;Hong You ,&nbsp;Ming-Hua Zheng","doi":"10.1016/j.jhepr.2025.101358","DOIUrl":"10.1016/j.jhepr.2025.101358","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>The relationship between biopsy-proven liver fibrosis progression and renal function decline in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) has not been fully elucidated. We used an automated quantitative liver fibrosis assessment (qFibrosis) technique to investigate the temporal changes in regional liver fibrosis.</div></div><div><h3>Methods</h3><div>This retrospective longitudinal study included 68 MASLD patients and their paired formalin-fixed sections of liver biopsies. One hundred eighty-four fibrosis parameters were quantified in five different hepatic regions, including portal tract, peri-portal, zone 2, peri-central and central vein regions, and qFibrosis continuous values were calculated for all samples based on 10 fibrosis parameters using qFibrosis assessment. Liver fibrosis progression (QLF⁺, n = 18) and regression (QLF^-, n = 23) was defined as at least a 20% relative change in qFibrosis over a 23-month follow-up. Renal function decline was assessed by estimated glomerular filtration rate (eGFR) changes.</div></div><div><h3>Results</h3><div>The eGFR decline was greater in the QLF⁺ group (106.53 ± 13.71 ml/min/1.73 m² <em>vs.</em> 105.28 ± 12.46 ml/min/1.73 m²) than in the QLF^- group (110.87 ± 14.58 ml/min/1.73 m² <em>vs.</em> 114.18 ± 14.81 ml/min/1.73 m²). In addition, liver fibrosis changes in the central vein and pericentral regions were more strongly associated with eGFR decline than in periportal, zone 2 and portal tract regions. We combined these parameters to construct a prediction model, which better differentiated eGFR decline (a cut-off value of qFibrosis combined index = 0.52, <em>p</em> &lt;0.001).</div></div><div><h3>Conclusions</h3><div>A decline in renal function is significantly related to liver fibrosis progression in MASLD. Regional qFibrosis assessment may efficiently predict eGFR decline, thus highlighting the importance of assessing renal function in patients with MASLD with worsening liver fibrosis.</div></div><div><h3>Impact and implications</h3><div>The study shows that liver fibrosis progression assessed by qFibrosis may be associated with renal function decline, which provides a new perspective for understanding complex pathological processes. A combination of artificial intelligence and digital pathology may earlier and more precisely quantify the progression of regional liver fibrosis, thus better identifying changes in renal function. This opens the possibility of early interventions, which are essential to improve patients’ outcomes.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 5","pages":"Article 101358"},"PeriodicalIF":9.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864471","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":"Multicenter evaluation of abbreviated MRI and ultrasound for detecting early-stage hepatocellular carcinoma","authors":"Karim Seif El Dahan ,&nbsp;Takeshi Yokoo ,&nbsp;Darine Daher ,&nbsp;Matthew S. Davenport ,&nbsp;David T. Fetzer ,&nbsp;Mishal Mendiratta-Lala ,&nbsp;Nicole E. Rich ,&nbsp;Edward Yang ,&nbsp;Neehar D. Parikh ,&nbsp;Amit G. Singal","doi":"10.1016/j.jhepr.2025.101357","DOIUrl":"10.1016/j.jhepr.2025.101357","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; aims&lt;/h3&gt;&lt;div&gt;Abbreviated MRI (AMRI) has been proposed as an alternative to ultrasound for hepatocellular carcinoma (HCC) surveillance; however, comparative data for AMRI and ultrasound are needed. Thus, we evaluated the sensitivity and specificity of dynamic contrast-enhanced (DCE)-AMRI and ultrasound for early-stage HCC detection in patients with cirrhosis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted a multicenter retrospective case–control study among patients with cirrhosis (cases with early-stage HCC as per Milan Criteria; controls without HCC) who underwent an ultrasound and a DCE-MRI within a 6-month period between 2012 and 2019. HCC diagnosis was confirmed by imaging alone in 85% and by histopathology in 15% of patients. Dynamic AMRI examinations were simulated from the full MRI by selecting relevant sequences. Independent, blinded interpretations of ultrasounds and AMRI results were performed using Liver Imaging Reporting and Data System algorithms. Ultrasounds were considered positive if US-3 observations were detected. AMRI was considered positive if LR-4, LR-5, or LR-M were detected. Per-patient sensitivity and specificity for early-stage HCC detection were estimated, and cross-modality differences were tested.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We included 216 cases and 432 controls. Patient-level sensitivity and specificity of AMRI were significantly higher compared with ultrasound: 80.1% (95% CI 76.1–83.6) &lt;em&gt;vs.&lt;/em&gt; 71.1% (95% CI 66.6–75.2), &lt;em&gt;p&lt;/em&gt; &lt;0.001, and 91.9% (95% CI 89.9–93.5) &lt;em&gt;vs.&lt;/em&gt; 72.3% (95% CI 69.3–75.2), &lt;em&gt;p&lt;/em&gt; &lt;0.001, respectively. AMRI sensitivity was significantly higher compared with ultrasound among patients with Child-Pugh B cirrhosis (80.8% &lt;em&gt;vs.&lt;/em&gt; 57.4%, &lt;em&gt;p&lt;/em&gt; &lt;0.001) but not among those with Child-Pugh A (84.7% &lt;em&gt;vs.&lt;/em&gt; 78.6%, &lt;em&gt;p&lt;/em&gt; = 0.07) or Child-Pugh C cirrhosis (52.6% &lt;em&gt;vs.&lt;/em&gt; 68.4%, &lt;em&gt;p&lt;/em&gt; = 0.18).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Dynamic AMRI may be more sensitive and specific for early-stage HCC detection in patients with cirrhosis compared with ultrasound, although its relative benefit might be smaller in patients with Child-Pugh A cirrhosis. Larger direct comparative data sets are needed, particularly among patients with Child-Pugh C cirrhosis who may benefit from alternative surveillance strategies.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;Abbreviated MRI (AMRI) is increasingly recognized as an alternative to ultrasound for hepatocellular carcinoma (HCC) surveillance. However, existing data are limited by single-center samples, spectrum bias, and lack of comparative data for AMRI &lt;em&gt;vs.&lt;/em&gt; ultrasound. We found that AMRI had significantly higher per-patient sensitivity and specificity compared with ultrasound for the detection of early-stage HCC, although its relative benefit might be smaller in patients with Child-Pugh A cirrhosis, and both modalities underperformed in patients with Child-Pu","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 5","pages":"Article 101357"},"PeriodicalIF":9.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864470","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":"Cirrhosis epidemiology in Denmark 1998–2022, and 2030 forecast","authors":"Linda Skibsted Kornerup ,&nbsp;Frederik Kraglund ,&nbsp;Gro Askgaard ,&nbsp;Hendrik Vilstrup ,&nbsp;Peter Jepsen","doi":"10.1016/j.jhepr.2025.101353","DOIUrl":"10.1016/j.jhepr.2025.101353","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>The incidence of cirrhosis resulting from alcohol-related liver disease (ALD) is decreasing in Denmark, whereas the incidence of obesity is increasing, driving an increase in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to perform an up-to-date study of the epidemiology of cirrhosis in Denmark, including etiologies, and a forecast through to 2030.</div></div><div><h3>Methods</h3><div>We identified all patients diagnosed with cirrhosis between 1998 and 2022, categorized into ALD and non-ALD cirrhosis, in nationwide Danish healthcare registries. Cirrhosis prevalence and incidence were computed. We used an age–period–cohort model to visualize impacts of age, calendar year, and birthyear on etiology-specific cirrhosis incidence rates (alcohol or non-alcohol, interpreted as mainly the result of MASLD), with predicted incidence rates for 2023–2030. The Kaplan-Meier function was used for survival probabilities.</div></div><div><h3>Results</h3><div>We included 30,747 (76%) patients with ALD cirrhosis and 9,548 (24%) with non-ALD cirrhosis. Patients with non-ALD cirrhosis were older and had more comorbidities compared with patients with ALD cirrhosis; median age at diagnosis was 66 <em>vs.</em> 59 years, increasing in both groups overall, from 56 years in 1998 to 66 years in 2022. The ALD cirrhosis proportion was stable at around 80% from 1998 to the end of 2014, and gradually declined to 58% in 2022. Overall cirrhosis prevalence will have peaked in 2024, and non-ALD cirrhosis will outnumber ALD cirrhosis from 2027. Thus, mortality among patients with cirrhosis is declining owing to fewer deaths the first year after cirrhosis diagnosis.</div></div><div><h3>Conclusions</h3><div>We forecast a change in cirrhosis epidemiology affecting hepatology practice in Denmark: patients will be older, fewer will have ALD, more will have MASLD, and their longer life expectancy and comorbidities will be more burdensome for healthcare systems.</div></div><div><h3>Impact and implications</h3><div>Alcohol-related liver (ALD) cirrhosis poses a substantial and growing burden on hospitals worldwide. Information about the current and imminent epidemiology of cirrhosis is important for our understanding of the public health, for researchers designing trials of interventions, and for planning of future assignments of healthcare systems. In the current study, we used Danish nationwide healthcare registries to study past, current, and future trends in the epidemiology of cirrhosis. Our results forecast a change in cirrhosis epidemiology and thereby a change in hepatology practice in Denmark. We expect that patients with ALD cirrhosis will be outnumbered by increasingly older patients who present in the outpatient clinic with cirrhosis from MASLD and a higher burden of comorbidities.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 5","pages":"Article 101353"},"PeriodicalIF":9.5,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759979","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":"Pravastatin reduces all-cause mortality in elderly individuals at risk of liver fibrosis: Post hoc analysis of the PROSPER trial","authors":"Vivian de Jong ,&nbsp;Willy Theel ,&nbsp;Manuel Castro Cabezas ,&nbsp;Diederick E. Grobbee ,&nbsp;Wouter Jukema ,&nbsp;Stella Trompet","doi":"10.1016/j.jhepr.2025.101337","DOIUrl":"10.1016/j.jhepr.2025.101337","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD), especially the progressive stages accompanied by liver fibrosis, are associated with liver-related and cardiovascular (CV) complications in middle-aged cohorts. We evaluated whether liver fibrosis is associated with increased mortality and cause-specific endpoints in an elderly population, and whether statin treatment could reduce these risks.</div></div><div><h3>Methods</h3><div>PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) was a double-blind randomized clinical trial comparing pravastatin to placebo in an elderly Caucasian population of 5,804 patients (&gt;70 years of age) at increased risk of CV disease. Endpoints were composite and single (CV) endpoints and all-cause mortality. The Fibrosis-4 index (FIB-4) score was classified as: low risk of liver fibrosis (FIB-4 &lt;2.0), indeterminate risk (2.0≤ FIB-4 ≤2.66), and high risk (FIB-4 ≥2.67). Time-to-event data were analyzed using the Cox proportional hazards model.</div></div><div><h3>Results</h3><div>Most participants were classified in the low FIB-4 class (n = 3,919), followed by the indeterminate (n = 1,269) and high classes (n = 561). In the placebo group, the risk of all-cause mortality increased with a high FIB-4 classification: high-class hazard ratio (HR) = 1.54 (95% CI, 1.10–2.17), compared with the low class (reference group). In the pravastatin group, the HR for all-cause mortality was not associated with FIB-4 classification: high-class HR = 1.01 (95% CI, 0.69–1.49). The interaction between FIB-4 class and treatment was significant (<em>p</em> = 0.049). High FIB-4 classifications were not significantly associated with major adverse cardiovascular events (MACE) or other endpoints in either arms.</div></div><div><h3>Conclusions</h3><div>A high FIB-4 classification is associated with increased all-cause mortality in the elderly, although pravastatin appears to mitigate this increased risk.</div></div><div><h3>Clinical Trials registration</h3><div>The study is registered at <span><span>www.isrctn.com/</span><svg><path></path></svg></span>(ISRCTN40976937).</div></div><div><h3>Impact and implications</h3><div>The progressive stages of MASLD (liver fibrosis) are associated with liver-related and CV complications in middle-aged cohorts (∼55 years of age). The impact of liver fibrosis in elderly populations is less well studied. In addition, the use of statins has long been debated, but evidence appears to point to a beneficial effect in populations with MASLD. However, data from prospective trials remain limited. Our findings indicate a potential survival benefit associated with pravastatin use in the elderly (&gt;70 years of age) with an indication of liver fibrosis.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 4","pages":"Article 101337"},"PeriodicalIF":9.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698144","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":"Second-line pembrolizumab for advanced HCC: Meta-analysis of the phase III KEYNOTE-240 and KEYNOTE-394 studies","authors":"Richard S. Finn ,&nbsp;Kangsheng Gu ,&nbsp;Xi Chen ,&nbsp;Philippe Merle ,&nbsp;Kyung-Hun Lee ,&nbsp;Mohamed Bouattour ,&nbsp;Peiguo Cao ,&nbsp;Wei Wang ,&nbsp;Ann-Lii Cheng ,&nbsp;Liangjun Zhu ,&nbsp;Ho Yeong Lim ,&nbsp;Masatoshi Kudo ,&nbsp;Yueyin Pan ,&nbsp;Ting-Tsung Chang ,&nbsp;Julien Edeline ,&nbsp;Wei Li ,&nbsp;Ping Yang ,&nbsp;Chen Li ,&nbsp;Jianfeng Li ,&nbsp;Abby B. Siegel ,&nbsp;Shukui Qin","doi":"10.1016/j.jhepr.2025.101350","DOIUrl":"10.1016/j.jhepr.2025.101350","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;We performed a meta-analysis of data from the KEYNOTE-240 and KEYNOTE-394 studies to obtain a more precise estimate of the pembrolizumab treatment effect in participants with previously treated advanced hepatocellular carcinoma (HCC).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Participants with confirmed HCC and disease progression after treatment with or intolerance of sorafenib or oxaliplatin-based chemotherapy (KEYNOTE-394 only), Barcelona Clinic Liver Cancer stage C or B disease not amenable to or refractory to locoregional therapy, and one or more measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were randomly assigned 2:1 to receive pembrolizumab or placebo for ≤35 cycles. Data from the KEYNOTE-240 and KEYNOTE-394 intention-to-treat populations were pooled, and the treatment effect was evaluated for pembrolizumab and placebo separately.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In total, 578 and 288 participants who received pembrolizumab and placebo, respectively, were included in this analysis. Compared with placebo, pembrolizumab improved overall survival (hazard ratio 0.79, 95% CI 0.67–0.93), progression-free survival (per RECIST v1.1 by blinded independent central review [BICR]; hazard ratio 0.76, 95% CI 0.64–0.89), and objective response rate (per RECIST v1.1 by BICR; 15.4% &lt;em&gt;vs.&lt;/em&gt; 2.8%, for an estimated treatment difference of 12.5%; 95% CI 8.8–16.2). Subgroup analyses showed that the treatment effect of pembrolizumab was generally similar across baseline participant characteristics, including viral status, Barcelona Clinic Liver Cancer stage, and geographic region.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Meta-analysis of KEYNOTE-240 and KEYNOTE-394 showed that pembrolizumab provides clinically meaningful improvement in overall survival, progression-free survival, and objective response rate. This analysis expands on findings from each study individually and provides further evidence of the global benefit of pembrolizumab as second-line therapy for advanced HCC after prior sorafenib- or oxaliplatin-based therapy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;To obtain a more precise estimate of the pembrolizumab treatment effect in participants with previously treated advanced hepatocellular carcinoma, we performed a meta-analysis of efficacy using pooled participant data from the phase III KEYNOTE-240 and KEYNOTE-394 studies. Subgroup analyses showed that the treatment effect of pembrolizumab was generally similar across baseline characteristics, including viral status, Barcelona Clinic Liver Cancer stage, and geographic region. This meta-analysis provides further evidence of the global benefit of pembrolizumab as second-line therapy for advanced hepatocellular carcinoma.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Clinical Trials Registration&lt;/h3&gt;&lt;div&gt;Registered at &lt;span&gt;&lt;span&gt;ClinicalTrials.gov&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt; NCT02702401 (KEYNOTE-240) and NCT03062358 (K","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 6","pages":"Article 101350"},"PeriodicalIF":9.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069553","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":"Non-invasive tests for fibrotic MASH for reducing screen failure in therapeutic trials","authors":"Jeanne Fichez ,&nbsp;Thomas Mouillot ,&nbsp;Luisa Vonghia ,&nbsp;Charlotte Costentin ,&nbsp;Clémence Moreau ,&nbsp;Marine Roux ,&nbsp;Adèle Delamarre ,&nbsp;Sven Francque ,&nbsp;Ming-Hua Zheng ,&nbsp;Jérôme Boursier","doi":"10.1016/j.jhepr.2025.101351","DOIUrl":"10.1016/j.jhepr.2025.101351","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;Therapeutic trials in metabolic dysfunction-associated steatohepatitis (MASH) are hampered by a high 70–80% screen failure rate mostly because of the absence of fibrotic MASH on baseline liver biopsies, underscoring the need for better selection of candidates. We compared the performance of eight non-invasive tests, designed or not for the diagnosis of fibrotic MASH.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A total of 1,005 patients with histologically proven MASLD were included in five tertiary care centers. Three non-invasive tests developed for fibrotic MASH were evaluated: the simple blood test Fibrotic NASH Index (FNI), the specialized blood test MACK-3, and the elastography-based test FAST. Five non-invasive tests recommended for advanced fibrosis were evaluated as well: the simple blood test FIB-4, the specialized blood tests FibroTest and Enhanced Liver Fibrosis test (ELF™), and the elastography-based tests FibroScan and Agile3+. Fibrotic MASH was defined as MASH with MASLD activity score ≥4 and fibrosis score F ≥2.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Among simple blood tests (n = 1,005), FNI had a significantly higher area under the receiver operating characteristic (AUROC) for fibrotic MASH than FIB-4 (0.709 [0.677–0.741] &lt;em&gt;vs.&lt;/em&gt; 0.662 [0.628–0.695], &lt;em&gt;p&lt;/em&gt; = 0.019). Among elastography-based tests (n = 817), FAST had a significantly higher AUROC (0.774 [0.743–0.806]) than FibroScan (0.728 [0.694–0.763], &lt;em&gt;p&lt;/em&gt; = 0.013) and Agile3+ (0.708 [0.672–0.744], &lt;em&gt;p&lt;/em&gt; = 0.004). Among specialized blood tests (n = 545), MACK-3 had a significantly higher AUROC (0.772 [0.734–0.811]) than FibroTest (0.615 [0.568–0.663], &lt;em&gt;p&lt;/em&gt; &lt;0.001) and ELF (0.700 [0.656–0.744], &lt;em&gt;p&lt;/em&gt; = 0.028). Sequential combination (FAST then Agile3+; MACK-3 then ELF) identified a subset including one-third of patients in whom the false-positive rate was only 30%.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Sequential combinations using first-line tests designed for fibrotic MASH improves the identification of candidates for MASH therapeutic trials.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;Drug development in metabolic dysfunction-associated steatohepatitis (MASH) is hampered by a high screen failure rate, one of the main reasons being the absence of MASH and significant fibrosis (fibrotic MASH) on the baseline liver biopsy, a key inclusion criterion in MASH therapeutic trials. Non-invasive tests represent an attractive opportunity to better select candidates for these trials, but most of them have been developed for advanced fibrosis and the new tests designed for the diagnosis of fibrotic MASH remain poorly validated. In this work, we demonstrate that the tests specifically designed for fibrotic MASH are more accurate for this diagnostic target than the tests currently recommended and initially developed for advanced fibrosis. We propose sequential combinations that will facilitate the identification of ","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 4","pages":"Article 101351"},"PeriodicalIF":9.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copyright and information","authors":"","doi":"10.1016/S2589-5559(25)00023-0","DOIUrl":"10.1016/S2589-5559(25)00023-0","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101347"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143296917","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":"Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab","authors":"Meng Wu ,&nbsp;Claudia A.M. Fulgenzi ,&nbsp;Antonio D’Alessio ,&nbsp;Alessio Cortellini ,&nbsp;Ciro Celsa ,&nbsp;Giulia F. Manfredi ,&nbsp;Bernardo Stefanini ,&nbsp;Y. Linda Wu ,&nbsp;Yi-Hsiang Huang ,&nbsp;Anwaar Saeed ,&nbsp;Angelo Pirozzi ,&nbsp;Tiziana Pressiani ,&nbsp;Lorenza Rimassa ,&nbsp;Martin Schoenlein ,&nbsp;Kornelius Schulze ,&nbsp;Johann von Felden ,&nbsp;Yehia Mohamed ,&nbsp;Ahmed O. Kaseb ,&nbsp;Arndt Vogel ,&nbsp;Natascha Roehlen ,&nbsp;Celina Ang","doi":"10.1016/j.jhepr.2024.101232","DOIUrl":"10.1016/j.jhepr.2024.101232","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS).</div></div><div><h3>Methods</h3><div>In this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B. The primary outcome of PPS was defined as time from first radiographic progression on A/B to death.</div></div><div><h3>Results</h3><div>A total of 406 patients alive after progression on first-line A/B were included in the final analysis, of whom 45.3% (n = 184) received best supportive treatment (BST) and 54.7% (n = 222) continued active systemic treatment. In the second line, 155 patients were treated with tyrosine kinase inhibitors (TKIs), 45 with immune checkpoint inhibitor (IO)-based regimens, and 3 had missing data. Median PPS of the whole cohort (mPPS) was 6.0 months (95% CI 5.2-7.2). On multivariate Cox regression analysis, absence of portal vein tumor thrombus, ECOG &lt;2, and continued active treatment were predictors of better PPS. mPPS was significantly longer for patients who continued active treatment <em>vs.</em> BST (9.7 <em>vs.</em> 2.6 months; HR 0.41, <em>p &lt;</em>0.001). In the second-line setting, patients treated with TKIs had a numerically shorter mPPS compared to those treated with IO (8.4 <em>vs.</em> 14.9 months; HR 1.37, <em>p =</em> 0.256).</div></div><div><h3>Conclusions</h3><div>Continuation of active therapy after A/B progression was independently associated with better survival even after adjusting for baseline disease characteristics. mPPS with IO-based therapy exceeded a year, suggesting that IO continuation post-progression may retain benefit. The precise sequencing of TKI and IO regimens warrants further investigation.</div></div><div><h3>Impact and implications:</h3><div>There is currently a lack of level 1 data on second-line treatment options for patients with advanced hepatocellular carcinoma who progress after frontline atezolizumab plus bevacizumab, as all second-line approvals were established during the frontline sorafenib era. Our study aims to fill in some of the knowledge gap by investigating real-world patient outcomes in the second-line treatment setting. Findings from this study show that patients who continued active treatment had improved post-progression survival compared to those who received best supportive care, and medication regimens incorporating tyrosine kinase inhibitors as well as immunotherapy agents were active. These results can help inform clinicians of possible treatment options for patients who progress after frontline atezolizumab plus bevacizumab while we await maturing data from randomized-controlled trials.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101232"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058145","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":"Progressive systemic inflammation precedes decompensation in compensated cirrhosis","authors":"Rubén Sánchez-Aldehuelo ,&nbsp;Càndid Villanueva ,&nbsp;Joan Genescà ,&nbsp;Juan Carlos García-Pagán ,&nbsp;Elisa Castillo ,&nbsp;José Luis Calleja ,&nbsp;Carles Aracil ,&nbsp;Rafael Bañares ,&nbsp;Luis Téllez ,&nbsp;Lorena Paule ,&nbsp;Rosa María Morillas ,&nbsp;María Poca ,&nbsp;Beatriz Peñas ,&nbsp;Salvador Augustin ,&nbsp;Juan G. Abraldes ,&nbsp;Edilmar Alvarado-Tapias ,&nbsp;Jaume Bosch ,&nbsp;Agustín Albillos","doi":"10.1016/j.jhepr.2024.101231","DOIUrl":"10.1016/j.jhepr.2024.101231","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Systemic inflammation is a driver of decompensation in cirrhosis with unclear relevance in the compensated stage. We evaluated inflammation and bacterial translocation markers in compensated cirrhosis and their dynamics in relation to the first decompensation.</div></div><div><h3>Methods</h3><div>This study is nested within the PREDESCI trial, which investigated non-selective beta-blockers for preventing decompensation in compensated cirrhosis and clinically significant portal hypertension (CSPH: hepatic venous pressure gradient ≥10 mmHg). Blood biomarkers were measured at baseline and at 1 and 2 years in patients who remained compensated and had available samples (n = 164). Values of patients with CSPH were split at each time point by decompensation development in the next time interval after sampling. We also included 54 patients with cirrhosis and subclinical portal hypertension (PH) and 35 controls. We assessed markers of inflammation (interleukin-6 [IL-6], tumor necrosis factor-alpha, von Willebrand factor [vWF], C-reactive protein), macrophage activation (CD14, CD163), intestinal barrier integrity (fatty acid-binding protein [FABP], haptoglobin), and bacterial translocation (lipopolysaccharide [LPS]).</div></div><div><h3>Results</h3><div>IL-6, CD163, and vWF were higher (<em>p &lt;</em>0.01) at baseline in patients with cirrhosis and CSPH compared to those with subclinical PH and controls. IL-6 increased (<em>p &lt;</em>0.05) at 1 year in patients with CSPH, with a greater rise in those who developed decompensation. CD163 was higher (<em>p &lt;</em>0.01) in patients who decompensated at baseline and 1 and 2 years. FABP was elevated (<em>p &lt;</em>0.01) in patients with CSPH compared to subclinical PH and controls at baseline and 1 year, while haptoglobin was lower (<em>p &lt;</em>0.01). LPS was higher (<em>p &lt;</em>0.01) in patients with CSPH than in those with subclinical PH and controls and increased at 1 year regardless of decompensation development.</div></div><div><h3>Conclusions</h3><div>Inflammation and bacterial products are present in the systemic circulation in patients with compensated cirrhosis and CSPH. Progressive inflammation precedes the first decompensation.</div></div><div><h3>Impact and implications</h3><div>Systemic inflammation drives cirrhosis progression during the decompensated stage, but its role in the compensated stage is unclear. We evaluated biomarkers of systemic inflammation, intestinal barrier integrity and bacterial translocation in patients with compensated cirrhosis and their dynamics in relation to the first decompensation. We demonstrate that low-grade inflammation and bacterial products are present in the systemic circulation in compensated cirrhosis, provided clinically significant portal hypertension has developed. We also show that worsening of systemic inflammation precedes the development of first clinical decompensation.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101231"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028960","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}