The Effect Of High-dose Immunoglobulin Pulse Therapy On The Prognosis Of Patients With Hepatitis B Virus-related Acute-on-chronic Liver Failure

Background Hepatitis B virus related acute-on-chronic liver failure(HBV-ACLF)is an acute liver failure based on a pre-existing HBV-related chronic liver disease.In China,HBV-ACLF is a high-incidence severe liver disease with a high mortality rate of about 70%,due to its serious physical condition,various complications as well as its difficulty of treatment.The current strategy of treating HBV-ACLF is very limited.In the pathogenesis of liver failure,the body’s immunity is mainly manifested as a "cytokine storm" cascade reaction,which leads to a strong systemic inflammatory response,causing massive necrosis of liver cells and dysfunction of multiple organs outside the liver within a short time.Intravenous immunoglobulin(IVIg)is a polyclonal product extracted from the mixed plasma of a large amount of healthy donors.The IVIg’s immunomodulatory effect has gradually gained recognition and attention.After the clinical practice of IVIg for many years,our research group has proposed that the administration of “high-dose IVIg pulse therapy” may suppress the “cytokine storm” in patients with liver failure.This novel therapy is expected to become a new strategy for curing HBV-ACLF,ameliorate the prognosis,and save more lives.ObjectiveTo explore whether HBV-ACLF patients receiving "high-dose immunoglobulin pulse therapy" on the basis of the comprehensive standard medical treatment could ameliorate their survival rate and key prognostic indicators,compared with the merely administration of the comprehensive standard medical treatment.MethodsFrom August 1,2013 to September 1,2020,our study recruited a number of 44 patients who were eligible for research criterions of HBV-ACLF in the Department of Hepatology and Infectious Diseases,the Second Affiliated Hospital of Shantou University Medical College.Among the eligible patients,22 cases were in the "standard medical treatment group(SMT group)" and 22 cases were in the "immunoglobulin pulse treatment group(IVIg group)".Patients in the SMT group were received a comprehensive standard medical treatment(SMT)of liver failure;patients in the IVIg group were received SMT plus “high-dose immunoglobulin pulse therapy”(a total IVIg dose of 1.5 g/kg body weight,0.5 g/kg/day ivdrip.on the first 2 days,0.1g/kg/day ivdrip.on days from day 3 to day 7).Then we analyzed whether the patients’ short-term and mid-term survival rates and key prognostic indicators(liver function,coagulation function,etc.)have ameliorated.Results1.The "high-dose immunoglobulin pulse therapy group(IVIg group)" significantly improved the84-day survival rate(P = 0.019 < 0.05)and 168-day survival rate(P = 0.036 < 0.05)of HBV-ACLF patients,compared with the "standard medical treatment group(SMT group)".2.The prognostic score of the model for end-stage liver disease(MELD,P = 0.005 < 0.01)and its derivative score(MELDNa score,P = 0.018 < 0.05),were significantly lower in the IVIg group after 7 days of treatment,compared with day 0(baseline);3.The IVIg group prevented the further deterioration of total bilirubin(TBIL,a key indicator of liver function)after 7 days of treatment,compared with day 0(P = 0.175 > 0.05);While under the condition of no difference between the two groups on day 0(P = 0.479 > 0.05),the liver function indicator of TBIL in the SMT group increased significantly after 7 days of treatment,compared with day 0(P = 0.002 < 0.01);4.The IVIg group significantly ameliorated the key indicators of coagulation function after 7days of treatment,compared with day 0(prothrombin time activity/PTA,P = 0.002 < 0.01,and international normalized ratio/INR,P = 0.002 < 0.01);ConclusionsThe "high-dose immunoglobulin pulse therapy(IVIg group)" can significantly improve the84-day and 168-day survival rates of patients with HBV-ACLF on the basis of administration the standard medical treatment.After 7 days of treatment,the IVIg group significantly ameliorated the patients’ MELD and MELDNa prognostic scores,prevented the further deterioration of the liver function indicator of TBIL,and significantly ameliorated the key coagulation function of PTA and INR.The IVIg group indicated a definite effect of improving the prognosis of the HBV-ACLF patients.This study is expected to provide an effective,economical and easy-to-promote novel treatment strategy for HBV-ACLF patients.