Pub Date : 2024-10-28DOI: 10.1016/j.jhep.2024.10.028
Zhujun Cao, Yujing Yao, Minghao Cai, Chenxi Zhang, Yuhan Liu, Haiguang Xin, Baoyan An, Hui Wang, Yide Lu, Ziqiang Li, Yaoxing Chen, Yan Huang, Min Xin, Ruokun Li, Zhuping Qian, Yi Zhou, Xiaogang Xiang, Richard Moreau, Qing Xie
Background and aims
In patients with acutely decompensated cirrhosis (ADC) who present with clinically apparent precipitants (i.e., infections, acute liver injury), alterations in blood markers of inflammation associate with progression toward severe phenotypes (e.g., acute-on-chronic liver failure, ACLF). It is unclear whether alterations in blood inflammatory markers may associate with progression of ADC independently of precipitants.
Methods
We prospectively enrolled 394 patients admitted for ADC who were classified into four phenotypes of increasing severity: no organ dysfunction (n=168), organ dysfunction alone (n=72), organ failure without ACLF (n=91), and ACLF (n=63). Clinical blood cell counts and serum levels of inflammatory markers (including soluble markers related to type-1, type-2, and type-3 inflammation) were obtained at enrollment. Ordinal regression with adjacent categories logit model adjusted for confounders (including precipitants) was used to analyze associations between changes in each blood inflammatory marker and the worsening of ADC.
Results
Inflammatory markers that were associated with higher risk of progressing to the next more severe stage were as follows: increasing neutrophil counts (adjusted common odds ratio [cOR] 1.17, 95%CI 1.06-1.28); increasing levels of the type-2 cytokine interleukin (IL)-25 (cOR 1.21, 95%CI 1.06-1.39), type-3 cytokines IL-6 (cOR 1.15, 95%CI 1.02-1.28) and IL-22 (cOR 1.16, 95%CI 1.03-1.30), or anti-inflammatory soluble CD163 (cOR 1.94, 95%CI 1.58-2.38); decreasing lymphocyte counts (cOR 0.77, 95%CI 0.68-0.87), or decreasing levels of the type-1 cytokine IFN-γ (cOR 0.85, 95%CI 0.75-0.95).
Conclusions
Among patients with ADC, alterations in blood levels of cytokines related to type-1, type-2 and type-3 inflammation, together with neutrophilia, lymphopenia and elevated anti-inflammatory signals were individually associated with an increased risk of progressing toward ACLF, independently of the presence of clinically apparent precipitants.
{"title":"Blood markers for type-1,-2, and -3 inflammation are associated with severity of acutely decompensated cirrhosis","authors":"Zhujun Cao, Yujing Yao, Minghao Cai, Chenxi Zhang, Yuhan Liu, Haiguang Xin, Baoyan An, Hui Wang, Yide Lu, Ziqiang Li, Yaoxing Chen, Yan Huang, Min Xin, Ruokun Li, Zhuping Qian, Yi Zhou, Xiaogang Xiang, Richard Moreau, Qing Xie","doi":"10.1016/j.jhep.2024.10.028","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.10.028","url":null,"abstract":"<h3>Background and aims</h3>In patients with acutely decompensated cirrhosis (ADC) who present with clinically apparent precipitants (i.e., infections, acute liver injury), alterations in blood markers of inflammation associate with progression toward severe phenotypes (e.g., acute-on-chronic liver failure, ACLF). It is unclear whether alterations in blood inflammatory markers may associate with progression of ADC independently of precipitants.<h3>Methods</h3>We prospectively enrolled 394 patients admitted for ADC who were classified into four phenotypes of increasing severity: no organ dysfunction (n=168), organ dysfunction alone (n=72), organ failure without ACLF (n=91), and ACLF (n=63). Clinical blood cell counts and serum levels of inflammatory markers (including soluble markers related to type-1, type-2, and type-3 inflammation) were obtained at enrollment. Ordinal regression with adjacent categories logit model adjusted for confounders (including precipitants) was used to analyze associations between changes in each blood inflammatory marker and the worsening of ADC.<h3>Results</h3>Inflammatory markers that were associated with higher risk of progressing to the next more severe stage were as follows: increasing neutrophil counts (adjusted common odds ratio [cOR] 1.17, 95%CI 1.06-1.28); increasing levels of the type-2 cytokine interleukin (IL)-25 (cOR 1.21, 95%CI 1.06-1.39), type-3 cytokines IL-6 (cOR 1.15, 95%CI 1.02-1.28) and IL-22 (cOR 1.16, 95%CI 1.03-1.30), or anti-inflammatory soluble CD163 (cOR 1.94, 95%CI 1.58-2.38); decreasing lymphocyte counts (cOR 0.77, 95%CI 0.68-0.87), or decreasing levels of the type-1 cytokine IFN-γ (cOR 0.85, 95%CI 0.75-0.95).<h3>Conclusions</h3>Among patients with ADC, alterations in blood levels of cytokines related to type-1, type-2 and type-3 inflammation, together with neutrophilia, lymphopenia and elevated anti-inflammatory signals were individually associated with an increased risk of progressing toward ACLF, independently of the presence of clinically apparent precipitants.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536590","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 : 2024-10-26DOI: 10.1016/j.jhep.2024.10.032
Zgjim Osmani, Willem Pieter Brouwer, Dwin G.B. Grashof, Youkyung Lim, Michael Doukas, Harry L.A. Janssen, Harmen J.G. van de Werken, Andre Boonstra
<h3>Background & Aims</h3>Chronic HBV patients with concomitant metabolic dysfunction-associated steatohepatitis (MASH) have been shown to develop more advanced fibrosis faster with more severe liver disease as compared to patients with chronic HBV alone. However, our understanding of the underlying mechanisms is limited. Here we study how MASH co-morbidity impact immune activity in the liver of patients with chronic HBV infection.<h3>Methods</h3>Bulk RNA sequencing was performed on liver biopsies from patients with only MASH (n=10), only HBeAg-negative chronic HBV (ENEG; n=11), combined MASH/ENEG (n=9) and healthy controls (n=9). Biopsies with no or minimal fibrosis (≤F2) were selected to avoid confounding effects of fibrosis. We compared whole transcriptome data from patients with MASH/ENEG to those with ENEG alone to determine the impact of MASH co-morbidity on chronic hepatitis B.<h3>Results</h3>There is a high degree of overlap of liver gene expression profiles in patients with only ENEG versus those with only MASH compared to healthy controls, suggesting a largely shared mechanism of liver dysfunction and immune activity for these distinct conditions. In patients with ENEG, MASH co-morbidity significantly reduced interferon pathway activity (NES=2.03, p.adj=0.0251), the expression of ISGs (e.g., <em>IFIT2</em>, <em>IFI27</em>, <em>IFITM1</em>, <em>IFI6</em>), and macrophage gene signatures (e.g., <em>MARCO</em>, <em>CD163</em>, <em>CD5L</em>, <em>CD63</em>), when compared to patients with ENEG alone.<h3>Conclusions</h3>Transcriptomic profiling of the liver suggests that MASH negatively impacts ISGs expression in the liver of patients with ENEG, which may affect antiviral immune pathways, viral replication and inflammatory responses resulting in an increased risk of advanced fibrosis in patients with chronic hepatitis B. Our study provides valuable insights for guiding future research aimed at developing effective, tailored strategies for managing patients with both conditions.<h3>Impact and implications</h3>In recent decades, obesity and associated health issues have reached epidemic levels, with steatotic liver disease affecting up to 30% of adults in developed countries, and this trend is also observed among chronic hepatitis B patients. Given the high and rising prevalence of steatotic liver disease and its frequent co-occurrence in chronic hepatitis B patients, it is essential to understand how conditions such as metabolic dysfunction-associated steatohepatitis (MASH) impact immune responses in the liver. This study provides unique insights into the impact of MASH on HBV antiviral immune activity in the liver of patients with chronic hepatitis B. The rising number of patients with both conditions affects treatment outcomes and highlights the urgent need for novel, tailored therapeutic strategies. Our study holds significant relevance for guiding future research on developing treatment strategies for patients with both MASH and chron
{"title":"Metabolic dysfunction-associated steatohepatitis reduces interferon and macrophage liver gene signatures in patients with chronic hepatitis B","authors":"Zgjim Osmani, Willem Pieter Brouwer, Dwin G.B. Grashof, Youkyung Lim, Michael Doukas, Harry L.A. Janssen, Harmen J.G. van de Werken, Andre Boonstra","doi":"10.1016/j.jhep.2024.10.032","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.10.032","url":null,"abstract":"<h3>Background & Aims</h3>Chronic HBV patients with concomitant metabolic dysfunction-associated steatohepatitis (MASH) have been shown to develop more advanced fibrosis faster with more severe liver disease as compared to patients with chronic HBV alone. However, our understanding of the underlying mechanisms is limited. Here we study how MASH co-morbidity impact immune activity in the liver of patients with chronic HBV infection.<h3>Methods</h3>Bulk RNA sequencing was performed on liver biopsies from patients with only MASH (n=10), only HBeAg-negative chronic HBV (ENEG; n=11), combined MASH/ENEG (n=9) and healthy controls (n=9). Biopsies with no or minimal fibrosis (≤F2) were selected to avoid confounding effects of fibrosis. We compared whole transcriptome data from patients with MASH/ENEG to those with ENEG alone to determine the impact of MASH co-morbidity on chronic hepatitis B.<h3>Results</h3>There is a high degree of overlap of liver gene expression profiles in patients with only ENEG versus those with only MASH compared to healthy controls, suggesting a largely shared mechanism of liver dysfunction and immune activity for these distinct conditions. In patients with ENEG, MASH co-morbidity significantly reduced interferon pathway activity (NES=2.03, p.adj=0.0251), the expression of ISGs (e.g., <em>IFIT2</em>, <em>IFI27</em>, <em>IFITM1</em>, <em>IFI6</em>), and macrophage gene signatures (e.g., <em>MARCO</em>, <em>CD163</em>, <em>CD5L</em>, <em>CD63</em>), when compared to patients with ENEG alone.<h3>Conclusions</h3>Transcriptomic profiling of the liver suggests that MASH negatively impacts ISGs expression in the liver of patients with ENEG, which may affect antiviral immune pathways, viral replication and inflammatory responses resulting in an increased risk of advanced fibrosis in patients with chronic hepatitis B. Our study provides valuable insights for guiding future research aimed at developing effective, tailored strategies for managing patients with both conditions.<h3>Impact and implications</h3>In recent decades, obesity and associated health issues have reached epidemic levels, with steatotic liver disease affecting up to 30% of adults in developed countries, and this trend is also observed among chronic hepatitis B patients. Given the high and rising prevalence of steatotic liver disease and its frequent co-occurrence in chronic hepatitis B patients, it is essential to understand how conditions such as metabolic dysfunction-associated steatohepatitis (MASH) impact immune responses in the liver. This study provides unique insights into the impact of MASH on HBV antiviral immune activity in the liver of patients with chronic hepatitis B. The rising number of patients with both conditions affects treatment outcomes and highlights the urgent need for novel, tailored therapeutic strategies. Our study holds significant relevance for guiding future research on developing treatment strategies for patients with both MASH and chron","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519458","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 : 2024-10-24DOI: 10.1016/j.jhep.2024.10.029
Puru Rattan, Kianna Nguyen, Daniel D. Penrice, Davide Povero, Douglas A. Simonetto
Section snippets
Authors' contributions:
P.R., K.N.: Writing - Original Draft, Data curation, Formal Analysis; D.D.P, D.P.: Data curation, Formal Analysis, Writing - Review & Editing; D.A.S.: Conceptualization, Methodology, Formal Analysis, Writing – Review and Editing, Supervision.
Financial support:
NoneThe recently published multicenter study of Porto-Sinusoidal Vascular Disorder (PSVD) patients by Magaz and Giudicelli-Lett et al thoroughly details the clinical findings and disease progression of PSVD.1 Given the rarity of PSVD yet improved prognosis with early recognition, the authors stress the importance of clinical awareness of associated conditions to expedite diagnosis. To this point, is it important to note that PSVD has also been observed in the setting of telomere biology
Declaration of Competing Interest:
DAS is funded by National Institute of Health U01AA026886–03. DAS has consulted for Mallinckrodt, Evive, Resolution Therapeutics, BioVie, AstraZeneca, Iota and PharmaIN.
{"title":"Underrecognized Association of Porto-Sinusoidal Vascular Disorder and Telomere Biology Disorders","authors":"Puru Rattan, Kianna Nguyen, Daniel D. Penrice, Davide Povero, Douglas A. Simonetto","doi":"10.1016/j.jhep.2024.10.029","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.10.029","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors' contributions:</h2>P.R., K.N.: Writing - Original Draft, Data curation, Formal Analysis; D.D.P, D.P.: Data curation, Formal Analysis, Writing - Review & Editing; D.A.S.: Conceptualization, Methodology, Formal Analysis, Writing – Review and Editing, Supervision.</section></section><section><section><h2>Financial support:</h2>NoneThe recently published multicenter study of Porto-Sinusoidal Vascular Disorder (PSVD) patients by Magaz and Giudicelli-Lett <em>et al</em> thoroughly details the clinical findings and disease progression of PSVD.<sup>1</sup> Given the rarity of PSVD yet improved prognosis with early recognition, the authors stress the importance of clinical awareness of associated conditions to expedite diagnosis. To this point, is it important to note that PSVD has also been observed in the setting of telomere biology</section></section><section><section><h2>Declaration of Competing Interest:</h2>DAS is funded by National Institute of Health U01AA026886–03. DAS has consulted for Mallinckrodt, Evive, Resolution Therapeutics, BioVie, AstraZeneca, Iota and PharmaIN.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488811","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 : 2024-10-24DOI: 10.1016/j.jhep.2024.10.030
Wukun Ge, Weiqin Chen, Haiyan Xie
Section snippets
Authors' contributions:
WG, WC and HX conceived and designed the study. WG and WC collected and analyzed the data. HX provided clinical expertise and interpreted the results. WG drafted the manuscript. All authors critically revised the manuscript and approved the final version.
Data Availability Statement
This data can be accessed through the FDA's FAERS Public Dashboard athttps://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html.
Funding information
The study was supported by Quzhou City Science and Technology Research Project in 2023 (Grant No. 2023k193).
{"title":"Real-World Evidence Supporting the Consensus-Driven DILI Control Compounds List: An Analysis of FAERS Data","authors":"Wukun Ge, Weiqin Chen, Haiyan Xie","doi":"10.1016/j.jhep.2024.10.030","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.10.030","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors' contributions:</h2>WG, WC and HX conceived and designed the study. WG and WC collected and analyzed the data. HX provided clinical expertise and interpreted the results. WG drafted the manuscript. All authors critically revised the manuscript and approved the final version.</section></section><section><section><h2>Data Availability Statement</h2>This data can be accessed through the FDA's FAERS Public Dashboard at<span><span>https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>.</section></section><section><section><h2>Funding information</h2>The study was supported by Quzhou City Science and Technology Research Project in 2023 (Grant No. 2023k193).</section></section><section><section><h2>Declaration of Competing Interest</h2>The authors disclose no conflicts.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488868","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}
Karina Raikhelson wrote the original draft, Sergey Okovityi, Dzhamal Abdurakhmanov reviewed and edited this Correspondence; All the authors approved the final manuscript.
Financial support
The authors received no financial support to produce this manuscript.
Declaration of Competing Interest
The authors declare no conflict of interest pertaining to this article.
{"title":"New nomenclature for fatty liver disease: problems of localization in the regions and the position of Russian Scientific Liver Society","authors":"Karina Raikhelson, Sergey Okovityi, Dzhamal Abdurakhmanov","doi":"10.1016/j.jhep.2024.10.023","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.10.023","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors' contributions</h2>Karina Raikhelson wrote the original draft, Sergey Okovityi, Dzhamal Abdurakhmanov reviewed and edited this Correspondence; All the authors approved the final manuscript.</section></section><section><section><h2>Financial support</h2>The authors received no financial support to produce this manuscript.</section></section><section><section><h2>Declaration of Competing Interest</h2>The authors declare no conflict of interest pertaining to this article.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487634","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 : 2024-10-23DOI: 10.1016/j.jhep.2024.10.027
M. Dandri, L. Allweiss, B. Downie, J.J. Wallin
Section snippets
Author contributions
all authors contributed equally to the reply letter
Financial support
The study was supported by Gilead Sciences and the German Center for Infection Research (TTU Hepatitis 05.822; 05.820).
Declaration of Competing Interest
LA declares no conflict of interest. JJW and BD are employees of Gilead Sciences and holders of Gilead stock. MD: Research collaboration with Gilead Science.
{"title":"Reply to: Optimising the treatment of HDV infection: efficacy of Bulevirtide, HBV-HDV interactions and the importance of statistical methods","authors":"M. Dandri, L. Allweiss, B. Downie, J.J. Wallin","doi":"10.1016/j.jhep.2024.10.027","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.10.027","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Author contributions</h2>all authors contributed equally to the reply letter</section></section><section><section><h2>Financial support</h2>The study was supported by Gilead Sciences and the German Center for Infection Research (TTU Hepatitis 05.822; 05.820).</section></section><section><section><h2>Declaration of Competing Interest</h2>LA declares no conflict of interest. JJW and BD are employees of Gilead Sciences and holders of Gilead stock. MD: Research collaboration with Gilead Science.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487632","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 : 2024-10-23DOI: 10.1016/j.jhep.2024.10.025
Mitra K. Nadim, John A. Kellum, François Durand
Section snippets
Authors’ contribution
MKN, JAK and FD wrote the manuscript and revised it
Financial support
none
章节片段作者贡献MKN、JAK和FD撰写并修改了手稿财务支持无
{"title":"Reply to correspondence on “Acute kidney Injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting”","authors":"Mitra K. Nadim, John A. Kellum, François Durand","doi":"10.1016/j.jhep.2024.10.025","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.10.025","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors’ contribution</h2>MKN, JAK and FD wrote the manuscript and revised it</section></section><section><section><h2>Financial support</h2>none</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487173","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 : 2024-10-23DOI: 10.1016/j.jhep.2024.10.026
Zobair M. Younossi, Maria Stepanova
Section snippets
Abbreviations
Metabolic dysfunction-associated steatotic liver disease (MASLD), non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic steatohepatitis (NASH), metabolic dysfunction-associated steatohepatitis (MASH)”Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a very common liver disease in the general population with an especially high
Uncited reference
2.; 3.; 4.; 15..
Funding
No funding was received for this work.
Declaration of Competing Interest
ZMY has received research funding and/or serve as consultant to Intercept, CymaBay, Boehringer Ingelheim, BMS, GSK, NovoNordisk, Ipsen, AstraZeneca, Siemens, Madridgal, Merck and Abbott
{"title":"Stigma Among Chinese Speaking Patients with Non-alcoholic Fatty Liver Disease and Their Providers","authors":"Zobair M. Younossi, Maria Stepanova","doi":"10.1016/j.jhep.2024.10.026","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.10.026","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Abbreviations</h2>Metabolic dysfunction-associated steatotic liver disease (MASLD), non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic steatohepatitis (NASH), metabolic dysfunction-associated steatohepatitis (MASH)”<u>Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a very common liver disease in the general population with an especially high</u></section></section><section><section><h2>Uncited reference</h2>2.; 3.; 4.; 15..</section></section><section><section><h2>Funding</h2>No funding was received for this work.</section></section><section><section><h2>Declaration of Competing Interest</h2>ZMY has received research funding and/or serve as consultant to Intercept, CymaBay, Boehringer Ingelheim, BMS, GSK, NovoNordisk, Ipsen, AstraZeneca, Siemens, Madridgal, Merck and Abbott</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487631","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 : 2024-10-22DOI: 10.1016/j.jhep.2024.09.046
Sunjae Lee, Bethlehem Arefaine, Neelu Begum, Marilena Stamouli, Elizabeth Witherden, Merianne Mohamad, Azadeh Harzandi, Ane Zamalloa, Haizhuang Cai, Roger Williams, Mike Curtis, Lindsey A. Edwards, Shilpa Chokshi, Adil Mardinoglu, Gordon Proctor, David Moyes, Mark J. McPhail, Debbie L. Shawcross, Mathias Uhlen, Saeed Shoaie, Vishal C. Patel
<h3>Background & Aims</h3>Cirrhosis complications are often triggered by bacterial infections with multidrug-resistant organisms. Alterations in the gut and oral microbiome in decompensated cirrhosis (DC) influence clinical outcomes. We interrogated: (i) gut and oral microbiome community structures, (ii) virulence factors (VFs) and antimicrobial resistance genes (ARGs) and (iii) oral-gut microbial overlap in patients with differing cirrhosis severity.<h3>Methods</h3>15 healthy controls (HC), 26 stable cirrhosis (SC), 46 DC, 14 acute-on-chronic liver failure (ACLF) and 14 with severe infection without cirrhosis (NLS) participated. Metagenomic sequencing was undertaken on paired saliva (S) and faecal (F) samples. ‘Salivatypes’ and ‘enterotypes’ based on genera clustering were assessed against cirrhosis severity and clinical parameters. VFs and ARGs were evaluated in oral and gut niches, and distinct resistotypes identified.<h3>Results</h3>Salivatypes and enterotypes revealed a greater proportion of pathobionts with concomitant reduction in autochthonous genera with increasing cirrhosis severity and hyperammonaemia. Increasing overlap between oral and gut microbiome communities was observed in DC and ACLF vs SC and HCs, independent of antimicrobial, beta-blocker and acid suppressant therapies. Two distinct gut microbiome clusters [ENT2/ENT3] harboured genes encoding for the phosphoenolpyruvate:sugar phosphotransferase system (PTS) system and other VFs in DC and ACLF. Substantial ARGs (oral: 1,218 and gut: 672) were detected [575 common to both sites]. The cirrhosis resistome was distinct, with three oral and four gut resistotypes identified, respectively.<h3>Discussion</h3>The degree of oral-gut microbial community overlap, frequency of VFs and ARGs all increment significantly with cirrhosis severity, with progressive dominance of pathobionts and loss of commensals. Despite similar antimicrobial exposure, patients with DC and ACLF have reduced microbial richness compared to NLS, supporting the additive pathobiological effect of cirrhosis.<h3>Impact and implications</h3>This research underscores the crucial role of microbiome alterations in the progression of cirrhosis in an era of escalating multidrug resistant infections, highlighting the association and potential impact of increased oral-gut microbial overlap, virulence factors, and antimicrobial resistance genes on clinical outcomes. These findings are particularly significant for patients with decompensated cirrhosis and acute-on-chronic liver failure, as they reveal the intricate relationship between microbiome alterations and cirrhosis complications. This is relevant in the context of multidrug-resistant organisms and reduced oral-gut microbial diversity that exacerbate cirrhosis severity, drive hepatic decompensation and complicate treatment. For practical applications, these insights could guide for cirrhosis patients the development of targeted microbiome-based therapeutics and personal
{"title":"Oral-gut microbiome interactions in advanced cirrhosis: characterisation of pathogenic enterotypes and salivatypes, virulence factors and antimicrobial","authors":"Sunjae Lee, Bethlehem Arefaine, Neelu Begum, Marilena Stamouli, Elizabeth Witherden, Merianne Mohamad, Azadeh Harzandi, Ane Zamalloa, Haizhuang Cai, Roger Williams, Mike Curtis, Lindsey A. Edwards, Shilpa Chokshi, Adil Mardinoglu, Gordon Proctor, David Moyes, Mark J. McPhail, Debbie L. Shawcross, Mathias Uhlen, Saeed Shoaie, Vishal C. Patel","doi":"10.1016/j.jhep.2024.09.046","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.09.046","url":null,"abstract":"<h3>Background & Aims</h3>Cirrhosis complications are often triggered by bacterial infections with multidrug-resistant organisms. Alterations in the gut and oral microbiome in decompensated cirrhosis (DC) influence clinical outcomes. We interrogated: (i) gut and oral microbiome community structures, (ii) virulence factors (VFs) and antimicrobial resistance genes (ARGs) and (iii) oral-gut microbial overlap in patients with differing cirrhosis severity.<h3>Methods</h3>15 healthy controls (HC), 26 stable cirrhosis (SC), 46 DC, 14 acute-on-chronic liver failure (ACLF) and 14 with severe infection without cirrhosis (NLS) participated. Metagenomic sequencing was undertaken on paired saliva (S) and faecal (F) samples. ‘Salivatypes’ and ‘enterotypes’ based on genera clustering were assessed against cirrhosis severity and clinical parameters. VFs and ARGs were evaluated in oral and gut niches, and distinct resistotypes identified.<h3>Results</h3>Salivatypes and enterotypes revealed a greater proportion of pathobionts with concomitant reduction in autochthonous genera with increasing cirrhosis severity and hyperammonaemia. Increasing overlap between oral and gut microbiome communities was observed in DC and ACLF vs SC and HCs, independent of antimicrobial, beta-blocker and acid suppressant therapies. Two distinct gut microbiome clusters [ENT2/ENT3] harboured genes encoding for the phosphoenolpyruvate:sugar phosphotransferase system (PTS) system and other VFs in DC and ACLF. Substantial ARGs (oral: 1,218 and gut: 672) were detected [575 common to both sites]. The cirrhosis resistome was distinct, with three oral and four gut resistotypes identified, respectively.<h3>Discussion</h3>The degree of oral-gut microbial community overlap, frequency of VFs and ARGs all increment significantly with cirrhosis severity, with progressive dominance of pathobionts and loss of commensals. Despite similar antimicrobial exposure, patients with DC and ACLF have reduced microbial richness compared to NLS, supporting the additive pathobiological effect of cirrhosis.<h3>Impact and implications</h3>This research underscores the crucial role of microbiome alterations in the progression of cirrhosis in an era of escalating multidrug resistant infections, highlighting the association and potential impact of increased oral-gut microbial overlap, virulence factors, and antimicrobial resistance genes on clinical outcomes. These findings are particularly significant for patients with decompensated cirrhosis and acute-on-chronic liver failure, as they reveal the intricate relationship between microbiome alterations and cirrhosis complications. This is relevant in the context of multidrug-resistant organisms and reduced oral-gut microbial diversity that exacerbate cirrhosis severity, drive hepatic decompensation and complicate treatment. For practical applications, these insights could guide for cirrhosis patients the development of targeted microbiome-based therapeutics and personal","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487079","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 : 2024-10-22DOI: 10.1016/j.jhep.2024.10.019
Edo J. Dongelmans, Milan J. Sonneveld, Harry L.A. Janssen
Section snippets
Clinical trial number:
not applicable.
Conflict of interest:
Edo Dongelmans has no conflicts of interests; Milan Sonneveld receives speakers’ fees and research support from Roche, Bristol Myers Squibb, Gilead Sciences, and Fujirebio. Harry Janssen received grants from: Gilead Sciences, GlaxoSmithKline, Janssen, Roche, Vir Biotechnology Inc. and is consultant for: Aligos, Gilead Sciences, GlaxoSmithKline, Janssen, Roche, Vir Biotechnology Inc., Precision Biosciences, Griffols.
Financial support:
No funding was received for this article.
Author contributions:
Edo Dongelmans, MD (Conceptualization: Equal; Writing – original draft: Lead). Milan Sonneveld, MD, PhD (Conceptualization: Equal; Writing – review & editing: Equal). Harry L.A. Janssen, MD, PhD (Conceptualization: Equal; Supervision: Lead; Writing – review & editing: Equal).
Data availability statement:
not applicable.Nucleo(s)tide analogues (NA) are well-tolerated and highly effective in suppressing HBV DNA in patients with chronic hepatitis B (CHB). Unfortunately, the risk of HCC may persist, particularly in patients who do not achieve functional cure, defined as loss of HBsAg loss. As functional cure is rarely achieved with NA mono-therapy,1 alternative strategies are explored to increase HBsAg clearance.Recent trials with novel compounds suggest that immune modulatory agents likely play a
{"title":"Increasing functional cure rates after nucleo(s)tide analogue withdrawal: is peg-IFN the answer?","authors":"Edo J. Dongelmans, Milan J. Sonneveld, Harry L.A. Janssen","doi":"10.1016/j.jhep.2024.10.019","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.10.019","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Clinical trial number:</h2>not applicable.</section></section><section><section><h2>Conflict of interest:</h2>Edo Dongelmans has no conflicts of interests; Milan Sonneveld receives speakers’ fees and research support from Roche, Bristol Myers Squibb, Gilead Sciences, and Fujirebio. Harry Janssen received grants from: Gilead Sciences, GlaxoSmithKline, Janssen, Roche, Vir Biotechnology Inc. and is consultant for: Aligos, Gilead Sciences, GlaxoSmithKline, Janssen, Roche, Vir Biotechnology Inc., Precision Biosciences, Griffols.</section></section><section><section><h2>Financial support:</h2>No funding was received for this article.</section></section><section><section><h2>Author contributions:</h2>Edo Dongelmans, MD (Conceptualization: Equal; Writing – original draft: Lead). Milan Sonneveld, MD, PhD (Conceptualization: Equal; Writing – review & editing: Equal). Harry L.A. Janssen, MD, PhD (Conceptualization: Equal; Supervision: Lead; Writing – review & editing: Equal).</section></section><section><section><h2>Data availability statement:</h2>not applicable.Nucleo(s)tide analogues (NA) are well-tolerated and highly effective in suppressing HBV DNA in patients with chronic hepatitis B (CHB). Unfortunately, the risk of HCC may persist, particularly in patients who do not achieve functional cure, defined as loss of HBsAg loss. As functional cure is rarely achieved with NA mono-therapy,<sup>1</sup> alternative strategies are explored to increase HBsAg clearance.Recent trials with novel compounds suggest that immune modulatory agents likely play a</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":25.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452534","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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