Hepatology Communications最新文献

{"title":"CRISPLD2 protects against liver inflammation and fibrosis via GRP78 to repress HMGB1/TLR4 axis-mediated STING palmitoylation.","authors":"Haoye Zhang, Juan Wang, Hui Yang, Yu Yan, Jiafeng Zou, Zhenguo Liu","doi":"10.1097/HC9.0000000000000954","DOIUrl":"10.1097/HC9.0000000000000954","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis caused by chronic inflammation remains the major driver of various liver diseases. However, limited effective therapies have been identified for liver fibrosis. Herein, we elucidated the complicated molecular mechanisms underlying liver fibrosis.</p><p><strong>Methods: </strong>Primary hepatocytes were co-cultured with JS-1 cells. Inflammatory cytokine levels were assessed by ELISA. Liver fibrosis markers and target molecular levels were detected by western blotting and immunohistochemical staining. Molecular mechanisms were analyzed by Acyl-biotin exchange (ABE) assay, Co-IP, proximity ligation assay, biotin pull-down, and GST pull-down assays. Co-localization and subcellular localization of molecules were observed by immunofluorescent staining. Liver fibrosis was induced by CCl4 in mice and determined by Masson Trichrome and Sirius Red staining. Liver injury was evaluated by HE staining, serum ALT, and AST levels.</p><p><strong>Results: </strong>High mobility group box 1 (HMGB1) bound to toll-like receptor 4 (TLR4) to facilitate palmitoylation of stimulator of interferon genes (STING), which led to hepatocyte inflammation and JS-1 cell activation in vitro. Furthermore, cysteine-rich secreted protein LCCL domain protein 2 (CRISPLD2) blocked HMGB1/TLR4 axis-mediated palmitoylation of STING, and subsequent liver fibrosis. Mechanistically, CRISPLD2 recruited 78 kDa glucose-regulated protein (GRP78) to trigger TLR4 degradation via an autophagic-lysosomal pathway. CRISPLD2 treatment alleviated CCl4-induced inflammation and liver fibrosis in mice via inactivation of the HMGB1/TLR4/STING pathway.</p><p><strong>Conclusions: </strong>CRISPLD2 mitigated hepatocyte inflammatory response and fibrosis via interaction with GRP78 to inactivate the HMGB1/TLR4 pathway and consequently restrain STING palmitoylation.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentiation of biliary atresia using a rapid point-of-care matrix metalloproteinase-7 assay: A multicenter diagnostic study.","authors":"Shuiqing Chi, Jinshi Huang, Pu Yu, Huizhong Niu, Zebing Zheng, Yun Zhou, Dayan Sun, Congli Cai, Junqing Hua, Pan Chen, Mengxin Zhang, Xi Zhang, Guoqing Cao, Shuai Li, Liying Rong, Yan Chen, Paul Kwong-Hang Tam, Shao-Tao Tang","doi":"10.1097/HC9.0000000000000953","DOIUrl":"https://doi.org/10.1097/HC9.0000000000000953","url":null,"abstract":"<p><strong>Background: </strong>Delayed diagnosis and surgery are the main causes of poor prognosis in biliary atresia (BA). This delay is frequently attributed to the complexity of current outpatient evaluation methods. While serum MMP-7 analysis via currently available methods, such as ELISA, offers high diagnostic accuracy, its utility in outpatient settings is often limited by turnaround time. To address this challenge, we developed and evaluated the MMP-7 Quick Test for accurately differentiating BA.</p><p><strong>Methods: </strong>This multicenter prospective diagnostic study was conducted between November 2021 and December 2024 at the pediatric surgery outpatient departments of 5 tertiary centers. A total of 423 patients aged <6 months who presented with persistent jaundice were included. Samples collected from November 2021 to May 2023 were analyzed by ELISA (n=221) in batches once or twice weekly. From June 2023 to December 2024, samples were measured using the MMP-7 Quick Test (n=202), in which residual serum was tested individually with routine liver function tests.</p><p><strong>Results: </strong>Among 202 infants evaluated using the rapid test, 98 were diagnosed with BA. The rapid test demonstrated a sensitivity of 91.84% (95% CI, 86.42%-97.26%), and a negative predictive value of 92.00% (95% CI, 86.68%-97.32%). These diagnostic parameters were comparable to the ELISA method, with a sensitivity of 90.82% and a negative predictive value of 91.74%. The rapid test provided results in 15 minutes at a cost of $14 per test, whereas the ELISA workflow required batch processing, taking an average of 3 days with a higher cost ($70).</p><p><strong>Conclusions: </strong>The MMP-7 Quick Test serves as a rapid, accurate, and cost-effective screening tool suitable for outpatient settings, thus facilitating the early diagnosis of BA.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The global epidemiology of alcohol-associated liver disease.","authors":"Pojsakorn Danpanichkul, Francisco Idalsoaga, Frank Murray, Juan Pablo Arab, Luis Antonio Díaz","doi":"10.1097/HC9.0000000000000947","DOIUrl":"10.1097/HC9.0000000000000947","url":null,"abstract":"<p><p>Alcohol-associated harm remains a major, largely preventable driver of global morbidity, mortality, and societal costs, and alcohol-associated liver disease (ALD) is a major consequence of long-term exposure. According to the World Health Organization, average consumption was 5.0 L of pure alcohol per person aged ≥15 years in 2022, with 21% unrecorded consumption and substantial regional variation. Per-capita intake declined from 5.7 L in 2010 to 5.0 L in 2022, yet current models forecast an increase to 5.7 L by 2030. In 2023, an estimated 3.15 million people were living with alcohol-associated cirrhosis, and 419,429 new cases occurred; while crude burden has risen, age-standardized prevalence was 34.6 per 100,000, reflecting demographic shifts. Age-standardized mortality due to ALD cirrhosis was highest in the European Region (5.8 per 100,000) and the Americas (5.0 per 100,000), and projections suggest crude ALD mortality will increase by 76% from 2021 to 2050 (354,200-624,150). Because alcohol exposure is frequently underreported, ascertainment using validated questionnaires and biomarkers is critical for surveillance and research. Scalable models linking alcohol-use detection with staged fibrosis assessment and triage pathways can narrow diagnostic gaps and support health system planning. Coupling these pathways with the implementation of high-impact \"best-buy\" alcohol control policies is essential to reduce the global ALD burden.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomized controlled trial of L-taurine for fatigue in decompensated cirrhosis.","authors":"Swarup Sasidharan, Cyriac Abby Philips, Ajit Tharakan, Rizwan Ahamed, Tharun Tom Oommen, John Menachery, Rosh Varghese, Philip Augustine","doi":"10.1097/HC9.0000000000000938","DOIUrl":"10.1097/HC9.0000000000000938","url":null,"abstract":"<p><strong>Background: </strong>Fatigue affects 60%-80% of patients with cirrhosis, yet no universally effective pharmacologic therapy exists. Taurine, an amino sulfonic acid with antioxidant and membrane-stabilizing properties, may address metabolic mechanisms underlying fatigue. We hypothesized that L-taurine supplementation would significantly reduce fatigue severity compared to standard care in patients with decompensated cirrhosis.</p><p><strong>Methods: </strong>This single-center, parallel-arm, open-label randomized controlled trial enrolled adults with decompensated cirrhosis (Child-Turcotte-Pugh score 7-13) and clinically significant fatigue (Fatigue Assessment Scale score >22) at a tertiary care center in South India. Participants were randomized via block randomization to L-taurine (1000 mg/d) plus standard care or standard care alone for 12 weeks. The primary outcome was the change in the Fatigue Assessment Scale score. Analysis of covariance examined treatment-by-anaemia interactions. Effect sizes were calculated using Cohen's d.</p><p><strong>Results: </strong>Of 220 randomized patients, 202 completed the study (standard care: n=100; taurine: n=102). The mean FAS change was -6.83±8.70 (standard care) versus -8.08±7.95 (taurine), with no significant difference (mean difference -1.25; 95% CI: -3.55 to 1.05; p=0.288; Cohen's d=-0.15). However, a significant treatment-by-anemia interaction was observed (p=0.009). In patients without anemia (n=41), taurine produced a large treatment effect (-11.90±4.04 vs. -4.57±9.23; p=0.002; Cohen's d=-1.02), whereas patients with anemia (n=161) showed no benefit (p=0.832). Adverse events occurred in 11.8% of patients treated with taurine, all of which were mild.</p><p><strong>Conclusions: </strong>L-taurine did not improve fatigue in unselected patients with decompensated cirrhosis. A post hoc subgroup analysis suggested potential benefit in patients without anemia; however, given the open-label design, small subgroup size, post hoc nature of the analysis, and the inherent limitations of unblinded patient-reported outcomes, this finding should be considered hypothesis-generating. A confirmatory, placebo-controlled trial enrolling patients without anemia is warranted (Clinical Trials Registry India number CTRI/2023/06/054455).</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell profiling reveals hepatic monocyte-derived macrophages heterogeneity during steatotic liver disease.","authors":"Haozhe Xu, Lu Yang, Peiyang Fang, Jie Sun, Xinjie Zhong, Wanqing Deng, Siqi Li, Longyang Zhou, Jinguo Fan, Dong Zhang, Guangyong Sun","doi":"10.1097/HC9.0000000000000928","DOIUrl":"10.1097/HC9.0000000000000928","url":null,"abstract":"<p><strong>Background: </strong>Monocyte-derived macrophages (MoMFs) play key roles in liver inflammation and fibrogenesis, with their heterogeneity affecting metabolic dysfunction-associated steatotic liver disease (MASLD) progression. However, current therapeutic strategies targeting macrophage-mediated inflammation have shown limited clinical efficacy in MASLD.</p><p><strong>Methods: </strong>We conducted single-cell RNA sequencing (scRNA-seq) of liver-infiltrating 7AAD-CD45+Ly6G-CD11bhiF4/80int MoMFs from NCD-fed and MCD-fed mice. Monocle 2 and CellChat analyses explored developmental trajectories and intercellular interactions, respectively.</p><p><strong>Results: </strong>Seven distinct clusters (c0-c6) with unique molecular signatures were identified. Beyond the classical CD206+ M2-polarized MoMFs, we identified 2 distinct subsets: CCR3+ (c3) MoMFs with enhanced pro-inflammatory and oxidative stress activities, and CCR7+ (c4) MoMFs with specialized antigen-presenting capacity in MASLD mouse livers. Although CCR2+ MoMFs are classically considered pro-inflammatory, our study revealed that the predominant CD14+CCR2+ (c0) MoMFs exhibit additional functional roles in fibrosis, lipid accumulation, and antigen presentation. Our pseudotime and in vitro data demonstrate that resident basal c1 MoMFs are phenotypically plastic, capable of acquiring CD14+/CCR7+ markers and transitioning toward c0-like and c4-like states, implying a potential intrahepatic origin for these subsets in diet-induced steatohepatitis. Notably, these MoMFs subsets and their dynamic changes during disease progression were conserved between the mouse models and human MASLD samples.</p><p><strong>Conclusions: </strong>Our study systematically characterized the heterogeneity and dynamic changes in intrahepatic MoMFs during MASLD progression. Resident c1 MoMFs are plastic and could be a local source for CD14+/CCR7+ subsets in MASLD without relying solely on bone marrow recruitment. These findings provide new insights into the therapeutic strategies that target macrophage-mediated inflammation in MASLD.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and clinical impact of hepatic steatosis on autoimmune liver disease: A systematic review and meta-analysis.","authors":"Jarell Jie-Rae Tan, Ellina Lytvyak, Joo Wei Ethan Quek, Corrine Lee Singh, Yuan Jie Aidan Low, Shi Jie Ong, Mark Muthiah, Yu Jun Wong, Aldo J Montano-Loza","doi":"10.1097/HC9.0000000000000959","DOIUrl":"10.1097/HC9.0000000000000959","url":null,"abstract":"<p><strong>Background: </strong>The clinical impact of hepatic steatosis (HS) among patients with autoimmune liver disease (AILD) remains unclear. We aim to determine the prevalence of HS and its clinical impact on treatment response and outcomes in patients with AILD.</p><p><strong>Methods: </strong>We systematically searched 3 electronic databases until 17 December 2025, including all studies that reported the prevalence, clinical impact, and treatment response of AILD patients with concomitant HS. The temporal trend of HS prevalence was analyzed using a quasi-Poisson regression model, with annual percent changes (APC, %) calculated.</p><p><strong>Results: </strong>Overall, 44 studies, comprising 19,898 patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) were included. The pooled prevalence of HS in patients with AIH, PBC, and PSC was 27.3%, 32.9%, and 21.6%, respectively. HS prevalence has significantly increased among PBC patients since 2010 (APC: +37.4%). While concomitant HS was associated with a higher risk of hepatic decompensation (OR: 1.6, 95% CI: 1.3-2.1, I2=0%) and hepatocellular carcinoma (OR: 1.8, 95% CI: 1.3-2.6, I2=0%) in patients with AIH, HS did not influence the clinical outcomes in patients with PBC. Treatment response in AIH and PBC was not influenced by concomitant HS. Available data on PSC with concomitant HS were insufficient to assess its association with clinical outcomes.</p><p><strong>Conclusions: </strong>AIH patients with concomitant HS had worse outcomes than those without HS; whereas HS did not influence the clinical outcomes in patients with PBC. Future research evaluating the impact of HS on PSC and overlap syndrome is much needed.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver transplantation is the major determinant of ≥10-year survival in patients with hepatocellular carcinoma.","authors":"Mohammad Saeid Rezaee-Zavareh, Joseph C Ahn, Hyunseok Kim, Michael Luu, Walid Ayoub, Alexander Kuo, Hirsh Trivedi, Yun Wang, Aarshi Vipani, Tsuyoshi Todo, Georgios Voidonikolas, Justin A Steggerda, Steven A Wisel, Todd V Brennan, Cristina Ferrone, Irene K Kim, Kambiz Kosari, Nicholas Nissen, Neehar D Parikh, Amit G Singal, Ju Dong Yang","doi":"10.1097/HC9.0000000000000951","DOIUrl":"10.1097/HC9.0000000000000951","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) has a poor long-term prognosis due to high recurrence and cirrhosis-related mortality, even after potentially curative treatments such as liver transplantation (LT), surgical resection, or ablation. This study aimed to identify factors associated with ≥10-year survival in HCC patients.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted among HCC patients diagnosed between 2004 and 2022 using the National Cancer Database. Multivariable Cox regression was used to identify predictors of overall survival, and logistic regression was used to identify predictors of ≥10-year survival.</p><p><strong>Results: </strong>Among 249,600 HCC patients, 177,585 (71.2%) died within 5 years, 8613 (3.5%) died at 5-10 years, 54,988 (22.0%) were alive with <10 years of follow-up, and 8219 (3.3%) survived ≥10 years. LT, resection, and ablation were performed in 6.6%, 9.3%, and 11% of patients, respectively. Compared with ablation as the reference group, LT [adjusted odds ratio (aOR) 11.96, 95% confidence interval (CI): 11.27-13.29] and resection (aOR: 2.83, 95% CI: 2.57-3.08) increased the odds of ≥10-year survival, while non-curative treatments reduced the odds compared with ablation (aOR: 0.50, 95% CI: 0.47-0.55). Cox regression results were consistent with the logistic model, confirming the association. Decision tree analysis confirmed LT as the dominant determinant of long-term survival. Black individuals were associated with lower odds of ≥10-year survival (aOR: 0.88, 95% CI: 0.820-0.96) and decreased likelihood of receiving LT (aOR: 0.73, 95% CI: 0.55-0.96).</p><p><strong>Conclusions: </strong>LT offers the best chance of ≥10-year survival in HCC. Ensuring equitable access is essential, especially for Black patients who have lower transplant rates and worse outcomes.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated behavioral care in general hepatology increases alcohol use disorder treatment in veterans.","authors":"Ponni V Perumalswami, Brittany L Cornwell, Peter P Grau, Alyssa C Meyers, Mayank Jayaram, Sarosh Irani, Parnnate Wongsirisakul, Suthat Liangpunsakul, Arpan Patel, Dominick DePhilippis, Joseph Liberto, Benjamin R Szymanski, John F McCarthy","doi":"10.1097/HC9.0000000000000956","DOIUrl":"10.1097/HC9.0000000000000956","url":null,"abstract":"<p><strong>Background: </strong>Hepatology visits present an opportunity to engage patients with alcohol-associated liver disease in care. This quality improvement pilot integrated a behavioral health provider (BHP) into the hepatology clinic at one Veterans Health Administration site and assessed its impact on alcohol use disorder (AUD) treatment.</p><p><strong>Methods and results: </strong>Hepatologists across Veterans Health Administration facilities developed a workflow to refer patients with signs of unhealthy alcohol use to a BHP co-located in the hepatology clinic. Data during the first year of BHP integration (December 2022 to January 2024) were obtained through chart reviews and the Veterans Health Administration Corporate Data Warehouse. t tests and χ2 tests compared baseline characteristics and assessed the associations of referral status with receipt of evidence-based AUD treatments within 6 months of referral or index liver clinic appointment. Two hundred ninety-three patients with signs of unhealthy alcohol use were identified, representing 19.9% of all liver clinic patients engaged in care during the pilot. Of these, 86.4% had a prior mental health diagnosis, 79.2% had an AUD diagnosis, 57.7% had a positive AUDIT-C screen, 40.3% had an alcohol-associated liver disease diagnosis, and 71 patients (24% of patients with unhealthy alcohol use) were referred to the BHP. Referred patients were more likely to receive AUD psychotherapy and/or pharmacotherapy and had significantly more AUD pharmacotherapy fill days (35.2 vs. 10.3, p<0.001) but not AUD psychotherapy visits (5.2 vs. 3.2, p=0.172).</p><p><strong>Conclusions: </strong>Referral to a co-located BHP was associated with a higher likelihood of receiving AUD treatment and a greater amount of AUD treatment, but gaps in referral remain and need to be addressed. Integrating BHPs into general hepatology clinics may improve AUD treatment uptake, addressing an important gap in care.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arrb2 in hepatocytes promotes M2 macrophage polarization, ameliorates hepatic ischemia-reperfusion injury through upregulating metabolite 6-ketoLCA.","authors":"Xiao-Wen Wang, Wen-Jie Zheng, Hao-Qi Chen, Tao Huang, Yuan Zhang, Xi-Jing Yan, Wen-Chao Li, Long Zou, Jie-Zhong Wu, Wen-Feng Zhu, Qi-Wei Yang, Gen-Shu Wang, Kun-Peng Hu","doi":"10.1097/HC9.0000000000000916","DOIUrl":"10.1097/HC9.0000000000000916","url":null,"abstract":"<p><strong>Background: </strong>Hepatic ischemia-reperfusion injury (IRI) is an important factor affecting the prognosis of liver transplantation patients. The role of Arrb2 in liver injury is unclear. Our study aimed to determine the role of Arrb2 in hepatic IRI and to identify its underlying mechanisms.</p><p><strong>Methods: </strong>An analysis of clinical samples was conducted to assess the association between Arrb2 expression and the prognosis of liver transplantation. A 70% hepatic ischemia/reperfusion model in mice was established to verify the mechanism of Arrb2 in hepatocytes promoting M2 macrophage polarization in attenuating hepatic IRI by regulating 6-ketoLCA. A model of hypoxia/reoxygenation in vitro was established to investigate the molecular mechanism of 6-ketoLCA in promoting M2 macrophage polarization and pharmacological screening.</p><p><strong>Results: </strong>Arrb2 in hepatocytes has been shown to provide significant liver protection against hepatic IRI, primarily through promoting the polarization of liver macrophages to M2. Arrb2 remodels bile acids and upregulates 6-ketoLCA through Cyp7a1 in hepatocytes, promoting M2 polarization of macrophages, thereby alleviating hepatic IRI. Mechanistically, TGR5 plays a crucial role in promoting the induction of M2 polarization in macrophages by 6-ketoLCA. Pharmacological screening indicates that dutasteride enhances the activity of the Arrb2 promoter and upregulates Arrb2 expression in hepatocytes, thereby mitigating hepatic IRI.</p><p><strong>Conclusions: </strong>Arrb2 in hepatocytes attenuates hepatic IRI by promoting macrophages toward the M2 phenotype through bile acid. Moreover, dutasteride, a selective agonist of Arrb2, emerges as a promising targeted therapeutic agent for the clinical management of liver injury.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-threshold analysis of the ELF Test versus histology for prognostication of disease progression and regression in MASH.","authors":"Matthew F W Gee, Rachel Fonstad, Edward B De Vol, Chadwick Brown, Jordan J Feld, Keyur Patel, Arun J Sanyal","doi":"10.1097/HC9.0000000000000931","DOIUrl":"10.1097/HC9.0000000000000931","url":null,"abstract":"<p><strong>Background: </strong>Patients with metabolic dysfunction-associated steatohepatitis (MASH) with advanced fibrosis are at risk for progression to cirrhosis and clinical outcomes, but can also experience fibrosis regression. The aim of this study was to compare risk stratification by the Enhanced Liver Fibrosis (ELF) Test to histological staging to assess patients at risk of disease progression and those likely to experience histological regression.</p><p><strong>Methods: </strong>Using pooled data from 6 large placebo-controlled trials of 2710 patients with advanced fibrosis due to MASH, 4 analyses of ELF and fibrosis stage were performed to evaluate the association with the following events: (1) liver-related clinical outcomes; (2) progression from bridging fibrosis to cirrhosis; (3) regression from bridging fibrosis; (4) regression from cirrhosis. Significance was assessed by interval likelihood ratio (iLR), Cox proportional hazard ratio (HR), and area under the receiver operator characteristic curve (AUROC).</p><p><strong>Results: </strong>In 2304 participants (17.8 mo mean follow-up), there was a progressive rise in liver-related outcome risk with increasing baseline ELF score [<9.00 (0%), ≥9.00 to <9.80 (2%), ≥9.80 to <11.30 (4%), ≥11.30 to <12.80 (13%), ≥12.80 (40%)]. In 1414 patients with bridging fibrosis, increasing baseline ELF scores were associated with a higher risk of progression to cirrhosis [<9.80 (9%), ≥9.80 to <11.30 (18%), ≥11.30 (45%)] and a lower likelihood of histological regression. In 1690 patients with cirrhosis, increasing baseline ELF scores were associated with a lower likelihood of histological regression [<9.80 (33%), ≥9.80 to <11.30 (16%), ≥11.30 (6%)]. In all analyses, the ELF Test provided more detailed information than histology.</p><p><strong>Conclusions: </strong>The ELF Test adds risk strata that are significantly different from fibrosis staging for the prediction of clinical events and histological changes, thereby improving risk stratification.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}