Epidemiological Study Of Spontaneous Hepatitis B Virus Reactivation Among HBsAg Carriers In Community

Background Hepatitis B virus(HBV)infection is a serious global health problem,it is estimated more than 2 billion people infected worldwide,and 350 million are suffering from chronic HBV infection.In China,HBV infection is highly endemic.With the implementation of infant vaccination since 1992,a remarkable progress has been made by the Chinese government in preventing and controlling the HBV transmission.However,we still face many issues in prevention and treatment for HBs Ag carriers,and the HBV reactivation is the very important challenge that needs to be addressed.Though many clinical researches have described the phenomenon when HBs Ag carriers were under chemotherapy or received immunosuppressive treatment after organ transplant,there still lack the epidemiological characteristics and risk factors of the spontaneous HBV reactivation basesd on a large community-population.Thus,an epidemiologic study based on community-population was performed to determine the spontaneous reactivation incidence and clarify the related risk factors of HBV infection in Wuwei City.Objective Based on a large community population cohort of HBs Ag carriers in Wuwei city,Gansu province,northwest China,to investigate the incidence rate of spontaneous reactivation among HBs Ag carriers,the epidemiological characteristics,and find out the related risk factors and provide scientific measurements for prevention and control of HBV reactivation.Methods 1.The diagnosis of HBV reactivation.The reactivation of hepatitis B was defined as:(1)a change in HBV DNA status from undetectable to detectable,the DNA negative means patients who had a baseline viral load below the level of detection(<100IU/m L);(2)HBV DNA increased >10 fold over baseline.2.Retrospective cohort study.This study population was made up of two cohorts.The first cohort originated from a stratified random cluster sampling investigation in 4 communities in Wuwei city(Liangzhou district,Minqin County,Gulang county and Tianzhu Tibetan Autonomic County),which was conducted at June 2010.At that time 1740 cases who carried HBs Ag were identified,then we followed up them for 3 times in 2011,2012 and 2014.The second cohort established in June 2011.Four towns(Qinyuan town,Yongchang town,Huangyang town and Yangxiaba town)were selected in Liangzhou District.With the whole population screening in the 4 towns,2913 HBs Ag carriers were identified.We followed up them in 2013 and 2014.All the enrolled people signed the informed consent before this study.Epidemiological and demographic data were collected by a face-to-face survey with a standard questionnaire,which included the age,education,occupation,marriage,household registration and others.Blood sample(5ml/person)was taken from cubital vein,and stored at-80? until assay.The serum markers of HBV infection including HBs Ag,HBs Ab and HBc Ab were detected by enzyme-linked immunoassay(ELISA)kit.Real-time quantitative polymerase chain reaction(PCR)with a detection threshold of 102 IU/ml was used to determine HBV viral load.3.Nested case-control study.On the basis of the first part study,277 cases of HBV reactivation were selected as case group,and 280 cases of non-reactivation were randomly selected as control group with a ratio 1:1.A questionnaire was used to collect risk factors,which focused on smoking,alcohol drinking,living habits,the history of diabetes,tuberculosis,hypertension,atherosclerosis,autoimmune diseases and medication use,history of surgery,and blood transfusion.In addition to those factors,negative events of life was also included.4.All the data were dual entry via Epidata(version 3.1)software,if the data was inconsistent when entering,the original questionnaire would be checked carefully to ensure the data accurate and consistent.SAS(version 9.4)and SPSS(version 23.0)software were used for statistical analysis.Chi-square test was used while the data was counting data,variance analysis and t-test were used while the data was metrological data.We also used the trend of chi-square test and Logistic regression to analyze the risk factors,and the statistical significance of the difference was defined as P=0.05.Whether the OR(odds ratio)value had a significance was mainly based on if the confidence interval included 1,if it included 1,which meant no significance,if not which meant the difference was significant.Results 1.The distribution characteristics of HBV reactivation.After an average of 1.95 ± 0.81 years(median follow-up time was 1.67 years,follow-up time range is 1.7 to 4 years)follow-up.A total of 385 HBs Ag carriers were reactivated among 1752 carriers during this period.The spontaneous reactivation incidence was 7.69% person-years.The incidence of Male was 8.01% person-years,and the female was 7.37% person-years.There was no significant difference among gender.The incidence of HBV reactivation increased with the increasing of age whether male or female,especially reached the peak at the age of 40-49,which was 8.91% person-years.It declined until to the age of 60-69,then a second peak of HBV reactivation incidence appeared,which reached to 8.30% person-years.Based on different HBV DNA level,the cohort was divided into 3 groups: the DNA load <1×103 IU/ml ? 103 ~ 105 IU/ml and >1×105IU/ml group.The incidence of HBV reactivation was 11.35%,3.97% and 4.65% person-years,respectively.The reactivation incidence of <1×103 IU/ml group was higher than other two groups(P<0.001).2.The clinical features of HBV reactivation.The average ALT and AST level were no significant difference between reactivated group and un-reactivaed group.Then the reactivated group was divided into two reactivated sub-groups:(1)HBV DNA status changed from undetectable to detectable;(2)HBV DNA load increased >10 fold over baseline.It seemed that average ALT(58.00±76.32IU/ml)level of reactivated sub-group which HBV DNA load increased >10 fold was much higher than the other reactivated sub-group(42.70±30.77 IU/ml)and un-reactivaed group(48.83±50.83 IU/ml).The average AST level among these groups was no significance.The study found that the proportion of clinical features(eg.lacking in strength,poor appetite,icteric sclera.etc)in reactivated group was higher than in un-reactivated group.While after Chi-square test,there was no statistic difference.Besides,the research found that 3.38%(13/385)HBs Ag carriers appeared the suspected hepatitis,their ALT level(>2ULN)and HBV DNA load(>2000IU/ml)had reached to the antiviral therapy conditions.3.The related risk factors of HBV reactivation.Nested case-control study showed that smoking(OR=1.976,95%CI:1.025-3.812,P=0.042),alcohol drinking(OR=1.976,95%CI: 1.025-3.812,P=0.042),history of surgery(OR=3.579,95%CI:1.030-12.441,P=0.027),negative life events(OR=2.536,95%CI:1.544-4.165,P<0.001),diabetes history(OR=4.769,95%CI:1.151-19.765,P=0.031)and many times of colds in one year(OR=1.600,95%CI:1.387-1.932,P=0.023)were risk factors for HBV reactivation.Conclusion 1.The incidence of HBV reactivation among HBs Ag carriers in community population was 7.69% person-years in Wuwei city,Gansu Province,which was much higher than that in community of other country.The incidence of HBV reactivation among 40-49 years old and >70 years old groups were higher.Health monitoring should be strengthened to this crowd.2.The study showed 3.38%(13/385)HBs Ag carriers in reactivated group appeared the suspected hepatitis.This part of the crowd should go to hospital in time,and initiate antiviral treatment prophylactically.3.The research showed smoking,alcohol drinking,negative life events,history of surgery,diabetes history and many times of colds in one year were related to HBV reactivation.To prevent HBV reactivation,measures should be taken for those risk factors.Such as to advise quit smoking;strictly to limit alcohol intake among HBs Ag carriers;to make a fully comprehensive evaluation before operation;timely to provide psychological intervention for the people who had experienced negative life events;to pay much more attention for the HBs Ag carriers who also had been diagnosed with diabetes and other diseases.The periodic of follow-up interval should be shorten if it is necessary both in medication and daily health management.