Hepatology Communications最新文献

{"title":"Lumican-TLR4 interaction accelerates hepatic fibrosis by activating hepatic stellate cells.","authors":"Yongqiang Xiong, Huanhuan Zhang, Ao Wang, Yaqian Cui, Jiaxi Ye, Leiming Jin, Mengsha Lin, Qianhui Zhang, Guang Liang, Wu Luo, Weiwei Zhu, Xiang Hu","doi":"10.1097/HC9.0000000000000948","DOIUrl":"10.1097/HC9.0000000000000948","url":null,"abstract":"<p><strong>Background: </strong>Lumican expression is associated with liver fibrosis across various etiologies. However, its precise role and underlying mechanisms in liver fibrosis remain unclear.</p><p><strong>Methods: </strong>Lumican knockout (Lum KO) mice were generated, and liver fibrosis was induced using bile duct ligation (BDL) and carbon tetrachloride (CCl4) to investigate the in vivo role of Lumican. Proteomic analyses and target validation were performed to elucidate the mechanisms by which Lumican contributes to liver fibrosis.</p><p><strong>Results: </strong>Lumican is predominantly expressed in hepatic stellate cells (HSCs) and promotes their activation. Lumican deficiency attenuates liver fibrosis progression in mice following BDL and CCl4 administration. Proteomic analysis identified Lumican as a ligand of toll-like receptor 4 (TLR4). Lumican directly binds to TLR4, activating downstream SMAD3-mediated pro-fibrotic signaling pathways, thereby promoting HSC activation and contributing to liver fibrosis development.</p><p><strong>Conclusions: </strong>Lumican plays a critical role in HSC activation and liver fibrosis progression via the Lumican-TLR4-SMAD3 axis, highlighting it as a potential therapeutic target for anti-fibrotic intervention.</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/PMC13120511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769987","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":"Rapamycin-modified novel tolerogenic dendritic cells induce liver graft tolerance through MHC-II+CD8+ regulatory T cells.","authors":"Lin Zhou, Yang Zhao, Jing Wang, Qing Chen, Ya-Nan Jia, Li-Chao Pan, Han-Xuan Wang, Hong-Wei Yang, Qiang He, Xian-Liang Li, Ren Lang, Guo-Sheng Du","doi":"10.1097/HC9.0000000000000942","DOIUrl":"10.1097/HC9.0000000000000942","url":null,"abstract":"<p><strong>Background: </strong>Inducing transplant tolerance to achieve long-term graft survival without immunosuppression remains a central objective in liver transplantation.</p><p><strong>Methods: </strong>Using a rat liver transplantation model, we evaluated the effects of infusing rapamycin-modified tolerogenic dendritic cells (Rapa-tolDCs) on graft survival and tolerance induction. Underlying molecular and cellular mechanisms were investigated through activation and inhibition experiments to assess the generation, signaling pathways, and suppressive functions of regulatory T and B cell populations.</p><p><strong>Results: </strong>Infusion of Rapa-tolDCs induced donor-specific tolerance and markedly prolonged graft survival (median survival time of 65 days, maximum of 102 days). Mechanistically, Rapa-tolDCs, characterized by low expression of Siglec1 and Spp1, functioned independently of the PI3K-mTOR pathway and promoted the differentiation and proliferation of CD8+CD45RClow/- regulatory T cells (CD8+CD45RClow/- Tregs). We identified that these Tregs acquired MHC-II molecules from donor cells via trogocytosis, becoming immune chimeric cells that predominantly secreted interleukin-10 (IL-10) to mediate immune suppression. The generation of these MHC-II+CD8+ Tregs was regulated by the Wnt5a/Fzd4/RhoD signaling axis. Furthermore, elevated levels of Foxp3+ Tregs and IL-10+ Bregs were found to contribute to prolonged graft survival following Rapa-tolDC infusion.</p><p><strong>Conclusions: </strong>These findings delineate a complete mechanistic pathway from cell therapy to donor-specific tolerance and provide a foundational strategy for clinical tolerance induction and post-transplant immunomodulation.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728920","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":"Deficiency of ZFP36L1 and ZFP36L2 impairs liver homeostasis and initiates cholestatic liver injury.","authors":"Rahul Kumar, Perry J Blackshear, Sonika Patial, Yogesh Saini","doi":"10.1097/HC9.0000000000000933","DOIUrl":"10.1097/HC9.0000000000000933","url":null,"abstract":"<p><strong>Background: </strong>RNA-binding proteins, Zinc Finger Protein 36-Like 1 (ZFP36L1) and Zinc Finger Protein 36-Like 2 (ZFP36L2), post-transcriptionally regulate the expression of a large number of genes involved in various cellular processes. However, specific or redundant functions of ZFP36L1 and ZFP36L2 in liver homeostasis have never been explored. Here, we hypothesized that ZFP36L1 and ZFP36L2 are functionally redundant in the liver, and their combined deficiency would stabilize their direct mRNA targets, which would alter liver homeostasis.</p><p><strong>Methods: </strong>We generated combined liver-specific ZFP36L1-deficient and ZFP36L2-deficient mice (L1/L2dKO) and compared their liver homeostatic parameters with flox control (L1/L2FLX) mice. We performed detailed analyses of liver histology, serum biomarkers of liver injury, liver transcriptome, bile flow rate, and biliary total bile acid (TBA) excretion.</p><p><strong>Results: </strong>We demonstrated that the combined liver-specific deficiency of ZFP36L1 and ZFP36L2 in mice (L1/L2dKO) results in spontaneous cholestatic liver injury, which was characterized by elevated hepatic and serum levels of TBAs and liver injury biomarkers, including ALP, ALT, and AST, presence of bile infarcts followed by marked inflammation, cellular proliferation, and fibrosis. To determine the impact of deficiency of ZFP36L1 and ZFP36L2 on the liver transcriptome and their relevance to cholestatic liver injury, RNA sequencing of whole livers of L1/L2dKO and L1/L2FLX mice was performed, which showed significant perturbation of ZFP36L1/ZFP36L2 target genes associated with cholestasis in L1/L2dKO mice. In addition, L1/L2dKO mice exhibited reduced bile flow rate and decreased biliary TBA excretion. Subsequent analyses revealed impaired bile canalicular morphogenesis by postnatal day 7, as evidenced by F-actin and zonula occludens-1 staining patterns.</p><p><strong>Conclusions: </strong>Our findings demonstrate beneficial roles of ZFP36L1 and ZFP36L2 in maintaining liver homeostasis.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728958","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":"Radioembolization (90Y) achieves higher response rates and reduces progression risk compared with DEB-TACE in hepatocellular carcinoma.","authors":"Kelley Núñez, Navid Hasani, Julie Cronan, Juan Gimenez, Ari Cohen, Tyler Sandow, Paul Thevenot","doi":"10.1097/HC9.0000000000000935","DOIUrl":"10.1097/HC9.0000000000000935","url":null,"abstract":"<p><strong>Background: </strong>Drug-eluting bead transarterial chemoembolization (DEB-TACE) and yttrium-90 (90Y) radioembolization are approved therapies to treat hepatocellular carcinoma (HCC). Several randomized controlled trials and propensity score-matched studies (PSM) have been conducted to compare these 2 treatments; many utilized 90Y standard dosimetry (<200 Gy), which produced inferior outcomes compared with modern-day 90Y personalized dosimetry, which yields tumor doses exceeding 205 Gy.</p><p><strong>Purpose: </strong>This study utilized PSM between DEB-TACE and 90Y with personalized dosimetry to compare treatment and patient outcomes in Barcelona Clinic Liver Cancer (BCLC) A-B HCC.</p><p><strong>Methods: </strong>This retrospective study included 258 patients with unresectable BCLC A-B stage HCC treated with DEB-TACE or 90Y as the initial treatment approach from 2015 to 2024. PSM was performed (90Y:DEB-TACE), matching for tumor burden and alpha-fetoprotein levels at diagnosis. The primary endpoint was target response rate with secondary endpoints of overall response, target retreatment rate (TTR), target and overall time-to-progression (TTP), and overall survival (OS).</p><p><strong>Results: </strong>Overall, 90Y achieved significantly higher target complete (CR) and objective response (OR) rates compared with DEB-TACE (71% vs. 33% and 88% vs. 58%), respectively. In multifocal disease, target CR rates were higher following 90Y (68% vs. 13%). 90Y also yielded a longer duration of CR with a 1-year target retreatment rate of 12% compared with 40% with DEB-TACE. This translated into a longer target TPP (p=0.030) with 90Y, although overall TPP and OS were similar between treatment modalities. In multifocal disease, 90Y generated superior response rates as well as target (p=0.007) and overall TTP (p=0.015).</p><p><strong>Conclusions: </strong>90Y with personalized dosimetry achieved higher response rates and extended the duration of complete responses compared with DEB-TACE. 90Y was also more effective at treating multifocal disease.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728938","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":"CD8 TRM-like T cells expressing perforin and IFN-γ define a pediatric activated T-cell acute liver failure endotype.","authors":"Tamir Diamond, Catherine A Chapin, Caroline J Diorio, Sarah McCuaig, Michelle Lau, Niansheng Chu, Nora M Gibson, Portia A Kreiger, Simon Horslen, Kathleen M Loomes, Anna M Banc-Husu, Jaime Chu, M Kyle Jensen, Daniel H Leung, Amrita Narang, Beth A Carter, Scott Elisofon, Ryan Fischer, Steven J Lobritto, Mike Leonis, Anna L Peters, Norberto Rodriguez-Baez, Rene Romero, Philip Rosenthal, David Rudnick, James Squires, Shikha Sundaram, Kyla M Tolliver, Pamela Valentino, Valerie Durkalski, Estella M Alonso, Edward M Behrens","doi":"10.1097/HC9.0000000000000926","DOIUrl":"10.1097/HC9.0000000000000926","url":null,"abstract":"<p><strong>Background: </strong>Activated T-cell pediatric acute liver failure (TC-PALF) is the most common cause of non-acetaminophen PALF, with poor transplant-free survival. Livers in TC-PALF are infiltrated by effector cytotoxic T lymphocytes with markers of tissue-resident memory function (CD8 Trm) and an interferon gamma (IFNγ) transcriptional signature. The PALF-Immune Response Network (PALF-IRN) and the prospective TReatment for ImmUne-Mediated PathopHysiology (TRIUMPH) clinical trial (NCT04862221) aim to characterize the TC-PALF immune pathology and utility of T-cell directed therapy to improve transplant-free survival.</p><p><strong>Methods: </strong>TRIUMPH patients with TC-PALF were compared with healthy children and disease controls utilizing multiparameter flow cytometry and 3' single-cell RNA sequencing from peripheral blood mononuclear cells. TC-PALF patient serum was compared with healthy children and those with PALF from other causes, utilizing the Olink Inflammation I 384 protein assay.</p><p><strong>Results: </strong>Two distinct endotypes of TC-PALF were identified, which differed in flow cytometry CD8+ Perforin1 (Prf) expression and liver biopsy staining of Prf. TC-PALF patients with high CD8+ Prf (TC-PALF High Prf) had monocytosis, with a unique circulating CD8 IFNγ+ Trm-like population and IFNγ-responsive CD14/CD16 monocyte ligand-receptor interaction. TC-PALF patients with normal CD8+ Prf expression had hypergammaglobulinemia, an increase in class-switched B-cells, and a decrease in serum inflammatory proteins associated with myeloid activation.</p><p><strong>Conclusions: </strong>TC-PALF high Prf patients have a unique circulating CD8+ IFNγ+ Trm-like population accompanied by monocyte proliferation and activation. Further understanding of the role of IFNγ in TC-PALF High Prf may provide a therapeutic target for this endotype to improve transplant-free survival.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591805","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":"Risk-stratified surveillance for hepatocellular carcinoma.","authors":"Thomas Hunold, Neehar D Parikh","doi":"10.1097/HC9.0000000000000943","DOIUrl":"10.1097/HC9.0000000000000943","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with most cases arising in patients with cirrhosis or chronic hepatitis B. Current guidelines recommend semi-annual ultrasound with or without alpha-fetoprotein (AFP) testing for all at-risk individuals; however, this one-size-fits-all approach has important limitations, including suboptimal sensitivity, frequent false-positive results, poor adherence, and failure to account for substantial heterogeneity in individual HCC risk. Risk-stratified surveillance has emerged as a potential strategy to better balance surveillance benefits and harms by tailoring surveillance intensity and modality to patient-specific risk. We summarize and critically evaluate existing HCC risk stratification models, including clinical, biomarker-based, and imaging-based or elastography-based approaches. Although several models demonstrate promising performance, many lack robust external validation, underrepresent patients with metabolic and alcohol-associated liver disease, and inadequately account for competing risks such as non-liver-related mortality. We further discuss key challenges to implementing risk-stratified surveillance in clinical practice. Overall, while risk-stratified HCC surveillance has several promising characteristics over current paradigms, prospective validation and implementation studies are needed before widespread adoption. Aligning surveillance strategies with individualized risk has the potential to improve outcomes in patients at risk for HCC.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591824","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":"Pain, uncertainty, and lack of clinical support drive emergency department utilization in cirrhosis: A qualitative study.","authors":"Swetha Parvataneni, Nicholas E Harrison, Bridget Hawryluk, Courtney Moore, Anurag Harishchandrakar, Eric S Orman, William E Bennett, Archita P Desai","doi":"10.1097/HC9.0000000000000936","DOIUrl":"10.1097/HC9.0000000000000936","url":null,"abstract":"<p><strong>Background: </strong>Individuals with cirrhosis frequently require Emergency Department (ED) care, with some experiencing repeated ED use, yet little is known about the patient and caregiver perspectives driving decisions to visit the ED. We aimed to explore perspectives of including high ED utilizers with cirrhosis and their caregivers to identify drivers of ED use and opportunities to optimize care.</p><p><strong>Methods: </strong>Using human-centered design methods, we conducted an in-person group engagement session with 7 adults with cirrhosis and their caregivers, recruited from recent ED encounters. A custom board-game activity facilitated the discussion. Data were analyzed using snippet extraction, affinity mapping, and affinity concept modeling.</p><p><strong>Results: </strong>Seven major themes emerged: (1) Mindset around symptoms, which includes fear, uncertainty, and caregiver burden. (2) Informational needs, including reliance on variable-quality online resources and lack of trusted education. (3) Day-to-day cirrhosis management, particularly challenges related to medications and symptom monitoring. (4) Symptom-driven ED triggers, with some prompting, urgent visits. (5) Decision-making factors, including limited alternatives to ED care and prior experiences, and mismatched patient-caregiver thresholds for seeking care. (6) Expectations of ED care, focused on pain relief and return to baseline health. (7) Challenges during ED care, including long wait times, misdiagnosis concerns, and stigma related to pain treatment. Concept modeling revealed that ED decision-making is a dynamic journey shaped by symptom severity, emotional states, logistical considerations, and evolving patient-caregiver-provider roles.</p><p><strong>Conclusions: </strong>Pain, uncertainty about symptom severity, and lack of accessible real-time clinical support were major drivers of ED utilization in cirrhosis. Interventions addressing these specific needs may reduce avoidable ED use. These findings provide a patient-informed foundation for care delivery redesign in cirrhosis.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591860","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":"Spatial and functional polarization of cancer-associated fibroblasts with CXCR4-mediated immune modulation in hepatocellular carcinoma.","authors":"Daichi Nakamura, Takahiro Nishio, Yo Oguma, Kojiro Taura, Yukinori Koyama, Mengyang Zhan, Yoshihiko Kurata, Keisuke Okura, Tomoaki Yoh, Hiroto Nishino, Masayuki Okuno, Kaori Teranaka, Hanako Ogawa, Masakazu Fujimoto, Hironori Haga, Keiko Iwaisako, Akira Watanabe, Etsuro Hatano","doi":"10.1097/HC9.0000000000000930","DOIUrl":"10.1097/HC9.0000000000000930","url":null,"abstract":"<p><strong>Background: </strong>Cancer-associated fibroblasts (CAFs) represent a predominant cell population in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). How the spatial distribution of CAF subtypes relates to immune modulation within the TME remains incompletely understood. This study aimed to characterize the spatial organization of CAF subtypes in HCC and to explore their potential associations with immune contexture.</p><p><strong>Methods: </strong>Spatial transcriptomic analysis was performed on 6 HCC cases to identify CAF-enriched clusters and their spatial localization. Immunohistochemical analyses were conducted on 132 HCC sections to examine the relationship between CAF-related features, immune cell distribution, and clinical outcomes.</p><p><strong>Results: </strong>Spatial transcriptomic analysis identified distinct CAF sub-clusters, including myofibroblastic CAFs (myCAFs), which were predominantly localized within tumor regions and enriched for extracellular matrix-related gene expression; inflammatory CAFs (iCAFs), which were preferentially localized within tumor septa and associated with inflammatory signaling; and antigen-presenting CAFs (apCAFs), which were enriched in the peritumoral zone and exhibited gene expression patterns suggestive of immune-related functions. Interactome analysis suggested that apCAFs in the peritumoral region showed transcriptional patterns consistent with CXCL12-CXCR4-related interactions with CD8+ T cells accumulating at the tumor periphery. The enrichment of apCAFs on the outer side of tumor septa was associated with reduced intra-tumoral CD8+ T-cell infiltration and poorer prognosis, suggesting a link between apCAF distribution and an immune-excluded TME.</p><p><strong>Conclusions: </strong>Spatial transcriptomic profiling suggests that CAFs exhibit functional and spatial polarization in the TME of HCC. ApCAFs are associated with CXCR4-related immune exclusion at the tumor-stroma interface and may represent a stromal component relevant to immune modulation. These findings provide a framework for CAF-immune interactions and serve as a basis for future functional studies targeting the CXCL12-CXCR4 axis.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591798","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 management of hepatorenal syndrome-acute kidney injury (HRS-AKI): A national survey of hepatology provider practices.","authors":"Giuseppe Cullaro, Gene Y Im, Shaun Chandna, Brian T Lee, Douglas A Simonetto, Elizabeth S Aby, Manhal Izzy, Stevan A Gonzalez, Courtney B Sherman, Joshua Aron, Jay Luther, Aparna Goel, Loretta L Jophlin, John Rice, Po-Hung Chen, Sumeet Asrani, Blanca Lizaola-Mayo, Mohamed Elfeki, Florence Wong, Scott W Biggins, Guadalupe Garcia-Tsao, Ashwani K Singal","doi":"10.1097/HC9.0000000000000905","DOIUrl":"10.1097/HC9.0000000000000905","url":null,"abstract":"<p><strong>Background: </strong>Hepatorenal syndrome-acute kidney injury (HRS-AKI) is associated with high mortality in cirrhosis. Recent FDA approval of terlipressin and updated clinical guidance have expanded management options, but real-world practice patterns remain unknown.</p><p><strong>Methods: </strong>We conducted a nationwide survey of U.S. hepatology providers regarding HRS-AKI management practices. The 33-question survey assessed provider demographics, vasoconstrictor selection, treatment timing, and adherence to guideline recommendations.</p><p><strong>Results: </strong>Among 162 respondents, most were hepatologists (94%) at academic centers (83%). Only 11% obtained a nephrology consultation at AKI detection, with 44% waiting until worsening renal function. Terlipressin was available at 80% of institutions but more commonly at academic centers (84% vs. 53%, p=0.003). Consistent with guideline recommendations, 77% of providers initiate vasoconstrictors only after completing a trial of volume expansion (if no renal improvement), particularly in academic centers (80% vs. 60% non-academic, p=0.03). Terlipressin (49%) and midodrine/octreotide (44%) were preferred first-line treatments, with providers at academic centers more likely to use midodrine/octreotide (46% vs. 30%, p=0.008). Mean arterial pressure was used by 62% of providers to guide vasoconstrictor dosing. Most providers (73%) discontinued vasoconstrictor treatment after 4 days if no improvement.</p><p><strong>Conclusions: </strong>Significant variations exist between guideline recommendations and real-world HRS-AKI management, especially first-line treatment choice, treatment monitoring, and nephrology consultation. These findings highlight opportunities to improve guideline implementation and identify areas where practice patterns might inform provider education and future guidance updates.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591849","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":"Second-line tacrolimus and mycophenolate mofetil in difficult-to-treat autoimmune hepatitis.","authors":"Alena Laschtowitz, Clara Vom Endt, Martin Kluge, Julian Pohl, Josephine Frohme, Leke Wiering, Joscha Vonderlin, Lena Maria Greverath, Paul Horn, Tobias Püngel, Caroline Zöllner, Julia Benckert, Cornelius Engelmann, Florian Roßner, Münevver Demir, Frank Tacke, Moritz Peiseler","doi":"10.1097/HC9.0000000000000921","DOIUrl":"10.1097/HC9.0000000000000921","url":null,"abstract":"<p><strong>Introduction: </strong>Azathioprine with corticosteroids is the first-line treatment for patients with autoimmune hepatitis (AIH). However, around 20% of patients require treatment alternatives, and second-line therapy for AIH is less well defined due to a lack of randomized controlled trials. We evaluated the efficacy and safety of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy.</p><p><strong>Methods: </strong>We performed a retrospective analysis of second-line therapies with MMF or tacrolimus for patients with AIH. Biochemical parameters were collected at the change of therapy, after 6 and 12 months, and at the last follow-up.</p><p><strong>Results: </strong>In total, 84/455 (18%) patients with AIH required second-line therapies, and 59 patients received MMF (47 patients) or tacrolimus (12 patients). Complete biochemical remission was achieved at a similar proportion in the tacrolimus group compared with MMF after 12 months (70.0% vs. 51.7%). In the subgroup of patients with insufficient response to first-line therapy, the rate of complete biochemical remission after 12 months was 70% in the tacrolimus group and 31% in the MMF group. Patients in the tacrolimus group had a higher mean ALT values compared with the MMF group and a higher prevalence of cirrhosis at the start of second-line therapy (50% vs. 19.1%).</p><p><strong>Conclusions: </strong>MMF and tacrolimus are effective and well-tolerated second-line therapies for AIH and should be part of the individualized second-line treatment algorithm of AIH. A trial of MMF is warranted after failure of first-line therapy. However, tacrolimus seems to be a safe and effective second-line option in patients with more advanced and aggressive disease.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591870","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}