Pub Date : 2025-02-01DOI: 10.1016/j.jhepr.2024.101263
Jinlin Hou , Thomas Berg , Arndt Vogel , Teerha Piratvisuth , Jörg Trojan , Enrico N. De Toni , Masatoshi Kudo , Katarina Malinowsky , Peter Findeisen , Johannes Kolja Hegel , Wenzel Schöning , Kairat Madin , Konstantin Kroeniger , Henry Lik-Yuen Chan , Ashish Sharma
<div><h3>Background & Aims</h3><div>We compared the clinical performance of the novel GAAD (gender [biological sex], age, alpha-fetoprotein [AFP], des-gamma carboxyprothrombin [DCP]) and GALAD (gender [biological sex], age, AFP, <em>Lens culinaris</em> agglutinin-reactive AFP [AFP-L3], DCP) algorithms to deduce the clinical utility of AFP-L3 for detecting early-stage hepatocellular carcinoma (HCC) from chronic liver disease (CLD).</div></div><div><h3>Methods</h3><div>An algorithm development study (STOP-HCC-ARP) and clinical validation study (STOP-HCC-MCE) were conducted, recruiting adult participants with HCC (confirmed by radiology or pathology) or CLD in an international, multicenter, case-control design. Serum biomarkers were measured using Elecsys assays (GAAD and GALAD [Cobas]) or μTASWAKO assays (GALAD [μTASWAKO]) while blinded to case/control status.</div></div><div><h3>Results</h3><div>In STOP-HCC-ARP (algorithm development cohort), 1,006 patients {297 HCC (41.4% early-stage [Barcelona Clinic Liver Cancer {BCLC} 0/A) and 709 CLD} were included. Area under the curve (AUCs) for discriminating between early-stage HCC <em>vs.</em> CLD were 91.4%, 91.4%, and 90.8% for GAAD (Cobas), GALAD (Cobas), and GALAD (μTASWAKO), respectively. The clinical validation cohort of STOP-HCC-MCE comprised 1,142 patients, (366 HCC cases [48% early-stage], 468 specificity samples and 302 CLD); AUCs for GAAD (Cobas), GALAD (Cobas), and GALAD (μTASWAKO) for discriminating between early-stage HCC <em>vs.</em> CLD were 91.4%, 91.5%, and 91.0%, respectively; AUCs were 94.7–95.0% for all-stage HCC. The GAAD and GALAD algorithms demonstrated similar good performance regardless of disease etiology, presence of cirrhosis, geographical region, and within pan-tumor specificity panels (<em>p</em> <0.001).</div></div><div><h3>Conclusions</h3><div>GAAD (Cobas) demonstrated good clinical performance, similar to GALAD (Cobas and μTASWAKO) algorithms, in differentiating HCC and CLD controls, across all disease stages, etiologies, and regions; therefore, AFP-L3 may have a negligible role in GALAD for HCC surveillance.</div></div><div><h3>Impact and implications</h3><div>To improve the detection of early-stage hepatocellular carcinoma (HCC) from benign chronic liver disease (CLD), algorithms combining demographic characteristics and serum biomarkers, such as GAAD and GALAD, have been developed. GAAD combines gender (biological sex), age, alpha-fetoprotein (AFP), des-gamma carboxy-prothrombin (DCP); GALAD combines the same characteristics and biomarkers as GAAD with the addition of <em>Lens culinaris</em> agglutinin-reactive AFP (AFP-L3). Changing disease etiologies and treatment paradigms have raised questions regarding the utility of AFP-L3 in HCC surveillance. Our work demonstrates that the GAAD (Cobas) algorithm demonstrated good clinical performance and was as sensitive and specific as the GALAD (Cobas) and GALAD (μTASWAKO) algorithms in differentiating HCC and CLD cont
{"title":"Comparative evaluation of multimarker algorithms for early-stage HCC detection in multicenter prospective studies","authors":"Jinlin Hou , Thomas Berg , Arndt Vogel , Teerha Piratvisuth , Jörg Trojan , Enrico N. De Toni , Masatoshi Kudo , Katarina Malinowsky , Peter Findeisen , Johannes Kolja Hegel , Wenzel Schöning , Kairat Madin , Konstantin Kroeniger , Henry Lik-Yuen Chan , Ashish Sharma","doi":"10.1016/j.jhepr.2024.101263","DOIUrl":"10.1016/j.jhepr.2024.101263","url":null,"abstract":"<div><h3>Background & Aims</h3><div>We compared the clinical performance of the novel GAAD (gender [biological sex], age, alpha-fetoprotein [AFP], des-gamma carboxyprothrombin [DCP]) and GALAD (gender [biological sex], age, AFP, <em>Lens culinaris</em> agglutinin-reactive AFP [AFP-L3], DCP) algorithms to deduce the clinical utility of AFP-L3 for detecting early-stage hepatocellular carcinoma (HCC) from chronic liver disease (CLD).</div></div><div><h3>Methods</h3><div>An algorithm development study (STOP-HCC-ARP) and clinical validation study (STOP-HCC-MCE) were conducted, recruiting adult participants with HCC (confirmed by radiology or pathology) or CLD in an international, multicenter, case-control design. Serum biomarkers were measured using Elecsys assays (GAAD and GALAD [Cobas]) or μTASWAKO assays (GALAD [μTASWAKO]) while blinded to case/control status.</div></div><div><h3>Results</h3><div>In STOP-HCC-ARP (algorithm development cohort), 1,006 patients {297 HCC (41.4% early-stage [Barcelona Clinic Liver Cancer {BCLC} 0/A) and 709 CLD} were included. Area under the curve (AUCs) for discriminating between early-stage HCC <em>vs.</em> CLD were 91.4%, 91.4%, and 90.8% for GAAD (Cobas), GALAD (Cobas), and GALAD (μTASWAKO), respectively. The clinical validation cohort of STOP-HCC-MCE comprised 1,142 patients, (366 HCC cases [48% early-stage], 468 specificity samples and 302 CLD); AUCs for GAAD (Cobas), GALAD (Cobas), and GALAD (μTASWAKO) for discriminating between early-stage HCC <em>vs.</em> CLD were 91.4%, 91.5%, and 91.0%, respectively; AUCs were 94.7–95.0% for all-stage HCC. The GAAD and GALAD algorithms demonstrated similar good performance regardless of disease etiology, presence of cirrhosis, geographical region, and within pan-tumor specificity panels (<em>p</em> <0.001).</div></div><div><h3>Conclusions</h3><div>GAAD (Cobas) demonstrated good clinical performance, similar to GALAD (Cobas and μTASWAKO) algorithms, in differentiating HCC and CLD controls, across all disease stages, etiologies, and regions; therefore, AFP-L3 may have a negligible role in GALAD for HCC surveillance.</div></div><div><h3>Impact and implications</h3><div>To improve the detection of early-stage hepatocellular carcinoma (HCC) from benign chronic liver disease (CLD), algorithms combining demographic characteristics and serum biomarkers, such as GAAD and GALAD, have been developed. GAAD combines gender (biological sex), age, alpha-fetoprotein (AFP), des-gamma carboxy-prothrombin (DCP); GALAD combines the same characteristics and biomarkers as GAAD with the addition of <em>Lens culinaris</em> agglutinin-reactive AFP (AFP-L3). Changing disease etiologies and treatment paradigms have raised questions regarding the utility of AFP-L3 in HCC surveillance. Our work demonstrates that the GAAD (Cobas) algorithm demonstrated good clinical performance and was as sensitive and specific as the GALAD (Cobas) and GALAD (μTASWAKO) algorithms in differentiating HCC and CLD cont","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101263"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jhepr.2024.101279
Nicolas Adamus , Julien Edeline , Julie Henriques , Nadim Fares , Thierry Lecomte , Anthony Turpin , Dewi Vernerey , Mathilde Vincens , Brice Chanez , David Tougeron , Christophe Tournigand , Eric Assenat , Matthieu Delaye , Sylvain Manfredi , Olivier Bouché , Nicolas Williet , Angelique Vienot , Lorraine Blaise , Léo Mas , Cindy Neuzillet , Gaël S. Roth
<div><h3>Background & Aims</h3><div>Selective internal radiation therapy (SIRT) is a promising option for liver-only unresectable intrahepatic cholangiocarcinoma (iCCA). The Real-SIRTCCA study retrospectively assessed the benefit of adding SIRT to chemotherapy in this setting within the French nationwide observational cohort ACABi-GERCOR-PRONOBIL.</div></div><div><h3>Methods</h3><div>Inclusion criteria were advanced iCCA with limited or no extrahepatic disease, treated with first-line gemcitabine plus platinum chemotherapy +/- concurrent SIRT. All patients treated with chemotherapy and concurrent SIRT were included. To ensure groups’ similarity, a rigorous selection was applied to the chemo-only group, with exclusion of patients with liver involvement >50% and extrahepatic metastases. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response rate (ORR) and tumor resection rate. Propensity score and inverse probability of treatment weighting (IPTW) propensity approaches were used to address confounding factors between groups.</div></div><div><h3>Results</h3><div>Between July 2007 and December 2023, 277 patients met the Real-SIRTCCA inclusion criteria, with 88 in the chemo-SIRT group and 189 in chemo-only group. Chemo-SIRT was associated with longer PFS (median = 10.8 <em>vs.</em> 5.5 months, hazard ratio [HR] 0.54, 95% CI 0.41-0.71, <em>p <</em>0.0001), a trend for longer OS (median = 22.5 <em>vs.</em> 15.1 months, HR 0.76, 95% CI 0.57-1.01), higher ORR (58.3% <em>vs.</em> 28.5%, odds ratio [OR] 3.51, 95% CI 2.03-6.09, <em>p <</em>0.0001), and resection rate (18.7% <em>vs</em>. 8.8%, <em>p</em> = 0.0279) compared to chemo-alone. After IPTW, the superiority of chemo-SIRT was confirmed with better PFS (HR 0.55, 95% CI 0.45-0.66, <em>p <</em>0,0001), OS (HR 0.70, 95% CI 0.58-0.85, <em>p</em> = 0.0004), ORR (OR 3.17, 95% CI 2.18-4.49, <em>p <</em>0.0001) and resection rate (OR 2.94, 95% CI 1.71-5.03, <em>p <</em>0.0001).</div></div><div><h3>Conclusions</h3><div>Adding SIRT to first-line chemotherapy significantly improved survival outcomes, ORR, and secondary tumor resection rates in locally advanced iCCA. Prospective randomized data are needed to confirm these results.</div></div><div><h3>Impact and implications:</h3><div>Herein, we report the results of the Real-SIRTCCA study, comparing the efficacy of the gemcitabine-platinum systemic first-line chemotherapy with or without selective internal radiation therapy (SIRT) in 277 patients with locally advanced intrahepatic cholangiocarcinoma within the cohort ACABi-PRONOBIL. An improvement of progression-free survival, overall survival, tumor response and secondary surgical resection rate was observed in favor of chemo-SIRT, before adjustment and after inverse probability of treatment weighting propensity score analyses. Even though prospective randomized data would be needed to confirm these findings, we believe that
{"title":"First-line chemotherapy with selective internal radiation therapy for intrahepatic cholangiocarcinoma: The French ACABi GERCOR PRONOBIL cohort","authors":"Nicolas Adamus , Julien Edeline , Julie Henriques , Nadim Fares , Thierry Lecomte , Anthony Turpin , Dewi Vernerey , Mathilde Vincens , Brice Chanez , David Tougeron , Christophe Tournigand , Eric Assenat , Matthieu Delaye , Sylvain Manfredi , Olivier Bouché , Nicolas Williet , Angelique Vienot , Lorraine Blaise , Léo Mas , Cindy Neuzillet , Gaël S. Roth","doi":"10.1016/j.jhepr.2024.101279","DOIUrl":"10.1016/j.jhepr.2024.101279","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Selective internal radiation therapy (SIRT) is a promising option for liver-only unresectable intrahepatic cholangiocarcinoma (iCCA). The Real-SIRTCCA study retrospectively assessed the benefit of adding SIRT to chemotherapy in this setting within the French nationwide observational cohort ACABi-GERCOR-PRONOBIL.</div></div><div><h3>Methods</h3><div>Inclusion criteria were advanced iCCA with limited or no extrahepatic disease, treated with first-line gemcitabine plus platinum chemotherapy +/- concurrent SIRT. All patients treated with chemotherapy and concurrent SIRT were included. To ensure groups’ similarity, a rigorous selection was applied to the chemo-only group, with exclusion of patients with liver involvement >50% and extrahepatic metastases. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response rate (ORR) and tumor resection rate. Propensity score and inverse probability of treatment weighting (IPTW) propensity approaches were used to address confounding factors between groups.</div></div><div><h3>Results</h3><div>Between July 2007 and December 2023, 277 patients met the Real-SIRTCCA inclusion criteria, with 88 in the chemo-SIRT group and 189 in chemo-only group. Chemo-SIRT was associated with longer PFS (median = 10.8 <em>vs.</em> 5.5 months, hazard ratio [HR] 0.54, 95% CI 0.41-0.71, <em>p <</em>0.0001), a trend for longer OS (median = 22.5 <em>vs.</em> 15.1 months, HR 0.76, 95% CI 0.57-1.01), higher ORR (58.3% <em>vs.</em> 28.5%, odds ratio [OR] 3.51, 95% CI 2.03-6.09, <em>p <</em>0.0001), and resection rate (18.7% <em>vs</em>. 8.8%, <em>p</em> = 0.0279) compared to chemo-alone. After IPTW, the superiority of chemo-SIRT was confirmed with better PFS (HR 0.55, 95% CI 0.45-0.66, <em>p <</em>0,0001), OS (HR 0.70, 95% CI 0.58-0.85, <em>p</em> = 0.0004), ORR (OR 3.17, 95% CI 2.18-4.49, <em>p <</em>0.0001) and resection rate (OR 2.94, 95% CI 1.71-5.03, <em>p <</em>0.0001).</div></div><div><h3>Conclusions</h3><div>Adding SIRT to first-line chemotherapy significantly improved survival outcomes, ORR, and secondary tumor resection rates in locally advanced iCCA. Prospective randomized data are needed to confirm these results.</div></div><div><h3>Impact and implications:</h3><div>Herein, we report the results of the Real-SIRTCCA study, comparing the efficacy of the gemcitabine-platinum systemic first-line chemotherapy with or without selective internal radiation therapy (SIRT) in 277 patients with locally advanced intrahepatic cholangiocarcinoma within the cohort ACABi-PRONOBIL. An improvement of progression-free survival, overall survival, tumor response and secondary surgical resection rate was observed in favor of chemo-SIRT, before adjustment and after inverse probability of treatment weighting propensity score analyses. Even though prospective randomized data would be needed to confirm these findings, we believe that ","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101279"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jhepr.2024.101249
Renqi Luo , Xue Ran , Ruihan Sun
{"title":"Understanding virologic heterogeneity in chronic hepatitis B treatment","authors":"Renqi Luo , Xue Ran , Ruihan Sun","doi":"10.1016/j.jhepr.2024.101249","DOIUrl":"10.1016/j.jhepr.2024.101249","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101249"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jhepr.2024.101280
Philippa C. Matthews , Tingyan Wang , Eleanor Barnes , the Health Informatics Collaborative for Viral Hepatitis
{"title":"Reply to: “Understanding virologic heterogeneity in chronic hepatitis B treatment”","authors":"Philippa C. Matthews , Tingyan Wang , Eleanor Barnes , the Health Informatics Collaborative for Viral Hepatitis","doi":"10.1016/j.jhepr.2024.101280","DOIUrl":"10.1016/j.jhepr.2024.101280","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101280"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jhepr.2024.101251
Jihye Lim , Ye-Jee Kim , Sehee Kim , Jonggi Choi
Background & Aims
Large-scale studies on the association between primary biliary cholangitis (PBC) and hepatocellular carcinoma (HCC) in Asians are scarce. This study aimed to evaluate the incidence of HCC and its risk factors in a nationwide cohort.
Methods
The data of 4,882 patients with PBC and 38,603 matched controls were extracted from the Korean National Health Insurance Service (2007–2020) and analyzed. The incidence of HCC and its risk factors in patients with PBC were assessed and compared with those in the matched controls. The results were validated in a multicenter hospital cohort of 862 patients with PBC, recruited from Asan Medical Center (n = 815) and Yeouido St. Mary’s Hospital (n = 47) in Korea.
Results
In total, 105 patients with PBC developed HCC over the median follow-up period of 5.42 years, yielding an incidence rate of 3.7/1,000 person-years (PYs), which was significantly higher than that in the controls (0.5/1,000 PYs; adjusted hazard ratio: 9.07; 95% CI: 6.71–12.27). PBC, older age, male sex, diabetes, and smoking were identified as significant risk factors for HCC. Twenty-three of the 862 patients with PBC developed HCC in the multicenter hospital cohort, yielding an incidence of 4.0/1,000 PYs (95% CI: 2.4–5.7). Older age (subdistribution hazard ratio [SHR]: 1.05, 95% CI: 1.00–1.10), male sex (SHR: 3.00, 95% CI: 1.11–8.13), current alcohol consumption (SHR: 3.70, 95% CI: 1.08–12.59), and cirrhosis (SHR: 5.17, 95% CI: 2.07–12.93) were identified as risk factors in the hospital cohort.
Conclusions
Patients with PBC were at a significantly higher risk of developing HCC. Older age and male sex were consistent risk factors in both cohorts.
Impact and implications:
Notable heterogeneity has been observed among different studies in terms of the incidence of hepatocellular carcinoma (HCC) in patients with primary biliary cholangitis (PBC). Large-scale studies on the association between PBC and HCC in Asians are scarce. In our nationwide cohort study, patients with PBC exhibited a significantly heightened risk of developing HCC and mortality than the age- and sex-matched controls. Individuals with PBC had a 9.1-fold higher risk of developing HCC than their matched counterparts, with an incidence rate of 3.7/1,000 person-years. Older age, male sex, smoking, and diabetes were identified as prominent risk factors for HCC in patients with PBC in the nationwide cohort. Older age, male sex, and alcohol consumption were identified as the factors significantly contributing to the elevated risk of HCC in patients with PBC in validation multicenter hospital cohort.
{"title":"Risk of hepatocellular carcinoma in Asian patients with primary biliary cholangitis: A nationwide and hospital cohort study","authors":"Jihye Lim , Ye-Jee Kim , Sehee Kim , Jonggi Choi","doi":"10.1016/j.jhepr.2024.101251","DOIUrl":"10.1016/j.jhepr.2024.101251","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Large-scale studies on the association between primary biliary cholangitis (PBC) and hepatocellular carcinoma (HCC) in Asians are scarce. This study aimed to evaluate the incidence of HCC and its risk factors in a nationwide cohort.</div></div><div><h3>Methods</h3><div>The data of 4,882 patients with PBC and 38,603 matched controls were extracted from the Korean National Health Insurance Service (2007–2020) and analyzed. The incidence of HCC and its risk factors in patients with PBC were assessed and compared with those in the matched controls. The results were validated in a multicenter hospital cohort of 862 patients with PBC, recruited from Asan Medical Center (n = 815) and Yeouido St. Mary’s Hospital (n = 47) in Korea.</div></div><div><h3>Results</h3><div>In total, 105 patients with PBC developed HCC over the median follow-up period of 5.42 years, yielding an incidence rate of 3.7/1,000 person-years (PYs), which was significantly higher than that in the controls (0.5/1,000 PYs; adjusted hazard ratio: 9.07; 95% CI: 6.71–12.27). PBC, older age, male sex, diabetes, and smoking were identified as significant risk factors for HCC. Twenty-three of the 862 patients with PBC developed HCC in the multicenter hospital cohort, yielding an incidence of 4.0/1,000 PYs (95% CI: 2.4–5.7). Older age (subdistribution hazard ratio [SHR]: 1.05, 95% CI: 1.00–1.10), male sex (SHR: 3.00, 95% CI: 1.11–8.13), current alcohol consumption (SHR: 3.70, 95% CI: 1.08–12.59), and cirrhosis (SHR: 5.17, 95% CI: 2.07–12.93) were identified as risk factors in the hospital cohort.</div></div><div><h3>Conclusions</h3><div>Patients with PBC were at a significantly higher risk of developing HCC. Older age and male sex were consistent risk factors in both cohorts.</div></div><div><h3>Impact and implications:</h3><div>Notable heterogeneity has been observed among different studies in terms of the incidence of hepatocellular carcinoma (HCC) in patients with primary biliary cholangitis (PBC). Large-scale studies on the association between PBC and HCC in Asians are scarce. In our nationwide cohort study, patients with PBC exhibited a significantly heightened risk of developing HCC and mortality than the age- and sex-matched controls. Individuals with PBC had a 9.1-fold higher risk of developing HCC than their matched counterparts, with an incidence rate of 3.7/1,000 person-years. Older age, male sex, smoking, and diabetes were identified as prominent risk factors for HCC in patients with PBC in the nationwide cohort. Older age, male sex, and alcohol consumption were identified as the factors significantly contributing to the elevated risk of HCC in patients with PBC in validation multicenter hospital cohort.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101251"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jhepr.2024.101222
Lakshmi Arivazhagan , Sofie Delbare , Robin A. Wilson , Michaele B. Manigrasso , Boyan Zhou , Henry H. Ruiz , Kaamashri Mangar , Ryoko Higa , Emily Brown , Huilin Li , Michael J. Garabedian , Ravichandran Ramasamy , Kathryn J. Moore , Edward A. Fisher , Neil D. Theise , Ann Marie Schmidt
<div><h3>Background & Aims</h3><div>Metabolic syndrome-associated steatotic liver disease (MASLD) and metabolic syndrome-associated steatohepatitis (MASH) have global prevalence rates exceeding 25% and 3-6%, respectively. The introduction of high-fructose corn syrup to the diet in the 1970s has been linked to metabolic and hepatic disturbances. Despite these associations, the potential for sex-dependent responses resulting from fructose-containing diets on MASLD/MASH has not been addressed.</div></div><div><h3>Methods</h3><div>Female and male C57BL/6J mice were fed a fructose-palmitate-cholesterol (FPC)-NASH diet <em>vs.</em> standard chow for 16 weeks (n = 40 mice). At sacrifice, plasma and liver were retrieved, the latter for single-nucleus RNA sequencing. Publicly available data sets of human male and female MASH liver were probed.</div></div><div><h3>Results</h3><div>The FPC-NASH diet-induced metabolic dysfunction in both female and male mice, with females exhibiting more severe hepatic steatosis (<em>p =</em> 0.0262), inflammation (<em>p =</em> 0.0206), and fibrosis (<em>p <</em>0.0001). Single-nucleus RNA sequencing revealed distinct sex-specific transcriptional profiles in hepatocytes and stellate cells responding to the FPC-NASH diet compared to the standard chow. In female mice, compared to males, pathways associated with lipid and metabolic processes in hepatocytes and cell-cell communication and adhesion in stellate cells were enriched. Metabolic flux analyses demonstrated reduced bile acid metabolism in female mice and human hepatocytes in FPC-NASH and MASH conditions, respectively, compared to their male counterparts.</div></div><div><h3>Conclusions</h3><div>Molecular profiling of hepatocytes and stellate cells in FPC-NASH diet-fed mice revealed significant sex differences mirrored in human MASH. The identification of intrinsic, within-sex, diet-dependent disparities underscores the critical need to include both male and female individuals in MAFLD/MASH studies and clinical trials.</div></div><div><h3>Impact and implications:</h3><div>Despite the importance of metabolic dysfunction-associated steatohepatitis (MASH) in impairment of human health, the potential for and mechanisms of sex-dependent responses have yet to be well-studied, particularly with respect to the possible influence of high-fructose corn syrup additives to the diet, which has been linked to metabolic and hepatic disturbances. In a mouse model of fructose supplementation to a NASH diet, female mice displayed significantly higher MASH scores (steatosis, inflammation and fibrosis) compared to male mice. Single-nucleus RNA sequencing of livers revealed intrinsic, diet-dependent molecular disparities within sex, which were exaggerated when comparing female <em>vs.</em> male mice fed the fructose-containing NASH diet; many of these findings were recapitulated in human female <em>vs.</em> male patients with MASH. These results highlight potential mechanistic explana
{"title":"Sex differences in murine MASH induced by a fructose-palmitate-cholesterol-enriched diet","authors":"Lakshmi Arivazhagan , Sofie Delbare , Robin A. Wilson , Michaele B. Manigrasso , Boyan Zhou , Henry H. Ruiz , Kaamashri Mangar , Ryoko Higa , Emily Brown , Huilin Li , Michael J. Garabedian , Ravichandran Ramasamy , Kathryn J. Moore , Edward A. Fisher , Neil D. Theise , Ann Marie Schmidt","doi":"10.1016/j.jhepr.2024.101222","DOIUrl":"10.1016/j.jhepr.2024.101222","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Metabolic syndrome-associated steatotic liver disease (MASLD) and metabolic syndrome-associated steatohepatitis (MASH) have global prevalence rates exceeding 25% and 3-6%, respectively. The introduction of high-fructose corn syrup to the diet in the 1970s has been linked to metabolic and hepatic disturbances. Despite these associations, the potential for sex-dependent responses resulting from fructose-containing diets on MASLD/MASH has not been addressed.</div></div><div><h3>Methods</h3><div>Female and male C57BL/6J mice were fed a fructose-palmitate-cholesterol (FPC)-NASH diet <em>vs.</em> standard chow for 16 weeks (n = 40 mice). At sacrifice, plasma and liver were retrieved, the latter for single-nucleus RNA sequencing. Publicly available data sets of human male and female MASH liver were probed.</div></div><div><h3>Results</h3><div>The FPC-NASH diet-induced metabolic dysfunction in both female and male mice, with females exhibiting more severe hepatic steatosis (<em>p =</em> 0.0262), inflammation (<em>p =</em> 0.0206), and fibrosis (<em>p <</em>0.0001). Single-nucleus RNA sequencing revealed distinct sex-specific transcriptional profiles in hepatocytes and stellate cells responding to the FPC-NASH diet compared to the standard chow. In female mice, compared to males, pathways associated with lipid and metabolic processes in hepatocytes and cell-cell communication and adhesion in stellate cells were enriched. Metabolic flux analyses demonstrated reduced bile acid metabolism in female mice and human hepatocytes in FPC-NASH and MASH conditions, respectively, compared to their male counterparts.</div></div><div><h3>Conclusions</h3><div>Molecular profiling of hepatocytes and stellate cells in FPC-NASH diet-fed mice revealed significant sex differences mirrored in human MASH. The identification of intrinsic, within-sex, diet-dependent disparities underscores the critical need to include both male and female individuals in MAFLD/MASH studies and clinical trials.</div></div><div><h3>Impact and implications:</h3><div>Despite the importance of metabolic dysfunction-associated steatohepatitis (MASH) in impairment of human health, the potential for and mechanisms of sex-dependent responses have yet to be well-studied, particularly with respect to the possible influence of high-fructose corn syrup additives to the diet, which has been linked to metabolic and hepatic disturbances. In a mouse model of fructose supplementation to a NASH diet, female mice displayed significantly higher MASH scores (steatosis, inflammation and fibrosis) compared to male mice. Single-nucleus RNA sequencing of livers revealed intrinsic, diet-dependent molecular disparities within sex, which were exaggerated when comparing female <em>vs.</em> male mice fed the fructose-containing NASH diet; many of these findings were recapitulated in human female <em>vs.</em> male patients with MASH. These results highlight potential mechanistic explana","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 2","pages":"Article 101222"},"PeriodicalIF":9.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jhepr.2024.101254
Zeyuan Yang , Vicki Wing-Ki Hui , Terry Cheuk-Fung Yip , Mandy Sze-Man Lai , Jimmy Che-To Lai , Vincent Wai-Sun Wong , Ramsey Cheung , Grace Lai-Hung Wong , Robert J. Wong
Background & Aims
Alcohol-associated liver disease (ALD) burden has been rising globally, fueled by increases in high-risk alcohol use following the coronavirus disease 2019 (COVID-19) pandemic. We evaluated trends in annual incidence of alcohol-associated hepatitis (AH) before and following the onset of the COVID-19 pandemic across two geographically distinct populations in the USA and Hong Kong.
Methods
Using US national Veterans Affairs (VA) data and Hong Kong territory-wide data, trends in annual incidence of AH were evaluated from 2000 to 2023. AH was identified using a combination of International Classification of Diseases (ICD)-9/10 diagnostic codes, laboratory data, and available alcohol use data.
Results
Among the VA data, annual incidence of AH rose steadily from 39.4 to 53.7 per 100,000 persons (2010–2020), then declined to 36.2 per 100,000 persons in 2023. Annual AH incidence was substantially lower in Hong Kong, but demonstrated similar trends, peaking at 0.28 per 100,000 persons during the first year of the pandemic. Among both cohorts, incidence of AH was significantly higher in men vs. women, but particularly for the VA cohort, the increase in AH incidence was more rapid in women. Among both cohorts, the highest incidence of AH in 2023 was among the 40–49-year age group (VA: 72.7 per 100,000 persons; Hong Kong: 1.89 per 100,000 persons).
Conclusions
We provide a comprehensive analysis of epidemiological trends in AH incidence across two distinct populations, highlighting the need for continued awareness of targeted interventions to curb unhealthy alcohol use and its complications.
Impact and implications:
Alcohol-associated hepatitis (AH) is a severe complication of high-risk alcohol use associated with significant morbidity and mortality. Increasing alcohol use fueled by the COVID-19 pandemic has led to parallel increases in alcohol-related comorbidities. The current study provides a comprehensive analysis of trends in the incidence of AH across two distinct world regions before and following the onset of the COVID-19 pandemic. Better identification of epidemiological trends in AH incidence as well as highlighting populations most affected can help target public health resources and health system interventions to address the dangers of high-risk alcohol use more effectively.
{"title":"Alcohol-associated hepatitis trends before and following the onset of the COVID-19 pandemic across two distinct cohorts in the United States and Hong Kong","authors":"Zeyuan Yang , Vicki Wing-Ki Hui , Terry Cheuk-Fung Yip , Mandy Sze-Man Lai , Jimmy Che-To Lai , Vincent Wai-Sun Wong , Ramsey Cheung , Grace Lai-Hung Wong , Robert J. Wong","doi":"10.1016/j.jhepr.2024.101254","DOIUrl":"10.1016/j.jhepr.2024.101254","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Alcohol-associated liver disease (ALD) burden has been rising globally, fueled by increases in high-risk alcohol use following the coronavirus disease 2019 (COVID-19) pandemic. We evaluated trends in annual incidence of alcohol-associated hepatitis (AH) before and following the onset of the COVID-19 pandemic across two geographically distinct populations in the USA and Hong Kong.</div></div><div><h3>Methods</h3><div>Using US national Veterans Affairs (VA) data and Hong Kong territory-wide data, trends in annual incidence of AH were evaluated from 2000 to 2023. AH was identified using a combination of International Classification of Diseases (ICD)-9/10 diagnostic codes, laboratory data, and available alcohol use data.</div></div><div><h3>Results</h3><div>Among the VA data, annual incidence of AH rose steadily from 39.4 to 53.7 per 100,000 persons (2010–2020), then declined to 36.2 per 100,000 persons in 2023. Annual AH incidence was substantially lower in Hong Kong, but demonstrated similar trends, peaking at 0.28 per 100,000 persons during the first year of the pandemic. Among both cohorts, incidence of AH was significantly higher in men <em>vs</em>. women, but particularly for the VA cohort, the increase in AH incidence was more rapid in women. Among both cohorts, the highest incidence of AH in 2023 was among the 40–49-year age group (VA: 72.7 per 100,000 persons; Hong Kong: 1.89 per 100,000 persons).</div></div><div><h3>Conclusions</h3><div>We provide a comprehensive analysis of epidemiological trends in AH incidence across two distinct populations, highlighting the need for continued awareness of targeted interventions to curb unhealthy alcohol use and its complications.</div></div><div><h3>Impact and implications:</h3><div>Alcohol-associated hepatitis (AH) is a severe complication of high-risk alcohol use associated with significant morbidity and mortality. Increasing alcohol use fueled by the COVID-19 pandemic has led to parallel increases in alcohol-related comorbidities. The current study provides a comprehensive analysis of trends in the incidence of AH across two distinct world regions before and following the onset of the COVID-19 pandemic. Better identification of epidemiological trends in AH incidence as well as highlighting populations most affected can help target public health resources and health system interventions to address the dangers of high-risk alcohol use more effectively.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 1","pages":"Article 101254"},"PeriodicalIF":9.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jhepr.2024.101225
Masahiko Ito , Jie Liu , Masayoshi Fukasawa , Koji Tsutsumi , Yumi Kanegae , Mitsutoshi Setou , Michinori Kohara , Tetsuro Suzuki
<div><h3>Background & Aims</h3><div>Hepatic steatosis, characterized by lipid accumulation in hepatocytes, is a key diagnostic feature in patients with chronic hepatitis C virus (HCV) infection. This study aimed to clarify the involvement of phospholipid metabolic pathways in the pathogenesis of HCV-induced steatosis.</div></div><div><h3>Methods</h3><div>The expression and distribution of lipid species in the livers of human liver chimeric mice were analyzed using imaging mass spectrometry. Triglyceride accumulation and lipid droplet formation were studied in phospholipase A2 group 4C (<em>PLA2G4C</em>) knockout or overexpressing cells.</div></div><div><h3>Results</h3><div>Imaging mass spectrometry of the infected mouse model revealed increased lysophosphatidylcholine levels and decreased phosphatidylcholine levels in HCV-positive regions of the liver. Among the transcripts associated with phosphatidylcholine biosynthesis, upregulation of <em>PLA2G4C</em> mRNA was most pronounced following HCV infection. Activation of the transcription factor NF-κB and upregulation of c-Myc were important for activation of <em>PLA2G4C</em> transcription by HCV infection and expression of the viral proteins Core-NS2. The amount and size of lipid droplets were reduced in <em>PLA2G4C</em>-knockout cells. Inhibition of NF-κB or c-Myc activity suppressed lipid droplet formation in HCV-infected cells. HCV infection promoted the stabilization of lipid droplets, but this stability was reduced in <em>PLA2G4C</em>-knockout cells. Overexpression of <em>PLA2G4C</em> decreased the levels of phosphatidylcholine species in the lipid droplet fraction and led to lower levels of key factors involved in lipolysis (breakdown of triglycerides into glycerol and free fatty acids), such as ATGL, PLIN1 and ABHD5 on the lipid droplets.</div></div><div><h3>Conclusions</h3><div>HCV infection markedly increases <em>PLA2G4C</em> expression. This may alter the phospholipid composition of the lipid droplet membrane, leading to stabilization and enlargement of the droplets.</div></div><div><h3>Impact and implications:</h3><div>The involvement of phospholipid metabolism pathways in the pathogenesis of hepatitis C virus (HCV)-related liver diseases remains unclear. We found that <em>PLA2G4C</em> expression is upregulated through NF-κB and c-Myc activation upon HCV infection, and this upregulation is associated with a decrease in phosphatidylcholine species. The increased expression of <em>PLA2G4C</em> resulted in changes in the phospholipid composition of lipid droplets, led to the dissociation of lipolysis-related factors from the lipid droplet surface and the accumulation of lipid content within the droplets. These findings suggest that the disruption of the phospholipid metabolism pathway caused by HCV infection may contribute to the development of HCV-associated fatty liver. It would be interesting to determine whether alcohol- and/or metabolic dysfunction-associated steatohepatitis are al
{"title":"Induction of phospholipase A2 group 4C by HCV infection regulates lipid droplet formation","authors":"Masahiko Ito , Jie Liu , Masayoshi Fukasawa , Koji Tsutsumi , Yumi Kanegae , Mitsutoshi Setou , Michinori Kohara , Tetsuro Suzuki","doi":"10.1016/j.jhepr.2024.101225","DOIUrl":"10.1016/j.jhepr.2024.101225","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Hepatic steatosis, characterized by lipid accumulation in hepatocytes, is a key diagnostic feature in patients with chronic hepatitis C virus (HCV) infection. This study aimed to clarify the involvement of phospholipid metabolic pathways in the pathogenesis of HCV-induced steatosis.</div></div><div><h3>Methods</h3><div>The expression and distribution of lipid species in the livers of human liver chimeric mice were analyzed using imaging mass spectrometry. Triglyceride accumulation and lipid droplet formation were studied in phospholipase A2 group 4C (<em>PLA2G4C</em>) knockout or overexpressing cells.</div></div><div><h3>Results</h3><div>Imaging mass spectrometry of the infected mouse model revealed increased lysophosphatidylcholine levels and decreased phosphatidylcholine levels in HCV-positive regions of the liver. Among the transcripts associated with phosphatidylcholine biosynthesis, upregulation of <em>PLA2G4C</em> mRNA was most pronounced following HCV infection. Activation of the transcription factor NF-κB and upregulation of c-Myc were important for activation of <em>PLA2G4C</em> transcription by HCV infection and expression of the viral proteins Core-NS2. The amount and size of lipid droplets were reduced in <em>PLA2G4C</em>-knockout cells. Inhibition of NF-κB or c-Myc activity suppressed lipid droplet formation in HCV-infected cells. HCV infection promoted the stabilization of lipid droplets, but this stability was reduced in <em>PLA2G4C</em>-knockout cells. Overexpression of <em>PLA2G4C</em> decreased the levels of phosphatidylcholine species in the lipid droplet fraction and led to lower levels of key factors involved in lipolysis (breakdown of triglycerides into glycerol and free fatty acids), such as ATGL, PLIN1 and ABHD5 on the lipid droplets.</div></div><div><h3>Conclusions</h3><div>HCV infection markedly increases <em>PLA2G4C</em> expression. This may alter the phospholipid composition of the lipid droplet membrane, leading to stabilization and enlargement of the droplets.</div></div><div><h3>Impact and implications:</h3><div>The involvement of phospholipid metabolism pathways in the pathogenesis of hepatitis C virus (HCV)-related liver diseases remains unclear. We found that <em>PLA2G4C</em> expression is upregulated through NF-κB and c-Myc activation upon HCV infection, and this upregulation is associated with a decrease in phosphatidylcholine species. The increased expression of <em>PLA2G4C</em> resulted in changes in the phospholipid composition of lipid droplets, led to the dissociation of lipolysis-related factors from the lipid droplet surface and the accumulation of lipid content within the droplets. These findings suggest that the disruption of the phospholipid metabolism pathway caused by HCV infection may contribute to the development of HCV-associated fatty liver. It would be interesting to determine whether alcohol- and/or metabolic dysfunction-associated steatohepatitis are al","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 1","pages":"Article 101225"},"PeriodicalIF":9.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jhepr.2024.101223
Vincent Merens , Elisabeth Knetemann , Elif Gürbüz , Vincent De Smet , Nouredin Messaoudi , Hendrik Reynaert , Stefaan Verhulst , Leo A. van Grunsven
Background & Aims
The progression of chronic liver disease (CLD) is characterized by excessive extracellular matrix deposition, disrupting hepatic architecture and function. Upon liver injury, hepatic stellate cells (HSCs) differentiate towards myofibroblasts and become inflammatory, proliferative and fibrogenic. To date, it is still unclear whether HSC activation is driven by similar mechanisms in different aetiologies.
Methods
HSCs from multiple publicly available single-cell RNA-sequencing datasets were annotated and merged into a single-cell HSC activation atlas. Spheroid co-cultures of primary mouse hepatocytes/HSCs (n = 5) and ELISAs on patient plasma samples (n = 80) were performed to validate the mechanistic insight obtained from the HSC atlas.
Results
We established an HSC activation atlas in which HSCs are clearly divided into three distinct transcriptomic profiles: quiescent HSCs, initiatory HSCs and myofibroblasts. These transcriptomic profiles are present in each of the investigated mouse liver injury models as well as in human CLDs, indicating that HSC activation is a conserved process. This activation process is driven by a core set of transcription factors independent of liver injury or species. Furthermore, we reveal novel ligands associated with activation of HSCs in multiple liver injury models and validate the profibrotic effect of parathyroid hormone. Finally, we identify COLEC10 as a conserved marker for quiescent HSCs and a biomarker of liver fibrosis in patients with different CLDs (p <0.0001).
Conclusions
We reveal unexpected similarities in the regulatory mechanisms of HSCs across diverse liver injury settings and species. The HSC activation atlas has the potential to provide novel insights into liver fibrosis and steer novel treatment options.
Impact and implications:
This study establishes a single-cell atlas of hepatic stellate cells across various liver injuries, highlighting a conserved activation process between different injuries and across species. The discovery of novel activating ligands and the biomarker COLEC10 in human plasma could be used to enhance diagnostic and therapeutic strategies. Additionally, the conserved activation process supports the use of any mouse model for mechanistic studies and testing of new anti-fibrotic compounds, streamlining preclinical research efforts.
{"title":"Hepatic stellate cell single cell atlas reveals a highly similar activation process across liver disease aetiologies","authors":"Vincent Merens , Elisabeth Knetemann , Elif Gürbüz , Vincent De Smet , Nouredin Messaoudi , Hendrik Reynaert , Stefaan Verhulst , Leo A. van Grunsven","doi":"10.1016/j.jhepr.2024.101223","DOIUrl":"10.1016/j.jhepr.2024.101223","url":null,"abstract":"<div><h3>Background & Aims</h3><div>The progression of chronic liver disease (CLD) is characterized by excessive extracellular matrix deposition, disrupting hepatic architecture and function. Upon liver injury, hepatic stellate cells (HSCs) differentiate towards myofibroblasts and become inflammatory, proliferative and fibrogenic. To date, it is still unclear whether HSC activation is driven by similar mechanisms in different aetiologies.</div></div><div><h3>Methods</h3><div>HSCs from multiple publicly available single-cell RNA-sequencing datasets were annotated and merged into a single-cell HSC activation atlas. Spheroid co-cultures of primary mouse hepatocytes/HSCs (n = 5) and ELISAs on patient plasma samples (n = 80) were performed to validate the mechanistic insight obtained from the HSC atlas.</div></div><div><h3>Results</h3><div>We established an HSC activation atlas in which HSCs are clearly divided into three distinct transcriptomic profiles: quiescent HSCs, initiatory HSCs and myofibroblasts. These transcriptomic profiles are present in each of the investigated mouse liver injury models as well as in human CLDs, indicating that HSC activation is a conserved process. This activation process is driven by a core set of transcription factors independent of liver injury or species. Furthermore, we reveal novel ligands associated with activation of HSCs in multiple liver injury models and validate the profibrotic effect of parathyroid hormone. Finally, we identify <em>COLEC10</em> as a conserved marker for quiescent HSCs and a biomarker of liver fibrosis in patients with different CLDs (<em>p <</em>0.0001).</div></div><div><h3>Conclusions</h3><div>We reveal unexpected similarities in the regulatory mechanisms of HSCs across diverse liver injury settings and species. The HSC activation atlas has the potential to provide novel insights into liver fibrosis and steer novel treatment options.</div></div><div><h3>Impact and implications:</h3><div>This study establishes a single-cell atlas of hepatic stellate cells across various liver injuries, highlighting a conserved activation process between different injuries and across species. The discovery of novel activating ligands and the biomarker COLEC10 in human plasma could be used to enhance diagnostic and therapeutic strategies. Additionally, the conserved activation process supports the use of any mouse model for mechanistic studies and testing of new anti-fibrotic compounds, streamlining preclinical research efforts.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 1","pages":"Article 101223"},"PeriodicalIF":9.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jhepr.2024.101292
Xavier Forns , Josep M. Llovet
{"title":"The first year of the new Editorial Team of JHEP Reports","authors":"Xavier Forns , Josep M. Llovet","doi":"10.1016/j.jhepr.2024.101292","DOIUrl":"10.1016/j.jhepr.2024.101292","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 1","pages":"Article 101292"},"PeriodicalIF":9.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}