The Expression Of Serum HBV PgRNA In Chronic Hepatitis B Patients Treated With NAs And Its Clinical Significance

Background:Chronic hepatitis B(CHB)is a chronic liver inflammatory disease caused by persistent hepatitis B virus(HBV)infection.Without effective antiviral treatment,CHB can progress to liver cirrhosis(LC)and hepatocellular carcinoma(HCC).The extensive application nucleos(t)ide analogs(NAs)leads the antiviral treatment of CHB patients to a new age,effectively control the replication of HBV and the inflammation of the liver,and significantly reduce the morbidity of cirrhosis and HCC.However,NAs can only reduce the level of hepatitis B virus deoxyribonucleic acid(HBV DNA)by inhibiting the reverse transcription activity of HBV DNA polymerase,but cannot eliminate the original template of HBV replication,that is,the covalently closed circular DNA(cccDNA)in the nucleus of hepatocytes.Thus,NAs usually need to be taken for a long time.At present,HBV DNA,hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg),etc.are routinely used to assess the effect of antiviral treatment and as indicators for discontinuation of treatment,while they cannot accurately reflect the transcriptional activity of cccDNA.Therefore,more effective indicators are needed to determine whether cccDNA is cleared or effectively controlled.In recent years,studies have found that the level of HBV pregenomic RNA(pgRNA)in peripheral blood is positively correlated with the level of cccDNA.Therefore,the dynamic levels of HBV pgRNA in peripheral blood of CHB patients undergoing NAs antiviral therapy and the correlation of HBV pgRNA with other HBV markers are of great significance for exploring new markers for evaluating antiviral efficacy.Objective:(1)Explore the value of HBV pgRNA in evaluating the efficacy of NAs against HBV.(2)To compare the expression differences and clinical significance of serum HBV pgRNA in patients after monotherapy with entecavir(ETV)and tenofovir(TDF).Methods:CHB Patients who were undergoing antiviral therapy with ETV or TDF for 48 weeks,144 weeks,240 weeks,with HBV DNA<20 IU/mL(Cobas TagMan(?),Roche Diagnostics)were enrolled in this study,from the outpatient and inpatient of the Department of Infectious Diseases,Taihe Hospital,Hubei Medicine University,Shiyan City,from May 2019 to September 2020.All the data of patients were retrieved from the hospital case database.Serum samples were collected.Serum HBsAg and HBeAg were detected using chemiluminescence microparticle immunoassay,and HBV pgRNA were detected by quantitative PCR.The χ2 test was used for the comparison of rates between groups,and the analysis of variance,independent sample t test and non-parametric rank sum test were used for the comparison between groups;Spearman correlation analysis was used for correlation analysis.Results:1.A total of 185 CHB patients were enrolled in this study,104 of which(56.22%)were positive in HBV pgRNA detection.2.The positive rates in detection of serum HBV pgRNA in CHB patients treated with NAs for 48weeks,144weeks,and 240weeks were 73.58%,54.10%,and 45.07%,respectively.There were significant differences in the positive rates in serum HBV pgRNA among the three groups(p<0.05),and the positive rates in serum HBV pgRNA showed a downward trend with the increase in time period of antiviral treatment.The serum HBV pgRNA levels between the three groups were significantly different(p<0.05).Further pairwise comparisons showed that the HBV pgRNA levels of patients undergoing NAs treatment for 144 weeks and 240 weeks were much lower than those for 48 weeks,and the difference was statistically significant(144 weeks vs.48 Weeks:2.46 vs.3.54 log10 copies/mL,p<0.05;240 weeks vs.48 weeks:1.70 vs.3.54 log10 copies/mL,p<0.05);the HBV pgRNA level in the 240 weeks group was also significantly lower than that in the 144 weeks group(1.70 vs.2.46 log10 copies/mL,p<0.05).There was a significant difference in HBsAg levels between the three groups(p<0.05).Further pairwise comparisons showed that HBsAg levels in the 240 weeks group were significantly lower than those in the 48 weeks group(2.26 vs.2.94 log10 IU/mL,p<0.05).3.The serum HBV pgRNA level of CHB patients was positively correlated with the HBsAg level(r=0.425,p<0.001),especially in HBeAg-positive patients(r=0.404,p<0.01),while not in HBeAg-negative patients(r=0.266,p>0.05).4.The detection rate of serum HBV pgRNA in HBeAg-positive CHB patients was significantly higher than that of HBeAg-negative CHB patients(86.79%vs.43.94%,p<0.05).The serum HBV pgRNA level of HBeAg-positive patients was significantly higher than that of HBeAg-negative patients(3.74 vs.1.70 log10 copies/mL,p<0.05).The level of HBsAg in HBeAg-positive patients was significantly higher than that in HBeAg-negative patients(3.02 vs.2.44 log10 IU/mL,p<0.05).5.There was no significant difference in the detection rate of HBV pgRNA between the two groups of CHB patients undergoing NAs treatment with ETV and TDF for144 weeks(53.13%vs.55.17%,p>0.05).There was no significant difference in HBV pgRNA levels and HBsAg levels(p>0.05).Conclusion:1.The detection of serum HBV pgRNA is simple and non-invasive,which may be clinically applied as a new marker for continuously monitoring the antiviral effect of NAs and predicting the response to antiviral therapy.2.The serum HBV pgRNA levels of patients after 3 years of ETV and TDF antiviral treatment were similar,further confirming a similar antiviral effects of the two drugs.