Hepatic Dysfunction And The Immune Function Analysis With Infectious Mononucleosis Infected Epstein-Barr Virus In Children

BackgroundEpidemiologically,the rate of EBV infection is high and the population is generally susceptible,with over 90%of adults worldwide having been infected with EBV.EBV can be carried for our lives.The annual incidence of primary EBV infection varies greatly in different regions.EBV is mainly transmitted through saliva,infecting B lymphocytes in the oropharynx and entering the body’s blood circulation to form viremia.EBV is Preferred to infect the lymphocytes,which can be aggressive the whole body’s lymphatic tissue and lymphocyte-containing tissues and organs,thus causing different degrees of immune dysfunction.It’s clinical manifestations vary widely,from asymptomatic infection or upper respiratory symptoms to the development of EBV-IM,CAEBV,EBV-HLH,or neoplastic disease,with diversely varying prognoses.In recent years,there has been an upward trend in the number of hospitalized children with EBV-IM.EBV-IM occurs in preschool age,mostly in males,with an incubation period of about 6 weeks in China.And the common clinical manifestations include fever,pharyngitis and cervical lymphadenopathy,called“the typical triad”of EBV-IM,possibly accompanied by bilateral eyelid swelling,hepato-splenomegaly,skin rash and abdominal pain.What’s more,the specific laboratory test is a significant increase in atypical lymphocytes in blood.Primary EBV infection is often associated with single or multiple organ damage.As we know,the liver is one of the most commonly involved organs,which is initially considered to be related to the immune status of the body.At present,the specific mechanism and risk factors are unknown.In this article,we will analyze the immune function status of EBV-IM in children with hepatic impairment,which will help clinicians assess the progression of EBV-IM in children and deepen understanding about EBV-IM.Methods1.The study subjects:All children with EBV-IM hospitalized from January 2019to August 2022 in the Infection Department of Guangzhou Women and Children Medical Center were collected.2.Data collection:The basic information(including age,gender,etc.),hospitalization time,hospitalization cost,clinical manifestations,related auxiliary tests,complications and disease regression of pediatric EBV-IM combined with liver function impairment cases are retrospe ctively analyzed.3.The Subgroups:Elevated serum aminotransferases(ALT,AST)can be used as a sensitive indicator of liver injury,and it will be set as the main observation indicator of liver function impairment,but not limited to hepatocellular damage,and also included damage of bile duct cell.According to whether the aminotransferases(ALT and/or AST)is abnormal or not,it is divided into normal liver function group and liver function impairment group.Mild,moderate,and severe impairment of liver function were respectively set as ALT and/or AST at<5×ULN(upper limit of normal),5-15×ULN,and>15×ULN.The time to return to normal was calculated by setting the day of discovery of abnormal biochemical indexes as the starting time.Meanwhile,indicators related to damage of bile duct cell were observed,includingγ-glutamyl transpeptidase(γ-GT),alkaline phosphatase(ALP),total bilirubin(TBIL)and direct bilirubin(DBIL).The time to return to normal was calculated by setting the day of discovery of abnormal biochemical indexes as the starting time,and the observation end point was the days of normal biochemical indexes in the reexamination test,the period being the time of liver function impairment.4.The main observations of hepatocyte injury:It were analyzed that the age distribu-tion and severity of the patients with EBV-IM damaging hepatocytes(ALT and/or AST indicators),as well as the time to return to normal levels from different levels of hepatocellular damage.5.The main observation of injury of bile duct cell:The levels of damaging bile duct cells,and the association between the damage in bile duct cell and the severity of liver dsyfunction were analyzed.6.The main observation of immune function:To detect the percentage and number of peripheral blood lymphocyte subpopulations by flow cytometry,it was analyzed the changes of lymphocyte subpopulations in patients with EBV-IM combined with liver function impairment.At the same time,the changes of immunoglobulins in EBV-IM combined with liver function impairment were observed.7.To analyze the independent risk factors of EBV-IM in children accompanying liver dsyfunction:It was analyzed that the influential factors and independent risk factors of EBV-IM in children using univariate analysis and applying binary logistics regression.Results1.The age distribution of enrolled cases:There were 76 cases(18.1%)in the group with normal liver function and 343 cases(81.9%)in the group with liver function impairment.The incidences of liver function impairment in the age groups of<1 year old,1 to<3 years old,3 to<6 years old,6 to<12 years old,and 12 to<18years old were 100%(3/3),78.9%(90/114),82.0%(169/206),84.4%(76/90),and83.3%(5/6),respectively,which incidences of liver function impairment with EBV-IM in each age group was There was no statistically significant difference in the proportion of EBV-IM showing liver function impairment.2.The severity distribution of patients with EBV-IM combined with hepatic impairment and their recovery time to normal levels:Mild(ALT and/or AST index),moderate and severe liver dysfunction were found in 256(74.6%),75(21.9%)and 12(3.5%)patients,respectively.There are 262 patients with elevated ALT at admission,of which 162 patients were followed up until elevated ALT returned to normal that the time to returned to normal levels was needed within 1 week,2 weeks,3 weeks,4weeks,5 weeks and at least 6 weeks in 49(30.2%),78(48.1%),23(14.2%),3(1.9%),4(2.5%)and 5(3.1%),respectively.There are 332 patients with elevated AST at admission,of which 135 patients were followed up until elevated ALT returned to normal that the time to returned to normal levels was needed within 1 week,2 weeks,3 weeks,4 weeks,5 weeks and at least 6 weeks in 50(37.0%),54(40.0%),8(5.9%),8(5.9%),5(3.7%)and 10(7.4%),respectively.3.The association with injury levels of the bile duct cells and liver function impairment of patients with EBV-IM:In the patients with damaged liver bile duct cell,there are 168(40.0%)patients with elevatedγ-GT,42(10.0%)with elevated ALP,19(4.5%)with elevated TBIL and 37(8.8%)with elevated DBIL.Two cases(2.6%)of children with EBV-IM showed bile duct were damaged when their liver function was normal,while the combination of mild,moderate and severe liver dsyfunction involving damaging bile duct was 89(34.8%),65(86.7%)and 12(100%)cases,respectively.4.The proportion and the absolute counting of peripheral blood lymphocyte sub-populations in children with EBV-IM:The proportion of CD8~+T lymphocytes in the liver dysfunction group with EBV-IM in children in the tested lymphocyte subpopulations was increased,the proportion of CD4~+T lymphocytes and CD19~+B cells was decreased,and the CD4~+/CD8~+ratio inverted(all P was 0.000),the proportion of the CD3~+T lymphocytes,CD8~+T lymphocytes and CD56~+NK cells significantly elevated(all P was 0.000).However,the proportion of CD56~+NK cell,and the counts of CD4~+T lymphocytes and CD19~+B cells were not statistically different between in the normal liver function group and the liver dysfunction group(P of them were respectively 0.941,0.437,0.366).The Ig G and Ig M were increased between in the normal liver function group and the liver dysfunction group(P were both 0.000)but the Ig A and Ig E were no statistical difference between the two groups(P>0.05).5.To analyze the independent risk factors of EBV-IM in children accompanying liver dsyfunction:By multivariate factor analysis of EBV-IM accompanied with liver dysfunction in children,it was found that gender,the heating course,lymphocyte percentage,ALP,γ-GT,LDH and the absolute count of CD56~+NK cells were deemed to be independent risk factors for abnormal liver function(P<0.05).Conclusions1.The occurrence of hepatic impairment in childhood diagnosed EBV infectious mononucleosis is a common complication that the prognosis most of patients is good.But the liver function in the quarter patients could moderate to severe liver dysfunction,which leaded to prolong the disease duration,increased hospitalization time and hospitalization expend,and the longest follow-up time to return to normal level for the abnormal indexes at least 2 months.2.The incidence of EBV-IM combined with injuring bile duct cell in children was39.6%.Among them,the incidence of children with moderate and severe hepatic impairment with bile duct cell injury was 86.7%and 100%,respectively.It is found that high sensitivity of bile duct damage to reflect liver function impairment.3.The lymphocyte subsets in children with EBV-IM accompanied with liver impairment showed an increased proportion of CD8~+T lymphocytes,CD4~+T lymphocytes and CD19~+B cells and the inverted CD4~+/CD8~+.CD3~+T lymphocytes,CD8~+T lymphocytes and CD56~+NK cells were significantly elevated.CD8~+T lymphocytes had been stimulated to proliferate and differentiate,then the activity for cytotoxic T cell had been increases and cytokine secretion capacity had been enhanced,which may lead to damage to hepatocytes and bile duct cells.Meanwhile,Ig G and Ig M are increased.4.It was found that gender,the heating course,lymphocyte percentage,ALP,γ-GT,LDH and the absolute count of CD56~+NK cells were deemed to be independent risk factors in the children with EBV-IM accompanied with liver impairment.