The value of studying Programmed Death-1 +T cell immunoglobulin mucin 3 + exhausted T cells in patients of Acute Myeloid Leukemia

Acute Myeloid Leukemia Cell-Intrinsic PD-1 Functions Promoting Leukemia Development By Recruiting SHP2

Pseudo-Exhaustion Of CD8+ T Cells in AML

Objective To look into the correlation analysis between blood levels of Latency associated peptide (LAP), Glioma-derived growth factor (GDGF), Ferritin, Neutrophil/Lymphocyte ratio, and Albumin/Fibrinogen ratio and the prognosis of patients with acute myeloid leukemia (AML). Methods The study group consisted of 384 AML patients who were hospitalized to the hospital between May 2022 and October 2024, whereas the control group was made up of 192 healthy people who were examined physically while they were there. The levels of serum LAP, GDGF, and Ferritin and the Neutrophil/Lymphocyte ratio and Albumin/Fibrinogen ratio were compared. Following their discharge, the study group's participants were monitored for a total of 12 months. Patients having a favorable prognosis and those with a bad prognosis were divided into two groups. The factors predicting a poor prognosis in AML patients were examined using multivariate logistic regression and a comparison of the clinical data from the two groups. Receiver operating characteristic (ROC) curves were developed to evaluate the predictive significance of LAP, GDGF, Neutrophil/Lymphocyte ratio, Albumin/Fibrinogen ratio, and Ferritin for a poor prognosis in AML patients. Results The GDGF level, Ferritin, Neutrophil/Lymphocyte ratio, and Albumin/ Fibrinogen ratio were all higher than those in the control group (P<0.05), although the study group's serum LAP level was lower (P<0.05). Among the AML patients, 116 had a poor prognosis (poor prognosis group), and 268 had a good prognosis (good prognosis group). The group with a bad prognosis had lower levels of GDGF, Ferritin, Neutrophil/Lymphocyte ratio, and Albumin/Fibrinogen ratio (P<0.05), although the group with a good prognosis had greater levels of serum LAP (P<0.05). Multivariate logistic regression analysis showed that elevated serum LAP levels were independent protective factors for poor prognosis in AML patients (P<0.05), while elevated serum GDGF and Ferritin levels, along with elevated Neutrophil/Lymphocyte ratios and Albumin/Fibrinogen ratios, were independent risk factors for poor prognosis in AML patients (P<0.05). According to the ROC curve study, the areas under the curve (AUCs) of LAP, GDGF, Ferritin, the Neutrophil/Lymphocyte ratio, and the Albumin/Fibrinogen ratio for forecasting a poor prognosis in AML patients were 0.747, 0.811, 0.804, 0.783, and 0.845, respectively. Conclusion Serum LAP levels are decreased in AML patients, whereas GDGF, Ferritin, Neutrophil/Lymphocyte ratio and Albumin/Fibrinogen ratio levels are increased. Additionally, each of the aforementioned signs has some prediction value for the poor prognosis of individuals with AML and is an independent influencing factor.

With the success of immune checkpoint inhibitors (ICI), such as anti- programmed death-1 (PD-1) antibody for solid tumors and lymphoma immunotherapy, a number of clinical trials with ICIs have been attempted for acute myeloid leukemia (AML) immunotherapy; however, limited clinical efficacy has been reported. This may be due to the heterogeneity of immune microenvironments and various degrees of T cell exhaustion in patients and may be involved in the IFN-γ pathway. In this study, we first characterized the percentage of PD-1+ and T cell immunoglobulin mucin-domain-containing-3 (Tim-3) +IFN-γ+ T cells in peripheral blood (PB) in AML compared with healthy individuals (HIs) by flow cytometry and further discussed the possibility of the reversal of T cell exhaustion to restore the secretion capacity of cytokines in T cells in AML based on blockade of PD-1 or Tim-3 (anti-PD-1 and anti-Tim-3 antibody) in vitro using a cytokine protein chip. A significantly increased percentage of PD-1+, Tim-3+, and PD-1+Tim-3+ IFN-γ+ T cells was observed in PB from patients with AML in comparison with HIs. Moreover, higher PD-1+IFN-γ+CD3+/CD8+ T cell levels were associated with poor overall survival in AML patients. Regarding leukemia cells, the percentage of Tim-3 in CD117+CD34+ AML cells was positively correlated with PD-1 in IFN-γ+CD4+ T cells. Furthermore, blocking PD-1 and Tim-3 may involve multiple cytokines and helper T cell subsets, mainly Th1 and Treg cells. Blockade of PD-1 or Tim-3 tends to restore cytokine secretion to a certain extent, a synergistic effect shown by the co-blockade of PD-1 and Tim-3. However, we also demonstrated the heterogeneity of secretory cytokines in ICI-treated T cells in AML patients.

BackgroundAltered expression of T cell immune inhibitory receptors may result in immunosuppression and associate with the poor prognosis of leukemia patients in which the leukemic bone marrow (BM) microenvironment may contribute to such immunosuppression. We found higher numbers of programmed death-1 (PD-1) + exhausted T cells in peripheral blood (PB) from acute myeloid leukemia (AML) patients. To investigate the leukemic BM influence on immunosuppression, we further compared the distributions of PD-1 and T cell immunoglobulin mucin-3 (Tim-3) and the exhausted T cell phenotype in PB and BM from AML patients and characterized their relationship with clinical outcome.MethodsPB and BM samples from 15 patients with newly diagnosed AML were collected and analyzed for the expression of PD-1, Tim-3, CD244, and CD57 on CD3+, CD4+, and CD8+ T cells by multicolor flow cytometry.ResultsThe proportions of PD-1 + CD3+ and PD-1 + CD8+ T cells were significantly higher in BM compared with PB. Similarly, higher PD-1 + CD244 + CD3+ and PD-1 + CD244 + CD8+ T cells were found in BM, and an increased tendency for PD-1 + CD244 + CD4+ T cells was also detected in this group. In contrast, increased Tim-3 + CD4+/Tim-3 + CD244 + CD4+ T cells were predominant in BM compared with PB, but there was no statistically significant difference in Tim-3 + CD8+ T cells. Moreover, PD-1 and Tim-3 double-positive CD3+/CD4+/CD8+ T cells were significantly increased in the BM group. In addition, a higher proportion of PD-1 + Tim-3 + CD3+ T cells in the BM and PD-1 + Tim-3 + CD4+ T cells in PB was detected in non-complete remission (NCR) compared with complete remission (CR) patients after first-cycle chemotherapy.ConclusionsUpregulation of PD-1 and Tim-3 and the exhausted phenotype of CD4+ and CD8+ T cells in the BM of AML patients may contribute to mediating the leukemic immunosuppressive microenvironment, and increased PD-1 + Tim-3+ CD8+ T cells may be related to T cell dysfunction in AML, which may influence clinical outcome.

Event Abstract Back to Event Pseudo-Exhaustion of CD8+ T cells in acute myeloid leukemia (AML) Frauke M. Schnorfeil1, 2*, Katharina Emmerig1, 2, Julia Neitz1, 2, Felix S. Lichtenegger1, 2, 3, Rika Draenert4, Wolfgang Hiddemann2 and Marion Subklewe1, 2 1 Helmholtz Zentrum München, Clinical Cooperation Group Immunotherapy, Germany 2 Klinikum der Universität München, Department of Internal Medicine III, Germany 3 Klinikum der Universität München, Division of Clinical Pharmacology, Germany 4 Klinikum der Universität München, Division of Infectious Diseases, Germany The prognosis of acute myeloid leukemia (AML) is poor due to high relapse rates after induction chemotherapy. Dendritic cell (DC)-based immunotherapy is a promising strategy to stimulate AML-specific immunity, particularly T cells. However, the functionality of T cells in AML patients is not well described. T cell exhaustion, characterized by an increased expression of inhibitory molecules and funtional deficits, has been suggested to contribute to immune evasion in various solid and hematological malignancies. To characterize T cell exhaustion in AML, CD8+ T cell surface expression of CD244, CD160, PD-1 and TIM-3 as well as proliferation and cytokine production were measured. Results were compared to healthy controls (HCs) and untreated HIV-infected patients. To specify the stimulatory effect of DCs on AML patient-derived T cells, we cocultured DCs with autologous T cells. We detected increased frequencies of CD244+, CD160+ and PD-1+ CD8+ T cells in HIV patients, while AML patients at time of diagnosis and relapse or during refractory disease had higher frequencies of CD244+ and TIM-3+ or PD-1+ CD8+ T cells, respectively. However, no functional impairment of AML patient-derived T cells was observed so far. DC stimulation resulted in upregulation of PD-1 and TIM-3, accompanied by high IFNγ secretion, that could be enhanced by PD-1 blockade. Thus, we found elevated levels of exhaustion-associated inhibitory molecules on CD8+ T cells of AML patients, which were further upregulated upon DC stimulation. Our data suggest that immunotherapeutic strategies combining DC vaccination and immunomodulatory antibodies directed against T cell inhibitory molecules are particularly suited for AML treatment. Keywords: Immunotherapy, t cell exhaustion, AML, Dendritic Cells, immunomodulatory antibodies Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Schnorfeil FM, Emmerig K, Neitz J, Lichtenegger FS, Draenert R, Hiddemann W and Subklewe M (2013). Pseudo-Exhaustion of CD8+ T cells in acute myeloid leukemia (AML). Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01189 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Jul 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Frauke M Schnorfeil, Helmholtz Zentrum München, Clinical Cooperation Group Immunotherapy, Munich, Germany, frauke.schnorfeil@helmholtz-muenchen.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Frauke M Schnorfeil Katharina Emmerig Julia Neitz Felix S Lichtenegger Rika Draenert Wolfgang Hiddemann Marion Subklewe Google Frauke M Schnorfeil Katharina Emmerig Julia Neitz Felix S Lichtenegger Rika Draenert Wolfgang Hiddemann Marion Subklewe Google Scholar Frauke M Schnorfeil Katharina Emmerig Julia Neitz Felix S Lichtenegger Rika Draenert Wolfgang Hiddemann Marion Subklewe PubMed Frauke M Schnorfeil Katharina Emmerig Julia Neitz Felix S Lichtenegger Rika Draenert Wolfgang Hiddemann Marion Subklewe Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Tryptase is a serine protease that is expressed in leukemic cells of chronic myeloid leukemia (CML) patients and in blasts of acute myeloid leukemia (AML) patients. Tryptase may be useful for diagnosis, assessment of severity of disease (leukemic cell burden), monitoring minimal residual disease and prognosis of AML and CML patients. The main objective of this study was to assess the serum levels of tryptase activity among CML and AML patients and to compare the serum levels of tryptase activity of acute and chronic myeloid leukemia patients with each other and with those of healthy controls. To meet this objective, a hospital-based comparative cross-sectional study was conducted among CML and AML patients from February 2016 up to December 2016. Serum samples were obtained from 24 AML, 60 CML and 35 healthy controls. Fluorogenic assays for serum tryptase activity using aminomethylcoumarin (AMC) peptide derivative were carried out. Statistical analysis was done by using SPSS version 20. Descriptive statistics, Paired Samples T-test, Wilcoxon Signed Rank test and Spearman’s rho test were used to investigate any correlation among different parameters. The minimum level of statistical significance was set at p-value <0.05. Accordingly, the mean and median serum levels of tryptase activity were significantly higher in patients with AML and CML than in the healthy controls (P-value < 0.05). CML patients in chronic phase (CP) and secondary AML patients had significantly higher mean and median serum levels of tryptase activity than CML patients in accelerated/blast phase (AP/BP) and de novo AML patients (p-value < 0.05). These elevated mean and median levels of serum tryptase activities were due to a subset of individuals with elevated serum tryptase levels (41.7 % of AML & 30 % of CML); the remaining leukemic individuals (58.3 % AML & 70 % of CML) had normal serum levels of tryptase activity. Finally, it was concluded that the serum tryptase level might be a useful diagnostic and prognostic marker in a subset of patients with CML and AML. However, further studies that incorporate other protocols such as tryptase immunoassay are warranted to exclude contaminant non-tryptase proteases from the serum samples.

The limited application of immunotherapy in acute myeloid leukemia (AML) may be due to poor understanding of the global Tcell immune dysfunction in AML. In this study, we analyzed the distribution characteristics of 24 TCR Vβ subfamilies in CD3+, CD4+, and CD8+ Tcells in AML patients and healthy controls. The percentage of TCR Vβ subfamily Tcells was predominately lower in most AML cases, while it was increased in some cases. TCR Vβ2+Tcells were increased in AML, particularly TCR Vβ2+CD4+Tcells, which were significantly higher. To further address the immunosuppression in different Vβ subfamilies, we characterized the distribution of program death-1 (PD-1)+Tcells in TCR Vβ subfamilies of CD4+ and CD8+Tcells. Significantly higher levels of PD-1+Vβ+Tcells were found for most Vβ subfamilies in most AML cases. A higher percentage of PD-1+Vβ2+Tcells with a high number of Vβ2+Tcells was found in all of the CD3+, CD4+, and CD8+ Tcell subsets. Moreover, increasing PD-1+Vβ7.2, Vβ8+, Vβ14+, Vβ16+, and Vβ22+CD8+Tcells were distributed in the AML-M5 subtype group compared with the AML-M3 group. In addition, higher PD-1+ Vβ5.2+ and PD-1+ Vβ12+CD8+Tcells were associated with AML patients who had a poor response to chemotherapy. In conclusion, increased PD-1+Vβ+Tcells is a common characteristic of AML, higher PD-1+Vβ2+Tcells may be associated with a low antileukemia effect, and higher PD-1+Vβ5.2+ and PD-1+Vβ12+CD8+Tcells may be related to poor prognosis in AML. These characteristics may be worth considering as immune biomarkers for clinical outcome in AML.

Immune checkpoints are involved in mechanisms by which tumours escape from the host immune system. Our aim was to evaluate acute myeloid leukaemia (AML) patients to determine expression levels of checkpoint molecules according to diagnosis and treatments, and to identify optimal candidates for checkpoint blockade. Bone marrow (BM) samples were obtained from 279 AML patients at different disease status and from 23 controls. Flow cytometric analyses of PD-1 and PD-L1/PD-L2 expression were performed. Programmed death-1 (PD-1) expression levels on CD8+ T-cells at AML diagnosis were increased compared to controls. PD-L1 and PD-L2 expression levels on leukaemic cells at diagnosis were significantly higher in secondary AML than in de novo AML. PD-1 levels on CD8+ and CD4+ T-cells after allo-SCT were significantly higher than those at diagnosis and after CTx. PD-1 expression on CD8+ T-cells increased in the acute GVHD group than in the non-GVHD group. The overall survival of patients with high PD-1 expression on CD8+ T-cells was significantly shorter than that of patients with low PD-1 expression. In conclusion, patients who underwent allo-SCT exhibited high PD-1 expression, suggesting that allo-SCT increases PD-1 expression on T-cells, and the patients with high PD-1 expression on CD8+ T-cells after allo-SCT showed the poor prognosis. For these patients, PD-1 blockade could be an immunotherapeutic strategy.

CHARACTERISTIC OF PD-1+VΒ+CD4+ AND PD-1+VΒ+CD8+ T CELLS IN PATIENTS WITH ACUTE MYELOID LEUKEMIA

Objective: To analyze the predictive value of serum signal peptide-CUB-epidermal growth factor domain-containing protein 1 (SCUBE1), C-type lectin-like receptor-2 (CLEC-2), and uncoupling protein 2 (UCP2) for poor outcome following intravenous thrombolysis (IVT) in patients who have experienced an acute ischemic stroke (AIS). Methods: A total of 116 AIS patients who received IVT treatment in this hospital from June 2023 to October 2024 were selected as the observation group, and the control group consisted of an additional 116 healthy people who were examined physically in this institution over the same time period. The patients were divided into good prognosis and poor prognosis groups according to the modified Rankin scale (mRS) score. After IVT, the factors predicting poor outcome in AIS patients were examined using multivariate logistic regression. The prognostic significance of serum SCUBE1, CLEC-2, and UCP2 for poor prognosis in AIS patients following IVT was examined using a receiver operating characteristic (ROC) curve. Results: While the observation group's serum UCP2 level was lower than the control group's, the observation group's levels of SCUBE1 and CLEC-2 were higher. P&lt;0.05 indicated that the differences were statistically significant. There were 75 patients in the good prognosis group and 41 patients in the poor prognosis group. While serum UCP2 levels were lower than those in the good prognosis group (P&lt;0.05), the percentage of patients with infarction regions &gt;4 cm³ and the levels of serum SCUBE1 and CLEC-2 were higher in the bad prognosis group than in the good prognosis group. According to multivariate logistic regression analysis, increased blood levels of SCUBE1 and CLEC-2 were associated with a poor prognosis for AIS patients following IVT (P&lt;0.05), and higher blood UCP2 levels were protective factors against a poor outcome in AIS patients following IVT (P&lt;0.05). The areas under the curve (AUCs) of serum SCUBE1, CLEC-2, and UCP2 alone for predicting a poor prognosis were found by the ROC curve analysis after IVT in AIS patients were 0.752, 0.694, and 0.776. SCUBE1, CLEC-2, and UCP2 had lower AUCs than the three indicators together, which had an AUC of 0.861. The AUC predicted separately (Z(3-item combination -SCUBE1)=2.358, Z(3-item combination -CLEC-2) =2.714, z 3-item combination -UCP2=2.591, P=0.018, 0.007, 0.010). Conclusion: The levels of serum SCUBE1 and CLEC-2 in AIS patients with poor prognosis after IVT increase, whereas the level of UCP2 decreases. The combined detection of these three indicators has high predictive value for the poor prognosis of AIS patients after IVT.

BackgroundT cell function is crucial for the success of several novel immunotherapeutic strategies for the treatment of acute myeloid leukemia (AML). However, changes in phenotype and function of T cells have been described in various hematologic malignancies, mimicking T cell exhaustion known from chronic viral infections. Detailed knowledge about phenotype and function of T cells in AML patients at different stages of the disease is indispensable for optimal development and application of immunotherapeutic strategies for this disease.MethodsWe used flow cytometry-based assays to characterize T cell phenotype and function in peripheral blood and bone marrow of AML patients at diagnosis, at relapse after intensive chemotherapy, and at relapse after allogeneic stem cell transplantation (SCT). Surface expression of CD244, PD-1, CD160, and TIM-3 was determined, and proliferation and production of IFN-γ, TNF-α, and IL-2 were measured.ResultsWe detected similar expression of inhibitory molecules on T cells from patients at diagnosis and from age-matched healthy controls. At relapse after SCT, however, PD-1 expression was significantly increased compared to diagnosis, both on CD4+ and CD8+ T cells. This pattern was not associated with age and cytomegalovirus (CMV) status but with a shift towards effector memory cells in relapsed AML patients. Proliferation and cytokine production assays did not reveal functional defects in T cells of AML patients, neither at diagnosis nor at relapse.ConclusionWe thus conclude that T cell exhaustion does not play a major role in AML. Immunotherapeutic strategies targeting autologous T cells thus have particularly good prospects in the setting of AML.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0189-2) contains supplementary material, which is available to authorized users.

Programmed death-1 (PD-1) and inducible costimulator (ICOS) are immune checkpoint receptors participating in tumor immune evasion, which counters the activation signal provided through the T-cell receptor ligation. This study aimed to investigate the relationship between the expression of PD-1 and ICOS on mononuclear cells (MNCs) isolated from the peripheral blood of acute myeloid leukemia (AML) patients and their response to induction chemotherapy. Peripheral blood samples (5 cc) were collected from 56 AML patients at first diagnosis before and after the induction therapy regimen for AML. PD-1 and ICOS expression were analyzed in all patients before and after the standard induction therapy regimen. The expression of PD-1 and ICOS significantly decreased (66.7 and 16.3 fold, respectively) in AML patients following chemotherapy compared to its baseline value (P=0.01 and P=0.001, respectively). The expressions of PD-1 and ICOS were significantly different between favorable and poor risk groups. Lower PD-1 and ICOS expressions on the surface of MNCs before induction therapy were associated with a better response to treatments. In addition, PD-1 and ICOS expression on MNCs decreased after induction therapy.

ObjectiveTo explore the correlation between Heart Rate Variability Index (HRV) and poor prognosis in patients with acute decompensated heart failure (ADHF).MethodsA retrospective compilation of clinical data encompassed 128 cases of patients afflicted with acute decompensated heart failure (ADHF) who were admitted to and discharged from our hospital between April 2019 and July 2022. Subsequent to assessing their follow-up progress during the tracking period, the subjects were categorized into two cohorts: the poor prognosis group (n = 31) and the good prognosis group (n = 97). Comparative analysis of clinical data and Heart Rate Variability (HRV) parameters was executed between these two groups. Moreover, a multiple linear regression analysis was employed to identify the contributing factors associated with adverse prognoses in ADHF patients. Furthermore, the receiver operating characteristic (ROC) curve was employed to evaluate the prognostic predictive capability of HRV parameters among ADHF patients.ResultsThe levels of SDNN (t = 3.924, P < 0.001), SDANN (t = 4.520, P < 0.001) and LF (t = 2.676, P = 0.018) in the poor prognosis group were significantly higher than those in the good prognosis group, and the differences were statistically significant (P < 0.05). The levels of PNN50 (t = 2.132, P = 0.035), HF (t = 11.781, P < 0.001) and LF/HF (t = 11.056, P < 0.001) in the poor prognosis group were significantly lower than those in the good prognosis group (P < 0.05). The results of multiple linear regression analysis indicated that SDNN, SDANN, LF, PNN50, and HF were factors influencing poor prognosis in ADHF patients (P < 0.05). The results of the ROC curve analysis indicate that the area under the curve (AUC) for predicting poor prognosis in ADHF patients using HRV parameters were as follows: SDNN (AUC = 0.818, 95% CI [0.722–0.914]), SDANN (AUC = 0.684, 95% CI [0.551–0.816]), PNN50 (AUC = 0.754, 95% CI [0.611–0.841]), LF/HF (AUC = 0.787, 95% CI [0.679–0.896]), and combined diagnosis (AUC = 0.901, 95% CI [0.832–0.970]). Among these, the combined diagnosis exhibited the highest AUC, sensitivity, and specificity for predicting poor prognosis in ADHF patients (P < 0.001).ConclusionThe HRV parameters of SDNN, SDANN, PNN50 and LF/HF are closely related to the prognosis of ADHF patients. The combined detection of the above HRV parameters can improve the efficacy of predicting the poor prognosis of ADHF patients. This suggests that clinical staff can identify ADHF patients at risk of poor prognosis by long-term monitoring of HRV in the future.

Background: We aimed to explore the prognostic factors in patients with decompensated hepatitis B cirrhosis (HBC) and to establish a risk prediction model. Methods: In this prospective study, 120 subjects were selected from patients with decompensated HBC who were hospitalized between January 2022 and January 2023. All patients were followed for one year. Using death during follow-up as the prognostic endpoint, patients were categorized into a good prognosis (survival) group and a poor prognosis (death) group. Demographic data and laboratory indicators were compared between the two groups. Risk factors were identified using multivariate logistic regression analysis, and a risk prediction model was subsequently established. Results: There were 30 cases (25%) in the poor prognosis group and 90 cases (75%) in the good prognosis group. The incidence of hypoproteinemia, international normalized ratio (INR), and the levels of total cholesterol (TC), cell-free deoxyribonucleic acid (cfDNA), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly higher in the poor prognosis group compared to the good prognosis group (P &lt; 0.05). Hypoproteinemia, cfDNA, GM-CSF, and INR were identified as risk factors for poor prognosis in patients with decompensated HBC [odds ratio (OR) &gt; 1, P &lt; 0.05], while TC was identified as a protective factor (OR &lt; 1, P &lt; 0.05). A regression equation was established as follows: Logit (P) = -12.544 + 1.376 × cfDNA + 1.051 × GM-CSF + 1.025 × INR + 0.675 × TC + 4.136 × hypoproteinemia. The area under the curve (AUC) for this model was 0.920 [95% confidence interval: 0.855 - 0.980, P &lt; 0.001], indicating high reliability and stability. Conclusions: Hypoproteinemia, INR, cfDNA, and GM-CSF are risk factors for poor prognosis in patients with decompensated HBC.