JHEP Reports最新文献

{"title":"Steatotic liver disease and liver transplantation: Candidate selection and post-transplant management","authors":"Jordi Colmenero ,&nbsp;Gonzalo Crespo ,&nbsp;Line Carolle Ntandja Wandji ,&nbsp;Yiliam Fundora ,&nbsp;Alexandre Louvet","doi":"10.1016/j.jhepr.2025.101704","DOIUrl":"10.1016/j.jhepr.2025.101704","url":null,"abstract":"<div><div>Steatotic liver disease (SLD), which encompasses alcohol-related liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and MASLD with increased alcohol intake (MetALD), is now the leading cause of liver transplantation (LT) worldwide. ALD and MASLD have become the first and second leading indications for LT (41% and 12% in Europe, respectively), with MetALD accounting for a rapidly increasing proportion of transplants (8-10%). Candidate evaluation must be multidisciplinary and account for the complex interplay between alcohol use, metabolic syndrome, cancer, cardiovascular disease, and obesity. Early LT for severe alcohol-related hepatitis is an established option in selected patients after the evaluation of alcohol use disorder (AUD) by addiction specialists. While the duration of abstinence remains a predictor of post-LT alcohol relapse in ALD recipients, an integrative assessment is required, and prolonged abstinence is no longer an absolute prerequisite. Cardiovascular risk stratification and assessment of frailty and metabolic comorbidities are essential. Obesity management includes lifestyle interventions, pharmacotherapy, and bariatric surgery in selected cases. SLD recipients generally demonstrate good 5-year survival (&gt;75%), but long-term outcomes are influenced by cardiovascular events, malignancies, and alcohol relapse, with survival falling below 65% at 10 years. Early detection and management of alcohol relapse after LT are critical to optimising long-term outcomes. MASLD recurrence is common, but its impact on graft survival appears modest. Management focuses on controlling cardiometabolic risk factors, with emerging roles for GLP-1 receptor agonists and multidisciplinary care. Donor SLD is a growing concern. Normothermic and hypothermic oxygenated perfusion substantially expand donor utilisation – with up to ∼70% of marginal or previously discarded grafts now salvaged – and improve graft viability by reducing early allograft dysfunction by 60%. Further research is needed to refine risk stratification, develop effective pharmacotherapies, and optimise perfusion protocols for steatotic grafts.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 2","pages":"Article 101704"},"PeriodicalIF":7.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034430","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":"Plasma IGFBP7 improves risk reclassification for liver-related outcomes: Insights from proteo-transcriptomic profiling","authors":"Zhuoshuai Liang ,&nbsp;Huizhen Jin ,&nbsp;Wenhui Gao ,&nbsp;Xinmeng Hu ,&nbsp;Ruofei Li ,&nbsp;Hongrui Zhang ,&nbsp;Yi Cheng ,&nbsp;Jikang Shi ,&nbsp;Yawen Liu","doi":"10.1016/j.jhepr.2025.101687","DOIUrl":"10.1016/j.jhepr.2025.101687","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;Advanced liver fibrosis is a pivotal predictor of liver-related outcomes (LROs), yet existing non-invasive tests offer limited prognostic accuracy. We aimed to identify novel plasma protein biomarkers that enhance long-term risk stratification for LROs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Proteomic analyses were first conducted in 191 patients with metabolic dysfunction-associated steatotic liver disease (MASLD), including 79 with advanced fibrosis and 112 with mild fibrosis, to identify differential plasma proteins. These proteomic findings were then integrated with liver transcriptional profiling from 206 patients with MASLD, comprising 68 with advanced fibrosis and 138 with mild fibrosis, to determine candidate biomarkers. The prognostic utility of these biomarkers was validated in 42,979 participants from the UK Biobank with a median follow-up of 13 years. Discriminatory performance and cumulative incidence were assessed using competing-risk methodologies.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Proteo-transcriptomic integration identified 123 concordant candidates, among which four plasma proteins (ADAMTSL2, IGFBP7, MFAP4, and CLSTN2) demonstrated robust diagnostic performance for advanced fibrosis (AUCs 0.821–0.889). In the UK Biobank cohort, IGFBP7 emerged as the strongest predictor of LROs, outperforming Fibrosis-4, AST to Platelet Ratio Index, and Chronic Liver Disease&lt;sub&gt;lab&lt;/sub&gt; score (CLivD&lt;sub&gt;lab&lt;/sub&gt;), with time-dependent AUCs of 0.815, 0.773, and 0.761 for cirrhosis prediction at 5, 10, and 15 years, respectively. Elevated IGFBP7 levels were detectable up to 15 years prior to diagnosis and, when combined with CLivD&lt;sub&gt;lab&lt;/sub&gt;, identified a high-risk subgroup with a 20% 15-year incidence of cirrhosis. Subgroup analyses showed consistent prognostic value across MASLD, metabolic dysfunction-associated alcohol-related liver disease, and alcohol-related liver disease, with particularly strong performance in MASLD (15-year AUCs &gt;0.85).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Plasma IGFBP7 is a robust and independent predictor of liver-related outcomes and significantly enhances risk stratification beyond conventional clinical tools.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;This study demonstrates that IGFBP7 is both a biomarker of advanced liver fibrosis and a strong long-term predictor of liver-related outcomes. The integration of IGFBP7 with conventional non-invasive tests enhances the refinement of risk prediction. Among individuals with low CLivD scores, those with high IGFBP7 levels had a substantially increased incidence of liver-related outcomes (2.5%), while low IGFBP7 levels were associated with favorable outcomes even in high CLivD groups (0.8%). This enables more precise identification of patients who may benefit from early referral &lt;em&gt;vs.&lt;/em&gt; those suitable for reduced monitoring, potentially optimizing care pathways in resource-limited settings. Moreover, IGFBP7 ","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 2","pages":"Article 101687"},"PeriodicalIF":7.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034310","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":"STAT1 drives the immune landscape of murine Toll-like receptor 9-induced liver inflammation","authors":"Amber De Visscher ,&nbsp;Jarne Beliën ,&nbsp;Eline Bernaerts ,&nbsp;Marte Vandeput ,&nbsp;Bert Malengier-Devlies ,&nbsp;Fran Prenen ,&nbsp;Hanne Meers ,&nbsp;Liliana Sokol ,&nbsp;Tania Mitera ,&nbsp;Nele Berghmans ,&nbsp;Seray Anak ,&nbsp;Olivier Govaere ,&nbsp;Philippe Van den Steen ,&nbsp;Jochen Lamote ,&nbsp;Niels Vandamme ,&nbsp;Anna Bujko ,&nbsp;Charlotte L. Scott ,&nbsp;Carine H. Wouters ,&nbsp;Patrick Matthys","doi":"10.1016/j.jhepr.2025.101668","DOIUrl":"10.1016/j.jhepr.2025.101668","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Persistent activation of Toll-like receptor 9 (TLR9) has been implicated in eliciting a cytokine storm syndrome, leading to systemic and hepatic inflammation in mice and humans. This study investigates the unexplored role of STAT1, a transcription factor in pathogen-driven immune responses, in mediating TLR9-induced liver inflammation.</div></div><div><h3>Methods</h3><div>We compared clinical, histological, and laboratory characteristics (in total nine parameters) of TLR9-induced liver inflammation between wild-type (WT) mice and STAT1-deficient (<em>Stat1</em>^<em>-/-</em>) mice (n = 3–31 mice/condition depending on the parameter measured) and explored their hepatic immune landscape using single-cell CITE-sequencing (total of 36,585 CD45⁺ liver cells from four to eight mice/condition). Findings were validated by flow cytometry, treatment with biologicals, <em>ex vivo</em> cell culture, and exploration of publicly available patient datasets.</div></div><div><h3>Results</h3><div><em>Stat1</em>^<em>-/-</em> mice are protected against TLR9-induced inflammation as they do not develop the typical features seen in WT counterparts (<em>p</em> &lt;0.05–0.0001, depending on the parameter). This protection is associated with the absence of hepatic cycling CD38⁺CD8⁺ T cells, type 2 conventional dendritic cells, and monocytes transitioning into inflammatory macrophages. These cell populations exhibit elevated STAT1 expression and type I and II interferon (IFN) signatures, resembling immune profiles of patients with cytokine storm syndromes and liver inflammation. <em>Ex vivo</em>, type I and II IFNs induce the phenotype of cycling T cells and transitioning monocytes through STAT1 signaling. <em>In vivo</em>, simultaneous treatment with anti-type I and II IFN antibodies in CpG-injected WT mice provide protection against systemic and liver inflammation (<em>p</em> &lt;0.05–0.001 for five mice/condition).</div></div><div><h3>Conclusions</h3><div>Type I and II IFN-induced STAT1 activation drives TLR9-induced liver inflammation, and support further exploration of JAK1/2 inhibitors, which indirectly inhibit STAT1 activity, in patients with cytokine storm syndromes and other inflammatory liver disorders.</div></div><div><h3>Impact and implications</h3><div>Our study reveals that interferon-induced STAT1 signaling is a central mediator of both systemic and hepatic inflammation during a TLR9-induced cytokine storm. Based on these findings, we support the therapeutic use of JAK1/2 inhibitors, such as ruxolitinib and baricitinib, which indirectly suppress STAT1 activity, in patients with cytokine storm syndromes and inflammatory liver disorders to alleviate both systemic and hepatic symptoms. Notably, our data also highlight the promise of direct STAT1 inhibition as a more and potentially refined approach for intervention.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 2","pages":"Article 101668"},"PeriodicalIF":7.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922400","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":"Editorial Board page","authors":"","doi":"10.1016/S2589-5559(26)00030-3","DOIUrl":"10.1016/S2589-5559(26)00030-3","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 2","pages":"Article 101759"},"PeriodicalIF":7.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188947","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":"Elexacaftor–tezacaftor–ivacaftor and cystic fibrosis liver disease: A turning point that calls for cautious optimism","authors":"Pierre-Emmanuel Rautou ,&nbsp;Sophie Hillaire ,&nbsp;Simone Gambazza ,&nbsp;Carla Colombo","doi":"10.1016/j.jhepr.2025.101688","DOIUrl":"10.1016/j.jhepr.2025.101688","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 2","pages":"Article 101688"},"PeriodicalIF":7.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922545","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":"Genome-wide association study identifies three PNPLA3/SAMM50 SNPs associated with HCC development in non-viral liver disease","authors":"Xia-Rong Liu ,&nbsp;Tsai-Hsuan Yang ,&nbsp;Tung-Hung Su ,&nbsp;Szu-Ching Yin ,&nbsp;Yi-Ting Chen ,&nbsp;Fen-Fang Chen ,&nbsp;See-Tong Pang ,&nbsp;Ming-Chih Hou ,&nbsp;Yen-Chun Peng ,&nbsp;Shun-Fa Yang ,&nbsp;Peng-Ju Huang ,&nbsp;Sing-Lian Lee ,&nbsp;Ming Chen ,&nbsp;Chih-Yang Huang ,&nbsp;Ya-Hsuan Chang ,&nbsp;Hsuan-Yu Chen ,&nbsp;Hwai-I Yang ,&nbsp;Ming-Lung Yu ,&nbsp;Chien-Jen Chen ,&nbsp;Jia-Horng Kao ,&nbsp;Mei-Hsuan Lee","doi":"10.1016/j.jhepr.2025.101673","DOIUrl":"10.1016/j.jhepr.2025.101673","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Few genome-wide association studies have examined genetic variants associated with hepatocellular carcinoma (HCC) risk in individuals seronegative for HBsAg and anti-HCV, and the long-term impact of these variants remains uncertain.</div></div><div><h3>Methods</h3><div>This multi-stage study analyzed adults &gt;30 years old who were seronegative for HBsAg and anti-HCV. In the genome-wide association study discovery phase, 765 HCC cases and 9,949 controls were analyzed for 308,693 SNPs, with significant SNPs confirmed in community-based (171 HCC cases, 684 controls) and hospital-based (470 HCC cases, 5,460 controls) validation sets. A cohort of 67,909 participants, followed from 2012 to 2021, was used to evaluate the long-term HCC risk associated with these variants.</div></div><div><h3>Results</h3><div>Ten SNPs in <em>PNPLA3/SAMM50</em> were significantly associated with HCC risk (<em>p</em> &lt;1.62 × 10^-7) and were in high linkage disequilibrium. Three SNPs (rs738409, rs2281135, rs2235776) were replicated and demonstrated strong associations with HCC, independent of steatosis. Over 267,238 person-years of follow-up, 32 new HCC cases occurred, with elevated risks observed in individuals homozygous for the risk genotypes: GG (rs738409), AA (rs2281135), and TT (rs2235776). The adjusted hazard ratios (95% CI) were 3.37 (1.32–8.63), 2.80 (1.06–7.37), and 2.64 (0.91–7.66), respectively. In allelic models, carriers of the risk allele had higher HCC risk, with adjusted hazard ratios (95% CI) of 1.88 (1.14–3.10) for rs738409, 1.68 (1.02–2.78) for rs2281135, and 1.61 (0.98–2.67) for rs2235776.</div></div><div><h3>Conclusions</h3><div>This study identified <em>PNPLA3/SAMM50</em> variants significantly associated with long-term HCC risk in individuals without viral hepatitis. These findings highlight their potential utility as biomarkers for HCC risk stratification and underscore the need for further research into underlying mechanisms.</div></div><div><h3>Impact and implications</h3><div>Variants in the <em>PNPLA3/SAMM50</em> locus were significantly associated with hepatocellular carcinoma (HCC) risk in individuals seronegative for HBsAg and anti-HCV. The stepwise increase in HCC risk with higher numbers of risk alleles suggests their potential utility as biomarkers to identify high-risk individuals without a history of chronic hepatitis B or C virus infection. These findings provide a foundation for genetic risk stratification and precision prevention strategies in populations where non-viral etiologies of HCC are becoming increasingly important.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 2","pages":"Article 101673"},"PeriodicalIF":7.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034432","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":"Goblet-cell muscarinic signaling at the gut barrier: A therapeutic checkpoint/target in alcohol-related liver disease","authors":"Salvatore Piano ,&nbsp;Gloria Bezzegato ,&nbsp;Agustin Albillos","doi":"10.1016/j.jhepr.2025.101641","DOIUrl":"10.1016/j.jhepr.2025.101641","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 2","pages":"Article 101641"},"PeriodicalIF":7.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187911","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":"External beam radiation for HCC: Ready for incorporation into guidelines?","authors":"Michael Buckstein ,&nbsp;Laura A. Dawson","doi":"10.1016/j.jhepr.2025.101683","DOIUrl":"10.1016/j.jhepr.2025.101683","url":null,"abstract":"<div><div>External beam radiation therapy is becoming an increasingly useful tool in the management of hepatocellular carcinoma at all clinical stages. The data supporting its use is now maturing, with randomised trials showing excellent results in early, intermediate, advanced, and palliative stages. This review details the current best evidence available and makes a compelling case that external beam radiation therapy should be included in clinical guidelines. Doing so will benefit patients with an effective, low cost, and globally available treatment that can dramatically improve outcomes.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 2","pages":"Article 101683"},"PeriodicalIF":7.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922547","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":"RIP3 and MLKL regulate ER stress in alcohol-associated liver disease and pharmacological ER stress models: Insights beyond necroptosis","authors":"Rakesh K. Arya ,&nbsp;Emily Huang ,&nbsp;Megan R. McMullen ,&nbsp;Kyle L. Poulsen ,&nbsp;Jianguo Wu ,&nbsp;Jared Travers ,&nbsp;Evi Paouri ,&nbsp;Dimitrios Davalos ,&nbsp;Laura E. Nagy","doi":"10.1016/j.jhepr.2025.101628","DOIUrl":"10.1016/j.jhepr.2025.101628","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background &amp; Aims&lt;/h3&gt;&lt;div&gt;Endoplasmic reticulum (ER) stress is an important contributor to liver disease progression, including alcohol-associated liver disease. Although receptor-interacting protein kinase-3 (RIP3) and mixed lineage kinase domain-like pseudokinase (MLKL) are known for their roles in necroptosis, emerging evidence highlights their non-canonical functions in metabolic regulation and cellular-stress responses. However, their specific role in regulating hepatic ER stress remains unclear. This study investigates how RIP3 and MLKL regulate ER stress pathways during chronic ethanol exposure and pharmacological ER stress induction.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Rip3&lt;/em&gt;&lt;sup&gt;&lt;em&gt;-/-&lt;/em&gt;&lt;/sup&gt;, &lt;em&gt;Rip3&lt;/em&gt;&lt;sup&gt;&lt;em&gt;K51A/K51A&lt;/em&gt;&lt;/sup&gt;, and &lt;em&gt;Mlkl&lt;/em&gt;&lt;sup&gt;&lt;em&gt;-/-&lt;/em&gt;&lt;/sup&gt; mice alongside wild-type (WT) and pharmacological necroptosis inhibitors were used to study the role of RIP3 and MLKL in modulating ER stress. Chronic ethanol feeding and pharmacological agents were utilized to induce ER stress &lt;em&gt;in vivo&lt;/em&gt; and in isolated primary hepatocytes. ER stress markers were assessed by qPCR and Western blot, ER expansion by confocal microscopy, and viability by MTS assay. (n = 8–11 for ethanol; n = 5–8 for tunicamycin; n = 3–12 for hepatocyte experiments).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Chronic ethanol increased expression of ER stress markers in WT mice; this response was attenuated in &lt;em&gt;Rip3&lt;/em&gt;&lt;sup&gt;&lt;em&gt;-/-&lt;/em&gt;&lt;/sup&gt; mice (&lt;em&gt;p&lt;/em&gt; &lt;0.05). Tunicamycin exposure increased hepatic ER stress markers in WT mice; this response was diminished in &lt;em&gt;Rip3&lt;/em&gt;&lt;sup&gt;&lt;em&gt;-/-&lt;/em&gt;&lt;/sup&gt;, &lt;em&gt;Rip3&lt;/em&gt;&lt;sup&gt;&lt;em&gt;K51A/K51A&lt;/em&gt;,&lt;/sup&gt; and &lt;em&gt;Mlkl&lt;/em&gt;&lt;sup&gt;&lt;em&gt;-/-&lt;/em&gt;&lt;/sup&gt; mice (&lt;em&gt;p&lt;/em&gt; &lt;0.05). In primary hepatocytes, genetic and pharmacological inhibition of RIP3 and MLKL also reduced thapsigargin-induced ER stress responses (&lt;em&gt;p&lt;/em&gt; &lt;0.05). Hepatocytes lacking &lt;em&gt;Rip3&lt;/em&gt;, RIP3 kinase activity, or &lt;em&gt;Mlkl&lt;/em&gt; showed enhanced viability (&lt;em&gt;p&lt;/em&gt; &lt;0.05) and greater ER expansion and sheet formation compared to WT hepatocytes (&lt;em&gt;p&lt;/em&gt; &lt;0.05), suggesting improved adaptive remodeling.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This study highlights a novel function of RIP3 and MLKL in regulating hepatic ER stress responses, expanding their known roles beyond programmed necrosis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Impact and implications&lt;/h3&gt;&lt;div&gt;This study provides new mechanistic insight into how RIP3 and MLKL regulate hepatic ER stress responses, extending their roles beyond necroptosis. By demonstrating that genetic or pharmacological inhibition of &lt;em&gt;Rip3&lt;/em&gt;, RIP3 kinase activity and &lt;em&gt;Mlkl&lt;/em&gt; attenuates ER stress signaling, reduces cell death, and promotes adaptive ER remodeling, our findings identify these proteins as key modulators of hepatocyte survival under stress. These results are important for researchers and clinicians focused on alcohol-associated liver disease and other ER stre","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 2","pages":"Article 101628"},"PeriodicalIF":7.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034364","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":"Statistical precision of p values: A note on “Liver fibrosis progression analyzed with AI predicts renal decline”","authors":"Jiang Bai ,&nbsp;Lijuan Zhang ,&nbsp;Yun Zhou","doi":"10.1016/j.jhepr.2025.101631","DOIUrl":"10.1016/j.jhepr.2025.101631","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 2","pages":"Article 101631"},"PeriodicalIF":7.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187913","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}