Hepatology Communications最新文献

{"title":"Polygenic risk score in cirrhosis: Does the etiology matter?","authors":"Marta Alonso-Peña, Maria Teresa Arias Loste, Joaquin Cabezas, Paula Iruzubieta, Javier Crespo","doi":"10.1097/HC9.0000000000000541","DOIUrl":"10.1097/HC9.0000000000000541","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004529","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":"Hydrogen peroxide damage to rat liver sinusoidal endothelial cells is prevented by n-acetyl-cysteine but not GSH.","authors":"Larissa D Kruse, Christopher Holte, Bartlomiej Zapotoczny, Eike C Struck, Jasmin Schürstedt, Wolfgang Hübner, Thomas Huser, Karolina Szafranska","doi":"10.1097/HC9.0000000000000617","DOIUrl":"10.1097/HC9.0000000000000617","url":null,"abstract":"<p><strong>Background: </strong>Reactive oxygen species (ROS) are prevalent in the liver during intoxication, infection, inflammation, and aging. Changes in liver sinusoidal endothelial cells (LSEC) are associated with various liver diseases.</p><p><strong>Methods: </strong>Isolated rat LSEC were studied under oxidative stress induced by H2O2 at different concentrations (0.5-1000 µM) and exposure times (10-120 min). LSEC functions were tested in a dose-dependent and time-dependent manner.</p><p><strong>Results: </strong>(1) Cell viability, reducing potential, and scavenging function decreased as H2O2 concentration and exposure time increased; (2) intracellular ROS levels rose with higher H2O2 concentrations; (3) fenestrations exhibited a dynamic response, initially closing but partially reopening at H2O2 concentrations above 100 µM after about 1 hour; (4) scavenging function was affected after just 10 minutes of exposure, with the impact being irreversible and primarily affecting degradation rather than receptor-mediated uptake; (5) the tubulin network was disrupted in high H2O2 concentration while the actin cytoskeleton appears to remain largely intact. Finally, we found that reducing agents and thiol donors such as n-acetyl cysteine and glutathione (GSH) could protect cells from ROS-induced damage but could not reverse existing damage as pretreatment with n-acetyl cysteine, but not GSH, reduced the negative effects of ROS exposure.</p><p><strong>Conclusions: </strong>The results suggest that LSEC does not store an excess amount of GSH but rather can readily produce it in the occurrence of oxidative stress conditions. Moreover, the observed thresholds in dose-dependent and time-dependent changes, as well as the treatments with n-acetyl cysteine/GSH, confirm the existence of a ROS-depleting system in LSEC.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752423","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: Polygenic risk score in cirrhosis: Does the etiology matter?","authors":"Tae-Hwi Schwantes-An, Timothy R Morgan, Devanshi Seth","doi":"10.1097/HC9.0000000000000543","DOIUrl":"10.1097/HC9.0000000000000543","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004531","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":"Duodenal-jejunal bypass ameliorates MASLD in rats by regulating gut microbiota and bile acid metabolism through FXR pathways.","authors":"Mengting Ren, Yi Xia, Hanghai Pan, Xinxin Zhou, Mosang Yu, Feng Ji","doi":"10.1097/HC9.0000000000000615","DOIUrl":"10.1097/HC9.0000000000000615","url":null,"abstract":"<p><strong>Background: </strong>Although bariatric and metabolic surgical methods, including duodenal-jejunal bypass (DJB), were shown to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in clinical trials and experimental rodent models, their underlying mechanisms remain unclear. The present study therefore evaluated the therapeutic effects and mechanisms of action of DJB in rats with MASLD.</p><p><strong>Methods: </strong>Rats with MASLD were randomly assigned to undergo DJB or sham surgery. Rats were orally administered a broad-spectrum antibiotic cocktail (Abx) or underwent fecal microbiota transplantation to assess the role of gut microbiota in DJB-induced improvement of MASLD. Gut microbiota were profiled by 16S rRNA gene sequencing and metagenomic sequencing, and bile acids (BAs) were analyzed by BA-targeted metabolomics.</p><p><strong>Results: </strong>DJB alleviated hepatic steatosis and insulin resistance in rats with diet-induced MASLD. Abx depletion of bacteria abrogated the ameliorating effects of DJB on MASLD. Fecal microbiota transplantation from rats that underwent DJB improved MASLD in high-fat diet-fed recipients by reshaping the gut microbiota, especially by significantly reducing the abundance of Clostridium. This, in turn, suppressed secondary BA biosynthesis and activated the hepatic BA receptor, farnesoid X receptor. Inhibition of farnesoid X receptor attenuated the ameliorative effects of post-DJB microbiota on MASLD.</p><p><strong>Conclusions: </strong>DJB ameliorates MASLD by regulating gut microbiota and BA metabolism through hepatic farnesoid X receptor pathways.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004513","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":"Comparison of clinical outcomes in patients with refractory ascites treated with either TIPS, tunneled peritoneal catheter, or ascites pump.","authors":"Sarah L Schütte, Anja Tiede, Jim B Mauz, Hannah Rieland, Martin Kabelitz, Robin Iker, Nicolas Richter, Bernhard Meyer, Benjamin Heidrich, Heiner Wedemeyer, Benjamin Maasoumy, Tammo L Tergast","doi":"10.1097/HC9.0000000000000620","DOIUrl":"10.1097/HC9.0000000000000620","url":null,"abstract":"<p><strong>Background: </strong>Refractory ascites (RA) remains a serious complication in patients with cirrhosis. Currently, the insertion of a TIPS is considered the standard of care in these patients. To achieve symptom control in those with TIPS contraindications, tunneled peritoneal catheters (PeCa) or ascites pumps were introduced. However, data comparing the available treatment options are scarce. This study aims to compare outcomes among patients with RA treated either with TIPS, PeCa, or ascites pump.</p><p><strong>Methods: </strong>All patients with RA and cirrhosis treated at Hannover Medical School between 2009 and 2023 were evaluated. Endpoints included mortality, acute kidney injury (AKI), hyponatremia, peritonitis, and rehospitalization rate. Propensity score matching was conducted to adjust for group differences.</p><p><strong>Results: </strong>First, 31 patients with ascites pump were compared to 62 patients with a PeCa after propensity score matching. There were no differences regarding mortality nor incidences of AKI, hyponatremia, or rehospitalization. However, incidences of peritonitis and explantation were lower in those with ascites pump (HR 0.32, 95% CI: 0.15-0.70, and HR 0.32, 95% CI: 0.14-0.71, respectively). Second, 35 ascites pump patients were matched with 70 individuals with TIPS. No differences regarding mortality or peritonitis incidence were observed. Ascites pump patients showed higher incidences of AKI (HR 4.55, 95% CI: 2.53-8.18) and hyponatremia (HR 4.13, 95% CI: 2.08-8.22). Last, 129 patients with TIPS were compared to 129 with PeCa. Mortality was comparable, while incidences of AKI (HR 5.01, 95% CI: 3.36-7.47), hyponatremia (HR 4.64, 95% CI: 3.03-7.12), and peritonitis (HR 2.19, 95% CI: 1.41-3.41) were higher in those with PeCa.</p><p><strong>Conclusions: </strong>While ascites pump was associated with lower incidences of device infections and explantations, TIPS was associated with the lowest incidence of clinical complications in patients with RA.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004511","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":"Environmental exposures and the risk of hepatocellular carcinoma.","authors":"Divya Rayapati, Katherine A McGlynn, John D Groopman, Amy K Kim","doi":"10.1097/HC9.0000000000000627","DOIUrl":"10.1097/HC9.0000000000000627","url":null,"abstract":"<p><p>The global epidemiology of HCC is shifting due to changes in both established and emerging risk factors. This transformation is marked by an emerging prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes, alongside traditional risks such as viral hepatitis (HBV and HCV), and exposure to chemical agents like aflatoxin, alcohol, tobacco, and air pollution. This review examines how environmental exposures and evolving liver pathology, exacerbated by lifestyle and metabolic conditions, are contributing to the rising worldwide incidence of HCC. Effective prevention strategies must not only address traditional risk factors through vaccination and therapeutic measures but also confront metabolic and socioeconomic disparities through comprehensive public health efforts. As the burden of liver cancer continues to grow, particularly in resource-limited settings, an expansive and inclusive approach is vital for mitigating its impact across diverse populations.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004515","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":"Increased MASH-associated liver cancer in younger demographics.","authors":"Pojsakorn Danpanichkul, Yanfang Pang, Kanokphong Suparan, Thanida Auttapracha, Supapitch Sirimangklanurak, Abdelrahman M Attia, Chanattha Thimphitthaya, Michelle Shi Ni Law, Zhenning Yu, Mostafa A Soliman, Natchaya Polpichai, Chanakarn Kanitthamniyom, Donghee Kim, Mazen Noureddin, Amit G Singal, Karn Wijarnpreecha, Ju Dong Yang","doi":"10.1097/HC9.0000000000000629","DOIUrl":"10.1097/HC9.0000000000000629","url":null,"abstract":"<p><strong>Background: </strong>The incidence of cancer and the prevalence of metabolic disease and metabolic dysfunction-associated steatotic liver disease is increasing in young adults. However, updated global data on metabolic dysfunction-associated steatohepatitis (MASH)-associated primary liver cancer (PLC) in young adults remains scarce.</p><p><strong>Methods: </strong>This study analyzed data from the Global Burden of Disease study between 2000 and 2021 to assess the age-standardized incidence, mortality, and disability-adjusted life years rates from MASH-associated PLC in young adults (15-49 y).</p><p><strong>Results: </strong>In 2021, there were 4300 incidence cases, 3550 deaths, and 179,340 disability-adjusted life years from MASH-associated PLC in young adults. Among various etiologies of PLC in young adults, only MASH-associated PLC had increased incidence rates (annual percent change: +0.26, 95% CI: 0.16%-0.35%), with the Eastern Mediterranean region having the largest observed increase (annual percent change: 1.46%, 95% CI: 1.40%-1.51%). In 2021, MASH-associated PLC in young adults made up 6% (+1% from 2000) incident cases, 6% (+2% from 2000) deaths, and 6% (+2% from 2000) disability-adjusted life years of all PLC in this age group. Over half of the countries exhibited an increase in age-standardized incidence rate from MASH-associated PLC in young adults from 2000 to 2021.</p><p><strong>Conclusions: </strong>The incidence of MASH-associated PLC in young adults is significantly increasing, signaling likely future increases in PLC incidence among older adults as this cohort ages. This trend necessitates urgent strategies worldwide to mitigate the epidemics of MASH-associated PLC in young adults.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947885","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":"Survival benefit associated with liver transplantation for hepatocellular carcinoma based on tumor burden scores at listing.","authors":"Hao Liu, Wei Zhang, Mengyang Di, Hang Lee, Liuhua Shi, Xixi Wang, Zhang Xingyu, Colin A Powers, Vrishketan Sethi, Xingjie Li, Yao Xiao, Andrew Crane, Christof Kaltenmeier, Ramon Bataller Alberola, Jaideep Behari, Andres Duarte-Rojo, Dempsey Hughes, Shahid Malik, Naudia Jonassaint, David Geller, Samer Tohme, Vikraman Gunabushanam, Amit Tevar, Ruy Cruz, Christopher Hughes, Stalin Dharmayan, Subhashini Ayloo, Abhinav Humar, Michele Molinari","doi":"10.1097/HC9.0000000000000619","DOIUrl":"10.1097/HC9.0000000000000619","url":null,"abstract":"<p><strong>Introduction: </strong>Liver transplantation (LT) provides significant survival benefits to patients with unresectable HCC. In the United States, organ allocation policies for HCCs within the United Network for Organ Sharing criteria do not prioritize patients based on their differences in oncological characteristics. This study assessed whether transplant-associated survival benefits (TASBs) vary among patients with different tumor burden scores (TBS) measured at the time of listing.</p><p><strong>Methods: </strong>We analyzed data from adults applying for HCC MELD exception points between 2002 and 2019, with follow-up until December 2023, using the Scientific Registry of Transplant Recipients. TBS was determined based on the largest tumor diameter and number of HCCs. Patients were categorized into low (≤3), intermediate (3.1-5), and high (>5) TBS groups. TASB was measured as the difference in 5-year survival with and without LT.</p><p><strong>Results: </strong>This study included 36,634 LT candidates. High-TBS patients had higher waitlist dropout rates and marginally lower post-transplant survival, resulting in a significantly greater TASB. The 5-year TASB for the low, intermediate, and high TBS groups were 15.7, 22.1, and 25.0 months, respectively. The adjusted survival benefit expressed in 5-year survival differences was 21.9%, 34.5%, and 39.4% in the low, intermediate, and high TBS groups, respectively (p<0.001).</p><p><strong>Conclusions: </strong>Higher TBS during listing correlates with greater LT benefits for patients with unresectable HCC within UNOS criteria. We conclude that organ allocation policies in the United States should prioritize patients with high TBS due to their increased risk of dropout and comparable post-transplant survival when compared to patients with less advanced tumors.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947995","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 evolving role of liver biopsy: Current applications and future prospects.","authors":"Purva Gopal, Xiaobang Hu, Marie E Robert, Xuchen Zhang","doi":"10.1097/HC9.0000000000000628","DOIUrl":"10.1097/HC9.0000000000000628","url":null,"abstract":"<p><p>Histopathologic evaluation of liver biopsy has played a longstanding role in the diagnosis and management of liver disease. However, the utility of liver biopsy has been questioned by some, given the improved imaging modalities, increased availability of noninvasive serologic tests, and development of artificial intelligence over the past several years. In this review, we discuss the current and future role of liver biopsy in both non-neoplastic and neoplastic liver diseases in the era of improved noninvasive laboratory, radiologic, and digital technologies.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948001","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":"Pemigatinib suppresses liver fibrosis and subsequent osteodystrophy in mice.","authors":"Taiki Mihara, Yoshiharu Tsuru, Tamaki Kurosawa, Yuma Nonoshita, Yuki Yamakawa, Masatoshi Hori","doi":"10.1097/HC9.0000000000000610","DOIUrl":"10.1097/HC9.0000000000000610","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis could lead to serious secondary diseases, including osteodystrophy. The interaction between liver and bone has not been fully elucidated, thus existing therapies for osteodystrophy secondary to liver fibrosis are often ineffective. FGF23 was initially found as an endocrine regulator of phosphate homeostasis, but recently, its involvement in fibrosis has been suggested. In this study, we hypothesized that the FGF23 level increases with liver injury, which in turn induces liver fibrosis and osteodystrophy.</p><p><strong>Methods: </strong>Liver fibrosis model mice were generated via carbon tetrachloride administration and bile duct ligation. Fibrosis was assessed using Masson trichrome staining and hydroxyproline assay. The bone structure was evaluated using dual-energy x-ray absorptiometry and microcomputed tomography. Human HSC lines LX-2 and primary rat HSCs were used for in vitro analyses.</p><p><strong>Results: </strong>Carbon tetrachloride-induced and bile duct ligation-induced liver injury increased the serum FGF23 level compared with that in control mice. RNA sequencing analysis of FGF23-treated LX-2 showed that FGF23 promotes the production of matrisome, which helps in forming the extracellular matrix. The FGF receptor antagonist pemigatinib alleviated carbon tetrachloride-induced and bile duct ligation-induced liver fibrosis and the deleterious alterations in bone density and microstructure in mice.</p><p><strong>Conclusions: </strong>The serum FGF23 level increased with liver injury, and FGF23 promoted liver fibrosis. Moreover, pemigatinib alleviated liver fibrosis and hepatic osteodystrophy. These findings suggest that FGF23 mediates the communication between the liver and bone and that FGF23 may be a new therapeutic target for liver fibrosis and subsequent osteodystrophy.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947985","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}