Dynamic Changes And Clinical Significance Of Serum HBV RNA Levels In Patients With Hepatitis B Virus Infection Treated With Entecavir

BackgroundCurrently,liver fibrosis,cirrhosis or even Hepatocellar carcinoma(HCC)caused by chronic Hepatitis B virus(HBV)infection is still one of the most important diseases threatening the health of people worldw-ide.Fortunately,the antiviral drugs can already be single-agent oral or combined oral simple way well inhibiting viral replication of HBV in the liver,but the existing drugs is not directly to restrain covalently closed circular DNA(cccDNA)in the liver tissue ang recurrence rate is high.So many cilnical guidlines pointed out that in order to reduce the risk of recurrence,we should extend the time of antiviral treatment before stopped taking the drug.At present,non-invasive serum markers for evaluating the treatment are hepatitis B virus deoxyribonucleic acid(HBV DNA),hepatitis B virus surface antigen(HBsAg),hepatitis B virus e antigen(HBeAg).Hepatitis B virus ribonucleicacid(HBV RNA)is a virus replication intermediate produced by cccDNA that only originates from the liver cells.HBV RNA is immune to antibodies and virus antigens.Its specific value is not affected by immune complexes,so it is of great value for predicting treatment response,guiding drug withdrawal and monitoring virus mutation.ObjectiveThe study was designed to observe the dynamical changes of serum HBV RNA and its correlation with serum HBV DNA,HBsAg and HBeAg in patients with chronic HBV infection under the initial antiviral treatment with Entecavir.MethodsPatients with Chronic hepatitis B(CHB)or hepatitis B cirrhosis who have been treated with Entecavir(ETV)for more than 6 months at Second hospital of Shandong University from October 2016 to December 2018 were included for the purpose of establishing a prospective cohort study.Blood samples were collected from all patients on day 0,3,7,14,28,2 months,3 months,6 months,9 months and 12 months of antiviral treatment,and serum HBV RNA,HBV DNA,HBsAg,HBeAg,Alanine aminotransferase(ALT)and other indicators were detected and relevant data were collected.Wilcoxon test was using to describe the variation trend between two time points of HBV RNA.Spearman rank correlation analysis was used to analyze the correlation between two variables at the same time point.Results1.This study comprised total of 42 patients with CHB or cirrhosis,these patients were divided into two groups according to whether they were positive for HBeAg.A total of 30 patients were in the HBeAg positive group,including 20 males(66.7%)and 10 females(33.3%).There were 12 patients in the HBeA negative group,including 4 males(33.3%)and 8 females(66.7%).All patients were followed up for more than half a year.23 patients were followed up for 12 months,including 18 patients in the HBeAg positive group,including 14 males(77.8%)and 4 females(22.2%).There were 5 patients in the HBeA negative group,including 2 males(40%)and 3 females(60%).All patients were initially treated with Entecavir(ETV)alone.2.On the third day of antiviral therapy,serum HBV RNA level was slightly increased at first,and gradually decreased with the extension of treatment time.The rapid decline was concentrated in the 2-12 weeks of antiviral therapy.After 12 weeks of antiviral therapy,serum HBV RNA showed a slow decline.3.Wheather the serm HBeAg is positive or not,serum HBV RNA had a strong correlation with serum HBV DNA at the initial stage of antiviral therapy,but the correlation gradually weakened with the extension of treatment time.4.Wheather the senn HBeAg is positive or not,the correlation between serum HBV RNA and serum HBsAg was strong within 12 weeks of antiviral treatment,and then decreased compared with the previous correlation.5.As for the serm HBeAg positive patients,the correlation between serum HBV RNA and serum HBeAg remained strong during the follow-up 12 months in this study.Conclusion1.Serum HBV RNA increased slightly at the initial stage of antiviral therapy,then decreased rapidly.With the prolongation of treatment time,the rate of decline gradually slowed down.2.Serum HBV RNA levels were strongly correlated with serum HBV DNA,HBsAg and HBeAg levels before and at the early stage of antiviral therapy,and the correlation gradually decreased with the prolongation of treatment time.