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Kumar R, Kumar A, Kumar S. Sepsis in liver failure patients: Diagnostic challenges and recent advancements. World J Crit Care Med 2025; 14:101587. [DOI: 10.5492/wjccm.v14.i2.101587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 01/19/2025] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
Acute liver failure (ALF) and acute-on-chronic LF (ACLF) are prevalent hepatic emergencies characterized by an increased susceptibility to bacterial infections (BI), despite significant systemic inflammation. Literature indicates that 30%–80% of ALF patients and 55%–81% of ACLF patients develop BI, attributed to immunological dysregulation. Bacterial sepsis in these patients is associated with adverse clinical outcomes, including prolonged hospitalization and increased mortality. Early detection of bacterial sepsis is critical; however, distinguishing between sterile systemic inflammation and sepsis poses a significant challenge due to the overlapping clinical presentations of LF and sepsis. Conventional sepsis biomarkers, such as procalcitonin and C-reactive protein, have shown limited utility in LF patients due to inconsistent results. In contrast, novel biomarkers like presepsin and sTREM-1 have demonstrated promising discriminatory performance in this population, pending further validation. Moreover, emerging research highlights the potential of machine learning-based approaches to enhance sepsis detection and characterization. Although preliminary findings are encouraging, further studies are necessary to validate these results across diverse patient cohorts, including those with LF. This article provides a comprehensive review of the magnitude, impact, and diagnostic challenges associated with BI in LF patients, focusing on novel advancements in early sepsis detection and characterization.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Abhishek Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Sudhir Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
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Wang N, Zheng Y, Tao S, Chen L. Risk factors and prognosis of pulmonary infection in hepatitis B-related acute-on-chronic liver failure: a retrospective cohort study. BMC Pulm Med 2025; 25:178. [PMID: 40229810 PMCID: PMC11995551 DOI: 10.1186/s12890-025-03628-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 03/25/2025] [Indexed: 04/16/2025] Open
Abstract
OBJECTIVE To identify risk factors for pulmonary infection in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), assess its impact on prognosis, and develop a prognostic prediction model. METHODS We retrospectively analyzed the clinical data of 393 patients with HBV-ACLF. Logistic regression was used to analyze the risk factors for lung infection in ACLF patients, as well as the factors affecting the prognosis of those who were infected. Additionally, a prognostic prediction model was established using the Nomogram method. RESULTS The incidence of pulmonary infections in patients with ACLF was 38.7%, and patients with ACLF combined with pulmonary infections had a higher short-term mortality rate than those without infections (65.71% vs. 35.02%). Multivariate logistic regression analysis indicated that independent risk factors for pulmonary infection included TBIL, CRP, invasive procedures, peritoneal effusion, and hepatic encephalopathy. Additionally, creatinine, INR, comorbid diabetes mellitus, neutrophil counts, and lymphocyte counts were identified as independent risk factors affecting 30-day mortality in patients with pulmonary infection. Incorporating these risk factors, a new predictive model was established, with an area under the receiver operating characteristic curve of 0.832 (95% CI, 0.765-0.900). This model demonstrated higher discriminatory performance compared to traditional prognostic models such as CTP, MELD, and MELD-Na, with statistically significant differences (P < 0.05). CONCLUSION HBV-ACLF patients are susceptible to pulmonary infection, with fungal infection posing a significant threat. Pulmonary infection is associated with worse prognosis in HBV-ACLF patients. Early identification of risk factors and prognostic assessment can facilitate timely intervention and improve prognosis.
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Affiliation(s)
- Neng Wang
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Yu Zheng
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China
| | - Shuai Tao
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Liang Chen
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
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Huang YS, Gao W, Sun AJ, Pu CW, Xu SS. Clinical characteristics of patients with hepatitis and cirrhosis and the construction of a prediction model. World J Hepatol 2025; 17:96506. [PMID: 40027562 PMCID: PMC11866140 DOI: 10.4254/wjh.v17.i2.96506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 09/30/2024] [Accepted: 01/02/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND Hepatitis B-associated cirrhosis is an important disease burden in China. However, there is a lack of effective predictors in clinical practice to drive delivery and enable early treatment to delay disease progression. AIM To analyzing the clinical characteristics of patients with hepatitis and cirrhosis, the nomogram model was established and validated. METHODS The clinical data of 1070 patients with hepatitis B who were treated in our hospital from October 2015 to July 2022 were collected. In a 7:3 ratio, 749 cases were divided into training cohorts and 321 cases were divided into validation cohorts. In addition, the training cohort and validation cohort were further divided into hepatitis group and hepatitis B-related cirrhosis group based on whether the patient progressed to cirrhosis. Binary logistic regression was used to analyze the influencing factors of hepatitis progression to cirrhosis. A roadmap prediction model was established, and the predictive effect of the model was evaluated by patient-subject receiver operating characteristic curve (ROC), and the effectiveness of the model was evaluated by decision curve analysis. RESULTS Binary logistic regression analysis was performed using hepatitis B-related cirrhosis = 1 and hepatitis = 0 as dependent variables, and univariate analysis of serological indicators was used as covariates. The results showed that glutamic oxaloacetate aminotransferase/glutamate acetone aminotransferase levels, prothrombin time activity, and hepatitis B e antigen levels were all contributing factors to the progression of hepatitis to cirrhosis. The area under the ROC curve was 0.693 [95% confidence interval (CI): 0.631 to 0.756] for the training cohort and 0.675 (95%CI: 0.561 to 0.790) for the validation cohort. In addition, the decision analysis curves of the prediction models of both the training cohort and the validation cohort confirmed the effectiveness of the nomogram prediction model. CONCLUSION Three independent factors influencing the progression to cirrhosis in patients with hepatitis B were identified. The construction of a nomogram prediction model from hepatitis to cirrhosis has high application value as a tool for predicting the occurrence of liver cirrhosis in hepatitis B patients.
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Affiliation(s)
- Yu-Shuang Huang
- Department of Infectious Diseases, Dalian Public Health Clinical Center, Dalian 116031, Liaoning Province, China
| | - Wei Gao
- Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
| | - Ai-Jun Sun
- Department of Infectious Diseases, Dalian Public Health Clinical Center, Dalian 116031, Liaoning Province, China.
| | - Chun-Wen Pu
- Dalian Public Health Clinical Center, Dalian Municipal Research Institute for Public Health, Dalian 116031, Liaoning Province, China
| | - Shuang-Shuang Xu
- Department of Infectious Diseases, Dalian Public Health Clinical Center, Dalian 116031, Liaoning Province, China
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Xu Z, Zhang X, Chen J, Shi Y, Ji S. Bacterial Infections in Acute-on-chronic Liver Failure: Epidemiology, Diagnosis, Pathogenesis, and Management. J Clin Transl Hepatol 2024; 12:667-676. [PMID: 38993512 PMCID: PMC11233977 DOI: 10.14218/jcth.2024.00137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 05/05/2024] [Accepted: 05/27/2024] [Indexed: 07/13/2024] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a distinct condition characterized by the abrupt exacerbation of pre-existing chronic liver disease, often leading to multi-organ failures and significant short-term mortalities. Bacterial infection is one of the most frequent triggers for ACLF and a common complication following its onset. The impact of bacterial infections on the clinical course and outcome of ACLF underscores their critical role in the pathogenesis of systemic inflammation and organ failures. In addition, the evolving epidemiology and increasing prevalence of multidrug-resistant bacteria in cirrhosis and ACLF highlight the importance of appropriate empirical antibiotic use, as well as accurate and prompt microbiological diagnosis. This review provided an update on recent advances in the epidemiology, diagnosis, pathogenesis, and management of bacterial infections in ACLF.
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Affiliation(s)
- Zhaoyu Xu
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Xiuding Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jiyang Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Yu Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Shangwei Ji
- Department of Infectious Diseases, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
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Wang J, Bai J, Wang H, Xu G, Yao R, Li J, Zhang W, Wang H, Yao J, Ren X. Relationship between skeletal muscle index at the third lumbar vertebra with infection risk and long-term prognosis in patients with acute-on-chronic liver failure. Front Nutr 2024; 10:1327832. [PMID: 38268672 PMCID: PMC10806060 DOI: 10.3389/fnut.2023.1327832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 12/19/2023] [Indexed: 01/26/2024] Open
Abstract
Objective Infection is a major cause of increased mortality in patients with acute-on-chronic liver failure (ACLF). This study aims to examine the potential correlation of the skeletal muscle index at the third lumbar vertebra (L3-SMI) with infections among ACLF patients and to evaluate its impact on the long-term survival. Methods This retrospective study included 126 patients who underwent abdominal computed tomography (CT) and were diagnosed with ACLF at our center between December 2017 and December 2021. L3-SMI was calculated using CT, and the clinical and biochemical data as well as MELD scores were also collected, so as to analyze the relationship between L3-SMI and infections in ACLF patients and the impact on long-term prognosis. Results Of the 126 ACLF patients enrolled, 50 had infections. In the multivariate logistic regression analysis, both L3-SMI [odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.81 - 0.97, P = 0.011] and hepatic encephalopathy (OR = 8.20, 95% CI = 1.70 - 39.59, P = 0.009) were independently associated with the risk of infection development. The overall survival (OS) estimates were obtained using Kaplan-Meier curves, and it was found that patients in the lowest tertile of L3-SMI had significantly lower 3-month, 6-month, 1-year, and 2-year survival rates than those in the highest tertile (P = 0.014; log-rank test). Conclusion Low L3-SMI is an independent risk factor for the development of infections and significantly influences the long-term survival in ACLF patients.
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Affiliation(s)
- Juan Wang
- Department of Gastroenterology, Third Hospital of Shanxi Medical University (Shanxi Bethune Hospital), Shanxi Medical University, Taiyuan, China
| | - Jinjia Bai
- Department of Gastroenterology, Third Hospital of Shanxi Medical University (Shanxi Bethune Hospital), Shanxi Medical University, Taiyuan, China
| | - Huimin Wang
- Endoscopy Center, Second Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, China
| | - Guofen Xu
- Department of Gastroenterology, Jincheng General Hospital, Shanxi Medical University, Taiyuan, China
| | - Ruoyu Yao
- Department of Gastroenterology, Third Hospital of Shanxi Medical University (Shanxi Bethune Hospital), Shanxi Medical University, Taiyuan, China
| | - Jing Li
- Department of Gastroenterology, Third Hospital of Shanxi Medical University (Shanxi Bethune Hospital), Shanxi Medical University, Taiyuan, China
| | - Wenrui Zhang
- Department of Gastroenterology, Third Hospital of Shanxi Medical University (Shanxi Bethune Hospital), Shanxi Medical University, Taiyuan, China
| | - Han Wang
- Department of Gastroenterology, Third Hospital of Shanxi Medical University (Shanxi Bethune Hospital), Shanxi Medical University, Taiyuan, China
| | - Jia Yao
- Department of Gastroenterology, Third Hospital of Shanxi Medical University (Shanxi Bethune Hospital), Shanxi Medical University, Taiyuan, China
| | - Xiaojing Ren
- Department of Gastroenterology, Third Hospital of Shanxi Medical University (Shanxi Bethune Hospital), Shanxi Medical University, Taiyuan, China
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Wu Z, Shi H, Zhang L, Shi H, Miao X, Chen L, Chen Y, Ma Y. Comparative analysis of monocyte-derived dendritic cell phenotype and T cell stimulatory function in patients with acute-on-chronic liver failure with different clinical parameters. Front Immunol 2023; 14:1290445. [PMID: 38111573 PMCID: PMC10725902 DOI: 10.3389/fimmu.2023.1290445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 11/15/2023] [Indexed: 12/20/2023] Open
Abstract
BACKGROUND Acute-on-Chronic Liver Failure (ACLF) patients experience systemic inflammation as well as immune dysfunction and exhaustion. The phenotype and functionality of monocyte-derived dendritic cells in ACLF patients with different clinical parameters have not been elucidated. METHODS This study included 37 cases of ACLF, 20 cases of Chronic Hepatitis B (CHB) patients, and 12 healthy controls. Demographic and laboratory parameters were collected from the enrolled patients. Peripheral blood samples were obtained from the participants. Monocyte-derived dendritic cells were induced and cultured, followed by co-culturing with T cells from the patients. Cell surface markers and intracellular markers were analyzed using flow cytometry. The relationship between these markers and clinical parameters was compared. RESULTS Our study found that ACLF patients had lower expression levels of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells compared to both CHB patients and healthy controls. IL-4, GM-CSF, and alcohol were found to promote the expression of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells. In ACLF patients, higher levels of procalcitonin (PCT), lower levels of albumin, decreased prothrombin activity and deceased patients were associated with lower expression of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells. Peripheral blood mononuclear cells (PBMCs), after removing adherent cells, were co-cultured with monocyte-derived DC. Our study revealed that patients with infection and low albumin levels exhibited a decreased proportion of T cell subsets within PBMCs. Additionally, these patients' T cells showed lower levels of Ki-67 and interferon-gamma (IFN-γ) production. CONCLUSION ACLF patients exhibit varying clinical states, with differences in the phenotype and the ability of monocyte-derived dendritic cells to stimulate T cells. Alcohol can stimulate the maturation of monocyte-derived dendritic cells.
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Affiliation(s)
- Zhipeng Wu
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Hongbo Shi
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing, China
- Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Lei Zhang
- Department of Nephrology, Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, Shanxi, China
- Department of Traditional Chinese Medicine, Qinhuangdao Shanhaiguan People's Hospital, Hebei, China
| | - Honglin Shi
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing, China
| | - Xingzhong Miao
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing, China
| | - Liangjuan Chen
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing, China
| | - Yu Chen
- Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Yingmin Ma
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
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Gao C, Ni J, Gao Y, Xie D, Yang L, Yang B, Lu X, Guo Q. Association of current hepatitis B virus infection with mortality in adults with sepsis. Epidemiol Infect 2023; 151:e94. [PMID: 37203184 PMCID: PMC10311682 DOI: 10.1017/s0950268823000729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Accepted: 05/04/2023] [Indexed: 05/20/2023] Open
Abstract
This study aimed to determine the impact of current hepatitis B virus (HBV) infection on patients hospitalised with sepsis. This was a retrospective cohort study. Patients from three medical centres in Suzhou from 10 January 2016 to 23 July 2022 participated in this study. Demographic characteristics and clinical characteristics were collected. A total of 945 adult patients with sepsis were included. The median age was 66.0 years, 68.6% were male, 13.1% presented with current HBV infection, and 34.9% of all patients died. In the multivariable-adjusted Cox model, patients with current HBV infection had significantly higher mortality than those without (hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.11-2.02). A subgroup analysis showed that being infected with HBV significantly increased in-hospital mortality in patients younger than 65 years old (HR 1.74, 95% CI 1.16-2.63), whereas no significant impact was observed in patients ≥65 years. The propensity score-matched case-control analysis showed that the rate of septic shock (91.4% vs. 62.1%, P < 0.001) and in-hospital mortality (48.3% vs. 35.3%, P = 0.045) were much higher in the propensity score-matched HBV infection group compared with the control group. In conclusion, current HBV infection was associated with mortality in adults with sepsis.
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Affiliation(s)
- Chang Gao
- Department of Emergency and Critical Care Medicine, Suzhou Dushu Lake Hospital (Dushu Lake Hospital Affiliated to Soochow University), Suzhou, China
- Medical Center of Soochow University, Suzhou, China
- Institute of Critical Care Medicine, Soochow University, Suzhou, China
| | - Jingjing Ni
- Department of Critical Care Medicine, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, China
| | - Ye Gao
- Department of Critical Care Medicine, Taicang Hospital Affiliated to Soochow University, Suzhou, China
| | - Dan Xie
- Department of Emergency and Critical Care Medicine, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, China
| | - Lijuan Yang
- Suzhou Medical College, Soochow University, Suzhou, China
| | - Bining Yang
- Department of Emergency and Critical Care Medicine, Suzhou Dushu Lake Hospital (Dushu Lake Hospital Affiliated to Soochow University), Suzhou, China
- Medical Center of Soochow University, Suzhou, China
- Institute of Critical Care Medicine, Soochow University, Suzhou, China
| | - Xiaoting Lu
- Department of Emergency and Critical Care Medicine, Suzhou Dushu Lake Hospital (Dushu Lake Hospital Affiliated to Soochow University), Suzhou, China
- Medical Center of Soochow University, Suzhou, China
- Institute of Critical Care Medicine, Soochow University, Suzhou, China
| | - Qiang Guo
- Department of Emergency and Critical Care Medicine, Suzhou Dushu Lake Hospital (Dushu Lake Hospital Affiliated to Soochow University), Suzhou, China
- Medical Center of Soochow University, Suzhou, China
- Institute of Critical Care Medicine, Soochow University, Suzhou, China
- Department of Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China
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