Pub Date : 2025-03-12DOI: 10.1016/j.jhepr.2025.101392
Yunfei Zhang , Ruofan Sheng , Xianling Qian , Heqing Wang , Fei Wu , Haoran Dai , Mingyue Song , Chun Yang , Jianjun Zhou , Weiguo Zhang , Mengsu Zeng
<div><h3>Background & Aims</h3><div>By reducing some magnetic resonance imaging (MRI) sequences, abbreviated MRI (aMRI) has shown extensive promise for detecting hepatocellular carcinoma (HCC). We aim to develop deep learning (DL)-based gadolinium-free contrast-enhanced (CE) aMRI protocols (DL-aMRI) for detecting HCC.</div></div><div><h3>Methods</h3><div>In total, 1,769 patients (913 with HCC) were retrospectively included from three institutions for training, testing, and external validation. Stable diffusion-based DL models were trained to generate CE-MRI, including T1-weighted arterial, portal venous, transitional, and hepatobiliary phase images (AP-syn, VP-syn, TP-syn, and HBP-syn, respectively). Non-contrast-MRI (NC-MRI), including T2-weighted, diffusion-weighted, and pre-contrast T1-weighted (Pre) sequences, along with either actual or DL-synthesized CE-MRI (AP, VP, TP, and HBP or AP-syn, VP-syn, TP-syn, and HBP-syn), were used to create conventional complete MRI (cMRI) and DL-aMRI protocols. An inter-method comparison of image quality between DL-aMRI and cMRI was conducted using a non-inferiority test. The sensitivity and specificity of DL-aMRI and cMRI for detecting HCC were statistically compared using the non-inferiority test and generalized estimating equations models.</div></div><div><h3>Results</h3><div>DL-aMRI showed a remarkable reduction in acquisition time compared with cMRI (4.1 <em>vs.</em> 28.1 min). The image quality of DL-synthesized CE-MRI was not inferior to that of actual CE-MRI (<em>p</em> <0.001). There was an excellent inter-method agreement between the HCC sizes measured by the two protocols (R<sup>2</sup> = 0.9436–0.9683). The pooled sensitivity and specificity of cMRI and DL-aMRI were 0.899 and 0.925 and 0.866 and 0.922, respectively. No significant differences were found between the sensitivity and specificity of the two protocols.</div></div><div><h3>Conclusions</h3><div>The proposed DL-aMRI could facilitate precise HCC diagnosis with no need for contrast agents, a substantial reduction in acquisition time, and preservation of both NC-MRI and CE-MRI data. DL-aMRI may serve as a valuable tool for HCC diagnosing.</div></div><div><h3>Impact and implications</h3><div>In this multi-center study involving 1,769 participants, we developed a generative deep learning-based abbreviated MRI (DL-aMRI) strategy that provides an efficient, contrast-agent-free alternative for detecting HCC with accuracy comparable to that of conventional complete MRI, significantly reducing acquisition time from 28.1 min to just 4.1 min. This strategy is valuable for clinicians who face significant workloads resulting from long MRI scanning times and the potential adverse effects of contrast agents, as well as for researchers focused on developing cost-effective and accessible diagnostic tools for HCC detection. The proposed DL-aMRI protocol has practical implications for clinical settings, enhancing diagnostic efficiency while maintainin
{"title":"Deep learning empowered gadolinium-free contrast-enhanced abbreviated MRI for diagnosing hepatocellular carcinoma","authors":"Yunfei Zhang , Ruofan Sheng , Xianling Qian , Heqing Wang , Fei Wu , Haoran Dai , Mingyue Song , Chun Yang , Jianjun Zhou , Weiguo Zhang , Mengsu Zeng","doi":"10.1016/j.jhepr.2025.101392","DOIUrl":"10.1016/j.jhepr.2025.101392","url":null,"abstract":"<div><h3>Background & Aims</h3><div>By reducing some magnetic resonance imaging (MRI) sequences, abbreviated MRI (aMRI) has shown extensive promise for detecting hepatocellular carcinoma (HCC). We aim to develop deep learning (DL)-based gadolinium-free contrast-enhanced (CE) aMRI protocols (DL-aMRI) for detecting HCC.</div></div><div><h3>Methods</h3><div>In total, 1,769 patients (913 with HCC) were retrospectively included from three institutions for training, testing, and external validation. Stable diffusion-based DL models were trained to generate CE-MRI, including T1-weighted arterial, portal venous, transitional, and hepatobiliary phase images (AP-syn, VP-syn, TP-syn, and HBP-syn, respectively). Non-contrast-MRI (NC-MRI), including T2-weighted, diffusion-weighted, and pre-contrast T1-weighted (Pre) sequences, along with either actual or DL-synthesized CE-MRI (AP, VP, TP, and HBP or AP-syn, VP-syn, TP-syn, and HBP-syn), were used to create conventional complete MRI (cMRI) and DL-aMRI protocols. An inter-method comparison of image quality between DL-aMRI and cMRI was conducted using a non-inferiority test. The sensitivity and specificity of DL-aMRI and cMRI for detecting HCC were statistically compared using the non-inferiority test and generalized estimating equations models.</div></div><div><h3>Results</h3><div>DL-aMRI showed a remarkable reduction in acquisition time compared with cMRI (4.1 <em>vs.</em> 28.1 min). The image quality of DL-synthesized CE-MRI was not inferior to that of actual CE-MRI (<em>p</em> <0.001). There was an excellent inter-method agreement between the HCC sizes measured by the two protocols (R<sup>2</sup> = 0.9436–0.9683). The pooled sensitivity and specificity of cMRI and DL-aMRI were 0.899 and 0.925 and 0.866 and 0.922, respectively. No significant differences were found between the sensitivity and specificity of the two protocols.</div></div><div><h3>Conclusions</h3><div>The proposed DL-aMRI could facilitate precise HCC diagnosis with no need for contrast agents, a substantial reduction in acquisition time, and preservation of both NC-MRI and CE-MRI data. DL-aMRI may serve as a valuable tool for HCC diagnosing.</div></div><div><h3>Impact and implications</h3><div>In this multi-center study involving 1,769 participants, we developed a generative deep learning-based abbreviated MRI (DL-aMRI) strategy that provides an efficient, contrast-agent-free alternative for detecting HCC with accuracy comparable to that of conventional complete MRI, significantly reducing acquisition time from 28.1 min to just 4.1 min. This strategy is valuable for clinicians who face significant workloads resulting from long MRI scanning times and the potential adverse effects of contrast agents, as well as for researchers focused on developing cost-effective and accessible diagnostic tools for HCC detection. The proposed DL-aMRI protocol has practical implications for clinical settings, enhancing diagnostic efficiency while maintainin","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 5","pages":"Article 101392"},"PeriodicalIF":9.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-10DOI: 10.1016/j.jhepr.2025.101332
Vincenzo Ronca , Alessandro Parente , Ellina Lytvyak , Bettina E. Hansen , Gideon Hirschfield , Alan Bonder , Maryam Ebadi , Saleh Elwir , Mohamad Alsaed , Piotr Milkiewicz , Maciej K. Janik , Hanns-Ulrich Marschall , Maria Antonella Burza , Cumali Efe , Ali Rıza Calışkan , Murat Harputluoglu , Gökhan Kabaçam , Débora Terrabuio , Fernanda de Quadros Onofrio , Nazia Selzner , Aldo J. Montano-Loza
<div><h3>Background & Aims</h3><div>A significant proportion of patients with variant syndromes (VSs), namely autoimmune hepatitis/primary biliary cholangitis or autoimmune hepatitis/primary sclerosing cholangitis, require liver transplantation (LT) despite treatment. The frequency of disease recurrence and the effect on graft survival are yet to be clarified. The aim of this international, multicentric, retrospective study is to evaluate the risk factors associated with recurrence and the impact of the disease recurrence after LT on graft and patient survival.</div></div><div><h3>Methods</h3><div>We evaluated 166 patients undergoing LT for VS in 33 centers in North America, South America, Europe, and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients with a higher risk of recurrence of autoimmune disease based on a histological and radiological diagnosis. Cumulative probabilities of graft and overall survival after LT were calculated using a semi-Markov model.</div></div><div><h3>Results</h3><div>The autoimmune pattern of recurrence resembled the original VS in 19 cases (61%). Recurrence of autoimmune liver disease (<em>r</em>ALD) after LT was observed in 23% and 33% of patients after 5 and 10 years, respectively. Increased alkaline phosphatase (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.13–2.25, <em>p</em> <0.01) and alanine aminotransferase (HR 1.25, 95% CI 1.01–1.53, <em>p</em> = 0.03) at 12 months after LT and acute rejection (HR 3.58, 95% CI 1.60–7.73, <em>p</em> <0.01) were associated with a higher risk of VS recurrence, whereas the use of predniso(lo)ne was associated with a reduced risk (HR 0.30, 95% CI 0.14–0.64, <em>p</em> <0.01). After adjusting for alanine aminotransferase and alkaline phosphatase at 12 months, the use of predniso(lo)ne was found to be independently and negatively associated with recurrent disease. The <em>r</em>ALD was found to be significantly associated with graft loss and patient survival in the multivariate Cox regression analysis with a time-dependent covariate. The 5- and 10-year probabilities of graft survival were 68% and 41% in patients with recurrent VS compared with 83% and 60% in patients without recurrent disease, respectively (<em>p</em> = 0.01). The overall survival was significantly reduced in patients with recurrent disease (<em>p</em> = 0.01), with event probability at 5 and 10 years of 75% and 49% <em>vs</em>. 84% and 60% in patients without recurrence, respectively.</div></div><div><h3>Conclusions</h3><div><em>r</em>ALD after LT is frequent and is associated with elevation in liver enzymes within the first year after LT and rejection episodes. According to our data, VS recurrence appears to be associated with poorer graft and patient survival. Further studies are needed to explore strategies that can prevent VS recurrence or mitigate its potential impact.</div></d
{"title":"Recurrence of autoimmune hepatitis cholestatic variant syndromes after liver transplantation affects graft and patient survival","authors":"Vincenzo Ronca , Alessandro Parente , Ellina Lytvyak , Bettina E. Hansen , Gideon Hirschfield , Alan Bonder , Maryam Ebadi , Saleh Elwir , Mohamad Alsaed , Piotr Milkiewicz , Maciej K. Janik , Hanns-Ulrich Marschall , Maria Antonella Burza , Cumali Efe , Ali Rıza Calışkan , Murat Harputluoglu , Gökhan Kabaçam , Débora Terrabuio , Fernanda de Quadros Onofrio , Nazia Selzner , Aldo J. Montano-Loza","doi":"10.1016/j.jhepr.2025.101332","DOIUrl":"10.1016/j.jhepr.2025.101332","url":null,"abstract":"<div><h3>Background & Aims</h3><div>A significant proportion of patients with variant syndromes (VSs), namely autoimmune hepatitis/primary biliary cholangitis or autoimmune hepatitis/primary sclerosing cholangitis, require liver transplantation (LT) despite treatment. The frequency of disease recurrence and the effect on graft survival are yet to be clarified. The aim of this international, multicentric, retrospective study is to evaluate the risk factors associated with recurrence and the impact of the disease recurrence after LT on graft and patient survival.</div></div><div><h3>Methods</h3><div>We evaluated 166 patients undergoing LT for VS in 33 centers in North America, South America, Europe, and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients with a higher risk of recurrence of autoimmune disease based on a histological and radiological diagnosis. Cumulative probabilities of graft and overall survival after LT were calculated using a semi-Markov model.</div></div><div><h3>Results</h3><div>The autoimmune pattern of recurrence resembled the original VS in 19 cases (61%). Recurrence of autoimmune liver disease (<em>r</em>ALD) after LT was observed in 23% and 33% of patients after 5 and 10 years, respectively. Increased alkaline phosphatase (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.13–2.25, <em>p</em> <0.01) and alanine aminotransferase (HR 1.25, 95% CI 1.01–1.53, <em>p</em> = 0.03) at 12 months after LT and acute rejection (HR 3.58, 95% CI 1.60–7.73, <em>p</em> <0.01) were associated with a higher risk of VS recurrence, whereas the use of predniso(lo)ne was associated with a reduced risk (HR 0.30, 95% CI 0.14–0.64, <em>p</em> <0.01). After adjusting for alanine aminotransferase and alkaline phosphatase at 12 months, the use of predniso(lo)ne was found to be independently and negatively associated with recurrent disease. The <em>r</em>ALD was found to be significantly associated with graft loss and patient survival in the multivariate Cox regression analysis with a time-dependent covariate. The 5- and 10-year probabilities of graft survival were 68% and 41% in patients with recurrent VS compared with 83% and 60% in patients without recurrent disease, respectively (<em>p</em> = 0.01). The overall survival was significantly reduced in patients with recurrent disease (<em>p</em> = 0.01), with event probability at 5 and 10 years of 75% and 49% <em>vs</em>. 84% and 60% in patients without recurrence, respectively.</div></div><div><h3>Conclusions</h3><div><em>r</em>ALD after LT is frequent and is associated with elevation in liver enzymes within the first year after LT and rejection episodes. According to our data, VS recurrence appears to be associated with poorer graft and patient survival. Further studies are needed to explore strategies that can prevent VS recurrence or mitigate its potential impact.</div></d","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 5","pages":"Article 101332"},"PeriodicalIF":9.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-04DOI: 10.1016/j.jhepr.2025.101386
Yongjian Liu , Joel D. Schilling
{"title":"Reply to: “Dynamic imaging of macrophages in MASLD: A major interest in insulin resistance and outside the liver”","authors":"Yongjian Liu , Joel D. Schilling","doi":"10.1016/j.jhepr.2025.101386","DOIUrl":"10.1016/j.jhepr.2025.101386","url":null,"abstract":"","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 5","pages":"Article 101386"},"PeriodicalIF":9.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738818","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 : 2025-03-04DOI: 10.1016/j.jhepr.2025.101370
Xiuji Cui , Jianwen Situ , Ting Tang , Zhiyu Li , Dongzhui Chen , Stanley Siu-Fung Ho , Hiu-Laam Chung , Tsz-Chung Wong , Yonghao Liang , Chaowen Deng , Yongxian Su , Huijun Cai , Simon Kam-Fai Lo , Shiyao Huang , Sheng Zeng , Liyuan Zhang , Yunchun Chen , Shusheng Wu , Estie Hon-Kiu Shun , Nicholas Foo-Siong Chew , Siddharth Sridhar
Background & Aims
Rocahepevirus ratti (rat hepatitis E virus; rHEV) is a ubiquitous pathogen of rats that has recently emerged as a cause of hepatitis in humans. Although several rHEV cases have been detected worldwide, the extent of human exposure to this hepatitis agent is still poorly defined. We conducted a multicenter surveillance study in China examining rHEV exposures in demographically diverse human populations from a One Health perspective.
Methods
In this multicenter cross-sectional study, we used fully validated rHEV IgG enzymatic immunoassays and reverse transcription PCR in 1,199 individuals with (n = 655) or without hepatitis (n = 544) recruited from three centers in China (Hainan, Hong Kong, and Shenzhen). The patient population included both urban and rural populations. Characteristics of infected individuals and phylogenetic links with rat epizootics were described.
Results
rHEV IgG seroprevalence was higher in the rural Hainan cohort (15/229, 6.6%) compared with Shenzhen (9/427, 2.1%) and Hong Kong cohorts (2/543, 0.4%) (p <0.0001). This difference persisted on multivariable logistic regression with an adjusted odds ratio of 20.52 (95% CI: 13.86–30.39). rHEV exposure was also associated with increasing age and environmental rodent exposure. We observed rHEV viraemia in two hepatitis patients (2/655; 0.3%) in Hainan and Hong Kong with hepatitis B and renal transplantation, respectively. The latter developed chronic hepatitis E. 19/509 (3.7%) rats captured in Hainan harbored rHEV. Both human rHEV isolates were phylogenetically related to rodent-derived rHEV strains circulating in Hainan and Hong Kong, respectively.
Conclusions
Humans are intermittently exposed to rHEV, especially in rural settings with rodent exposure. Overt hepatitis occurs in individuals with liver disease or immunosuppression. Spillover strains are related to epizootics in rodents offering opportunities for targeted disinfestation.
Impact and implications
Building on our previous work finding that Rocahepevirus ratti (rHEV) is a novel cause of sporadic viral hepatitis in humans, we studied rHEV exposures in humans from various epidemiological settings. We found intermittent exposure to rat hepatitis E in individuals living in both urban and rural settings with a markedly higher seroprevalence in the latter. Spillover viremic infections in individuals with underlying liver disease or immunosuppression were closely linked to epizootic rHEV strains circulating in rodents. Physicians and diagnostic laboratories should incorporate rHEV testing in algorithms for viral hepatitis while policymakers should consider rHEV surveillance in rodents to guide disinfestation efforts.
{"title":"Prevalence of Rocahepevirus ratti (rat hepatitis E virus) in humans and rats in China","authors":"Xiuji Cui , Jianwen Situ , Ting Tang , Zhiyu Li , Dongzhui Chen , Stanley Siu-Fung Ho , Hiu-Laam Chung , Tsz-Chung Wong , Yonghao Liang , Chaowen Deng , Yongxian Su , Huijun Cai , Simon Kam-Fai Lo , Shiyao Huang , Sheng Zeng , Liyuan Zhang , Yunchun Chen , Shusheng Wu , Estie Hon-Kiu Shun , Nicholas Foo-Siong Chew , Siddharth Sridhar","doi":"10.1016/j.jhepr.2025.101370","DOIUrl":"10.1016/j.jhepr.2025.101370","url":null,"abstract":"<div><h3>Background & Aims</h3><div><em>Rocahepevirus ratti</em> (rat hepatitis E virus; rHEV) is a ubiquitous pathogen of rats that has recently emerged as a cause of hepatitis in humans. Although several rHEV cases have been detected worldwide, the extent of human exposure to this hepatitis agent is still poorly defined. We conducted a multicenter surveillance study in China examining rHEV exposures in demographically diverse human populations from a One Health perspective.</div></div><div><h3>Methods</h3><div>In this multicenter cross-sectional study, we used fully validated rHEV IgG enzymatic immunoassays and reverse transcription PCR in 1,199 individuals with (n = 655) or without hepatitis (n = 544) recruited from three centers in China (Hainan, Hong Kong, and Shenzhen). The patient population included both urban and rural populations. Characteristics of infected individuals and phylogenetic links with rat epizootics were described.</div></div><div><h3>Results</h3><div>rHEV IgG seroprevalence was higher in the rural Hainan cohort (15/229, 6.6%) compared with Shenzhen (9/427, 2.1%) and Hong Kong cohorts (2/543, 0.4%) (<em>p</em> <0.0001). This difference persisted on multivariable logistic regression with an adjusted odds ratio of 20.52 (95% CI: 13.86–30.39). rHEV exposure was also associated with increasing age and environmental rodent exposure. We observed rHEV viraemia in two hepatitis patients (2/655; 0.3%) in Hainan and Hong Kong with hepatitis B and renal transplantation, respectively. The latter developed chronic hepatitis E. 19/509 (3.7%) rats captured in Hainan harbored rHEV. Both human rHEV isolates were phylogenetically related to rodent-derived rHEV strains circulating in Hainan and Hong Kong, respectively.</div></div><div><h3>Conclusions</h3><div>Humans are intermittently exposed to rHEV, especially in rural settings with rodent exposure. Overt hepatitis occurs in individuals with liver disease or immunosuppression. Spillover strains are related to epizootics in rodents offering opportunities for targeted disinfestation.</div></div><div><h3>Impact and implications</h3><div>Building on our previous work finding that <em>Rocahepevirus ratti</em> (rHEV) is a novel cause of sporadic viral hepatitis in humans, we studied rHEV exposures in humans from various epidemiological settings. We found intermittent exposure to rat hepatitis E in individuals living in both urban and rural settings with a markedly higher seroprevalence in the latter. Spillover viremic infections in individuals with underlying liver disease or immunosuppression were closely linked to epizootic rHEV strains circulating in rodents. Physicians and diagnostic laboratories should incorporate rHEV testing in algorithms for viral hepatitis while policymakers should consider rHEV surveillance in rodents to guide disinfestation efforts.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 5","pages":"Article 101370"},"PeriodicalIF":9.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jhepr.2025.101380
Patrick Huang , Francisco J. Rodriguez-Matos , Jonathan Qi , Rajiv Trehan , Yuta Myojin , Xiao Bin Zhu , Tim F. Greten , Chi Ma
Background & Aims
Inbred mouse strains are critical tools for studying immune regulation of metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC). Here, we profiled mouse strain-associated hepatic immune differences, and performed mice–human cross-species immune comparisons.
Methods
Immune landscapes of C57BL/6, BALB/c, and FVB/N mice were compared under healthy, MASH, or HCC state using high-dimensional spectral flow cytometry (n = 4 per condition). MASH was induced by feeding methionine- and choline-deficient or Western diet + carbon tetrachloride. HCC was caused by hydrodynamic plasmid injection of MYC/sg-p53. Public mouse and human scRNA-seq datasets were used for validation and cross-species comparisons.
Results
In healthy mice, liver CD4+ T (24% vs. 14% vs. 34%, p <0.05) and B cells (36.5% vs. 35% vs.18%, p <0.05) varied the most among three strains. C57BL/6 mice showed TH1 dominance, whereas BALB/c and FVB/N mice had TH2 dominance (log[TH1:TH2] = 0.17, -0.31, -0.17). In MASH mice, expansion of liver myeloid cells and innate lymphocytes were commonly found, but changes of B cells (log(fold-change) = -0.38, -0.28, -0.58, p <0.05) and T subsets (e.g. CD4+ T log(fold-change) = -0.21, -0.07, -0.15, p <0.05) varied greatly among strains. MYC/sg-p53 HCC induced a consistent expansion of liver Tregs and CD8+ T cells (p <0.05), but differential shifts of liver immune landscape were seen among strains. The flow cytometry data was supported by public scRNA-seq datasets matching C57BL/6 background. Further cross-species comparison in MASH condition confirmed shared changes of adaptive lymphocytes between mice and humans. In two MASH models, BALB/c or C57BL/6 mice were more consistent to recapture loss of CD4+ T or B cells, respectively (p <0.05).
Conclusions
Substantial liver immune differences exist among common mouse strains. Mice can recapitulate certain human liver immune changes with strain variations.
Impact and implications
Our immune cell profiling study revealed that the liver immune environment can be quite different among common mouse strains both under healthy and pathologic states, such as steatohepatitis or neoplastic processes. Our results serve as a data resource for studies investigating liver immunology and provide valuable insights for the design of studies on various immune cells in the livers of mice.
{"title":"Hepatic immune environment differences among common mouse strains in models of MASH and liver cancer","authors":"Patrick Huang , Francisco J. Rodriguez-Matos , Jonathan Qi , Rajiv Trehan , Yuta Myojin , Xiao Bin Zhu , Tim F. Greten , Chi Ma","doi":"10.1016/j.jhepr.2025.101380","DOIUrl":"10.1016/j.jhepr.2025.101380","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Inbred mouse strains are critical tools for studying immune regulation of metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC). Here, we profiled mouse strain-associated hepatic immune differences, and performed mice–human cross-species immune comparisons.</div></div><div><h3>Methods</h3><div>Immune landscapes of C57BL/6, BALB/c, and FVB/N mice were compared under healthy, MASH, or HCC state using high-dimensional spectral flow cytometry (n = 4 per condition). MASH was induced by feeding methionine- and choline-deficient or Western diet + carbon tetrachloride. HCC was caused by hydrodynamic plasmid injection of MYC/sg-p53. Public mouse and human scRNA-seq datasets were used for validation and cross-species comparisons.</div></div><div><h3>Results</h3><div>In healthy mice, liver CD4<sup>+</sup> T (24% <em>vs.</em> 14% <em>vs.</em> 34%, <em>p</em> <0.05) and B cells (36.5% <em>vs.</em> 35% <em>vs.</em>18%, <em>p</em> <0.05) varied the most among three strains. C57BL/6 mice showed T<sub>H</sub>1 dominance, whereas BALB/c and FVB/N mice had T<sub>H</sub>2 dominance (log[T<sub>H</sub>1:T<sub>H</sub>2] = 0.17, -0.31, -0.17). In MASH mice, expansion of liver myeloid cells and innate lymphocytes were commonly found, but changes of B cells (log(fold-change) = -0.38, -0.28, -0.58, <em>p</em> <0.05) and T subsets (<em>e.g.</em> CD4<sup>+</sup> T log(fold-change) = -0.21, -0.07, -0.15, <em>p</em> <0.05) varied greatly among strains. MYC/sg-p53 HCC induced a consistent expansion of liver Tregs and CD8<sup>+</sup> T cells (<em>p</em> <0.05), but differential shifts of liver immune landscape were seen among strains. The flow cytometry data was supported by public scRNA-seq datasets matching C57BL/6 background. Further cross-species comparison in MASH condition confirmed shared changes of adaptive lymphocytes between mice and humans. In two MASH models, BALB/c or C57BL/6 mice were more consistent to recapture loss of CD4<sup>+</sup> T or B cells, respectively (<em>p</em> <0.05).</div></div><div><h3>Conclusions</h3><div>Substantial liver immune differences exist among common mouse strains. Mice can recapitulate certain human liver immune changes with strain variations.</div></div><div><h3>Impact and implications</h3><div>Our immune cell profiling study revealed that the liver immune environment can be quite different among common mouse strains both under healthy and pathologic states, such as steatohepatitis or neoplastic processes. Our results serve as a data resource for studies investigating liver immunology and provide valuable insights for the design of studies on various immune cells in the livers of mice.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"7 5","pages":"Article 101380"},"PeriodicalIF":9.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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