Hepatology Communications最新文献

{"title":"Development and validation of a disease-specific health-related quality of life questionnaire for alcohol-associated liver disease: The CLDQ-ALD.","authors":"Zobair M Younossi, Maria Stepanova, Issah Younossi, Leyla deAvila","doi":"10.1097/HC9.0000000000000963","DOIUrl":"10.1097/HC9.0000000000000963","url":null,"abstract":"<p><strong>Background: </strong>Accurate assessment of health-related quality of life (HRQL) is essential in clinical research and therapeutic trials in alcohol-associated liver disease (ALD). The study aimed to develop and validate an ALD-specific HRQL instrument using a standard protocol for disease-specific HRQL instrument development.</p><p><strong>Methods: </strong>A comprehensive list of HRQL items was generated based on ALD patients' individual interviews and focus groups, existing HRQL instruments, and input from expert health care providers. Items were reduced through administration to patients with ALD, calculation of item impact scores, assessment of face validity, exploratory factor analysis, and evaluation of within-domain consistency and redundancy. The final Chronic Liver Disease Questionnaire (CLDQ)-ALD instrument underwent initial steps for psychometric validation.</p><p><strong>Results: </strong>The initial questionnaire comprised 90 items. Across 2 rounds of item reduction, it was completed by 72 patients with ALD (32% <45 y, 69% male, 18% with T2D, 39% cirrhosis, 40% current alcohol use) and reduced to 40 final items. Exploratory factor analysis identified 9 factors explaining 95% of the total variance. Based on the factor loadings, items were assigned to 9 domains (Fatigue, Alcohol, Function, Physical, Abdominal Symptoms, Itching, Sleep, Emotional, and Worry). Face and construct validity were assessed, along with concordance with another validated CLDQ instrument (CLDQ-metabolic dysfunction-associated steatohepatitis). The final CLDQ-ALD demonstrated good to excellent psychometric performance, with high internal consistency (Cronbach α >0.85 across all domains and >0.90 in 5 of 9 domains). Known-groups validity demonstrated mean score differences >0.5 (on a scale 1-7) in relevant domains by sex, presence of T2D, current alcohol use, depression, clinically overt fatigue, and cirrhosis.</p><p><strong>Conclusions: </strong>CLDQ-ALD version 1 is a disease-specific HRQL instrument for use in clinical research and therapeutic trials involving patients with ALD.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13209475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148029765","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":"Monocyte-derived IL-1β predicts and promotes HBsAg decline in chronic hepatitis B patients under nucleoside analogue therapy.","authors":"Satoshi Shigeno, Takahiro Kodama, Kazuhiro Murai, Emi Sometani, Kentaro Yasuda, Yuki Tahata, Akira Nishio, Satoshi Tanaka, Masanori Miyazaki, Kazuyoshi Ohkawa, Naruyasu Kakita, Seiichi Tawara, Takayuki Yakushijin, Hayato Hikita, Hidenori Toyoda, Tetsuo Takehara","doi":"10.1097/HC9.0000000000000957","DOIUrl":"10.1097/HC9.0000000000000957","url":null,"abstract":"<p><strong>Background: </strong>Although nucleos(t)ide analogs (NAs) suppress HBV replication, functional cure-defined by hepatitis B surface antigen (HBsAg) loss-is rarely achieved in chronic hepatitis B (CHB). Immune correlates of HBsAg decline may inform new therapeutic strategies.</p><p><strong>Methods: </strong>We profiled peripheral blood mononuclear cells (PBMCs) from NA-treated CHB patients with declining versus sustained HBsAg levels by single-cell RNA sequencing (scRNA-seq), followed by validation in an independent multicenter cohort using transcriptomic and functional assays. In a retrospective cohort, we evaluated serum interleukin-1β (IL-1β) as a predictor of HBsAg decline during long-term follow-up.</p><p><strong>Results: </strong>scRNA-seq revealed that CD14+CD16- classical monocytes in the HBsAg-declining group expressed significantly higher levels of IL-1β, along with genes involved in antigen presentation and phagocytosis. In the validation cohort, IL-1β expression in circulating CD14+ classical monocytes was also significantly higher in the declining group. Ex vivo stimulation assays demonstrated that recombinant HBsAg induced IL-1β production in monocytes, with stronger responses in the declining group. Recombinant IL-1β suppressed HBsAg secretion from HBV-producing HepG2.2.15 cells in vitro in a dose-dependent manner. In a longitudinal cohort, elevated serum IL-1β predicted subsequent HBsAg decline with an AUROC of 0.71. Multivariate analysis confirmed IL-1β as an independent predictor.</p><p><strong>Conclusions: </strong>Monocyte-derived IL-1β is linked to HBsAg decline during NA therapy and may serve as both a predictive biomarker and a potential therapeutic target to achieve functional cure.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13209470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148029774","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":"Neutrophil extracellular traps: A central player in liver diseases.","authors":"Han Wang, Allan Tsung, Hongji Zhang","doi":"10.1097/HC9.0000000000000970","DOIUrl":"10.1097/HC9.0000000000000970","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) are known for their propensity to expel decondensed chromatin embedded with inflammatory proteins, which can entrap and kill pathogens. The destructive role of NETs in sterile liver inflammation has also been elucidated. Therefore, NETs appear to have both beneficial and pathogenic roles for varying diseases of the liver. In this review, we discuss recent findings related to NETs in inflammatory and fibrotic liver diseases as well as liver cancer. We provide a comprehensive overview of the underlying factors contributing to NET formation within the hepatic microenvironment, encompassing diverse pathological contexts. Moreover, we shed light on the multifaceted involvement of NETs in processes such as liver inflammation, fibrosis, and premalignant conditions. We also provide insights into the roles of NETs in providing a tumor-feeding niche for HCC survival and liver metastasis of other cancers. Finally, we will discuss potential therapies targeting NETs for future application in liver diseases. By reviewing these intricate interactions, we aim to enhance our understanding of the complex role played by NETs in hepatic pathophysiology.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13209486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148029761","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":"Epigenetic drug control of Clec4g/LSECtin expression reduces fibrosis burden in cirrhosis.","authors":"Enrique Ángel-Gomis, Isabel Gómez-Hurtado, Maite G Fernández-Barrena, Oriol Juanola, Sebastián Martínez-López, Paula Boix, Matías A Ávila, Esther Caparrós, Rubén Francés","doi":"10.1097/HC9.0000000000000961","DOIUrl":"10.1097/HC9.0000000000000961","url":null,"abstract":"<p><strong>Background: </strong>Liver and lymph node endothelial cell C-type lectin (LSECtin) loss in liver sinusoidal endothelial cells (LSECs) during cirrhosis favors hepatic pro-inflammatory T-cell infiltration. We characterize histone protein post-translational modifications and DNA methylation in LSECs that may control LSECtin expression and evaluate methyltransferase inhibitors' capacity to retrieve LSECtin.</p><p><strong>Methods: </strong>DNA-methylation levels and histone post-translational modifications were studied by methylation array and ChIP-Seq experiments carried out on LSECs isolated by FACS from control and cirrhotic mice. Immortalized LSECs were treated with epigenetic effector inhibitory drugs (OTS186935-Suv39h2i, UNC0642-G9a/Glpi, UNC1999-EZH2/1i, 5-Aza-2'-deoxycitidine-DNMTi), alone and with IL-4, an LSECtin expression inducer. Drugs with regulatory potential were tested in vivo. LSECtin gene and protein expression, lymphocyte differentiation, and Th17-subpopulation proliferation were studied.</p><p><strong>Results: </strong>H3K9me3 and H3K27Me3 were reduced in LSECs of cirrhotic versus control mice. Suv39h2 and Ezh2/1 methyltransferase inhibitors OTS186935 and UNC1999, respectively, reduced Clec4g/LSECtin expression in immortalized LSECs. Murine primary LSECs showed H3K27me3 and H3K9me3 significantly enriched (controls) and reduced (cirrhotics) regions located upstream of the Clec4g promoter. OTS186935 and UNC1999 treated immortalized LSECs reduced H3K9me3 and H3K27me3 enrichment in these regions. Clec4g/LSECtin expression was also controlled by DNA methylation, as confirmed by Clec4g/LSECtin induction after 5-Aza-2'-deoxycitidine-DNMTi treatment in vitro and in vivo. Epigenetic drugs induced LSECtin in LSECs, contracted the hepatic Th17 compartment, attenuated hepatic structural damage, and improved liver function in cirrhosis.</p><p><strong>Conclusion: </strong>H3K9me3 and H3K27me3, and DNA-methylation regulate Clec4g expression in LSECs during cirrhosis. Inhibitory epigenetic-enzyme drugs increase Clec4g/LSECtin expression and provide evidence on relevant genomic regions for Clec4g reprogramming. The LSECtin-modulated hepatic Th17 compartment is contracted in cirrhosis by targeting these modifications.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13200999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005205","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 wait times for hepatology referrals in a prospective quality improvement initiative.","authors":"Ofodile Joe-Uzuegbu, Yashasavi Sachar, Abdel Aziz Shaheen, Stephen Congly, Kelly W Burak, Greg Heather, Crystal Ormond, Matthew D Sadler, Meredith A Borman, Victor Dong, Henry H Nguyen, Alexander I Aspinall, Peter Wang, Alexander Frolkis, Carla S Coffin, Laura M Stinton, Mark Swain, Mayur Brahmania","doi":"10.1097/HC9.0000000000000952","DOIUrl":"10.1097/HC9.0000000000000952","url":null,"abstract":"<p><strong>Background: </strong>Waitlist volumes for hepatology referrals in Calgary, Alberta, have increased with population growth and rising chronic liver disease [alcohol-related, metabolic dysfunction-associated steatotic liver disease, hepatitis B virus (HBV) infection, and cirrhosis complications]. Prolonged waits threaten timely surveillance, diagnosis, and treatment. We conducted a QI (quality improvement) project in the Calgary Liver Unit at the University of Calgary Medical Clinic (UCMC), a tertiary clinic using a central access and triage (CAT) system serving ~2 million residents.</p><p><strong>Methods: </strong>Our aim was to cut the median wait for routine referrals from 78.4 to 39 weeks (50%) between October 2023 and August 2025. Six Plan-Do-Study-Act cycles targeted referral coding (ICD-10 groupings), a dedicated HBV clinic, clearer triage acuity criteria, standardized waitlist management, redirecting benign liver neoplasms to primary care with guidance, and recruiting 2 additional hepatologists to expand capacity. The primary outcome was median routine wait time; secondary outcomes included urgent and emergent wait times and total waitlist size. Net waitlist accrual (accepted referrals minus new patients seen per month) tracked the flow. Data from CAT and scheduling systems were analyzed using statistical process control (SPC) charts.</p><p><strong>Results: </strong>By August 2025, the median routine wait fell to 8.4 weeks, the urgent wait fell from 28.3 to 6.6 weeks, and the emergent wait remained near the 2-week target (2.4 to ~2.7 weeks). The waitlist decreased from 1426 to 158 patients, and net accrual shifted from persistently positive to sustained negative values, reflecting backlog reduction. Routine-wait SPC charts showed special-cause variation and a sustained performance shift after key interventions.</p><p><strong>Conclusion: </strong>This multi-component, data-driven strategy within a CAT model improved access for routine referrals while protecting timely care for higher-acuity patients and may translate to other subspecialty clinics facing similar constraints.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13200950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005221","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":"Reply: Validation of MELD 3.0 in 2 centers from different continents.","authors":"Nikki Duong, Daniel J Huynh, Newsha Nikzad, W Ray Kim, Neil Shah, Scott W Biggins, Allison Kwong","doi":"10.1097/HC9.0000000000000958","DOIUrl":"10.1097/HC9.0000000000000958","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13201025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005219","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":"Midodrine versus placebo in patients with acute-on-chronic liver failure with ascites-A randomized trial (MIDAS trial).","authors":"Anand V Kulkarni, Shantan Venishetty, Sridevi Prasanna, Sowmya Iyengar, Sai V Sarada, Madhumita Premkumar, Mithun Sharma, Manasa Alla, Padaki Nagaraja Rao, Duvvur N Reddy, K Rajender Reddy","doi":"10.1097/HC9.0000000000000966","DOIUrl":"10.1097/HC9.0000000000000966","url":null,"abstract":"<p><strong>Background: </strong>Ascites is common in patients with acute-on-chronic liver failure (ACLF) and can complicate the course of ACLF due to circulatory dysfunction and hemodynamic compromise. Oral midodrine has been variably reported to improve hemodynamics and reduce complications of ascites in patients with decompensated cirrhosis, but its role in patients with high MELD ACLF remains unknown, which we aimed to assess.</p><p><strong>Methods: </strong>In this single-center, double-blind, randomized trial, patients with ACLF were assigned 1:1 to receive midodrine (5-7.5 mg tid) or a placebo for 30 days, alongside standard care. Transplant-free survival (TFS) at 1 month was the primary outcome, while secondary outcomes included TFS at 3 months, the proportion of patients achieving ascites control, changes in mean arterial pressure (MAP) and plasma renin activity at 1 month, the incidence of cirrhosis complications, and diuretic-related complications.</p><p><strong>Results: </strong>One hundred thirty patients with ACLF were enrolled. Midodrine use was not associated with improvement in TFS at 1 (HR, 0.99 [95% CI: 0.37-2.65]) and 3 months (HR, 0.93 [95% CI: 0.48-1.8]). Ascites control at day 30 (placebo: 9.2% [95% CI: 3.5-19] vs. midodrine: 20% [95% CI: 12.3-33.5]; p=0.08) and 90 (placebo: 44.6% [95% CI: 32.2-57.5] vs. midodrine: 53.8% [95% CI: 41-66.3]; p=0.29) was comparable. Midodrine increased the MAP (1.9 vs. 6.9 mm Hg; p=0.003) with an insignificant reduction in plasma renin activity levels (delta change: 0.22±1.6 vs. -1.6±2.2; p=0.09). Cirrhosis-related and diuretic-related complications were similar in both groups.</p><p><strong>Conclusions: </strong>Midodrine increases MAP in patients with ACLF and high MELD scores without TFS benefit and does not reduce the rate of ascites-related complications.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13201049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005255","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":"Secretion of the HBV small surface antigen is driven by an ER autophagic pathway.","authors":"Hong Cao, Eugene Krueger, Jing Chen, Huiling Yang, Jia Jun Chia, Rudolf K Beran, Jane Tam, Dmytro Kornyeyev, Meghan M Holdorf, Mark A McNiven","doi":"10.1097/HC9.0000000000000939","DOIUrl":"10.1097/HC9.0000000000000939","url":null,"abstract":"<p><p>Chronic hepatitis B (CHB), a major global public health burden, is characterized by the presence of high circulating levels of non-infectious subviral particles (SVPs). These SVPs are mainly composed of small hepatitis B surface antigen (SHBs) and are associated with a dysfunctional HBV-specific immune response. Previous studies exploring the cellular mechanisms and molecular pathways by which SVPs are secreted from hepatocytes have utilized either non-hepatic cells or whole-genome HBV-integrated hepatoma cell lines in which SHBs can also be secreted as a component of the virion envelope. In this study, we provide a detailed examination of SHBs trafficking using biochemical approaches coupled with high-resolution confocal microscopy and live-cell imaging via a novel fluorophore-tagged SHBs probe in both HepG2 and primary human hepatocytes stably expressing SHBs. Our results provide evidence that SHBs utilize a modified ER-Golgi secretory pathway with transit from the ER to the multivesicular body and lysosomal/late endosomal compartments. Importantly, we identified the autophagy adapters ATG5 and LC3B, and the ER-phagy protein atlastin 3 (ATL3), central to mediating SHBs secretion. These findings suggest that SHBs is trafficked through a non-canonical path for secretion and provides new potential therapeutic targets for the treatment of CHB.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13200969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005246","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 tailored pain self-management intervention for patients with cirrhosis is acceptable and improves pain control.","authors":"Shari S Rogal, Angela D Phares, Marilyn Brach, Matthew J Chinman, Sandra Gibson, Jane M Liebschutz, Jessica Merlin","doi":"10.1097/HC9.0000000000000955","DOIUrl":"10.1097/HC9.0000000000000955","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain is common and uniquely challenging to manage in people with cirrhosis. The purpose of this pilot study was to evaluate the feasibility and acceptability of a tailored pain self-management (PSM) intervention for people with cirrhosis and chronic pain.</p><p><strong>Methods: </strong>This single-arm, single-site pilot study recruited patients with a diagnosis of cirrhosis and chronic pain to a virtual, health coach-led, modular PSM intervention. After 6 weekly one-on-one sessions, patients were invited to attend 6 weekly group sessions. Outcomes were measured at baseline, 6 weeks, 12 weeks (end of intervention), and 24 weeks (maintenance). The primary outcomes were acceptability, defined by a 4/5 rating on the Treatment Acceptability Questionnaire, and feasibility, defined as the ability to retain patients in 80% of the intervention sessions. Secondary outcomes of pain and function were measured using the Pain intensity, Enjoyment of life, and General activity (PEG) scales, and a rating of percent improvement with the intervention.</p><p><strong>Results: </strong>Among 21 participants who started the intervention, 16 (76%) attended ≥80% of sessions. Acceptability thresholds were met at all time points. On a scale of 0-100, where 30 is considered to be a meaningful change, participants rated their improvement in pain symptoms an average of 50 ± 25. The average PEG score decreased from 6.1 at baseline to 5.3 at 24 weeks. Participants reported increases in PSM behaviors, including cognitive and stress-reduction methods, physical activity, healthy sleep behaviors, and changes in diet.</p><p><strong>Conclusions: </strong>This pilot identified a reduction in pain and an increase in PSM activities and demonstrated the acceptability of a health coach-led PSM intervention for adults with chronic pain and cirrhosis.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13201042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005214","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":"Effect of tiomolibdate choline on copper balance in patients with Wilson disease: An open-label phase 2 trial.","authors":"Aftab Ala, Thomas D Sandahl, Karl H Weiss, Valentina Medici, Chandler D Robinson, Andrew Cittadine, Declan Tuffy, Edward Gane, Fred K Askari","doi":"10.1097/HC9.0000000000000971","DOIUrl":"10.1097/HC9.0000000000000971","url":null,"abstract":"<p><strong>Background: </strong>Wilson disease (WD) is a rare disorder of copper (Cu) disposition. Tiomolibdate choline (TMC, bis-choline tetrathiomolybdate, ALXN1840), an oral Cu-binding agent, was investigated for the treatment of WD. The effect of repeat-dose TMC on Cu balance, serum Cu parameters, and safety was evaluated in an open-label, single-arm phase 2 study in 9 patients with WD.</p><p><strong>Methods: </strong>Enrolled patients with WD were admitted to a clinical research unit (CRU) and initiated on a Cu-controlled diet. Copper intake (food and drink) and output (feces and urine) were collected during a baseline period (days -4 through -1) and after initiation of daily TMC (days 1-8 and 25-39). Patients were allowed to leave the CRU during an interim period (days 9-24) but continued outpatient TMC treatment. Patients started on 15 mg/day TMC on day 1 with planned dose escalation to 30 mg/day TMC on day 29.</p><p><strong>Results: </strong>TMC showed a statistically significant reduction in daily Cu balance from baseline over the entire study period (days 1-39), attributed to increased fecal Cu excretion. The decrease in Cu balance was rapid, with a statistically significant decrease beginning on day 4. The cumulative mean decrease from baseline in Cu balance was -6.08 mg over 21 days. Plasma total Cu and directly measured non-ceruloplasmin-bound Cu levels increased immediately, consistent with Cu mobilization into blood and formation of stable tripartite complexes of Cu, TMC, and albumin. TMC was well tolerated. Alanine aminotransferase elevations that occurred were mild and reversible with dose modulation.</p><p><strong>Conclusion: </strong>TMC's reduction in Cu balance in WD patients, along with strong mobilization of Cu, supports the therapeutic potential of TMC in WD.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971964","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}