Pub Date : 2024-09-23DOI: 10.1097/HEP.0000000000001103
Vinh V Tran, Fasiha Kanwal, George Cholankeril
{"title":"Beyond the baseline: Longitudinal surveillance with non-invasive tests for fibrosis in MASLD.","authors":"Vinh V Tran, Fasiha Kanwal, George Cholankeril","doi":"10.1097/HEP.0000000000001103","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001103","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":null,"pages":null},"PeriodicalIF":12.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-21DOI: 10.1097/hep.0000000000001044
Eric M. Przybyszewski, Juan Pablo Arab
{"title":"Setting the standard: Quality indicators in variceal hemorrhage","authors":"Eric M. Przybyszewski, Juan Pablo Arab","doi":"10.1097/hep.0000000000001044","DOIUrl":"https://doi.org/10.1097/hep.0000000000001044","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":null,"pages":null},"PeriodicalIF":13.5,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-21DOI: 10.1097/hep.0000000000001042
Robert M. Wilechansky
{"title":"FIB-4 and VITRO: A new dynamic duo in noninvasive testing?","authors":"Robert M. Wilechansky","doi":"10.1097/hep.0000000000001042","DOIUrl":"https://doi.org/10.1097/hep.0000000000001042","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":null,"pages":null},"PeriodicalIF":13.5,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-21DOI: 10.1097/hep.0000000000001041
Jack W. Sample
{"title":"Beyond monotherapy: Combining radiotherapy with sintilimab and bevacizumab for hepatocellular carcinoma with portal vein tumor thrombus","authors":"Jack W. Sample","doi":"10.1097/hep.0000000000001041","DOIUrl":"https://doi.org/10.1097/hep.0000000000001041","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":null,"pages":null},"PeriodicalIF":13.5,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND AND AIMSHyperactivated inflammatory responses induced by cytokine release syndrome (CRS) are the primary causes of tissue damage and even death. The translation process is precisely regulated to control the production of proinflammatory cytokines. However, it is largely unknown whether targeting translation can effectively limit the hyperactivated inflammatory responses during acute hepatitis and graft-versus-host disease (GVHD).APPROACH AND RESULTSBy using in vitro translation and cellular overexpression systems, we have found that the non-structural protein gene NS2A of Zika virus (ZIKV) functions as RNA molecules to suppress the translation of both ectopic genes and endogenous proinflammatory cytokines. Mechanistically, results from RNA pulldown and co-immunoprecipitation (Co-IP) assays have demonstrated that NS2A RNA interacts with the translation initiation factor eIF2α to disrupt the dynamic balance of the eIF2/eIF2B complex and translation initiation, which is the rate-limiting step during the translation process. In the acetaminophen (APAP)-, LPS/D-galactosamine (D-GalN)-, viral infection-induced acute hepatitis, and GVHD mouse models, mice with myeloid cell-specific knock-in of NS2A show decreased levels of serum proinflammatory cytokines and reduced tissue damage.CONCLUSIONSZIKV NS2A dampens the production of proinflammatory cytokines and alleviates inflammatory injuries by interfering translation process as RNA molecules, which suggests that NS2A RNA is potentially used to treat numerous acute inflammatory diseases characterized by CRS.
{"title":"Harnessing ZIKV NS2A RNA for alleviating acute hepatitis and cytokine release storm by targeting translation machinery.","authors":"Jingfei Zhu,Rongsheng Wu,Tao Yang,Yi Yuan,Guodi Liu,Shengchuan Chen,Zhiqiang Chen,Siying Liu,Shiyou Wang,Dapei Li,Haiping Yao,Yuanqing He,Sudan He,Cheng-Feng Qin,Jianfeng Dai,Feng Ma","doi":"10.1097/hep.0000000000001101","DOIUrl":"https://doi.org/10.1097/hep.0000000000001101","url":null,"abstract":"BACKGROUND AND AIMSHyperactivated inflammatory responses induced by cytokine release syndrome (CRS) are the primary causes of tissue damage and even death. The translation process is precisely regulated to control the production of proinflammatory cytokines. However, it is largely unknown whether targeting translation can effectively limit the hyperactivated inflammatory responses during acute hepatitis and graft-versus-host disease (GVHD).APPROACH AND RESULTSBy using in vitro translation and cellular overexpression systems, we have found that the non-structural protein gene NS2A of Zika virus (ZIKV) functions as RNA molecules to suppress the translation of both ectopic genes and endogenous proinflammatory cytokines. Mechanistically, results from RNA pulldown and co-immunoprecipitation (Co-IP) assays have demonstrated that NS2A RNA interacts with the translation initiation factor eIF2α to disrupt the dynamic balance of the eIF2/eIF2B complex and translation initiation, which is the rate-limiting step during the translation process. In the acetaminophen (APAP)-, LPS/D-galactosamine (D-GalN)-, viral infection-induced acute hepatitis, and GVHD mouse models, mice with myeloid cell-specific knock-in of NS2A show decreased levels of serum proinflammatory cytokines and reduced tissue damage.CONCLUSIONSZIKV NS2A dampens the production of proinflammatory cytokines and alleviates inflammatory injuries by interfering translation process as RNA molecules, which suggests that NS2A RNA is potentially used to treat numerous acute inflammatory diseases characterized by CRS.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":null,"pages":null},"PeriodicalIF":13.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-20DOI: 10.1097/hep.0000000000001106
Francesco Vizzutti,Dominique Thabut
{"title":"Editorial: Looking at Neptune with a binocular.","authors":"Francesco Vizzutti,Dominique Thabut","doi":"10.1097/hep.0000000000001106","DOIUrl":"https://doi.org/10.1097/hep.0000000000001106","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":null,"pages":null},"PeriodicalIF":13.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1097/hep.0000000000001095
Matthew Untalan, Nancy Crimmins, Katherine P. Yates, Ali Mencin, Stavra Xanthakos, Vidhu V. Thaker
Background: Studies on adults have shown an association between overt or subclinical hypothyroidism (SH) and metabolic dysfunction-associated steatotic liver disease (MASLD). The goal of this study was to assess the relationship between thyroid-stimulating hormone (TSH) levels and the histological characteristics of MASLD in youth. Methods: This observational study used prospectively collected liver biopsy and clinical data from youth enrolled in two pediatric clinical trials in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Thyroid assays were compared between youth with MASLD and population-based controls aged ≤18 years from the National Health and Nutrition Examination Survey (NHANES). Individuals with overt hypothyroidism, abnormal anti-thyroid antibody, or thyroid-related medications were excluded. SH was defined as TSH between 4.5–10.0 uIU/L. Multinomial logistic regression was used to test the association between TSH and MASLD histological changes at baseline, adjusting for age, sex, race/ethnicity, and body mass index. Mixed-effect models, including treatment and time, were used for the longitudinal analysis. Results: Mean TSH, total thyroxine (T4), total triiodothyronine (T3), and free T4 levels were higher (p<0.001) in the NASH CRN cohort (n=218; 421 observations) than in the NHANES cohort (n=2,198). TSH levels were positively associated with increased steatosis over time (p=0.03). SH was associated with borderline or definite metabolic-associated steatohepatitis on histology at baseline (p=0.03) and with changes in fibrosis over time (p=0.01). Conclusion: The association between TSH and steatosis severity in individuals with normal thyroid hormone concentrations suggests an independent role of TSH in MASLD.
{"title":"Prevalence of subclinical hypothyroidism and longitudinal thyroid stimulating hormone changes in youth with metabolic dysfunction-associated steatotic liver disease: an observational study","authors":"Matthew Untalan, Nancy Crimmins, Katherine P. Yates, Ali Mencin, Stavra Xanthakos, Vidhu V. Thaker","doi":"10.1097/hep.0000000000001095","DOIUrl":"https://doi.org/10.1097/hep.0000000000001095","url":null,"abstract":"Background: Studies on adults have shown an association between overt or subclinical hypothyroidism (SH) and metabolic dysfunction-associated steatotic liver disease (MASLD). The goal of this study was to assess the relationship between thyroid-stimulating hormone (TSH) levels and the histological characteristics of MASLD in youth. Methods: This observational study used prospectively collected liver biopsy and clinical data from youth enrolled in two pediatric clinical trials in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Thyroid assays were compared between youth with MASLD and population-based controls aged ≤18 years from the National Health and Nutrition Examination Survey (NHANES). Individuals with overt hypothyroidism, abnormal anti-thyroid antibody, or thyroid-related medications were excluded. SH was defined as TSH between 4.5–10.0 uIU/L. Multinomial logistic regression was used to test the association between TSH and MASLD histological changes at baseline, adjusting for age, sex, race/ethnicity, and body mass index. Mixed-effect models, including treatment and time, were used for the longitudinal analysis. Results: Mean TSH, total thyroxine (T4), total triiodothyronine (T3), and free T4 levels were higher (<jats:italic toggle=\"yes\">p</jats:italic><0.001) in the NASH CRN cohort (n=218; 421 observations) than in the NHANES cohort (n=2,198). TSH levels were positively associated with increased steatosis over time (<jats:italic toggle=\"yes\">p</jats:italic>=0.03). SH was associated with borderline or definite metabolic-associated steatohepatitis on histology at baseline (<jats:italic toggle=\"yes\">p</jats:italic>=0.03) and with changes in fibrosis over time (<jats:italic toggle=\"yes\">p</jats:italic>=0.01). Conclusion: The association between TSH and steatosis severity in individuals with normal thyroid hormone concentrations suggests an independent role of TSH in MASLD.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":null,"pages":null},"PeriodicalIF":13.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1097/hep.0000000000001098
Gavin Fredrickson, Kira Florczak, Fanta Barrow, Shamsed Mahmud, Katrina Dietsche, Haiguang Wang, Preethy Parthiban, Andrew Hakeem, Rawan Almutlaq, Oyedele Adeyi, Adam Herman, Alessandro Bartolomucci, Christopher Staley, Xiao Dong, Cyrus Jahansouz, Jesse W. Williams, Douglas G. Mashek, Sayeed Ikramuddin, Xavier S. Revelo
For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating metabolic dysfunction-associated steatohepatitis (MASH). While the effects of bariatric surgeries have been mainly attributed to nutrient restriction and malabsorption, whether immuno-modulatory mechanisms are involved remains unclear. Using murine models, we report that VSG ameliorates MASH progression in a weight loss-independent manner. Single-cell RNA sequencing revealed that hepatic lipid-associated macrophages (LAMs) expressing the triggering receptor expressed on myeloid cells 2 (TREM2) repress inflammation and increase their lysosomal activity in response to VSG. Remarkably, TREM2 deficiency in mice ablates the reparative effects of VSG, suggesting that TREM2 is required for MASH resolution. Mechanistically, TREM2 prevents the inflammatory activation of macrophages and is required for their efferocytic function. Overall, our findings indicate that bariatric surgery improves MASH through a reparative process driven by TREM2+ macrophages, providing insights into the mechanisms of disease reversal that may result in new therapies and improved surgical interventions.
{"title":"TREM2 macrophages mediate the beneficial effects of bariatric surgery against MASH","authors":"Gavin Fredrickson, Kira Florczak, Fanta Barrow, Shamsed Mahmud, Katrina Dietsche, Haiguang Wang, Preethy Parthiban, Andrew Hakeem, Rawan Almutlaq, Oyedele Adeyi, Adam Herman, Alessandro Bartolomucci, Christopher Staley, Xiao Dong, Cyrus Jahansouz, Jesse W. Williams, Douglas G. Mashek, Sayeed Ikramuddin, Xavier S. Revelo","doi":"10.1097/hep.0000000000001098","DOIUrl":"https://doi.org/10.1097/hep.0000000000001098","url":null,"abstract":"For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating metabolic dysfunction-associated steatohepatitis (MASH). While the effects of bariatric surgeries have been mainly attributed to nutrient restriction and malabsorption, whether immuno-modulatory mechanisms are involved remains unclear. Using murine models, we report that VSG ameliorates MASH progression in a weight loss-independent manner. Single-cell RNA sequencing revealed that hepatic lipid-associated macrophages (LAMs) expressing the triggering receptor expressed on myeloid cells 2 (TREM2) repress inflammation and increase their lysosomal activity in response to VSG. Remarkably, TREM2 deficiency in mice ablates the reparative effects of VSG, suggesting that TREM2 is required for MASH resolution. Mechanistically, TREM2 prevents the inflammatory activation of macrophages and is required for their efferocytic function. Overall, our findings indicate that bariatric surgery improves MASH through a reparative process driven by TREM2<jats:sup>+</jats:sup> macrophages, providing insights into the mechanisms of disease reversal that may result in new therapies and improved surgical interventions.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":null,"pages":null},"PeriodicalIF":13.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1097/hep.0000000000001094
Yanfei Yang, Xu Luo, Shimeng Cui, Zhikun Lin
{"title":"Letter to the Editor: Benchmarking clinical risk prediction algorithms with ensemble machine learning for the non-invasive diagnosis of liver fibrosis in NAFLD","authors":"Yanfei Yang, Xu Luo, Shimeng Cui, Zhikun Lin","doi":"10.1097/hep.0000000000001094","DOIUrl":"https://doi.org/10.1097/hep.0000000000001094","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":null,"pages":null},"PeriodicalIF":13.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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