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Investigating Notch3 expression in hepatocellular carcinoma and its interplay with KDM2A
IF 4 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.dld.2025.01.032
I. De Giorgi , T. Caruso , M.C. Scavuzzo , S. Piaggi , F. Scolari , P. Faviana , S. Pillozzi , R. Del Frate , G. Paties Montagner , F. Bartoli , A. Corti , G. Cavallini , V. Carloni , L. Gragnani

Introduction

Notch3 receptor is involved in different aspects of hepatocellular carcinoma (HCC). Nevertheless, to unlock Notch3 therapeutic/diagnostic/prognostic potential a deeper understanding of its role in HCC onset/progression is needed. KDM2A demethylase epigenetically regulates gene expression. Its levels increase with HCC grading.

Aim

To investigate the involvement of KDM2A in controlling Notch3 expression in HCC.

Material and Methods

An expression analysis of Notch3 and KDM2A was conducted by Real-Time PCR on mRNA from formalin-fixed paraffin-embedded (FFPE) HCCs and peritumoral tissue (PT). Huh7 cells were transiently silenced for KDM2A using siRNAs for a first evaluation of Notch3/KDM2A association. KDM2A and Notch3 levels after silencing were assessed by Real-Time PCR and Western-Blotting (WB). The stem-cell marker CD133, associated with Epithelial Mesenchymal Transition, was evaluated in Notch3-silenced cells. Immunohistochemistry (IHC) was conducted using anti-Notch3 and anti-KDM2A antibodies.

Results

Notch3 and KDM2A in FFPE samples were higher in HCCs compared to PT (p<0.001 and p<0.01, respectively) and increased from G1 to G3 HCC. In well differentiated HCC the staining was mainly localized in the vascular endothelium while in G3 HCC it involved clusters of tumoral hepatocytes, sometimes invading portal areas. CD34 staining showed that the Notch3 positive blood vessels were consequences of neo-angiogenesis. The transient KDM2A silencing resulted in Notch3 transcript downregulation (p≤0.001), confirmed by WB (p≤0.01). CD133 was downregulated in Notch3-silenced Huh7 (p≤0.0001).

Conclusions

An increasing Notch3 expression was observed during HCC progression. IHC revealed the involvement of Notch3 in neo-angiogenesis in early HCC and a role in invasiveness of stromal portal areas in G3 tumors. This latter, together with Notch3/CD133 association, suggests an involvement of Notch3 in local invasiveness. Furthermore, we found an association between Notch3 and KDM2A suggesting a possible mechanism of epigenetic regulation that could be responsible for the higher Notch3 expression in poorly differentiated HCC with high KDM2A levels.
{"title":"Investigating Notch3 expression in hepatocellular carcinoma and its interplay with KDM2A","authors":"I. De Giorgi ,&nbsp;T. Caruso ,&nbsp;M.C. Scavuzzo ,&nbsp;S. Piaggi ,&nbsp;F. Scolari ,&nbsp;P. Faviana ,&nbsp;S. Pillozzi ,&nbsp;R. Del Frate ,&nbsp;G. Paties Montagner ,&nbsp;F. Bartoli ,&nbsp;A. Corti ,&nbsp;G. Cavallini ,&nbsp;V. Carloni ,&nbsp;L. Gragnani","doi":"10.1016/j.dld.2025.01.032","DOIUrl":"10.1016/j.dld.2025.01.032","url":null,"abstract":"<div><h3>Introduction</h3><div>Notch3 receptor is involved in different aspects of hepatocellular carcinoma (HCC). Nevertheless, to unlock Notch3 therapeutic/diagnostic/prognostic potential a deeper understanding of its role in HCC onset/progression is needed. KDM2A demethylase epigenetically regulates gene expression. Its levels increase with HCC grading.</div></div><div><h3>Aim</h3><div>To investigate the involvement of KDM2A in controlling Notch3 expression in HCC.</div></div><div><h3>Material and Methods</h3><div>An expression analysis of Notch3 and KDM2A was conducted by Real-Time PCR on mRNA from formalin-fixed paraffin-embedded (FFPE) HCCs and peritumoral tissue (PT). Huh7 cells were transiently silenced for KDM2A using siRNAs for a first evaluation of Notch3/KDM2A association. KDM2A and Notch3 levels after silencing were assessed by Real-Time PCR and Western-Blotting (WB). The stem-cell marker CD133, associated with Epithelial Mesenchymal Transition, was evaluated in Notch3-silenced cells. Immunohistochemistry (IHC) was conducted using anti-Notch3 and anti-KDM2A antibodies.</div></div><div><h3>Results</h3><div>Notch3 and KDM2A in FFPE samples were higher in HCCs compared to PT (p&lt;0.001 and p&lt;0.01, respectively) and increased from G1 to G3 HCC. In well differentiated HCC the staining was mainly localized in the vascular endothelium while in G3 HCC it involved clusters of tumoral hepatocytes, sometimes invading portal areas. CD34 staining showed that the Notch3 positive blood vessels were consequences of neo-angiogenesis. The transient KDM2A silencing resulted in Notch3 transcript downregulation (p≤0.001), confirmed by WB (p≤0.01). CD133 was downregulated in Notch3-silenced Huh7 (p≤0.0001).</div></div><div><h3>Conclusions</h3><div>An increasing Notch3 expression was observed during HCC progression. IHC revealed the involvement of Notch3 in neo-angiogenesis in early HCC and a role in invasiveness of stromal portal areas in G3 tumors. This latter, together with Notch3/CD133 association, suggests an involvement of Notch3 in local invasiveness. Furthermore, we found an association between Notch3 and KDM2A suggesting a possible mechanism of epigenetic regulation that could be responsible for the higher Notch3 expression in poorly differentiated HCC with high KDM2A levels.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Page S18"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unravelling MASLD heterogeneity at single cell level in the switching towards progressive disease
IF 4 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.dld.2025.01.028
M. Meroni , E. Paolini , M. Longo , M. Battistin , E. Mosca , P. Pelucchi , A. Chiodi , A. Sula , S. Gatti , P. Dongiovanni

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) embraces different conditions, including metabolic dysfunction-associated steatohepatitis (MASH), fibrosis/cirrhosis and hepatocarcinoma. The landscape of cellular abnormalities occurring in the different stages of MASLD and the processes which drive its evolution are not elucidated.

Aim

We aimed to investigate cell population heterogeneity involved in progressive MASLD at single cell resolution, to define the role of hepatic cell types in the disease transition.

Materials and Methods Results

C57Bl6 male mice were fed standard (SD) or high fat high fructose (AMLN) diets for 14 (steatosis), 22 (MASH) and 28 (MASH-fibrosis) weeks to resemble human MASLD. Single cell RNA-sequencing (scRNAseq) was applied to decipher cell populations, differentiation and genes/pathways guiding MASLD progression.
By considering the expression of canonical markers, we classified 32 clusters (Cls), including hepatocytes (HEPs), hepatic stellate cells (HSCs), endothelial cells (Endo), Kupffer cells (KCs), and immune cells. We observed changes in HEPs Cls across disease severity, with a mixed pericentral/periportal localization in steatosis and a periportal one in MASH and MASH-fibrosis, reflecting the advanced damage in this area. The latter conditions were featured by Endo Cls which induced the expression of vascular angiogenesis and ECM molecules whereas endothelial mesenchymal transition (EndMT) markers gradually appeared during the disease. Among KCs, we found Cls of resident cells and immune cells recruited from the circulation with a M1 phenotype which increased throughout diet exposure. Regarding HSCs, MASH-fibrosis was featured by Cls with mesenchymal markers. Among the 32 Cls, we identified 5 chimeric populations named HSCs/Endo (Cl 21), HEPs/Endo (Cl 15), KCs/Endo (Cl 26) and HEPs/KCs (Cl 10 and Cl 17). Evolutionary trajectory outlined the directions of cell differentiation, which was more pronounced in MASH-fibrosis.

Conclusions

We observed an evolution of cellular heterogeneity during MASLD and identified chimeric populations in the advanced stages thus suggesting their involvement in disease progression.
{"title":"Unravelling MASLD heterogeneity at single cell level in the switching towards progressive disease","authors":"M. Meroni ,&nbsp;E. Paolini ,&nbsp;M. Longo ,&nbsp;M. Battistin ,&nbsp;E. Mosca ,&nbsp;P. Pelucchi ,&nbsp;A. Chiodi ,&nbsp;A. Sula ,&nbsp;S. Gatti ,&nbsp;P. Dongiovanni","doi":"10.1016/j.dld.2025.01.028","DOIUrl":"10.1016/j.dld.2025.01.028","url":null,"abstract":"<div><h3>Introduction</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) embraces different conditions, including metabolic dysfunction-associated steatohepatitis (MASH), fibrosis/cirrhosis and hepatocarcinoma. The landscape of cellular abnormalities occurring in the different stages of MASLD and the processes which drive its evolution are not elucidated.</div></div><div><h3>Aim</h3><div>We aimed to investigate cell population heterogeneity involved in progressive MASLD at single cell resolution, to define the role of hepatic cell types in the disease transition.</div></div><div><h3>Materials and Methods Results</h3><div>C57Bl6 male mice were fed standard (SD) or high fat high fructose (AMLN) diets for 14 (steatosis), 22 (MASH) and 28 (MASH-fibrosis) weeks to resemble human MASLD. Single cell RNA-sequencing (scRNAseq) was applied to decipher cell populations, differentiation and genes/pathways guiding MASLD progression.</div><div>By considering the expression of canonical markers, we classified 32 clusters (Cls), including hepatocytes (HEPs), hepatic stellate cells (HSCs), endothelial cells (Endo), Kupffer cells (KCs), and immune cells. We observed changes in HEPs Cls across disease severity, with a mixed pericentral/periportal localization in steatosis and a periportal one in MASH and MASH-fibrosis, reflecting the advanced damage in this area. The latter conditions were featured by Endo Cls which induced the expression of vascular angiogenesis and ECM molecules whereas endothelial mesenchymal transition (EndMT) markers gradually appeared during the disease. Among KCs, we found Cls of resident cells and immune cells recruited from the circulation with a M1 phenotype which increased throughout diet exposure. Regarding HSCs, MASH-fibrosis was featured by Cls with mesenchymal markers. Among the 32 Cls, we identified 5 chimeric populations named HSCs/Endo (Cl 21), HEPs/Endo (Cl 15), KCs/Endo (Cl 26) and HEPs/KCs (Cl 10 and Cl 17). Evolutionary trajectory outlined the directions of cell differentiation, which was more pronounced in MASH-fibrosis.</div></div><div><h3>Conclusions</h3><div>We observed an evolution of cellular heterogeneity during MASLD and identified chimeric populations in the advanced stages thus suggesting their involvement in disease progression.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Page S16"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
AI-based estimation of cardiovascular risk in MASLD patients using non-contrast CT imaging and clinical data
IF 4 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.dld.2025.01.080
A. Cirella , P. Bruno , V. Caputo , P. Palumbo , SJ Santini , A. Quarta , F. Calimeri , P. Palumbo , E. Di Cesare , C. Balsano

Introduction

Accurate cardiovascular risk (CVR) assessment is crucial for apparently healthy individuals. Metabolic-dysfunction associated steatotic liver disease (MASLD), formerly NAFLD, affects 38% of the population worldwide and the cardiovascular diseases (CVD) represent the primary cause of death in these patients, suggesting that MASLD could be considered as an independent risk factor for a novel CVR assessment score.

Aim

our study aims at modelling non-contrast Cardio-CT scans and clinical data with artificial intelligence (AI) approaches to develop a predictive model for CVR assessment in MASLD.

Materials and Methods, Results

A retrospective study analyzed clinical and imaging data from 174 patients who underwent Cardio-CT in S.Salvatore Hospital in L'Aquila and S.Pertini Hospital in Rome. Based on Coronary Artery Calcium (CAC) scores and Hunsfield units (HU), 50% of patients were affected by MASLD and CVD, the rest of patients were healthy controls. 96 Patients were enlisted for training and 78 for the internal validation cohort to obtain performance metrics.
A U-Net convolutional neural network was used to segment liver parenchyma, and a Gray-Level Co-occurrence Matrix (GLCM) was applied to extract radiomic features and evaluate levels of steatosis. The relevant features were combined with clinical data and used as input into a multilayer perceptron neural network to perform binary classification of CAC.

Results

Our trained algorithm automatically defines the severity of CAC, based on liver steatosis and patient clinical data, thereby assessing the level of CVR. Notably, the related important features were represented by dyslipidemia, diabetes and age. By testing images and clinical data from both centers, the most performing model was the Stacking Model achieving an AUC of 80%.

Conclusion

Our AI model estimates CVR in MASLD patients undergoing abdominal CT, integrating radiomic and clinical data, it could be useful also for cirrhotic patients undergoing HCC screening or awaiting OLT.
{"title":"AI-based estimation of cardiovascular risk in MASLD patients using non-contrast CT imaging and clinical data","authors":"A. Cirella ,&nbsp;P. Bruno ,&nbsp;V. Caputo ,&nbsp;P. Palumbo ,&nbsp;SJ Santini ,&nbsp;A. Quarta ,&nbsp;F. Calimeri ,&nbsp;P. Palumbo ,&nbsp;E. Di Cesare ,&nbsp;C. Balsano","doi":"10.1016/j.dld.2025.01.080","DOIUrl":"10.1016/j.dld.2025.01.080","url":null,"abstract":"<div><h3>Introduction</h3><div>Accurate cardiovascular risk (CVR) assessment is crucial for apparently healthy individuals. Metabolic-dysfunction associated steatotic liver disease (MASLD), formerly NAFLD, affects 38% of the population worldwide and the cardiovascular diseases (CVD) represent the primary cause of death in these patients, suggesting that MASLD could be considered as an independent risk factor for a novel CVR assessment score.</div></div><div><h3>Aim</h3><div>our study aims at modelling non-contrast Cardio-CT scans and clinical data with artificial intelligence (AI) approaches to develop a predictive model for CVR assessment in MASLD.</div></div><div><h3>Materials and Methods, Results</h3><div>A retrospective study analyzed clinical and imaging data from 174 patients who underwent Cardio-CT in S.Salvatore Hospital in L'Aquila and S.Pertini Hospital in Rome. Based on Coronary Artery Calcium (CAC) scores and Hunsfield units (HU), 50% of patients were affected by MASLD and CVD, the rest of patients were healthy controls. 96 Patients were enlisted for training and 78 for the internal validation cohort to obtain performance metrics.</div><div>A U-Net convolutional neural network was used to segment liver parenchyma, and a Gray-Level Co-occurrence Matrix (GLCM) was applied to extract radiomic features and evaluate levels of steatosis. The relevant features were combined with clinical data and used as input into a multilayer perceptron neural network to perform binary classification of CAC.</div></div><div><h3>Results</h3><div>Our trained algorithm automatically defines the severity of CAC, based on liver steatosis and patient clinical data, thereby assessing the level of CVR. Notably, the related important features were represented by dyslipidemia, diabetes and age. By testing images and clinical data from both centers, the most performing model was the Stacking Model achieving an AUC of 80%.</div></div><div><h3>Conclusion</h3><div>Our AI model estimates CVR in MASLD patients undergoing abdominal CT, integrating radiomic and clinical data, it could be useful also for cirrhotic patients undergoing HCC screening or awaiting OLT.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Page S43"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Features and factors related to intensive care unit admission of cirrhotic patients with Acute-on-Chronic Liver Failure: a single-center observational study
IF 4 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.dld.2025.01.065
L. De Marco , A. Dalbeni , M. Bevilacqua , R. Stupia , F. Cattazzo , K. Donadello , D. Sacerdoti

Introduction and Aims

Acute-on-chronic liver failure (ACLF) is a severe form of acutely decompensated cirrhosis. Infections play a crucial role in precipitating and complicating ACLF. This study aimed to evaluate the characteristics of a population of patients with ACLF admitted to our unit, with the goal of identifying factors predisposing to intensive care unit (ICU) admission and to death or liver transplantation (LT).

Materials and Methods

This is a single-center prospective study conducted from January 2018 to July 2024. Demographic, clinical, laboratory, and radiologic data of 94 consecutive cirrhotic patients diagnosed with ACLF and admitted to our department were collected and analyzed. ACLF-related ICU admission, mortality, or LT were recorded. Infections that triggered ACLF or occurred during hospitalization for ACLF, prior to potential ICU admission, were categorized.

Results

During hospitalization, 37% of patients were admitted to ICU. 80% of the patients either died or underwent LT. Infections, either triggering or complicating ACLF occurred in 87% of patients prior to potential admission to the ICU. In survival analysis, ACLF patients who had undergone tertiary hepatological follow-up for at least six months prior to hospitalization (49%) exhibited a significantly reduced risk of ICU admission following ACLF (HR 0.21, 95% CI 0.07–0.37, p<0.001), and a reduced risk of ACLF-related death or need of LT (HR 0.12, 95% CI 0.07–0.24, p<0.001). Fungal infections, on the other hand, were strongly associated with a higher likelihood of ICU admission (HR 2.93, 95% CI 1.31–6.54, p=0.009), and multidrug-resistant (MDR) infections markedly increased the risk of death or LT (HR 2.16, 95% CI 1.13–4.10, p=0.019).

Conclusions

Fungal infections have been identified as a risk factor for ICU admission in patients with ACLF. Moreover, MDR infections significantly increase the risk of ACLF-related death or LT. Therefore, strategies aimed at preventing and rapidly managing these infections are essential. Finally, outpatient tertiary hepatological follow-up appears to be protective in cirrhotic patients, reducing the risk of ICU admission, as well as of death or LT when developing ACLF.
{"title":"Features and factors related to intensive care unit admission of cirrhotic patients with Acute-on-Chronic Liver Failure: a single-center observational study","authors":"L. De Marco ,&nbsp;A. Dalbeni ,&nbsp;M. Bevilacqua ,&nbsp;R. Stupia ,&nbsp;F. Cattazzo ,&nbsp;K. Donadello ,&nbsp;D. Sacerdoti","doi":"10.1016/j.dld.2025.01.065","DOIUrl":"10.1016/j.dld.2025.01.065","url":null,"abstract":"<div><h3>Introduction and Aims</h3><div>Acute-on-chronic liver failure (ACLF) is a severe form of acutely decompensated cirrhosis. Infections play a crucial role in precipitating and complicating ACLF. This study aimed to evaluate the characteristics of a population of patients with ACLF admitted to our unit, with the goal of identifying factors predisposing to intensive care unit (ICU) admission and to death or liver transplantation (LT).</div></div><div><h3>Materials and Methods</h3><div>This is a single-center prospective study conducted from January 2018 to July 2024. Demographic, clinical, laboratory, and radiologic data of 94 consecutive cirrhotic patients diagnosed with ACLF and admitted to our department were collected and analyzed. ACLF-related ICU admission, mortality, or LT were recorded. Infections that triggered ACLF or occurred during hospitalization for ACLF, prior to potential ICU admission, were categorized.</div></div><div><h3>Results</h3><div>During hospitalization, 37% of patients were admitted to ICU. 80% of the patients either died or underwent LT. Infections, either triggering or complicating ACLF occurred in 87% of patients prior to potential admission to the ICU. In survival analysis, ACLF patients who had undergone tertiary hepatological follow-up for at least six months prior to hospitalization (49%) exhibited a significantly reduced risk of ICU admission following ACLF (HR 0.21, 95% CI 0.07–0.37, p&lt;0.001), and a reduced risk of ACLF-related death or need of LT (HR 0.12, 95% CI 0.07–0.24, p&lt;0.001). Fungal infections, on the other hand, were strongly associated with a higher likelihood of ICU admission (HR 2.93, 95% CI 1.31–6.54, p=0.009), and multidrug-resistant (MDR) infections markedly increased the risk of death or LT (HR 2.16, 95% CI 1.13–4.10, p=0.019).</div></div><div><h3>Conclusions</h3><div>Fungal infections have been identified as a risk factor for ICU admission in patients with ACLF. Moreover, MDR infections significantly increase the risk of ACLF-related death or LT. Therefore, strategies aimed at preventing and rapidly managing these infections are essential. Finally, outpatient tertiary hepatological follow-up appears to be protective in cirrhotic patients, reducing the risk of ICU admission, as well as of death or LT when developing ACLF.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Page S34"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of diagnostic performances of HDV RNA quantification assays used in clinical practice in Italy: data from the first national quality control multicenter study
IF 4 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.dld.2025.01.099
L. Piermatteo , R. Salpini , GP Caviglia , A. Bertoli , MR. Brunetto , B. Bruzzone , A. Callegaro , C. Caudai , D. Cavallone , L. Chessa , F. Coghe , N. Coppola , N. Cuomo , S. D'Anna , M. Di Stefano , F. Facchetti , C. Farina , D. Ferraro , E. Franchin , D. Francisci , Valentina Svicher

Introduction

A reliable quantification of serum hepatitis D virus (HDV) RNA is of paramount importance for a proper monitoring of patients under antiviral therapy.

Aim

This quality-control study compares the diagnostic performances of quantitative HDV-RNA assays, used in clinical-practice.

Methods

Two HDV-RNA sample panels were quantified at 30 laboratories by 6 commercial assays: RoboGene(N=9 laboratories), Eurobio/EliTech-platform(N=7), Altona(N=5), Anatolia(N=3), DiaPro(N=2), Nuclear-Laser-Medicine(N=1) and 3 in-house assays. Panel-A and -B comprised 8 serial dilutions of WHO/HDV standard(range:5-0.5logIU/ml) and 20 clinical samples(range:6-0.5logIU/ml), respectively. Laboratories quantified dilutions of Panel-A and -B 9 and 5 times, respectively, in order to define for each assay: i)sensitivity by 95%LOD(limit of detection), ii)precision by intra- and inter-run CV(coefficient of variation), iii)accuracy by the differences between expected-observed HDV-RNA loads, iv)linearity by linear-regression analysis.

Results

In Panel-A, 95%LOD varied across the assays underlining heterogeneous sensitivities: Altona had the lowest median 95%LOD (10[min-max:3-316]IU/ml), followed by Robogene (31[3-316] IU/ml), Nuclear-Laser-Medicine (31IU/ml) and EliTech (100[100-316]IU/ml). Moreover, 5 assays (Robogene/EliTech/Altona, Nuclear-Laser-Medicine/In-house) showed <0.5logIU/ml differences between expected and observed HDV-RNA for all dilutions while the remaining assays had HDV-RNA underestimations>1logIU/ml. In Panel-B, Altona and EliTech had the highest precision (mean intra-run CV<20%), followed by Robogene and Nuclear-Laser-Medicine (<30%). Inter-run CV was higher for all assays with only Altona, Nuclear-Laser-Medicine and EliTech maintaining this parameter<25%. Five assays (Robogene/Altona/EliTech/Nuclear-Laser-Medicine/In-house) showed a good linearity(R2>0.9) between LLOQ and 6.7logIU/ml. Conversely, a linearity drop emerged for HDV-RNA<1000IU/ml, with only Altona and Robogene retaining R2>0.85.

Conclusions

This study underlines heterogeneous sensitivities (inter- and intra-assays), that could hamper the proper HDV-RNA quantification, particularly at low viral-loads. This raises the need to improve the diagnostic performance of most assays for properly identifying virological response to anti-HDV drugs.
{"title":"Comparison of diagnostic performances of HDV RNA quantification assays used in clinical practice in Italy: data from the first national quality control multicenter study","authors":"L. Piermatteo ,&nbsp;R. Salpini ,&nbsp;GP Caviglia ,&nbsp;A. Bertoli ,&nbsp;MR. Brunetto ,&nbsp;B. Bruzzone ,&nbsp;A. Callegaro ,&nbsp;C. Caudai ,&nbsp;D. Cavallone ,&nbsp;L. Chessa ,&nbsp;F. Coghe ,&nbsp;N. Coppola ,&nbsp;N. Cuomo ,&nbsp;S. D'Anna ,&nbsp;M. Di Stefano ,&nbsp;F. Facchetti ,&nbsp;C. Farina ,&nbsp;D. Ferraro ,&nbsp;E. Franchin ,&nbsp;D. Francisci ,&nbsp;Valentina Svicher","doi":"10.1016/j.dld.2025.01.099","DOIUrl":"10.1016/j.dld.2025.01.099","url":null,"abstract":"<div><h3>Introduction</h3><div>A reliable quantification of serum hepatitis D virus (HDV) RNA is of paramount importance for a proper monitoring of patients under antiviral therapy.</div></div><div><h3>Aim</h3><div>This quality-control study compares the diagnostic performances of quantitative HDV-RNA assays, used in clinical-practice.</div></div><div><h3>Methods</h3><div>Two HDV-RNA sample panels were quantified at 30 laboratories by 6 commercial assays: RoboGene(N=9 laboratories), Eurobio/EliTech-platform(N=7), Altona(N=5), Anatolia(N=3), DiaPro(N=2), Nuclear-Laser-Medicine(N=1) and 3 in-house assays. Panel-A and -B comprised 8 serial dilutions of WHO/HDV standard(range:5-0.5logIU/ml) and 20 clinical samples(range:6-0.5logIU/ml), respectively. Laboratories quantified dilutions of Panel-A and -B 9 and 5 times, respectively, in order to define for each assay: i)sensitivity by 95%LOD(limit of detection), ii)precision by intra- and inter-run CV(coefficient of variation), iii)accuracy by the differences between expected-observed HDV-RNA loads, iv)linearity by linear-regression analysis.</div></div><div><h3>Results</h3><div>In Panel-A, 95%LOD varied across the assays underlining heterogeneous sensitivities: Altona had the lowest median 95%LOD (10[min-max:3-316]IU/ml), followed by Robogene (31[3-316] IU/ml), Nuclear-Laser-Medicine (31IU/ml) and EliTech (100[100-316]IU/ml). Moreover, 5 assays (Robogene/EliTech/Altona, Nuclear-Laser-Medicine/In-house) showed &lt;0.5logIU/ml differences between expected and observed HDV-RNA for all dilutions while the remaining assays had HDV-RNA underestimations&gt;1logIU/ml. In Panel-B, Altona and EliTech had the highest precision (mean intra-run CV&lt;20%), followed by Robogene and Nuclear-Laser-Medicine (&lt;30%). Inter-run CV was higher for all assays with only Altona, Nuclear-Laser-Medicine and EliTech maintaining this parameter&lt;25%. Five assays (Robogene/Altona/EliTech/Nuclear-Laser-Medicine/In-house) showed a good linearity(R<sup>2</sup>&gt;0.9) between LLOQ and 6.7logIU/ml. Conversely, a linearity drop emerged for HDV-RNA&lt;1000IU/ml, with only Altona and Robogene retaining R<sup>2</sup>&gt;0.85.</div></div><div><h3>Conclusions</h3><div>This study underlines heterogeneous sensitivities (inter- and intra-assays), that could hamper the proper HDV-RNA quantification, particularly at low viral-loads. This raises the need to improve the diagnostic performance of most assays for properly identifying virological response to anti-HDV drugs.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Pages S53-S54"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NOSTRIN is an emerging positive regulator of decompensated cirrhotic patients with portal hypertension NOSTRIN 是门静脉高压肝硬化失代偿期患者的一种新兴负调控因子。
IF 4 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.dld.2024.08.050
Balasubramaniyan Vairappan , Ravikumar TS , Amit Kumar Ram , Pazhanivel Mohan , Biju Pottakkat

Background and aims

Decreased nitric oxide (NO) bioavailability in a cirrhotic liver contributes to high intrahepatic vascular resistance (IHVR) and portal hypertension (PHT). Nostrin is an inhibitory protein of NO synthesising enzyme endothelial NO synthase (eNOS), shown to increase in cirrhosis with PHT, however, the precise molecular mechanism is poorly documented. This study aimed to elucidate the role of Nostrin and associated derangement in hepatic NO generation in cirrhotic liver. Further, we investigate whether Nostrin could be a biomarker in the progression of cirrhosis.

Methods

This study was conducted on sixty healthy subjects and 120 cirrhotic patients. In addition, liver tissue samples were collected from cirrhotic patients for the analysis of Nostrin, eNOS and inflammatory markers.

Results

When compared to healthy controls, systemic levels of Nostrin and cGMP were elevated in compensated cirrhosis. In decompensated cirrhosis, further robust increases in Nostrin and cGMP were noted. Furthermore, Nostrin expression was considerably higher whilst reduced eNOS activity and hepatic cGMP levels in cirrhotic liver compared to control liver.

Conclusions

In cirrhotic patients, a robust increase in hepatic Nostrin expression may reduce eNOS activity and associated local NO generation. Furthermore, Blood Nostrin concentration was higher and parallel to disease severity and could be a key diagnostic and prognostic biomarker in cirrhotic patients with PHT.
背景和目的肝硬化患者体内一氧化氮(NO)生物利用率降低,导致肝内血管阻力(IHVR)增高和门静脉高压(PHT)。Nostrin是一氧化氮合成酶内皮一氧化氮合酶(eNOS)的抑制蛋白,在肝硬化伴门静脉高压时Nostrin会增加,但其确切的分子机制却鲜有记载。本研究旨在阐明 Nostrin 在肝硬化肝脏 NO 生成中的作用及相关失调。方法本研究以 60 名健康受试者和 120 名肝硬化患者为对象。结果与健康对照组相比,代偿期肝硬化患者全身 Nostrin 和 cGMP 水平升高。失代偿期肝硬化患者的 Nostrin 和 cGMP 水平进一步升高。此外,与对照组肝脏相比,肝硬化肝脏中的 Nostrin 表达明显升高,同时 eNOS 活性和肝脏 cGMP 水平降低。此外,血Nostrin浓度较高,且与疾病严重程度平行,可作为PHT肝硬化患者诊断和预后的关键生物标志物。
{"title":"NOSTRIN is an emerging positive regulator of decompensated cirrhotic patients with portal hypertension","authors":"Balasubramaniyan Vairappan ,&nbsp;Ravikumar TS ,&nbsp;Amit Kumar Ram ,&nbsp;Pazhanivel Mohan ,&nbsp;Biju Pottakkat","doi":"10.1016/j.dld.2024.08.050","DOIUrl":"10.1016/j.dld.2024.08.050","url":null,"abstract":"<div><h3>Background and aims</h3><div>Decreased nitric oxide (NO) bioavailability in a cirrhotic liver contributes to high intrahepatic vascular resistance (IHVR) and portal hypertension (PHT). Nostrin is an inhibitory protein of NO synthesising enzyme endothelial NO synthase (eNOS), shown to increase in cirrhosis with PHT, however, the precise molecular mechanism is poorly documented. This study aimed to elucidate the role of Nostrin and associated derangement in hepatic NO generation in cirrhotic liver. Further, we investigate whether Nostrin could be a biomarker in the progression of cirrhosis.</div></div><div><h3>Methods</h3><div>This study was conducted on sixty healthy subjects and 120 cirrhotic patients. In addition, liver tissue samples were collected from cirrhotic patients for the analysis of Nostrin, eNOS and inflammatory markers.</div></div><div><h3>Results</h3><div>When compared to healthy controls, systemic levels of Nostrin and cGMP were elevated in compensated cirrhosis. In decompensated cirrhosis, further robust increases in Nostrin and cGMP were noted. Furthermore, Nostrin expression was considerably higher whilst reduced eNOS activity and hepatic cGMP levels in cirrhotic liver compared to control liver.</div></div><div><h3>Conclusions</h3><div>In cirrhotic patients, a robust increase in hepatic Nostrin expression may reduce eNOS activity and associated local NO generation. Furthermore, Blood Nostrin concentration was higher and parallel to disease severity and could be a key diagnostic and prognostic biomarker in cirrhotic patients with PHT.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 2","pages":"Pages 427-435"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Incidence and risk factors for thromboembolic events in pediatric-onset inflammatory bowel disease: A French population-based study 儿科炎症性肠病血栓栓塞事件的发生率和风险因素:一项基于法国人口的研究。
IF 4 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.dld.2024.09.005
Nicolas Richard , Ariane Leroyer , Delphine Ley , Claire Dupont , Valérie Bertrand , Pauline Wils , Corine Gower-Rousseau , Dominique Turck , Nathalie Guillon , Hélène Sarter , Guillaume Savoye , Mathurin Fumery

Introduction

Patients with inflammatory bowel disease (IBD) are at higher risk of thromboembolic events (TE). In pediatric-onset IBD, more data on incidence and risk factors of venous (VTE) and arterial events (ATE) at the population level are needed to guide thromboprophylaxis.

Methods

All patients aged ≤ 16 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 1988 and 2011 in the prospective EPIMAD population-based registry were followed until 2013. Every TE occurring during the follow-up period was included.

Results

A total of 1,344 patients were included: 1,007 with CD and 337 with UC, and a median diagnosis age of 14.3 years. After a median follow-up of 8.3 years, 2 (0.15 %) ATE and 15 (1.1 %) VTE occurred at median age of 20.4 years. The global incidence rate of thromboembolic events was 1.32 per 1000 person-years. Periods of active disease (HR=8.4, p = 0.0002), the 3-month-period following surgery (HR=16.4, p = 0.0002) and hospitalization (HR=21.7, p < 0.0001) were found to be associated with an increased risk of VTE. A lower rate of VTE was found in patients treated with 5-aminosalicylates (HR=0.1, p = 0.002).

Conclusion

The risk of TE was low in this population. VTE were strongly associated with active disease, surgery and hospitalization.
导言:炎症性肠病(IBD)患者发生血栓栓塞事件(TE)的风险较高。在小儿IBD患者中,需要更多关于静脉(VTE)和动脉事件(ATE)发生率和风险因素的数据,以指导血栓预防:方法:对1988年至2011年间在前瞻性EPIMAD人群登记中确诊为克罗恩病(CD)或溃疡性结肠炎(UC)的所有年龄≤16岁的患者进行随访,直至2013年。随访期间发生的所有TE均被纳入:结果:共纳入 1,344 名患者:结果:共纳入 1,344 名患者:1,007 名 CD 患者和 337 名 UC 患者,中位诊断年龄为 14.3 岁。中位随访 8.3 年后,2 例(0.15%)ATE 和 15 例(1.1%)VTE 发生,中位年龄为 20.4 岁。血栓栓塞事件的总体发病率为每千人年 1.32 例。活动期(HR=8.4,p = 0.0002)、术后 3 个月(HR=16.4,p = 0.0002)和住院期(HR=21.7,p < 0.0001)与 VTE 风险增加有关。使用5-氨基水杨酸盐治疗的患者VTE发生率较低(HR=0.1,P=0.002):结论:在这一人群中,TE 的风险较低。VTE与活动性疾病、手术和住院密切相关。
{"title":"Incidence and risk factors for thromboembolic events in pediatric-onset inflammatory bowel disease: A French population-based study","authors":"Nicolas Richard ,&nbsp;Ariane Leroyer ,&nbsp;Delphine Ley ,&nbsp;Claire Dupont ,&nbsp;Valérie Bertrand ,&nbsp;Pauline Wils ,&nbsp;Corine Gower-Rousseau ,&nbsp;Dominique Turck ,&nbsp;Nathalie Guillon ,&nbsp;Hélène Sarter ,&nbsp;Guillaume Savoye ,&nbsp;Mathurin Fumery","doi":"10.1016/j.dld.2024.09.005","DOIUrl":"10.1016/j.dld.2024.09.005","url":null,"abstract":"<div><h3>Introduction</h3><div>Patients with inflammatory bowel disease (IBD) are at higher risk of thromboembolic events (TE). In pediatric-onset IBD, more data on incidence and risk factors of venous (VTE) and arterial events (ATE) at the population level are needed to guide thromboprophylaxis.</div></div><div><h3>Methods</h3><div>All patients aged ≤ 16 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 1988 and 2011 in the prospective EPIMAD population-based registry were followed until 2013. Every TE occurring during the follow-up period was included.</div></div><div><h3>Results</h3><div>A total of 1,344 patients were included: 1,007 with CD and 337 with UC, and a median diagnosis age of 14.3 years. After a median follow-up of 8.3 years, 2 (0.15 %) ATE and 15 (1.1 %) VTE occurred at median age of 20.4 years. The global incidence rate of thromboembolic events was 1.32 per 1000 person-years. Periods of active disease (HR=8.4, <em>p</em> = 0.0002), the 3-month-period following surgery (HR=16.4, <em>p</em> = 0.0002) and hospitalization (HR=21.7, <em>p</em> &lt; 0.0001) were found to be associated with an increased risk of VTE. A lower rate of VTE was found in patients treated with 5-aminosalicylates (HR=0.1, <em>p</em> = 0.002).</div></div><div><h3>Conclusion</h3><div>The risk of TE was low in this population. VTE were strongly associated with active disease, surgery and hospitalization.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 2","pages":"Pages 584-594"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development and validation of the PHM-CPA model to predict in-hospital mortality for cirrhotic patients with acute kidney injury 开发并验证用于预测急性肾损伤肝硬化患者院内死亡率的 PHM-CPA 模型。
IF 4 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.dld.2024.09.012
Luyan Zheng, Jing Yang, Lingzhu Zhao, Chen Li, Kailu Fang, Shuwen Li, Jie Wu , Min Zheng

Background

The presence of acute kidney injury (AKI) significantly increases in-hospital mortality risk for cirrhotic patients. Early prognosis prediction for these patients is crucial. We aimed to develop and validate a machine learning model for in-hospital mortality prediction for cirrhotic patients with AKI.

Methods

Data from cirrhotic patients with AKI hospitalized at the First Affiliated Hospital of Zhejiang University between January 1, 2013, and December 31, 2020 were used to train and validate an extreme Gradient Boosting model to predict in-hospital mortality risk. The Boruta algorithm was used for variable selection. The optimal model was selected and named as PHM-CPA (Prediction of in-Hospital Mortality for Cirrhotic Patients with AKI). The PHM-CPA model was then externally validated in patients from eICU Collaborative Research Database (eICU-CRD) and Medical Information Mart for Intensive Care III dataset (MIMIC). The predictive performance of PHM-CPA model was compared with that of logistic regression (LR) model and 25 previously reported models.

Results

A total of 519 cirrhotic patients with AKI were enrolled in model training cohort, of whom 118 (23%) died during hospitalization. Fifteen variables from common laboratory tests were selected to develop the PHM-CPA model. The PHM-CPA model achieved an AUROC of 0.816 (95% CI, 0.763–0.861) in the internal validation cohort and 0.787 (95% CI, 0.745–0.830) in the external validation cohort. The PHM-CPA model consistently outperformed the LR model and 25 previously reported models.

Conclusion

We developed and validated the PHM-CPA model, comprising readily available clinical variables, which demonstrated superior performance and calibration in predicting in-hospital mortality for cirrhotic patients with AKI.
背景:急性肾损伤(AKI)的出现大大增加了肝硬化患者的院内死亡风险。对这些患者进行早期预后预测至关重要。我们旨在开发并验证一种机器学习模型,用于预测 AKI 肝硬化患者的院内死亡率:我们使用浙江大学附属第一医院 2013 年 1 月 1 日至 2020 年 12 月 31 日期间住院的 AKI 肝硬化患者的数据,训练并验证了预测院内死亡风险的极端梯度提升模型。变量选择采用 Boruta 算法。选出的最优模型被命名为 PHM-CPA(肝硬化 AKI 患者院内死亡率预测)。随后,PHM-CPA 模型在来自 eICU 合作研究数据库(eICU-CRD)和重症监护医学信息市场 III 数据集(MIMIC)的患者中进行了外部验证。PHM-CPA模型的预测性能与逻辑回归(LR)模型和之前报道的25个模型进行了比较:共有 519 名肝硬化 AKI 患者加入模型训练队列,其中 118 人(23%)在住院期间死亡。PHM-CPA模型选取了常见实验室检测中的15个变量。PHM-CPA 模型在内部验证队列中的 AUROC 为 0.816(95% CI,0.763-0.861),在外部验证队列中的 AUROC 为 0.787(95% CI,0.745-0.830)。PHM-CPA模型的表现一直优于LR模型和之前报道的25种模型:我们开发并验证了 PHM-CPA 模型,该模型由现成的临床变量组成,在预测 AKI 肝硬化患者的院内死亡率方面表现出卓越的性能和校准性。
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引用次数: 0
Pancreatic steatosis is a strong risk factor for post-ERCP pancreatitis: An emerging concept 胰腺脂肪变性是ERCP术后胰腺炎的一个重要风险因素:一个新概念。
IF 4 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.dld.2024.10.005
Caroline Prouvot , Myriam Boumaiza , Khawla Maoui , Anne Sophie Peaucelle , Soiwafi Mohamed , Hanae Boutallaka , Claire Boutet , Xavier Roblin , Jean-Marc Phelip , Rémi Grange , Nicolas Williet

Objective

The Endoscopic Retrograde Cholangiopancreatography (ERCP) is the treatment of choice for biliary obstruction but is associated with post-ERCP pancreatitis (PEP) in around 5 % of cases. No radiological criteria have been evaluated for predicting PEP risk.

Design

This retrospective study examined records of 1365 patients who underwent ERCP at our center between 2014–2023. Only sphincterotomy-naïve patients were included. CT scans within 30 days of ERCP were reviewed for radiological criteria. The optimal pancreatic density cut-off was determined using AUROC and Youden index. Logistic regression was used for analyses.

Results

PEP occurred in 75 patients (6.1 %). The CT scan was performed before ERCP for 565 of the total population. A fatty pancreas, defined as a spontaneous density less than -50HU, was statistically associated with PEP (OR: 7.35; 95 % CI: 1.56–26.5 p = 0.004), as well as with biliary obstruction due to stones (OR: 0.61; 95 % CI: 0.38–0.98; P = 0.04), the need for precut (OR: 2.19; 95 % CI: 1.35–3.51; P = 0.001), cannulation of the main pancreatic duct (OR: 2.23; 95 % CI: 1.36–3.59; P = 0.001), and the use of a pancreatic stent (OR: 2.48; 95 % CI: 1.29–4.47; P = 0.004). In multivariate analyses, only obstruction unrelated to gallstones (OR = 2.63; 95 % CI: 1.16–6.25; P = 0.024) and a low pancreatic density (<-50HU) (OR=7.94, 95 %CI: 1.59–31.09; P = 0.005) remains significantly associated with the risk of PEP, including after adjustment for age and sex (P = 0.006).

Conclusion

A very low pancreatic fat density could be a significant risk factor for post-ERCP pancreatitis with potential clinical and research implications. Further validation is needed.
目的:内镜逆行胰胆管造影术(ERCP)是治疗胆道梗阻的首选方法,但约有5%的病例与ERCP术后胰腺炎(PEP)有关。目前尚未对预测 PEP 风险的放射学标准进行评估:这项回顾性研究检查了 2014-2023 年间在本中心接受 ERCP 的 1365 名患者的记录。仅纳入了括约肌切开术无效的患者。对ERCP术后30天内的CT扫描进行了放射学标准审查。使用AUROC和Youden指数确定最佳胰腺密度临界值。分析采用逻辑回归法:结果:75 名患者(6.1%)出现 PEP。所有患者中有 565 人在 ERCP 之前进行了 CT 扫描。脂肪胰腺(定义为自发密度小于 -50HU)与 PEP(OR:7.35;95 % CI:1.56-26.5;P = 0.004)以及结石导致的胆道梗阻(OR:0.61;95 % CI:0.38-0.98;P = 0.04)有统计学关联。04)、需要预先切开(OR:2.19;95 % CI:1.35-3.51;P = 0.001)、主胰管插管(OR:2.23;95 % CI:1.36-3.59;P = 0.001)和使用胰腺支架(OR:2.48;95 % CI:1.29-4.47;P = 0.004)。在多变量分析中,只有与胆结石无关的梗阻(OR = 2.63;95 % CI:1.16-6.25;P = 0.024)和胰腺脂肪密度低(结论:胰腺脂肪密度非常低会导致胆结石)才会导致胆结石:胰腺脂肪密度极低可能是ERCP术后胰腺炎的重要风险因素,具有潜在的临床和研究意义。需要进一步验证。
{"title":"Pancreatic steatosis is a strong risk factor for post-ERCP pancreatitis: An emerging concept","authors":"Caroline Prouvot ,&nbsp;Myriam Boumaiza ,&nbsp;Khawla Maoui ,&nbsp;Anne Sophie Peaucelle ,&nbsp;Soiwafi Mohamed ,&nbsp;Hanae Boutallaka ,&nbsp;Claire Boutet ,&nbsp;Xavier Roblin ,&nbsp;Jean-Marc Phelip ,&nbsp;Rémi Grange ,&nbsp;Nicolas Williet","doi":"10.1016/j.dld.2024.10.005","DOIUrl":"10.1016/j.dld.2024.10.005","url":null,"abstract":"<div><h3>Objective</h3><div>The Endoscopic Retrograde Cholangiopancreatography (ERCP) is the treatment of choice for biliary obstruction but is associated with post-ERCP pancreatitis (PEP) in around 5 % of cases. No radiological criteria have been evaluated for predicting PEP risk.</div></div><div><h3>Design</h3><div>This retrospective study examined records of 1365 patients who underwent ERCP at our center between 2014–2023. Only sphincterotomy-naïve patients were included. CT scans within 30 days of ERCP were reviewed for radiological criteria. The optimal pancreatic density cut-off was determined using AUROC and Youden index. Logistic regression was used for analyses.</div></div><div><h3>Results</h3><div>PEP occurred in 75 patients (6.1 %). The CT scan was performed before ERCP for 565 of the total population. A fatty pancreas, defined as a spontaneous density less than -50HU, was statistically associated with PEP (OR: 7.35; 95 % CI: 1.56–26.5 <em>p</em> = 0.004), as well as with biliary obstruction due to stones (OR: 0.61; 95 % CI: 0.38–0.98; <em>P</em> = 0.04), the need for precut (OR: 2.19; 95 % CI: 1.35–3.51; <em>P</em> = 0.001), cannulation of the main pancreatic duct (OR: 2.23; 95 % CI: 1.36–3.59; <em>P</em> = 0.001), and the use of a pancreatic stent (OR: 2.48; 95 % CI: 1.29–4.47; <em>P</em> = 0.004). In multivariate analyses, only obstruction unrelated to gallstones (OR = 2.63; 95 % CI: 1.16–6.25; <em>P</em> = 0.024) and a low pancreatic density (&lt;-50HU) (OR=7.94, 95 %CI: 1.59–31.09; <em>P</em> = 0.005) remains significantly associated with the risk of PEP, including after adjustment for age and sex (<em>P</em> = 0.006).</div></div><div><h3>Conclusion</h3><div>A very low pancreatic fat density could be a significant risk factor for post-ERCP pancreatitis with potential clinical and research implications. Further validation is needed.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 2","pages":"Pages 542-548"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Translating knowledge into policy: Organizational model and minimum requirements for the implementation of a regional pancreas unit network 将知识转化为政策:实施地区胰腺单位网络的组织模式和最低要求。
IF 4 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.dld.2024.05.022
Gianpaolo Balzano , Michele Reni , Maria Di Bartolomeo , Marta Scorsetti , Augusto Caraceni , Piero Rivizzigno , Alessandro Amorosi , Alessandro Scardoni , Mohammad Abu Hilal , Giovanni Ferrari , Roberto Labianca , Massimo Venturini , Claudio Doglioni , Luca Riva , Riccardo Caccialanza , Silvia Carrara
Pancreatic and periampullary cancers pose significant challenges in oncological care due to their complexity and diagnostic difficulties. Global experiences underscore the crucial role of multidisciplinary collaboration and centralized care in improving patient outcomes in this context. Recognizing these challenges, Lombardy, Italy's most populous region, embarked on establishing pancreas units across its territory to enhance clinical outcomes and organizational efficiency. This initiative, driven by a multistakeholder approach involving the Lombardy Welfare Directorate, clinicians, and a patient association, emphasizes the centralization of complex care in high-volume hospitals, adopting a hub-and-spoke model and a multidisciplinary approach. This article outlines the process and criteria set forth for pancreas unit implementation, aiming to provide a structured framework for enhancing pancreatic cancer care. Central to this initiative is the establishment of structured criteria and minimal requirements, not only for surgery but also for other essential components of care, ensuring a comprehensive approach to pancreatic cancer management. The Lombardy model offers a structured framework for enhancing pancreatic cancer care, with potential applicability to other regions and countries seeking to improve their cancer care infrastructure
胰腺癌和胰腺周围癌因其复杂性和诊断困难,给肿瘤治疗带来了巨大挑战。全球经验表明,多学科协作和集中治疗在改善患者预后方面发挥着至关重要的作用。认识到这些挑战后,意大利人口最多的伦巴第大区开始在全境建立胰腺科,以提高临床疗效和组织效率。这一举措由伦巴第大区福利局、临床医生和患者协会等多方共同推动,强调将复杂的医疗服务集中到大容量医院,采用中心辐射模式和多学科方法。本文概述了胰腺单元的实施过程和标准,旨在为加强胰腺癌护理提供一个结构化框架。这一举措的核心是建立结构化的标准和最低要求,不仅针对手术,还针对其他重要的护理环节,确保以全面的方法管理胰腺癌。伦巴第模式为加强胰腺癌治疗提供了一个结构化框架,有可能适用于寻求改善癌症治疗基础设施的其他地区和国家。
{"title":"Translating knowledge into policy: Organizational model and minimum requirements for the implementation of a regional pancreas unit network","authors":"Gianpaolo Balzano ,&nbsp;Michele Reni ,&nbsp;Maria Di Bartolomeo ,&nbsp;Marta Scorsetti ,&nbsp;Augusto Caraceni ,&nbsp;Piero Rivizzigno ,&nbsp;Alessandro Amorosi ,&nbsp;Alessandro Scardoni ,&nbsp;Mohammad Abu Hilal ,&nbsp;Giovanni Ferrari ,&nbsp;Roberto Labianca ,&nbsp;Massimo Venturini ,&nbsp;Claudio Doglioni ,&nbsp;Luca Riva ,&nbsp;Riccardo Caccialanza ,&nbsp;Silvia Carrara","doi":"10.1016/j.dld.2024.05.022","DOIUrl":"10.1016/j.dld.2024.05.022","url":null,"abstract":"<div><div><span>Pancreatic and periampullary cancers pose significant challenges in oncological care due to their complexity and diagnostic difficulties. Global experiences underscore the crucial role of multidisciplinary collaboration and centralized care in improving patient outcomes in this context. Recognizing these challenges, Lombardy, Italy's most populous region, embarked on establishing pancreas units across its territory to enhance clinical outcomes and organizational efficiency. This initiative, driven by a multistakeholder approach involving the Lombardy Welfare Directorate, clinicians, and a patient association, emphasizes the centralization of complex care in high-volume hospitals, adopting a hub-and-spoke model and a multidisciplinary approach. This article outlines the process and criteria set forth for pancreas unit implementation, aiming to provide a structured framework for enhancing </span>pancreatic cancer care. Central to this initiative is the establishment of structured criteria and minimal requirements, not only for surgery but also for other essential components of care, ensuring a comprehensive approach to pancreatic cancer management. The Lombardy model offers a structured framework for enhancing pancreatic cancer care, with potential applicability to other regions and countries seeking to improve their cancer care infrastructure</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 2","pages":"Pages 370-377"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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Digestive and Liver Disease
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