Hepatitis C virus (HCV) vaccines are urgently needed to achieve WHO's goal for the elimination of viral hepatitis by 2030. The lack of suitable animal models for evaluating vaccine efficacy has greatly hindered the development of HCV vaccines. By using the rat model chronically infected with rodent hepacivirus from Rattus norvegicus (RHV-rn1), a hepacivirus homologously close to HCV as a surrogate model of HCV infection, we assessed the protective effectiveness of the RHV-rn1 vaccine Sad23L-RHVns.
Methods
Sad23L-RHVns vaccine was constructed with the nonstructural proteins (NS) 3–5B genes of RHV-rn1. SD rats were immunised with Sad23L-RHVns by prime or prime-boost regimen via intramuscular injection, then challenged 4 weeks post vaccination by RHV-rn1. A part of the rats were rechallenged with a variant 15 weeks post the first challenge of RHV-rn1.
Results
The specific T-cell responses to NS3-5B antigens were induced by prime immunisation, which were significantly enhanced by boost vaccination. The inoculated rats and controls were challenged by wild-type RHV-rn1, of all the primed and control rats having persistently high levels of viremia, whereas 7 of 9 (77.8%) boosted rats cleared RHV-rn1 infection. Interestingly, the resolver acquired immune protection against re-challenging with variant and showed significantly higher T-cell responses than the nonresolver in 25 weeks post rechallenge.
Conclusions
Sad23L-RHVns with prime-boost regimen protected 77.8% of rats against wild-type RHV-rn1 infection, and resolvers showed high levels and maintenance of T cell immunity against the variant. Our findings that maintenance of effective T cell immunity is required for RHV-rn1 resolution may provide insight to develop the HCV vaccine in humans.
{"title":"Protection of Novel Adenovirus Vectored Vaccine in Rats Against Wild-Type Hepacivirus and Variant Infections","authors":"Shengxue Luo, Qitao Deng, Chaolan Liang, Panli Zhang, Peng Zou, Shikai Deng, Meng Zhang, Feifeng Zeng, Ling Zhang, Yongshui Fu, Chengyao Li, Tingting Li","doi":"10.1111/liv.70045","DOIUrl":"https://doi.org/10.1111/liv.70045","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Hepatitis C virus (HCV) vaccines are urgently needed to achieve WHO's goal for the elimination of viral hepatitis by 2030. The lack of suitable animal models for evaluating vaccine efficacy has greatly hindered the development of HCV vaccines. By using the rat model chronically infected with rodent hepacivirus from <i>Rattus norvegicus</i> (RHV-rn1), a hepacivirus homologously close to HCV as a surrogate model of HCV infection, we assessed the protective effectiveness of the RHV-rn1 vaccine Sad23L-RHVns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sad23L-RHVns vaccine was constructed with the nonstructural proteins (NS) 3–5B genes of RHV-rn1. SD rats were immunised with Sad23L-RHVns by prime or prime-boost regimen via intramuscular injection, then challenged 4 weeks post vaccination by RHV-rn1. A part of the rats were rechallenged with a variant 15 weeks post the first challenge of RHV-rn1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The specific T-cell responses to NS3-5B antigens were induced by prime immunisation, which were significantly enhanced by boost vaccination. The inoculated rats and controls were challenged by wild-type RHV-rn1, of all the primed and control rats having persistently high levels of viremia, whereas 7 of 9 (77.8%) boosted rats cleared RHV-rn1 infection. Interestingly, the resolver acquired immune protection against re-challenging with variant and showed significantly higher T-cell responses than the nonresolver in 25 weeks post rechallenge.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Sad23L-RHVns with prime-boost regimen protected 77.8% of rats against wild-type RHV-rn1 infection, and resolvers showed high levels and maintenance of T cell immunity against the variant. Our findings that maintenance of effective T cell immunity is required for RHV-rn1 resolution may provide insight to develop the HCV vaccine in humans.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Real-World Case Supporting Drug-Induced Autoimmune Hepatitis: Updated Insights and Analysis of the FAERS Data","authors":"Duoqin Huang, Jianglong Shi","doi":"10.1111/liv.70055","DOIUrl":"https://doi.org/10.1111/liv.70055","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clémence Ramier, Camelia Protopopescu, Vincent Di Beo, Lucia Parlati, Fabienne Marcellin, Fabrice Carrat, Tarik Asselah, Marc Bourlière, Patrizia Carrieri, the ANRS/AFEF CO22 HEPATHER Study Group
Background and Aims
Early assessment of hepatocellular carcinoma (HCC) risk could improve long-term outcomes in people with chronic hepatitis B virus (HBV) infection. Some existing HCC predictive scores are not easily implementable. We developed easy-to-use HCC predictive scores based on behavioural and routine bio-clinical data in people with chronic HBV infection.
Methods
Eight-year follow-up data was analysed from people with chronic HBV infection enrolled in the French ANRS CO22 HEPATHER cohort. Patients were randomly split into two samples (training/testing). A multivariable Cox model for time to HCC was estimated on the training sample. The HCC predictive score was computed by summing the points assigned to model predictors, normalising their coefficients over a 10-year age increment, and rounding to the nearest integer. The Youden index identified the score's optimal risk threshold. Comparisons with existing predictive scores were performed on the testing sample.
Results
In the study population (N = 4370; 63% of men; 65% of < 50 years old), 56 HCC cases occurred during 25,900 follow-up person-years. Two HCC predictive scores were defined: SADAPTT (daily soft drink consumption, age, hepatitis Delta infection, unhealthy alcohol use, platelet count, heavy tobacco smoking, and HBV treatment) and ADAPTT (the same predictors except for daily soft drink consumption), with ranges 0–13 and 0–14, respectively, and values ≥ 3 indicating a high HCC risk. Their performances were similar to existing scores.
Conclusions
We developed two effective behaviour-based HCC predictive scores, implementable in many settings, including primary care and decentralised areas. Further studies are needed to validate these scores in other datasets.
{"title":"Behaviour-Based Predictive Scores of Hepatocellular Carcinoma in People With Chronic Hepatitis B (ANRS CO22 HEPATHER)","authors":"Clémence Ramier, Camelia Protopopescu, Vincent Di Beo, Lucia Parlati, Fabienne Marcellin, Fabrice Carrat, Tarik Asselah, Marc Bourlière, Patrizia Carrieri, the ANRS/AFEF CO22 HEPATHER Study Group","doi":"10.1111/liv.70065","DOIUrl":"https://doi.org/10.1111/liv.70065","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Early assessment of hepatocellular carcinoma (HCC) risk could improve long-term outcomes in people with chronic hepatitis B virus (HBV) infection. Some existing HCC predictive scores are not easily implementable. We developed easy-to-use HCC predictive scores based on behavioural and routine bio-clinical data in people with chronic HBV infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eight-year follow-up data was analysed from people with chronic HBV infection enrolled in the French ANRS CO22 HEPATHER cohort. Patients were randomly split into two samples (training/testing). A multivariable Cox model for time to HCC was estimated on the training sample. The HCC predictive score was computed by summing the points assigned to model predictors, normalising their coefficients over a 10-year age increment, and rounding to the nearest integer. The Youden index identified the score's optimal risk threshold. Comparisons with existing predictive scores were performed on the testing sample.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the study population (<i>N</i> = 4370; 63% of men; 65% of < 50 years old), 56 HCC cases occurred during 25,900 follow-up person-years. Two HCC predictive scores were defined: SADAPTT (daily soft drink consumption, age, hepatitis Delta infection, unhealthy alcohol use, platelet count, heavy tobacco smoking, and HBV treatment) and ADAPTT (the same predictors except for daily soft drink consumption), with ranges 0–13 and 0–14, respectively, and values ≥ 3 indicating a high HCC risk. Their performances were similar to existing scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We developed two effective behaviour-based HCC predictive scores, implementable in many settings, including primary care and decentralised areas. Further studies are needed to validate these scores in other datasets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ville Liukkonen, Maria Semenova, Kati Hyvärinen, Jouni Lauronen, Jukka Partanen, Johanna Arola, Arno Nordin, Martti Färkkilä, Fredrik Åberg
Background
The role of genetic risk factors for steatotic liver disease (SLD) is intriguing in liver transplantation (LT), as both donor and recipient genetic factors may play a role. There are only a few small-scale studies published so far.
Methods
We analysed the incidence and risk factors for post-LT SLD and the impact of 56 SLD-associated genetic variants in 595 donor-recipient pairs with liver biopsy available ≥ 6 months after LT. We evaluated whether the polygenic risk score (PRS-5) improves the ability to predict post-LT SLD in addition to non-genetic risk factors.
Results
SLD after LT was diagnosed in 34.5% of patients during a median 7.6-year follow-up. In multivariate analysis including non-genetic risk factors, donor PNPLA3 rs738409-G (HR for SLD: C/G 1.34, p = 0.051, G/G 2.25, p = 0.004), donor HSD17B13 rs72613567-TA (HR for SLD: TA/T 0.68, p = 0.02 TA/TA HR 0.50, p = 0.10) and recipient UCP2 rs695366-G (HR for SLD: A/G 0.63, p = 0.002, G/G HR 0.50, p = 0.04) appeared as the most important genetic risk factors for post-LT SLD. The addition of PRS-5 to a multivariate regression model (including non-genetic risk factors) improved the predictive ability for SLD only modestly (AUC 0.78 to 0.80).
Conclusions
Various genetic variants contribute to post-LT SLD with separate variants among recipients and donors, with donor PNPLA3 rs738409-G as the most significant risk allele. Still, donor and recipient genotyping provide only modest additional value for individual risk stratification over phenotype data, highlighting the role of modifiable risk factors.
{"title":"Genetic Risk Factors for Steatotic Liver Disease After Liver Transplantation","authors":"Ville Liukkonen, Maria Semenova, Kati Hyvärinen, Jouni Lauronen, Jukka Partanen, Johanna Arola, Arno Nordin, Martti Färkkilä, Fredrik Åberg","doi":"10.1111/liv.70067","DOIUrl":"https://doi.org/10.1111/liv.70067","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The role of genetic risk factors for steatotic liver disease (SLD) is intriguing in liver transplantation (LT), as both donor and recipient genetic factors may play a role. There are only a few small-scale studies published so far.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed the incidence and risk factors for post-LT SLD and the impact of 56 SLD-associated genetic variants in 595 donor-recipient pairs with liver biopsy available ≥ 6 months after LT. We evaluated whether the polygenic risk score (PRS-5) improves the ability to predict post-LT SLD in addition to non-genetic risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SLD after LT was diagnosed in 34.5% of patients during a median 7.6-year follow-up. In multivariate analysis including non-genetic risk factors, donor PNPLA3 rs738409-G (HR for SLD: C/G 1.34, <i>p</i> = 0.051, G/G 2.25, <i>p</i> = 0.004), donor HSD17B13 rs72613567-TA (HR for SLD: TA/T 0.68, <i>p</i> = 0.02 TA/TA HR 0.50, <i>p</i> = 0.10) and recipient UCP2 rs695366-G (HR for SLD: A/G 0.63, <i>p</i> = 0.002, G/G HR 0.50, <i>p</i> = 0.04) appeared as the most important genetic risk factors for post-LT SLD. The addition of PRS-5 to a multivariate regression model (including non-genetic risk factors) improved the predictive ability for SLD only modestly (AUC 0.78 to 0.80).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Various genetic variants contribute to post-LT SLD with separate variants among recipients and donors, with donor PNPLA3 rs738409-G as the most significant risk allele. Still, donor and recipient genotyping provide only modest additional value for individual risk stratification over phenotype data, highlighting the role of modifiable risk factors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Early-stage hepatocellular carcinoma (HCC), defined as a single tumour or up to three lesions < 3 cm, according to the Barcelona Clinic Liver Cancer (BCLC) classification, is eligible for curative treatment [<span>1</span>]. Curative options include liver transplantation, surgical resection or percutaneous ablation. Ablation can be selected as a first-line therapy over surgery for tumour(s) < 3 cm due to its advantages, such as lower complication rates, reduced mortality and minimal invasiveness, making it feasible even when liver function is slightly impaired or in the presence of portal hypertension. Moreover, for transplant-eligible patients, the strategy of first-line percutaneous ablation followed by salvage transplantation in case of recurrence is gaining traction worldwide in the context of graft shortages [<span>2</span>]. However, unlike surgery, ablation does not allow for a full histopathological analysis of the resected specimen, limiting the tumour tissue analysis to samples obtained via micro-biopsies prior to the ablation. This is a limitation for prognostic stratification following a first curative treatment, especially for transplantable patients, as recognised histological markers of tumour aggressiveness, such as microvascular invasion and satellites, cannot be captured by biopsies. Intratumoral heterogeneity (ITH) is another promising marker with the potential to provide valuable information on prognosis and the risk of early recurrence. As ITH can only be fully assessed through histological and genomic evaluation of the entire lesion, imaging features of ITH, using modalities such as radiomics and/or deep-learning, could serve as surrogate markers in advanced HCC or in early-stage HCCs treated with ablation where, by definition, no surgical specimen is available.</p><p>In this issue of Liver International, Zhang et al. describe a transformer-based quantitative ITH model that integrates signatures extracted from ultrasound (US), contrast-enhanced US (CEUS) and magnetic resonance imaging (MRI), acquired before ablation, along with demographic, clinicopathological and laboratory variables to predict individual early recurrence risk [<span>3</span>]. The model was tested on cohorts of patients treated with radiofrequency ablation (RFA) and microwave ablation (MWA), and then validated on external cohorts undergoing RFA, laser ablation (LA) and irreversible electroporation (IRE) treatments. The primary structure of the network used to extract ITH-related features from imaging is referred to as the vision-transformer-based quantitative intratumoral heterogeneity (ViT-Q-ITH) model. This deep learning model segments images into patches and employs a self-attention mechanism to analyse correlations between these patches, capturing both global and local relationships to enhance the understanding of complex visual structures. A combined model was then developed by integrating the ViT-Q-ITH score with clinical factors. The study
{"title":"AI-Based Prognostic Stratification in HCC, Towards a Personalised Treatment Approach","authors":"Olivier Sutter, Lorenzo-Carlo Pescatori","doi":"10.1111/liv.16153","DOIUrl":"https://doi.org/10.1111/liv.16153","url":null,"abstract":"<p>Early-stage hepatocellular carcinoma (HCC), defined as a single tumour or up to three lesions < 3 cm, according to the Barcelona Clinic Liver Cancer (BCLC) classification, is eligible for curative treatment [<span>1</span>]. Curative options include liver transplantation, surgical resection or percutaneous ablation. Ablation can be selected as a first-line therapy over surgery for tumour(s) < 3 cm due to its advantages, such as lower complication rates, reduced mortality and minimal invasiveness, making it feasible even when liver function is slightly impaired or in the presence of portal hypertension. Moreover, for transplant-eligible patients, the strategy of first-line percutaneous ablation followed by salvage transplantation in case of recurrence is gaining traction worldwide in the context of graft shortages [<span>2</span>]. However, unlike surgery, ablation does not allow for a full histopathological analysis of the resected specimen, limiting the tumour tissue analysis to samples obtained via micro-biopsies prior to the ablation. This is a limitation for prognostic stratification following a first curative treatment, especially for transplantable patients, as recognised histological markers of tumour aggressiveness, such as microvascular invasion and satellites, cannot be captured by biopsies. Intratumoral heterogeneity (ITH) is another promising marker with the potential to provide valuable information on prognosis and the risk of early recurrence. As ITH can only be fully assessed through histological and genomic evaluation of the entire lesion, imaging features of ITH, using modalities such as radiomics and/or deep-learning, could serve as surrogate markers in advanced HCC or in early-stage HCCs treated with ablation where, by definition, no surgical specimen is available.</p><p>In this issue of Liver International, Zhang et al. describe a transformer-based quantitative ITH model that integrates signatures extracted from ultrasound (US), contrast-enhanced US (CEUS) and magnetic resonance imaging (MRI), acquired before ablation, along with demographic, clinicopathological and laboratory variables to predict individual early recurrence risk [<span>3</span>]. The model was tested on cohorts of patients treated with radiofrequency ablation (RFA) and microwave ablation (MWA), and then validated on external cohorts undergoing RFA, laser ablation (LA) and irreversible electroporation (IRE) treatments. The primary structure of the network used to extract ITH-related features from imaging is referred to as the vision-transformer-based quantitative intratumoral heterogeneity (ViT-Q-ITH) model. This deep learning model segments images into patches and employs a self-attention mechanism to analyse correlations between these patches, capturing both global and local relationships to enhance the understanding of complex visual structures. A combined model was then developed by integrating the ViT-Q-ITH score with clinical factors. The study ","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Burcin Özdirik, Hilmar Berger, Fernanda Raya Tonetti, Noemí Cabré, Nicole Treichel, Thomas Clavel, Frank Tacke, Michael Sigal, Bernd Schnabl
Background and Aims
Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy without treatment options beyond liver transplantation. The gut–liver axis, especially the role of gut microbes, has emerged as a crucial pathway contributing to PSC pathogenesis. Recent research has revealed Enterococcus (E.) faecalis and its virulence factor cytolysin to increase mortality risk in patients with alcohol-associated hepatitis. Thus, we studied the role of enterococci, particularly E. faecalis and its virulence factor genes cytolysin and gelatinase, in faecal samples from patients with PSC.
Methods
To assess the relevance of Enterococcus species, we performed 16S rRNA gene amplicon analysis in faecal samples from 60 patients with PSC. We validated our findings by qPCR of faecal microbial DNA in an extended cohort of 105 patients with PSC, 104 patients with inflammatory bowel disease (IBD) and 68 healthy subjects.
Results
High-throughput 16S rRNA amplicon analysis revealed an increased relative abundance of enterococci in PSC patients compared with healthy controls and IBD patients, respectively, (p < 0.0001). PSC patients with high enterococci abundance had a decreased probability of transplant-free survival (p = 0.028). E. faecalis and its virulence factors cytolysin and gelatinase were more abundant in patients with PSC. Higher faecal cytolysin was associated with lower overall survival (p = 0.04), while survival was independent of gelatinase levels.
Conclusion
Our data highlight the association of E. faecalis and faecal cytolysin with lower survival in patients with PSC. These data should prompt further research into the pathogenic role of cytolysin-positive E. faecalis, and to explore its role as a potential therapeutic target.
{"title":"Faecal Cytolysin is Associated With Worse Survival in Patients With Primary Sclerosing Cholangitis","authors":"Burcin Özdirik, Hilmar Berger, Fernanda Raya Tonetti, Noemí Cabré, Nicole Treichel, Thomas Clavel, Frank Tacke, Michael Sigal, Bernd Schnabl","doi":"10.1111/liv.16181","DOIUrl":"https://doi.org/10.1111/liv.16181","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy without treatment options beyond liver transplantation. The gut–liver axis, especially the role of gut microbes, has emerged as a crucial pathway contributing to PSC pathogenesis. Recent research has revealed <i>Enterococcus (E.) faecalis</i> and its virulence factor cytolysin to increase mortality risk in patients with alcohol-associated hepatitis. Thus, we studied the role of enterococci, particularly <i>E. faecalis</i> and its virulence factor genes cytolysin and gelatinase, in faecal samples from patients with PSC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To assess the relevance of <i>Enterococcus</i> species, we performed 16S rRNA gene amplicon analysis in faecal samples from 60 patients with PSC. We validated our findings by qPCR of faecal microbial DNA in an extended cohort of 105 patients with PSC, 104 patients with inflammatory bowel disease (IBD) and 68 healthy subjects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High-throughput 16S rRNA amplicon analysis revealed an increased relative abundance of enterococci in PSC patients compared with healthy controls and IBD patients, respectively, (<i>p</i> < 0.0001). PSC patients with high enterococci abundance had a decreased probability of transplant-free survival (<i>p</i> = 0.028). <i>E. faecalis</i> and its virulence factors cytolysin and gelatinase were more abundant in patients with PSC. Higher faecal cytolysin was associated with lower overall survival (<i>p</i> = 0.04), while survival was independent of gelatinase levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data highlight the association of <i>E. faecalis</i> and faecal cytolysin with lower survival in patients with PSC. These data should prompt further research into the pathogenic role of cytolysin-positive <i>E. faecalis,</i> and to explore its role as a potential therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Surveillance corresponds to the systematic and repeated action of a screening test during the time with the goal of improving survival [<span>1</span>]. In the hepatocellular carcinoma (HCC) realm, surveillance aims to reduce the risk of cancer-related death through the detection and treatment of HCC at an early stage. However, to recommend or not recommend surveillance in a specific population, it is crucial to integrate the incidence of a specific cancer together with the careful consideration of the competing risks for death and cost-efficacy analysis. As an example, for patients with decompensated liver cirrhosis not candidates for liver transplantation and untreatable for HCC due to liver function or comorbidities, the benefit of detecting an HCC vanishes since survival is dismal due to non-HCC-liver-related events (overdiagnosis) [<span>2</span>]. While the future of HCC surveillance probably leans toward personalised approaches (i.e., with the integration of new biomarkers, and with more sensitive techniques such as magnetic resonance [MR]), bi-annual abdominal ultrasound (US) with or without alpha-fetoprotein (AFP) [<span>3</span>] remains the cornerstone of current practice. Despite the strong recommendation of international guidelines [<span>4-6</span>], surveillance is underused, and this may depend on both physicians (i.e., lower rates for primary care doctors) and patients (low adherence) issues [<span>7, 8</span>]. Therefore, improving the training of both doctors and patients is a key objective in strategies aimed at enhancing surveillance adherence. A variety of approaches have been explored, such as the education of primary care physicians, nurse-led programmes, mailed outreach strategy, and EMR-led best practice alerts [<span>9-12</span>]. The results are heterogeneous but can achieve interesting results in nurse-led programmes, with 53% up to 80%–90% of adherence. However, these results should be confirmed in large-scale populations, and the availability of expert and dedicated nurses should be encouraged. Finally, it is to be noted that a widely expert opinion suggests that US surveillance should be performed by physicians with extensive expertise in liver US.</p><p>In the study by Brahmania et al. [<span>13</span>] in <i>Liver International</i>, the authors performed a retrospective study aiming to evaluate the impact of a region-wide automated recall program on adherence to HCC surveillance Specifically, in 2013 in Calgary (Canada) a diagnostic-image (DI) provider created an automated protocol-based surveillance strategy based on the software used for a breast cancer surveillance program using mammography for patients eligible for HCC screening.</p><p>A healthcare provider (gastroenterologist, hepatologist or primary care) was allowed to enrol patients in the program by submitting a completed one-page requisition with demographic characteristics, reason for screening, and the presence or absence of liver cirrhosis. Patien
{"title":"Surveillance in HCC: Making the Most of What We Have Today","authors":"Marco Sanduzzi-Zamparelli, Giuseppe Cabibbo","doi":"10.1111/liv.70057","DOIUrl":"https://doi.org/10.1111/liv.70057","url":null,"abstract":"<p>Surveillance corresponds to the systematic and repeated action of a screening test during the time with the goal of improving survival [<span>1</span>]. In the hepatocellular carcinoma (HCC) realm, surveillance aims to reduce the risk of cancer-related death through the detection and treatment of HCC at an early stage. However, to recommend or not recommend surveillance in a specific population, it is crucial to integrate the incidence of a specific cancer together with the careful consideration of the competing risks for death and cost-efficacy analysis. As an example, for patients with decompensated liver cirrhosis not candidates for liver transplantation and untreatable for HCC due to liver function or comorbidities, the benefit of detecting an HCC vanishes since survival is dismal due to non-HCC-liver-related events (overdiagnosis) [<span>2</span>]. While the future of HCC surveillance probably leans toward personalised approaches (i.e., with the integration of new biomarkers, and with more sensitive techniques such as magnetic resonance [MR]), bi-annual abdominal ultrasound (US) with or without alpha-fetoprotein (AFP) [<span>3</span>] remains the cornerstone of current practice. Despite the strong recommendation of international guidelines [<span>4-6</span>], surveillance is underused, and this may depend on both physicians (i.e., lower rates for primary care doctors) and patients (low adherence) issues [<span>7, 8</span>]. Therefore, improving the training of both doctors and patients is a key objective in strategies aimed at enhancing surveillance adherence. A variety of approaches have been explored, such as the education of primary care physicians, nurse-led programmes, mailed outreach strategy, and EMR-led best practice alerts [<span>9-12</span>]. The results are heterogeneous but can achieve interesting results in nurse-led programmes, with 53% up to 80%–90% of adherence. However, these results should be confirmed in large-scale populations, and the availability of expert and dedicated nurses should be encouraged. Finally, it is to be noted that a widely expert opinion suggests that US surveillance should be performed by physicians with extensive expertise in liver US.</p><p>In the study by Brahmania et al. [<span>13</span>] in <i>Liver International</i>, the authors performed a retrospective study aiming to evaluate the impact of a region-wide automated recall program on adherence to HCC surveillance Specifically, in 2013 in Calgary (Canada) a diagnostic-image (DI) provider created an automated protocol-based surveillance strategy based on the software used for a breast cancer surveillance program using mammography for patients eligible for HCC screening.</p><p>A healthcare provider (gastroenterologist, hepatologist or primary care) was allowed to enrol patients in the program by submitting a completed one-page requisition with demographic characteristics, reason for screening, and the presence or absence of liver cirrhosis. Patien","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Risk of Acute Liver Injury Following the Nirmatrelvir/Ritonavir Use","authors":"Jiliang Ning","doi":"10.1111/liv.16206","DOIUrl":"https://doi.org/10.1111/liv.16206","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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