Peripheral T lymphocytes predict the severity and prognosis in patients with HBV-related acute-on-chronic liver failure

Supplemental Digital Content is available in the text Abstract Background: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening syndrome with high mortality. Biomarkers are urgently needed to predict the prognosis of HBV-ACLF. Recent evidence suggests a key role for immune system in the pathology of HBV-ACLF. Here, we analyzed the correlation between peripheral blood T lymphocytes and the severity and prognosis in HBV-ACLF patients. Method: Sixty-six patients with HBV-ACLF received conventional medical treatments for 4 weeks. Twenty-five healthy subjects and 20 HBV patients were enrolled for comparison. We determined white blood cell count, lymphocytes, CD3+, CD4+ and CD8+ T cells, and CD4+CD25+ Treg cells in the blood of all subjects. Their associations with laboratory parameters before or after treatments were statistically analyzed. Result: The results showed that compare normal subjects and chronic hepatitis B patients, HBV-ACLF patients had significantly increased white blood count, CD4+ T cells and decreased lymphocytes, CD3+ T cells, and Treg cells. Correlation analysis showed that white blood cell, lymphocytes, and peripheral T lymphocytes were correlated with prothrombin activity (PTA) and model for end-stage liver disease (MELD) scores. After treatment, white blood cell, lymphocytes, and peripheral T lymphocytes were also correlated with PTA and MELD scores. Additionally, total bilirubin (TBIL), alanine aminotransferase (ALT), international standard ratio (INR), MELD, and white blood cell count were potential prognostic criteria for HBV-ACLF patients. Conclusion: HBV-ACLF patients had depletion and dysfunction of immune system. Changes of peripheral T lymphocytes were closely related to the pathogenesis and prognosis of disease. Our results may contribute to predict the severity of HBV-ACLF, and provide a prognosis response to improve the treatment of HBV-ACLF.

[1]  W. Sui,et al.  Next generation sequencing reveals novel alterations in B-cell heavy chain receptor repertoires associated with acute-on-chronic liver failure , 2018, International journal of molecular medicine.

[2]  Hong Zhao,et al.  Prognostic utility of novel biomarkers in acute‐on‐chronic liver failure (ACLF) associated with hepatitis B: A multicenter prospective study , 2018, Hepatology research : the official journal of the Japan Society of Hepatology.

[3]  Hong Zhao,et al.  Acute-on-chronic liver failure in chronic hepatitis B: an update , 2018, Expert review of gastroenterology & hepatology.

[4]  Jun Yu Li,et al.  Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-on-chronic liver failure , 2017, Gut.

[5]  G. Auzinger,et al.  Increased Expression of Cytotoxic T-Lymphocyte−Associated Protein 4 by T Cells, Induced by B7 in Sera, Reduces Adaptive Immunity in Patients With Acute Liver Failure , 2017, Gastroenterology.

[6]  T. Gustot,et al.  New concepts in acute‐on‐chronic liver failure: Implications for liver transplantation , 2017, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[7]  R. Moreau,et al.  Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B. , 2016, Scientific Reports.

[8]  Zheng Zhang,et al.  The global burden of liver disease: The major impact of China , 2014, Hepatology.

[9]  Q. Ning,et al.  Hepatitis B virus genotype B and mutations in basal core promoter and pre-core/core genes associated with acute-on-chronic liver failure: a multicenter cross-sectional study in China , 2014, Hepatology International.

[10]  M. Arababadi,et al.  NK cells in hepatitis B virus infection: a potent target for immunotherapy , 2014, Archives of Virology.

[11]  Y. Chawla,et al.  Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014 , 2009, Hepatology International.

[12]  W. Vogel,et al.  Acute‐on‐chronic liver failure: Excellent outcomes after liver transplantation but high mortality on the wait list , 2013, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[13]  Hai Li,et al.  Imbalance between circulating CD4+ regulatory T and conventional T lymphocytes in patients with HBV‐related acute‐on‐chronic liver failure , 2013, Liver international : official journal of the International Association for the Study of the Liver.

[14]  A. Abu-Hanna,et al.  A systematic review on prognostic indicators of acute on chronic liver failure and their predictive value for mortality , 2013, Liver international : official journal of the International Association for the Study of the Liver.

[15]  W. Guo,et al.  Nucleoside analogs prevent disease progression in HBV-related acute-on-chronic liver failure: validation of the TPPM model , 2013, Hepatology International.

[16]  13th Asia-Pacific Congress of Clinical Microbiology and Infection Consensus Guidelines for diagnosis and treatment of liver failure. , 2013, Hepatobiliary & pancreatic diseases international : HBPD INT.

[17]  P. Kamath,et al.  Acute-on chronic liver failure. , 2012, Journal of hepatology.

[18]  M. Yuen,et al.  Acute‐on‐chronic liver failure in chronic hepatitis B , 2012, Journal of gastroenterology and hepatology.

[19]  P. Kamath,et al.  Acute-on-Chronic Liver Failure: What are the Implications? , 2012, Current Gastroenterology Reports.

[20]  Shixia Wang,et al.  Dynamic changes of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, and natural killer T (NKT) cells in patients with acute hepatitis B infection , 2011, Virology Journal.

[21]  Q. Ning,et al.  Acute liver failure: mechanisms of immune‐mediated liver injury , 2010, Liver international : official journal of the International Association for the Study of the Liver.

[22]  矢野 崇 Diagnosis and treatment of liver failure , 2009 .

[23]  Y. Chawla,et al.  Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL) , 2009, Hepatology international.

[24]  Zheng Zhang,et al.  Severe dendritic cell perturbation is actively involved in the pathogenesis of acute-on-chronic hepatitis B liver failure. , 2008, Journal of hepatology.

[25]  L. Li,et al.  Altered immune function of monocytes in different stages of patients with acute on chronic liver failure , 2006, Clinical and experimental immunology.

[26]  S. Lewin,et al.  Immunopathogenesis: Role of Innate and Adaptive Immune Responses , 2006, Seminars in liver disease.

[27]  F. Lammert,et al.  Patients with acute on chronic liver failure display "sepsis-like" immune paralysis. , 2005, Journal of hepatology.

[28]  L. Forman,et al.  Predicting the prognosis of chronic liver disease: An evolution from child to MELD , 2001, Hepatology.