Highly multiplexed 2-dimensional imaging mass cytometry analysis of HBV-infected liver

Traum, Daniel; Wang, Yue J.; Schwarz, Kathleen B.; Schug, Jonathan; Wong, David; Janssen, Harry L.A.; Terrault, Norah A.; Khalili, Mandana; Wahed, Abdus S.; Murray, Karen F.; Rosenthal, Phillip; Ling, Simon C.; Rodriguez‐Baez, Norberto; Sterling, Richard K.; Lau, Daryl; Block, Timothy M.; Feldman, Michael D.; Furth, Elizabeth E.; Lee, William M.; Kleiner, David E.; Lok, Anna S.; Kaestner, Klaus H.; Chang, Kyong Mi

doi:10.1172/jci.insight.146883

Cited by 20 publications

(11 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other researchers(28) investigated immune-related changes in the aged liver and found that the levels of in ammatory cytokines, chemokines, and in ammatory genes were higher in aged animals. The latest results (29) (30). Thus, age-associated changes in intrahepatic immune subsets appear trivial in ACLF patients, and we did not nd that recipient age affects the therapeutic effects of UCMSCs in the ACLF group.…”

Section: Discussionmentioning

confidence: 63%

The impact of recipient age on the effects of umbilical cord mesenchymal stem cells on HBV- related acute-on-chronic liver failure and liver cirrhosis

Zhang

Sun

Cao

et al. 2021

Preprint

View full text Add to dashboard Cite

Background The results of a previous study verified that umbilical cord mesenchymal stem cells (UCMSCs) have good therapeutic effects for the treatment of HBV-related acute-on-chronic liver failure (ACLF) and liver cirrhosis (LC). Nevertheless, it is still unknown whether the effects of UCMSCs are affected by recipient age. Methods Patients treated with UCMSCs who met the criteria of HBV-related ACLF and liver cirrhosis were identified in this retrospective observational study. Patients were divided into subgroups according to the World Health Organization (WHO) age criteria (< 45 vs. ≥45 years). Group A included young ACLF patients (< 45 y), and group B included older ACLF patients (≥ 45 y). Young LC patients (< 45 y) were assigned to group C, and group D included older LC patients (≥ 45 y). Patients’ clinical characteristics, demographics, biochemical factors, and model for end-stage liver disease (MELD) scores were compared for 24 weeks. Results Sixty-four ACLF patients and 59 LC patients were enrolled in this study. Compared with patients in groups B and C, patients in group A did not show significant superiority in terms of the levels of ALT, AST, TBIL, AFP, and PTA and MELD scores. However, the median decrease and cumulative decrease in the TBIL and ALT levels of patients in group C were larger than those of patients in group D after four weeks of UCMSC transfusions. For older patients (≥ 45 y), the cumulative decrease and the median decrease in the TBIL of ACLF patients were significantly greater than those of LC patients after UCMSC treatment. However, the median decrease in ALT levels of ACLF patients was significantly greater than that of LC patients during UCMSC treatment, and the cumulative decrease in ALT levels of ACLF patients was significantly greater than that of LC patients at all time points. Conclusion The therapeutic effects of UCMSCs for HBV-related acute-on-chronic liver failure and liver cirrhosis varied partly by patient age. Assessing patient age is necessary prior to UCMSC clinical use.

show abstract

Section: Discussionmentioning

confidence: 63%

The impact of recipient age on the effects of umbilical cord mesenchymal stem cells on HBV- related acute-on-chronic liver failure and liver cirrhosis

Zhang

Sun

Cao

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Other researchers [ 28 ] investigated immune-related changes in the aged liver and found that the levels of inflammatory cytokines, chemokines, and inflammatory genes were higher in aged animals. The latest results [ 29 ] revealed that older age was associated with increased hepatic accumulation of Kupffer and CD11b+ cells, as well as with adaptive immune activation and clinical evolution in chronic hepatitis B associated with age-associated changes in intrahepatic immune subsets. In this study, we mainly focused on whether the effects of UCMSCs on patients with HBV-related acute-on-chronic liver failure and liver cirrhosis were affected by recipient age.…”

Section: Discussionmentioning

confidence: 99%

The impact of recipient age on the effects of umbilical cord mesenchymal stem cells on HBV-related acute-on-chronic liver failure and liver cirrhosis

et al. 2021

View full text Add to dashboard Cite

Background The results of a previous study verified that umbilical cord mesenchymal stem cells (UCMSCs) have good therapeutic effects for the treatment of HBV-related acute-on-chronic liver failure (ACLF) and liver cirrhosis (LC). Nevertheless, it is still unknown whether the effects of UCMSCs are affected by recipient age. Methods Patients treated with UCMSCs who met the criteria of HBV-related ACLF and liver cirrhosis were identified in this retrospective observational study. Patients were divided into subgroups according to the World Health Organization (WHO) age criteria (< 45 vs. ≥ 45 years). Group A included young ACLF patients (< 45 y), and group B included older ACLF patients (≥ 45 y). Young LC patients (< 45 y) were assigned to group C, and group D included older LC patients (≥ 45 y). Patients’ clinical characteristics, demographics, biochemical factors, and model for end-stage liver disease (MELD) scores were compared for 24 weeks. Results Sixty-four ACLF patients and 59 LC patients were enrolled in this study. Compared with patients in groups B and C, patients in group A did not show significant superiority in terms of the levels of ALT, AST, TBIL, AFP, and PTA and MELD scores. However, the median decrease and cumulative decrease in the TBIL and ALT levels of patients in group C were larger than those of patients in group D after four weeks of UCMSC transfusions. For older patients (≥ 45 y), the cumulative decrease and the median decrease in the TBIL of ACLF patients were significantly greater than those of LC patients after UCMSC treatment. However, the median decrease in ALT levels of ACLF patients was significantly greater than that of LC patients during UCMSC treatment, and the cumulative decrease in ALT levels of ACLF patients was significantly greater than that of LC patients at all time points. Conclusion The therapeutic effects of UCMSCs for HBV-related acute-on-chronic liver failure and liver cirrhosis varied partly by patient age. Assessing patient age is necessary prior to UCMSC clinical use.

show abstract

“…Infiltration of activated CD8 T cells is a hallmark of HBV-associated liver damage in CHB patients (Maini et al, 2000;Traum et al, 2021), but our understanding of their role in viral hepatitis has relied largely on animal models. Longitudinal human liver sampling with core biopsies is impractical and invasive.…”

Section: Discussionmentioning

confidence: 99%

Pathogenic CD8 T cells defined by longitudinal liver sampling in chronic hepatitis B patients starting antiviral therapy

Nkongolo

Mahamed

Kuipery

et al. 2021

Preprint

View full text Add to dashboard Cite

SummaryAccumulation of activated immune cells results in non-specific hepatocyte killing in chronic hepatitis B (CHB), leading to fibrosis and cirrhosis. We enrolled 15 CHB patients with active liver damage to receive antiviral therapy, and performed longitudinal liver sampling using fine-needle aspiration to investigate mechanisms of CHB pathogenesis in the human liver. Single-cell sequencing of total liver cells revealed a distinct liver-resident, polyclonal CD8 T cell population that was enriched at baseline and displayed a highly activated immune signature during liver damage. Cytokine combinations, identified by in silico prediction of ligand-receptor interaction, induced the activated phenotype in healthy liver CD8 T cells, resulting in non-specific Fas ligand-mediated killing of target cells. These results define a CD8 T cell population in the human liver that can drive pathogenesis, and a key pathway involved in their function in CHB patients.

show abstract

Highly multiplexed 2-dimensional imaging mass cytometry analysis of HBV-infected liver

Cited by 20 publications

References 52 publications

The impact of recipient age on the effects of umbilical cord mesenchymal stem cells on HBV- related acute-on-chronic liver failure and liver cirrhosis

The impact of recipient age on the effects of umbilical cord mesenchymal stem cells on HBV- related acute-on-chronic liver failure and liver cirrhosis

The impact of recipient age on the effects of umbilical cord mesenchymal stem cells on HBV-related acute-on-chronic liver failure and liver cirrhosis

Pathogenic CD8 T cells defined by longitudinal liver sampling in chronic hepatitis B patients starting antiviral therapy

Contact Info

Product

Resources

About