Pub Date : 2024-11-16DOI: 10.1016/j.jhep.2024.11.013
Femke H.C. de Goeij, Chase J. Wehrle, Fariba Abassi, Sangeeta Satish, Mingyi Zhang, Rebecca Panconesi, Koji Hashimoto, Charles M. Miller, Wojciech G. Polak, Pierre-Alain Clavien, Jeroen de Jonge, Andrea Schlegel
Liver transplantation is associated with a high risk of postoperative complications due to the complexity of the surgical procedure, recipient disease severity and wide range of graft quality which remains somewhat unpredictable. However, survival rates after transplantation continue to improve and the focus has thus turned to other clinically relevant endpoints including posttransplant complications, patient quality of life and costs. Procedures like liver transplantation offer the entire spectrum of postsurgical events, even in donor-recipient constellations deemed of low risk within recently defined benchmark criteria. The Clavien-Dindo classification and the Comprehensive Complication Index (CCI®) were established to assess postoperative morbidity and are widely utilized across surgical specialties. However, these scores unfortunately are associted with observer variability when used in practice, mainly due to the lack of uniform definitions. Interventions required to treat a specific complication are the main drivers of clinically relevant complications, which may result in under- or over-scoring of posttransplant events.The number and grade of complications is frequently used as a metric assessing specific donor-recipient-risk-profiles and in assessing new approaches such as machine perfusion. Thus, accurate stratification is critical to comparing various potential risk factors. The concept of Benchmarking was recently introduced in surgery and transplantation as a mechanism of standardizing expected donor/recipient risk with outcomes within the first year after surgery. The management of complications, however, differs significantly worldwide, as does the rating scale assigned to various complications. This may lead to inhomogeneous interpretation of study results, leading to difficulty in assessing the clinical effects of novel preservation technologies and other therapeutics in liver transplantation. It also limits generalizability of study findings between countries, centers, and even providers.This article critically discusses frequent challenges associated with risk and outcome assessment following major surgery with a particular focus in liver transplantation.
{"title":"Mastering the Narrative: Precision Reporting of Risk and Outcomes in Liver Transplantation","authors":"Femke H.C. de Goeij, Chase J. Wehrle, Fariba Abassi, Sangeeta Satish, Mingyi Zhang, Rebecca Panconesi, Koji Hashimoto, Charles M. Miller, Wojciech G. Polak, Pierre-Alain Clavien, Jeroen de Jonge, Andrea Schlegel","doi":"10.1016/j.jhep.2024.11.013","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.11.013","url":null,"abstract":"Liver transplantation is associated with a high risk of postoperative complications due to the complexity of the surgical procedure, recipient disease severity and wide range of graft quality which remains somewhat unpredictable. However, survival rates after transplantation continue to improve and the focus has thus turned to other clinically relevant endpoints including posttransplant complications, patient quality of life and costs. Procedures like liver transplantation offer the entire spectrum of postsurgical events, even in donor-recipient constellations deemed of low risk within recently defined benchmark criteria. The Clavien-Dindo classification and the Comprehensive Complication Index (CCI®) were established to assess postoperative morbidity and are widely utilized across surgical specialties. However, these scores unfortunately are associted with observer variability when used in practice, mainly due to the lack of uniform definitions. Interventions required to treat a specific complication are the main drivers of clinically relevant complications, which may result in under- or over-scoring of posttransplant events.The number and grade of complications is frequently used as a metric assessing specific donor-recipient-risk-profiles and in assessing new approaches such as machine perfusion. Thus, accurate stratification is critical to comparing various potential risk factors. The concept of Benchmarking was recently introduced in surgery and transplantation as a mechanism of standardizing expected donor/recipient risk with outcomes within the first year after surgery. The management of complications, however, differs significantly worldwide, as does the rating scale assigned to various complications. This may lead to inhomogeneous interpretation of study results, leading to difficulty in assessing the clinical effects of novel preservation technologies and other therapeutics in liver transplantation. It also limits generalizability of study findings between countries, centers, and even providers.This article critically discusses frequent challenges associated with risk and outcome assessment following major surgery with a particular focus in liver transplantation.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"12 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642706","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 : 2024-11-15DOI: 10.1016/j.jhep.2024.11.015
Peng Luo, Anqi Lin, Kai Miao
{"title":"Balancing strengths and limitations of ctDNA in advanced biliary tract cancer genomic profiling.","authors":"Peng Luo, Anqi Lin, Kai Miao","doi":"10.1016/j.jhep.2024.11.015","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.11.015","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":26.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647945","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 : 2024-11-15DOI: 10.1016/j.jhep.2024.09.021
Paolo Angeli
{"title":"My last Editorial as Editor-in-Chief of the Journal of Hepatology","authors":"Paolo Angeli","doi":"10.1016/j.jhep.2024.09.021","DOIUrl":"10.1016/j.jhep.2024.09.021","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"81 6","pages":"Pages 918-920"},"PeriodicalIF":26.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637635","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 : 2024-11-15DOI: 10.1016/j.jhep.2024.09.001
Tongxin Wang , Kai Chen , Weilei Yao , Ruilong Zheng , Qiongyu He , Jun Xia , Juan Li , Yafei Shao , Li Zhang , Lu Huang , Longshan Qin , Mingming Xu , Zheng Zhang , Dingyu Pan , Zhen Li , Feiruo Huang
{"title":"Retraction notice to “Acetylation of lactate dehydrogenase B drives NAFLD progression by impairing lactate clearance” [J Hepatol 74 (5) 2021 1038–1052]","authors":"Tongxin Wang , Kai Chen , Weilei Yao , Ruilong Zheng , Qiongyu He , Jun Xia , Juan Li , Yafei Shao , Li Zhang , Lu Huang , Longshan Qin , Mingming Xu , Zheng Zhang , Dingyu Pan , Zhen Li , Feiruo Huang","doi":"10.1016/j.jhep.2024.09.001","DOIUrl":"10.1016/j.jhep.2024.09.001","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"81 6","pages":"Page 1100"},"PeriodicalIF":26.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637671","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 : 2024-11-15DOI: 10.1016/S0168-8278(24)02588-1
{"title":"JHEP at a Glance December 2024","authors":"","doi":"10.1016/S0168-8278(24)02588-1","DOIUrl":"10.1016/S0168-8278(24)02588-1","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"81 6","pages":"Pages e251-e260"},"PeriodicalIF":26.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637633","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 : 2024-11-15DOI: 10.1016/j.jhep.2024.11.016
Avik Majumdar, Manuel Luis Rodríguez-Perálvarez, Emmanuel Tsochatzis
Section snippets
Authors Contributions
AM drafted the letter. All authors (AM, MRP and ET) contributed equally to the study concept, reviewed and approved the final version of letter.
Financial Support
NilGEMA-Na: a crucial step in solving to the MELD-Creatinine dilemmaWe read with great interest the study by Dr Rosenstengle and colleagues examining MELD subtypes and the effect on intention-to-treat survival using the Scientific Registry of Transplant Recipients1. In their comprehensive analysis, the authors clearly demonstrate that the creatinine subtype of MELD (MELD-Cr) conferred inferior survival at one-year compared to bilirubin or INR subtypes. Furthermore, females had poorer survival
{"title":"GEMA-Na: a crucial step in solving the MELD-Creatinine dilemma","authors":"Avik Majumdar, Manuel Luis Rodríguez-Perálvarez, Emmanuel Tsochatzis","doi":"10.1016/j.jhep.2024.11.016","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.11.016","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors Contributions</h2>AM drafted the letter. All authors (AM, MRP and ET) contributed equally to the study concept, reviewed and approved the final version of letter.</section></section><section><section><h2>Financial Support</h2>NilGEMA-Na: a crucial step in solving to the MELD-Creatinine dilemmaWe read with great interest the study by Dr Rosenstengle and colleagues examining MELD subtypes and the effect on intention-to-treat survival using the Scientific Registry of Transplant Recipients<sup>1</sup>. In their comprehensive analysis, the authors clearly demonstrate that the creatinine subtype of MELD (MELD-Cr) conferred inferior survival at one-year compared to bilirubin or INR subtypes. Furthermore, females had poorer survival</section></section><section><section><h2>Declaration of Competing Interest</h2>No relevant conflicts of interest</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"78 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637626","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 : 2024-11-15DOI: 10.1016/j.jhep.2024.10.048
Yang Wang, Sen Hong, Hannah Hudson, Nora Kory, Lisa N. Kinch, Julia Kozlitina, Jonathan C. Cohen, Helen H. Hobbs
Background & Aims
PNPLA3(148M) (patatin-like phospholipase domain-containing protein 3) is the most impactful genetic risk factor for steatotic liver disease (SLD). A key unresolved issue is whether PNPLA3(148M) confers a loss- or gain-of-function. Here we test the hypothesis that PNPLA3 causes steatosis by sequestering ABHD5 (α/β hydrolase domain containing protein 5), the cofactor of ATGL (adipose TG lipase), thus limiting mobilization of hepatic triglyceride (TG).
Methods
We quantified and compared the physical interactions between ABHD5 and PNPLA3/ATGL in cultured hepatocytes using NanoBiT complementation assays and immunocytochemistry. Recombinant proteins purified from human cells were used to compare TG hydrolytic activities of PNPLA3 and ATGL in the presence or absence of ABHD5. Adenoviruses and adeno-associated viruses were used to express PNPLA3 in liver-specific Atgl-/- mice and to express ABHD5 in livers of Pnpla3M/M mice, respectively.
Results
ABHD5 interacted preferentially with PNPLA3 relative to ATGL in cultured hepatocytes. No differences were seen in the strength of the interactions between ABHD5 with PNPLA3(WT) and PNPLA3(148M). In contrast to prior findings, we found that PNPLA3, like ATGL, is activated by ABHD5 in in vitro assays using purified proteins. PNPLA3(148M)-associated inhibition of TG hydrolysis required that ATGL be expressed and that PNPLA3 be located on LDs. Finally, overexpression of ABHD5 reversed the hepatic steatosis in Pnpla3M/M mice.
Conclusions
These findings support the premise that PNPLA3(148M) is a gain-of-function mutation that promotes hepatic steatosis by accumulating on LDs and inhibiting ATGL-mediated lipolysis in an ABHD5-dependent manner. Our results predict that reducing, rather that increasing, PNPLA3 expression will be the best strategy to treat PNPLA3(148M)-associated SLD.
Impact and implications
Steatotic liver disease (SLD) is a common complex disorder associated with both environmental and genetic risk factors. PNPLA3(148M) is the most impactful genetic risk factor for SLD and yet its pathogenic mechanism remains controversial. Here we provide evidence that PNPLA3(148M) promotes triglyceride (TG) accumulation by sequestering ABHD5, thus limiting its availability to activate ATGL. Although the substitution of methionine for isoleucine reduces the TG hydrolase activity of PNPLA3, the loss of enzymatic function is not directly related to the steatotic effect of the variant. It is the resulting accumulation of PNPLA3 on LDs that confers a gain-of-function by interfering with ATGL-mediated TG hydrolysis. These findings have implications for the design of potential PNPLA3(148M)-based therapies. Reducing, rather than increasing, PNPLA3 levels is predicted to reverse steatosis in susceptible individuals.
{"title":"PNPLA3(148M) is a gain-of-function mutation that promotes hepatic steatosis by inhibiting ATGL-mediated triglyceride hydrolysis","authors":"Yang Wang, Sen Hong, Hannah Hudson, Nora Kory, Lisa N. Kinch, Julia Kozlitina, Jonathan C. Cohen, Helen H. Hobbs","doi":"10.1016/j.jhep.2024.10.048","DOIUrl":"https://doi.org/10.1016/j.jhep.2024.10.048","url":null,"abstract":"<h3>Background & Aims</h3>PNPLA3(148M) (patatin-like phospholipase domain-containing protein 3) is the most impactful genetic risk factor for steatotic liver disease (SLD). A key unresolved issue is whether PNPLA3(148M) confers a loss- or gain-of-function. Here we test the hypothesis that PNPLA3 causes steatosis by sequestering ABHD5 (α/β hydrolase domain containing protein 5), the cofactor of ATGL (adipose TG lipase), thus limiting mobilization of hepatic triglyceride (TG).<h3>Methods</h3>We quantified and compared the physical interactions between ABHD5 and PNPLA3/ATGL in cultured hepatocytes using NanoBiT complementation assays and immunocytochemistry. Recombinant proteins purified from human cells were used to compare TG hydrolytic activities of PNPLA3 and ATGL in the presence or absence of ABHD5. Adenoviruses and adeno-associated viruses were used to express PNPLA3 in liver-specific <em>Atgl</em><sup><em>-/-</em></sup> mice and to express ABHD5 in livers of <em>Pnpla3</em><sup><em>M/M</em></sup> mice, respectively.<h3>Results</h3>ABHD5 interacted preferentially with PNPLA3 relative to ATGL in cultured hepatocytes. No differences were seen in the strength of the interactions between ABHD5 with PNPLA3(WT) and PNPLA3(148M). In contrast to prior findings, we found that PNPLA3, like ATGL, is activated by ABHD5 in <em>in vitro</em> assays using purified proteins. PNPLA3(148M)-associated inhibition of TG hydrolysis required that ATGL be expressed and that PNPLA3 be located on LDs. Finally, overexpression of ABHD5 reversed the hepatic steatosis in <em>Pnpla3</em><sup><em>M/M</em></sup> mice.<h3>Conclusions</h3>These findings support the premise that PNPLA3(148M) is a gain-of-function mutation that promotes hepatic steatosis by accumulating on LDs and inhibiting ATGL-mediated lipolysis in an ABHD5-dependent manner. Our results predict that reducing, rather that increasing, PNPLA3 expression will be the best strategy to treat PNPLA3(148M)-associated SLD.<h3>Impact and implications</h3>Steatotic liver disease (SLD) is a common complex disorder associated with both environmental and genetic risk factors. PNPLA3(148M) is the most impactful genetic risk factor for SLD and yet its pathogenic mechanism remains controversial. Here we provide evidence that PNPLA3(148M) promotes triglyceride (TG) accumulation by sequestering ABHD5, thus limiting its availability to activate ATGL. Although the substitution of methionine for isoleucine reduces the TG hydrolase activity of PNPLA3, the loss of enzymatic function is not directly related to the steatotic effect of the variant. It is the resulting accumulation of PNPLA3 on LDs that confers a gain-of-function by interfering with ATGL-mediated TG hydrolysis. These findings have implications for the design of potential PNPLA3(148M)-based therapies. Reducing, rather than increasing, PNPLA3 levels is predicted to reverse steatosis in susceptible individuals.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"246 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637627","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 : 2024-11-15DOI: 10.1016/S0168-8278(24)02609-6
{"title":"LIVERAIM is an IHI funded project that is working to improve early detection of chronic liver disease through the development of a new biomarker-based personalized risk calculator","authors":"","doi":"10.1016/S0168-8278(24)02609-6","DOIUrl":"10.1016/S0168-8278(24)02609-6","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"81 6","pages":"Page v"},"PeriodicalIF":26.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637632","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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