Pub Date : 2025-01-16DOI: 10.1097/hep.0000000000001169
Binbin Li
{"title":"BileMet: A new frontier in distinguishing malignant from benign biliary conditions","authors":"Binbin Li","doi":"10.1097/hep.0000000000001169","DOIUrl":"https://doi.org/10.1097/hep.0000000000001169","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"54 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987605","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 : 2025-01-16DOI: 10.1097/hep.0000000000001168
Kevin Harris
{"title":"An unmet need in MetALD","authors":"Kevin Harris","doi":"10.1097/hep.0000000000001168","DOIUrl":"https://doi.org/10.1097/hep.0000000000001168","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"30 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986371","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 : 2025-01-16DOI: 10.1097/hep.0000000000001170
John Grady, Juan Pablo Arab
{"title":"Hide and Seek: Detecting HCC with novel surveillance algorithms","authors":"John Grady, Juan Pablo Arab","doi":"10.1097/hep.0000000000001170","DOIUrl":"https://doi.org/10.1097/hep.0000000000001170","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"7 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987585","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 : 2025-01-14DOI: 10.1097/hep.0000000000001232
Déborah Rousseau, Stéphanie Bonnafous, Frédéric Soysouvanh, Dorian Sarrail, Manon Bourinet, Axelle Strazzulla, Stéphanie Patouraux, Arnaud Borderie, Bastien Dolfi, Alexandre Gallerand, Marwin A Farrugia, Véronique Orian-rousseau, Yingzheng Xu, Jesse W. Williams, Stoyan Ivanov, Albert Tran, Rodolphe Anty, Carmelo Luci, Philippe Gual
Background and Aims: Alcohol-related liver disease (ALD) is one of the leading causes of severe liver disease with limited pharmacological treatments for alcohol-related steatohepatitis (ASH). CD44, a glycoprotein mainly expressed in immune cells, has been implicated in multiple inflammatory diseases but has never been studied in the ALD context. We therefore studied its contribution to ASH development in mice and its expression in ALD patients Approach and Results: Here, we report that liver CD44 expression is associated with liver injury and inflammation and its deficiency (Cd44-/-) partially protected mice upon chronic plus binge ethanol feeding (CPB-EtOH). CD44 deletion in myeloid cells (Cd44 myel-KO ) recapitulated the same protective effects associated with reduced inflammatory monocyte infiltration and neutrophil activation in the liver and diminished blood neutrophil-lymphocyte ratio (NLR). CD44-deficient neutrophils displayed reduced PMA-induced inflammatory mediator expression and increased phagocytosis of live bacteria. Cd44 myel-KO mice were also protected against hepatic steatosis mediated by CPB-EtOH or chronic ethanol feeding, due in part to increased SIRT1 mediated fatty acid beta-oxidation. CD44 neutralization with antibodies strongly decreased liver injury and inflammation (hepatic neutrophil frequency) and blood NLR upon CPB-EtOH. In samples from ALD patients, hepatic CD44 expression increased with ALD severity, correlated with hepatic TNFα and CD11b expression, and CD44-expressing neutrophils were enriched in alcohol-associated hepatitis. Conclusions: Human and experimental evidence supports CD44 as a marker of hepatic inflammation in ALD. In addition, CD44 modulates neutrophil mobilization and functions and its targeting partially prevents liver inflammation and injury in the context of acute-on-chronic alcohol drinking.
{"title":"CD44 in myEloid cells is a major driver of liver inflammation and injury in alcohol-related liver disease","authors":"Déborah Rousseau, Stéphanie Bonnafous, Frédéric Soysouvanh, Dorian Sarrail, Manon Bourinet, Axelle Strazzulla, Stéphanie Patouraux, Arnaud Borderie, Bastien Dolfi, Alexandre Gallerand, Marwin A Farrugia, Véronique Orian-rousseau, Yingzheng Xu, Jesse W. Williams, Stoyan Ivanov, Albert Tran, Rodolphe Anty, Carmelo Luci, Philippe Gual","doi":"10.1097/hep.0000000000001232","DOIUrl":"https://doi.org/10.1097/hep.0000000000001232","url":null,"abstract":"Background and Aims: Alcohol-related liver disease (ALD) is one of the leading causes of severe liver disease with limited pharmacological treatments for alcohol-related steatohepatitis (ASH). CD44, a glycoprotein mainly expressed in immune cells, has been implicated in multiple inflammatory diseases but has never been studied in the ALD context. We therefore studied its contribution to ASH development in mice and its expression in ALD patients Approach and Results: Here, we report that liver CD44 expression is associated with liver injury and inflammation and its deficiency (<jats:italic toggle=\"yes\">Cd44</jats:italic> <jats:sup>-/-</jats:sup>) partially protected mice upon chronic plus binge ethanol feeding (CPB-EtOH). CD44 deletion in myeloid cells (<jats:italic toggle=\"yes\">Cd44</jats:italic> <jats:sup> myel-KO </jats:sup>) recapitulated the same protective effects associated with reduced inflammatory monocyte infiltration and neutrophil activation in the liver and diminished blood neutrophil-lymphocyte ratio (NLR). CD44-deficient neutrophils displayed reduced PMA-induced inflammatory mediator expression and increased phagocytosis of live bacteria. <jats:italic toggle=\"yes\">Cd44</jats:italic> <jats:sup> myel-KO </jats:sup> mice were also protected against hepatic steatosis mediated by CPB-EtOH or chronic ethanol feeding, due in part to increased SIRT1 mediated fatty acid beta-oxidation. CD44 neutralization with antibodies strongly decreased liver injury and inflammation (hepatic neutrophil frequency) and blood NLR upon CPB-EtOH. In samples from ALD patients, hepatic CD44 expression increased with ALD severity, correlated with hepatic TNFα and CD11b expression, and CD44-expressing neutrophils were enriched in alcohol-associated hepatitis. Conclusions: Human and experimental evidence supports CD44 as a marker of hepatic inflammation in ALD. In addition, CD44 modulates neutrophil mobilization and functions and its targeting partially prevents liver inflammation and injury in the context of acute-on-chronic alcohol drinking.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"9 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981470","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 : 2025-01-14DOI: 10.1097/hep.0000000000001231
Edison Xu, Parissa Tabrizian, Julio Gutierrez, Maarouf Hoteit, Tara Ghaziani, Kali Zhou, Neehar Parikh, Veeral Ajmera, Elizabeth Aby, Amy Shui, Rebecca Marino, Allison Martin, Christopher Wong, Karissa Kao, Shravan Dave, Sander Florman, Francis Yao, Neil Mehta
Background & Aims: Patients with hepatocellular carcinoma (HCC) meeting UNOS-downstaging (DS) criteria have excellent post-liver transplantation (LT) outcomes. Studies on HCC beyond UNOS-DS criteria (“All-comers” (AC)) have been limited by small sample size and short follow-up time, prompting this analysis. Approach & Results: 326 patients meeting UNOS-DS and 190 meeting AC criteria from 9 LT centers across 5 UNOS regions were enrolled from 2015 to 2023 and prospectively followed. Competing risk analysis and Kaplan-Meier method were used to evaluate downstaging and LT outcomes, and Fine-and-Gray and Cox models were used to identify predictors of outcomes. AC and UNOS-DS had similar median alpha-fetoprotein (15 vs. 12 ng/mL;p=0.08), MELD (9 vs. 9;p=0.52), and Child-Pugh (A vs. A;p=0.30). At 2 years from first local regional therapy, 82% of UNOS-DS and 66% of AC were successfully downstaged (p<0.001). In AC, DS rates were 72% for tumor number plus diameter of largest lesion<10, 51% for sum 10-12, and 39% for sum>12 (p=0.01). Y-90 achieved higher DS success than transarterial chemoembolization (TACE) in AC (74% vs. 65%;p<0.001). 48% of UNOS-DS and 40% of AC underwent LT (p=0.10). 5-year post-LT survival was similar between UNOS-DS and AC (74% vs. 72%;p=0.77), although 5-year post-LT recurrence was higher in AC (30% vs. 14%;p=0.02). Conclusions: Despite higher HCC recurrence and lower ITT survival in AC, post-LT survival was comparable between UNOS-DS and AC. Y-90 attained higher DS success than TACE in AC. LT after downstaging is feasible in AC, though defining an upper limit in tumor burden may be necessary.
{"title":"Downstaging of hepatocellular carcinoma before liver transplantation: Results from a national multi-center prospective cohort study","authors":"Edison Xu, Parissa Tabrizian, Julio Gutierrez, Maarouf Hoteit, Tara Ghaziani, Kali Zhou, Neehar Parikh, Veeral Ajmera, Elizabeth Aby, Amy Shui, Rebecca Marino, Allison Martin, Christopher Wong, Karissa Kao, Shravan Dave, Sander Florman, Francis Yao, Neil Mehta","doi":"10.1097/hep.0000000000001231","DOIUrl":"https://doi.org/10.1097/hep.0000000000001231","url":null,"abstract":"Background & Aims: Patients with hepatocellular carcinoma (HCC) meeting UNOS-downstaging (DS) criteria have excellent post-liver transplantation (LT) outcomes. Studies on HCC beyond UNOS-DS criteria (“All-comers” (AC)) have been limited by small sample size and short follow-up time, prompting this analysis. Approach & Results: 326 patients meeting UNOS-DS and 190 meeting AC criteria from 9 LT centers across 5 UNOS regions were enrolled from 2015 to 2023 and prospectively followed. Competing risk analysis and Kaplan-Meier method were used to evaluate downstaging and LT outcomes, and Fine-and-Gray and Cox models were used to identify predictors of outcomes. AC and UNOS-DS had similar median alpha-fetoprotein (15 vs. 12 ng/mL;<jats:italic toggle=\"yes\">p</jats:italic>=0.08), MELD (9 vs. 9;<jats:italic toggle=\"yes\">p</jats:italic>=0.52), and Child-Pugh (A vs. A;<jats:italic toggle=\"yes\">p</jats:italic>=0.30). At 2 years from first local regional therapy, 82% of UNOS-DS and 66% of AC were successfully downstaged (<jats:italic toggle=\"yes\">p</jats:italic><0.001). In AC, DS rates were 72% for tumor number plus diameter of largest lesion<10, 51% for sum 10-12, and 39% for sum>12 (<jats:italic toggle=\"yes\">p</jats:italic>=0.01). Y-90 achieved higher DS success than transarterial chemoembolization (TACE) in AC (74% vs. 65%;<jats:italic toggle=\"yes\">p</jats:italic><0.001). 48% of UNOS-DS and 40% of AC underwent LT (<jats:italic toggle=\"yes\">p</jats:italic>=0.10). 5-year post-LT survival was similar between UNOS-DS and AC (74% vs. 72%;<jats:italic toggle=\"yes\">p</jats:italic>=0.77), although 5-year post-LT recurrence was higher in AC (30% vs. 14%;<jats:italic toggle=\"yes\">p</jats:italic>=0.02). Conclusions: Despite higher HCC recurrence and lower ITT survival in AC, post-LT survival was comparable between UNOS-DS and AC. Y-90 attained higher DS success than TACE in AC. LT after downstaging is feasible in AC, though defining an upper limit in tumor burden may be necessary.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"118 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981469","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 : 2025-01-14DOI: 10.1097/hep.0000000000001227
Hiroyuki Suzuki, Naoto Fujiwara, Amit G. Singal, Thomas F. Baumert, Raymond T. Chung, Takumi Kawaguchi, Yujin Hoshida
Preventive interventions are expected to substantially improve the prognosis of patients with primary liver cancer, predominantly hepatocellular carcinoma (HCC) and cholangiocarcinoma. HCC prevention is challenging in the face of the evolving etiological landscape, particularly the sharp increase in obesity-associated metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). Next-generation anti-HCV and HBV drugs have substantially reduced, but not eliminated, the risk of HCC and have given way to new challenges in identifying at-risk patients. The recent development of new therapeutic agents and modalities has opened unprecedented opportunities to refine primary, secondary, and tertiary HCC prevention strategies. For primary prevention (before exposure to risk factors), public health policies, such as universal HBV vaccination, have had a substantial prognostic impact. Secondary prevention (after or during active exposure to risk factors) includes regular HCC screening and chemoprevention. Emerging biomarkers and imaging modalities for HCC risk stratification and detection may enable individual risk-based personalized and cost-effective HCC screening. Clinical studies have suggested the potential utility of lipid-lowering, anti-diabetic/obesity, and anti-inflammatory agents for secondary prevention, and some of them are being evaluated in prospective clinical trials. Computational and experimental studies have identified potential chemopreventive strategies directed at diverse molecular, cellular, and systemic targets for etiology-specific and/or agnostic interventions. Tertiary prevention (in conjunction with curative-intent therapies for HCC) is an area of active research with the development of new immune-based neo/adjuvant therapies. Cholangiocarcinoma prevention may advance with recent efforts to elucidate risk factors. These advances will collectively lead to substantial improvements in liver cancer mortality rates.
{"title":"Prevention of liver cancer in the era of next-generation antivirals and obesity epidemic","authors":"Hiroyuki Suzuki, Naoto Fujiwara, Amit G. Singal, Thomas F. Baumert, Raymond T. Chung, Takumi Kawaguchi, Yujin Hoshida","doi":"10.1097/hep.0000000000001227","DOIUrl":"https://doi.org/10.1097/hep.0000000000001227","url":null,"abstract":"Preventive interventions are expected to substantially improve the prognosis of patients with primary liver cancer, predominantly hepatocellular carcinoma (HCC) and cholangiocarcinoma. HCC prevention is challenging in the face of the evolving etiological landscape, particularly the sharp increase in obesity-associated metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). Next-generation anti-HCV and HBV drugs have substantially reduced, but not eliminated, the risk of HCC and have given way to new challenges in identifying at-risk patients. The recent development of new therapeutic agents and modalities has opened unprecedented opportunities to refine primary, secondary, and tertiary HCC prevention strategies. For primary prevention (before exposure to risk factors), public health policies, such as universal HBV vaccination, have had a substantial prognostic impact. Secondary prevention (after or during active exposure to risk factors) includes regular HCC screening and chemoprevention. Emerging biomarkers and imaging modalities for HCC risk stratification and detection may enable individual risk-based personalized and cost-effective HCC screening. Clinical studies have suggested the potential utility of lipid-lowering, anti-diabetic/obesity, and anti-inflammatory agents for secondary prevention, and some of them are being evaluated in prospective clinical trials. Computational and experimental studies have identified potential chemopreventive strategies directed at diverse molecular, cellular, and systemic targets for etiology-specific and/or agnostic interventions. Tertiary prevention (in conjunction with curative-intent therapies for HCC) is an area of active research with the development of new immune-based neo/adjuvant therapies. Cholangiocarcinoma prevention may advance with recent efforts to elucidate risk factors. These advances will collectively lead to substantial improvements in liver cancer mortality rates.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"7 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981467","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}