Hepatology Communications最新文献

{"title":"Gastroenterology and hepatology journals should increase women authorship representation: Room for improvement in trends from 2017 to 2024.","authors":"Christina Tsai, Arielle Greenberg, David Flomenbaum, Zoe Verzani, Danielle Garfunkel, Kiera Brennan, Vineela Nagamalla, Diana M Mathew, Sarah A Tupchong, Lynna Zhong, Michelle A Phillippi, Brett E Fortune, Nitya Abraham, Clara Y Tow","doi":"10.1097/HC9.0000000000000661","DOIUrl":"10.1097/HC9.0000000000000661","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500710","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":"Identification of immunogenic HLA-A*02:01 epitopes associated with HCC for immunotherapy development.","authors":"Anthony Maino, Ekaterina Bourov A-Flin, Thomas Decaens, Saadi Khochbin, Zuzana Macek Jilkova, Sophie Rousseaux, Joel Plumas, Philippe Saas, Laurence Chaperot, Olivier Manches","doi":"10.1097/HC9.0000000000000659","DOIUrl":"10.1097/HC9.0000000000000659","url":null,"abstract":"<p><strong>Background: </strong>HCC is the most common form of primary liver cancer, and despite recent advances in cancer treatment, it remains associated with poor prognosis and a lack of response to conventional therapies. Immunotherapies have emerged as a promising approach for cancer treatment, especially through the identification of tumor-specific immunogenic epitopes that can trigger a targeted immune response. This study aimed to identify immunogenic epitopes associated with HCC for the development of specific immunotherapies.</p><p><strong>Methods: </strong>We used high-throughput data screening and bioinformatics tools for antigens and epitope selection. The immunogenicity of the selected epitopes was studied after coculture of peripheral blood mononuclear cells obtained from healthy donors or HCC patients with a plasmacytoid dendritic cell line loaded with the selected peptides. Specific CD8+ T cell amplification and functionality were determined by labeling with tetramers and by IFN-γ and CD107a expression (flow cytometry and ELISpot).</p><p><strong>Results: </strong>We analyzed the transcriptional gene expression landscape of HCC to screen for a set of 16 ectopically expressed genes in a majority of HCC samples. Epitopes predicted to bind to HLA-A*02:01 with high affinity were further validated for their immunogenicity using the previously described plasmacytoid dendritic cell line in ex vivo CD8+ activation assays using patient immune cells. Three out of the 30 tested epitopes, namely FLWGPRALV (MAGE-A3), FMNKFIYEI (AFP), and KMFHTLDEL (LRRC46), elicited a strong T-cell response, in activation assays, degranulation assays, and IFN-γ secretion assays.</p><p><strong>Conclusions: </strong>These results highlight the potential of these peptides to be considered as targets for immunotherapies. The discovery of such immunogenic epitopes should improve immune-based treatments for liver cancer in combination with the current treatment approach.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500718","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":"Reduced short-term survival following liver transplant in patients with acute-on-chronic liver failure: Reevaluating OPTN data.","authors":"Tomohiro Tanaka, Emily K Roberts, Jonathan Platt","doi":"10.1097/HC9.0000000000000651","DOIUrl":"10.1097/HC9.0000000000000651","url":null,"abstract":"<p><strong>Background: </strong>Prior studies show severe acute-on-chronic liver failure (ACLF) at liver transplantation (LT) negatively impacts short-term, but not long-term, post-LT outcomes. However, not accounting for ACLF's time-varying effect on the waitlist may underappreciate its dynamic nature. Moreover, excluding those who died or dropped off the waitlist raises concerns about selection bias.</p><p><strong>Methods: </strong>This US nationwide retrospective cohort study estimated the effect of severe ACLF (grade 3) (ACLF-3) on post-LT outcomes, including adult, first-time deceased donor LT candidates listed from June 2013 to May 2023. A marginal structural model (MSM) to address selection bias and time-varying exposure (ACLF-3) was applied, with extended Cox proportional hazard models using a Heaviside step function to assess the hazard of death after LT.</p><p><strong>Results: </strong>Among 31,267 eligible candidates for LT (baseline cohort), 11.3% (n = 3518) had ACLF-3 at listing; 13.6% (n = 4243) died or dropped out while on the LT waitlist. Of the 27,024 patients who received LT (transplanted cohort), 12.3% (n = 3333) had ACLF-3 at LT. ACLF-3 at LT (but not at waitlisting) was associated with a higher hazard of death, with the hazard ratio of 1.80 (95% CI: 1.09-2.97) within 1 year after LT but not thereafter. This marginal structural model effect size was 9% higher than conventional multivariable Cox proportional hazard models. Sensitivity analyses corroborated these findings.</p><p><strong>Conclusions: </strong>Compared to previous studies, ACLF-3 at LT in our marginal structural model was associated with a discernible increase in short-term mortality after transplant, presumably due to our addressing of selection bias, while long-term survival was similar to those without severe ACLF at LT. However, potential vulnerability to posttransplant complications warrants further investigation.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448659","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":"Automated identification of incidental hepatic steatosis on Emergency Department imaging using large language models.","authors":"Tyrus Vong, Nicholas Rizer, Vedant Jain, Valerie L Thompson, Mark Dredze, Eili Y Klein, Jeremiah S Hinson, Tanjala Purnell, Stephen Kwak, Tinsay Woreta, Alexandra T Strauss","doi":"10.1097/HC9.0000000000000638","DOIUrl":"10.1097/HC9.0000000000000638","url":null,"abstract":"<p><strong>Background: </strong>Hepatic steatosis is a precursor to more severe liver disease, increasing morbidity and mortality risks. In the Emergency Department, routine abdominal imaging often reveals incidental hepatic steatosis that goes undiagnosed due to the acute nature of encounters. Imaging reports in the electronic health record contain valuable information not easily accessible as discrete data elements. We hypothesized that large language models could reliably detect hepatic steatosis from reports without extensive natural language processing training.</p><p><strong>Methods: </strong>We identified 200 adults who had CT abdominal imaging in the Emergency Department between August 1, 2016, and December 31, 2023. Using text from imaging reports and structured prompts, 3 Azure OpenAI models (ChatGPT 3.5, 4, 4o) identified patients with hepatic steatosis. We evaluated model performance regarding accuracy, inter-rater reliability, sensitivity, and specificity compared to physician reviews.</p><p><strong>Results: </strong>The accuracy for the models was 96.2% for v3.5, 98.3% for v4, and 98.8% for v4o. Inter-rater reliability ranged from 0.99 to 1.00 across 10 iterations. Mean model confidence scores were 2.9 (SD 0.8) for v3.5, 3.9 (SD 0.3) for v4, and 4.0 (SD 0.07) for v4o. Incorrect evaluations were 76 (3.8%) for v3.5, 34 (1.7%) for v4, and 25 (1.3%) for v4o. All models showed sensitivity and specificity above 0.9.</p><p><strong>Conclusions: </strong>Large language models can assist in identifying incidental conditions from imaging reports that otherwise may be missed opportunities for early disease intervention. Large language models are a democratization of natural language processing by allowing for a user-friendly, expansive analyses of electronic medical records without requiring the development of complex natural language processing models.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448204","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":"Erratum: Pain in chronic liver disease compared to other chronic conditions: Results from a nationally representative cohort study.","authors":"Grace Y Zhang, Aly Cortella, Jennifer C Lai, Jessica B Rubin","doi":"10.1097/HC9.0000000000000676","DOIUrl":"10.1097/HC9.0000000000000676","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448653","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":"Safety and efficacy of a defined bacterial consortium, VE303, to treat HE.","authors":"Patricia P Bloom, Christine M Bassis, Emily Crossette, Jeffrey L Silber, Jason M Norman, Vincent B Young, Anna S F Lok","doi":"10.1097/HC9.0000000000000650","DOIUrl":"10.1097/HC9.0000000000000650","url":null,"abstract":"<p><strong>Background: </strong>Novel therapies are needed to treat HE, and microbiome modulation is a promising target. VE303 is a defined consortium of 8 purified, clonal bacterial strains, known to produce metabolites that may be beneficial in HE. We evaluated the safety and efficacy of VE303 to treat HE.</p><p><strong>Methods: </strong>We performed a single-center, randomized, placebo-controlled trial of VE303 in adult patients with a history of overt HE (NCT04899115). Eligible patients were taking lactulose and rifaximin, had no recent systemic antibiotics, and had MELD ≤20. All patients received 5 days of oral vancomycin followed by randomization to 14 days of VE303 or placebo (2:1). The primary endpoints were incidence of serious adverse events and change in psychometric HE score (PHES) from baseline to 4 weeks after treatment. Stool samples underwent metagenomic sequencing and metabolite quantification.</p><p><strong>Results: </strong>Eighteen patients completed the trial, 56% men, with a mean age of 59 years and a mean MELD of 11. Patients who received VE303 had a mean change in PHES of +1.5 versus -1.0 in those who received a placebo (p=0.20). Two of the 12 patients who received VE303 had at least 1 serious adverse event (all overt HE hospitalizations), compared with 0/6 patients who received a placebo. In the patients who received VE303, 2 of 8 strains engrafted in >50% of patients. Both VE303 strain engraftment and increased stool butyrate production had a trend toward improved PHES.</p><p><strong>Conclusions: </strong>VE303 was well tolerated in patients with cirrhosis and a history of overt HE, leading to the engraftment of certain VE303 strains and a higher percentage of patients with improved PHES.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448847","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":"Silencing FAF2 mitigates alcohol-induced hepatic steatosis by modulating lipolysis and PCSK9 pathway.","authors":"Nazmul Huda, Praveen Kusumanchi, Yanchao Jiang, Hui Gao, Themis Thoudam, Ge Zeng, Nicholas J Skill, Zhaoli Sun, Suthat Liangpunsakul, Jing Ma, Zhihong Yang","doi":"10.1097/HC9.0000000000000641","DOIUrl":"10.1097/HC9.0000000000000641","url":null,"abstract":"<p><strong>Background: </strong>Chronic alcohol consumption leads to lipid accumulation, oxidative stress, cellular damage, and inflammation in the liver, collectively referred to as alcohol-associated liver disease (ALD). FAF2/UBXD8/ETEA (Fas-associated factor 2) is a ubiquitin ligase adaptor protein that plays a crucial role in the ubiquitin-mediated degradation of misfolded proteins in the endoplasmic reticulum. A recent genome-wide association study indicated an association between FAF2 and ALD; however, the exact contribution of FAF2 to ALD pathogenesis remains unclear.</p><p><strong>Methods: </strong>FAF2 was knocked down using AAV-delivered shRNA in C57/BL6 mice. Mice were subjected to a chronic-plus-single binge ethanol feeding (NIAAA) model. Nine hours after gavage, liver, blood, and other organs of interest were collected for gene expression and biochemical analyses.</p><p><strong>Results: </strong>We first observed a significant elevation in hepatic FAF2 protein expression in individuals with ALD and in mice subjected to an ethanol-binge model. Interestingly, knocking down FAF2 in the liver using adeno-associated virus serotype 8-delivered short hairpin RNA conferred a protective effect against alcohol-induced liver steatosis in ethanol-binged mice. Transcriptomic analysis revealed that differentially expressed genes were enriched in multiple lipid metabolism regulation pathways. Further analysis of transcription factors regulating these differentially expressed genes suggested potential regulation by SREBP1. Several SREBP1 target genes, including Fasn, Scd1, Lpin1, and Pcsk9 (proprotein convertase subtilisin/kexin type 9), were dysregulated in the livers of ethanol-fed FAF2 knockdown mice. Additionally, Pcsk9 could be regulated through the FOXO3-SIRT6 pathway in the livers of ethanol-fed FAF2 knockdown mice, leading to increased liver low-density lipoprotein receptor expression and reduced plasma LDL cholesterol levels. Furthermore, FAF2 knockdown in mouse liver enhanced adipose triglyceride lipase lipolytic activity by upregulating the adipose triglyceride lipase activator, comparative gene identification-58, and downregulating the adipose triglyceridelipase transport inhibitor, Elmod2, contributing to the alleviation of liver steatosis.</p><p><strong>Conclusions: </strong>Our study uncovers a novel mechanism involving FAF2 in the pathogenesis of ALD.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448924","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":"Deep immune profiling of intrahepatic cholangiocarcinoma with CODEX multiplexed imaging.","authors":"Marina Baretti, Soumya Shekhar, Vaibhav Sahai, Daniel Shu, Kathryn Howe, Valerie Gunchick, Naziheh Assarzadegan, Emma Kartalia, Qingfeng Zhu, Elsa Hallab, Archit Sheth-Shah, Aya Kondo, Nilofer S Azad, Mark Yarchoan","doi":"10.1097/HC9.0000000000000632","DOIUrl":"10.1097/HC9.0000000000000632","url":null,"abstract":"<p><strong>Background: </strong>Intrahepatic cholangiocarcinoma (iCCA) may be genomically subclassified by the presence of potentially actionable molecular aberrations, of which pathogenic alterations in isocitrate dehydrogenase (IDH)1 and fibroblast growth factor receptor (FGFR)2 are the most frequently observed. The impact of these molecular alterations on the tumor immune microenvironment remains incompletely understood.</p><p><strong>Methods: </strong>We performed a high-parameter spatial immune phenotyping of iCCA samples with pathogenic FGFR2 or IDH1 alterations and FGFR2/IDH1 wild-type controls at the single-cell level using CO-Detection by indEXing.</p><p><strong>Results: </strong>A total of 24 tumors were examined. Tumors with FGFR2 alterations were characterized by fewer CD8+ T cells and \"M2-like\" macrophages but higher levels of polymorphonuclear myeloid-derived suppressor cells as compared to FGFR2 wild-type tumors. Spatial relationships between polymorphonuclear myeloid-derived suppressor cells and multiple other cell types in the tumor microenvironment (including tumor cells, CD4+, and CD8+ T cells) were enriched in tumors with FGFR2 alterations. Tumors with IDH1 mutations had a trend toward more fibroblasts and were characterized by a closer proximity of tumor cells to CD4+ T cells, and between macrophages and multiple structural tumor microenvironment components as compared to other subtypes.</p><p><strong>Conclusions: </strong>iCCAs with pathogenic FGFR2 fusions/rearrangements and IDH1 mutations have distinct immunophenotypes. Tailoring immunotherapeutic approaches to specific molecular subsets could improve treatment outcomes across the divergent molecularly defined iCCA subtypes.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448562","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 involvement in a large cohort of patients with erythropoietic protoporphyria or X-linked protoporphyria.","authors":"Cynthia Levy, Hetanshi Naik, Jessica Overbey, Karli Hedstrom, Kelly Wang, Catherine McDonough, Mary Freeman, Siobán B Keel, Angelika L Erwin, Amy K Dickey, Rebecca K Leaf, John Quigley, Marshall Mazepa, Bruce Wang, John Phillips, Charles Parker, Brendan McGuire, Mohamed Kazamel, Herbert Bonkovsky, Sean Rudnick, Karl E Anderson, Akshata Moghe, Manish Thapar, Behnam Saberi, Kristen Wheeden, Robert Desnick, Manisha Balwani","doi":"10.1097/HC9.0000000000000657","DOIUrl":"10.1097/HC9.0000000000000657","url":null,"abstract":"<p><strong>Background: </strong>Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by the accumulation of protoporphyrin in the marrow, erythrocytes, plasma, skin, and liver, and present clinically with painful cutaneous phototoxicity. Liver abnormalities have been reported in over 25% of patients with EPP. Further characterization of liver involvement in protoporphyria is needed.</p><p><strong>Methods: </strong>Patients with EPP or XLP enrolled in the longitudinal studies of the NIH-supported Porphyrias Consortium were included. Medical history, laboratory, and liver histology data were abstracted and described.</p><p><strong>Results: </strong>A total of 322 patients were enrolled; 28 (8.7%) had XLP, 52% were female, and the median age at enrollment was 33.3 years. Liver chemistries were available for 235 patients, and 132 (56.2%) had abnormalities, mostly mild. Abnormal liver enzymes were associated with higher erythrocyte protoporphyrin levels. Eleven patients had advanced protoporphyric hepatopathy. In total, 54 (16.8%) underwent cholecystectomy, 8 (2.5%) had a liver transplant, 4 (1.2%) had a bone marrow transplant, and 8 (2.5%) died. At least 4 deaths were caused by liver failure due to protoporphyric hepatopathy, 2 were complications of bone marrow transplant, and 1 from HCC, which developed in a patient with EPP without cirrhosis. Patients with XLP were more likely to develop liver-related complications compared to EPP.</p><p><strong>Conclusions: </strong>Liver abnormalities are common in patients with EPP and XLP. In this national registry, only 3.4% had protoporphyric hepatopathy, with most requiring a transplant. Of the deaths, 62.5% were attributable to liver disease. Further observations are needed for guiding hepatic evaluation and management of patients with protoporphyria with or without initial hepatic abnormalities.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448627","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":"Pervasive role of pruritus in impaired quality of life in patients with primary biliary cholangitis: Data from the GLIMMER study.","authors":"Helen T Smith, Sugato Das, James Fettiplace, Robyn von Maltzahn, Philip J F Troke, Megan M McLaughlin, David E Jones, Andreas E Kremer","doi":"10.1097/HC9.0000000000000635","DOIUrl":"10.1097/HC9.0000000000000635","url":null,"abstract":"<p><strong>Background: </strong>Pruritus affects up to 80% of patients with primary biliary cholangitis (PBC) and reduces health-related quality of life (HRQoL). GLIMMER (NCT02966834) was a randomized, placebo-controlled phase IIb study of linerixibat in patients with PBC and pruritus. Using patient-reported outcome data from GLIMMER, we characterize the impact of pruritus in PBC.</p><p><strong>Methods: </strong>To objectively assess HRQoL impact, EQ-5D-5L data from GLIMMER (0-1 scale; 0 = death, 1 = perfect health) were analyzed post-hoc across pruritus severities. Inter-relationships between pruritus severity (0-10 numerical rating scale [NRS]), depression (Beck Depression Inventory-II, post-hoc), and sleep interference (0-10 NRS) and their impact on HRQoL were explored.</p><p><strong>Results: </strong>In patients with PBC (n = 147), severe pruritus was associated with worse HRQoL. EQ-5D-5L scores were lower in those with severe pruritus (≥7-10 NRS) versus mild/moderate pruritus (mean [SD]: 0.49 [0.28] and 0.75 [0.17]/0.76 [0.17], respectively). Among patients with severe pruritus, 31% had severe depression, versus 9/3% with mild/moderate pruritus. Patients with both severe pruritus and depression had a mean EQ-5D-5L score of 0.30. In those with severe pruritus, 54% reported severe sleep interference. Improvements in pruritus were accompanied by stepwise improvements in EQ-5D-5L scores.</p><p><strong>Conclusions: </strong>This analysis of patients in the largest investigational trial of cholestatic pruritus to date shows a clear association between pruritus and impaired HRQoL. Patients with severe pruritus had HRQoL comparable to patients with severe Parkinson's disease. Severe pruritus alongside depression was associated with extremely poor HRQoL, indicating the importance of evaluating itch and managing depression. Sleep interference appears to be a major cofactor for reduced HRQoL. For each 1-point improvement in NRS HRQoL improved, clinicians should offer appropriate and timely intervention.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448657","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}