Study On Relationship Between HBV Relapse And Serum Low-load HBV DNA In CHB Patients Meeting NAs Cessation Criteria

Obsjective:To explore the relationship between HBV relapse and serumlow-load HBV DNA in CHB patients meeting NAs cessation criteria。Methods:72chronic hepatitis B patients who were received NAs treatment(21with ADV,14ETV,24LAM,9LDT,4LAM plus ADV) and had reached thetherapy endpoint of2008APASL CHB guideline were recruited,33of themwith e antigen positive and39of them negative. The liver function,HBVserological markers and HBV DNA were detected at every month within6months,every2months over6months and every3months over one year afterstopping therapy. Patients were followed up until relapse, non-relapse patientswere observed until the last visting date after stopping treatment.serum low-loadHBV DNA at cessation was detected by single copy sensitive reagents (hepatitisB virus nucleic acid reagents),the lowest detectable level was2copies/ml. Theinfluence factors on low-load HBV DNA which were gender,age,drugs,baselineHBeAg status,HBeAg serological conversion time,virologic responsetime,prolonged duration after reaching therapy endpoint and total duration oftreatment were analyze.The detectable rate of serum low-load HBV DNA wascompared with Chi-Square test between the relapse and non-relapse groups. Thecut off value of predicting relapse with serum low-load HBV DNA was calculated by ROC curves, and the cumulative relapse rate of tow group (＜2.24copies/ml group,≥2.24copies/ml group) was compared with Kaplan-Meiermethod and Chi-square test(χ~2test).Result:(1) The mean total duration of all72patients was32.6±7.23monthsand the prolonged duration was11.7±6.62months.65.3%（47/72）of patientsrelapsed,80.9%of patients relapsed accumulated in the first year after drugswithdrawal.The relapse rate of patients with HBeAg positive and negative were66.7%（22/33）and64.1%（25/39）respectively.(2) The detectable rate of serumlow-load HBV DNA was41.7%. The detectable rate of patietnts with prolongedduration <18months was higher than that with prolonged duration≥18months(47.5%vs15.4%χ~2=4.509P=0.034),and the detectable rate of patientswith HBeAg serum conversion time＜6months was significant lower than≥6months (25.0%vs61.5%χ~2=4.406P=0.036).(3)The serum low-load HBVDNA level and detectable rate showed significant differences between relapsedand non-relapsed patients（130.4±420.90vs44.6±155.16Z=-2.920P=0.004,55.3%vs16.0%χ~2=10.380P=0.001）. The cut off value predicting relapse was2.24copies/ml with a sensitivity of0.553, specificity of0.840, positivepredictive value of86.7%and negative predictive value of50.0%. Cumulativerelapse rates between HBV DNA＜2.24copies/ml group and≥2.24copies/mlgroup were significantly different(50.0%vs86.7%χ~2=11.871P＜0.001）, whichalso showed significant differences by Log-Rank longitudinal analysis.(P＜0.001).Conclusions:(1) Hepatitis B virus nucleic acid reagents is practicality toassay single copy HBV DNA with good sensitivity and high specificity.(2)Low-load HBV DNA still were detectable in those patients who met NAstreatment cessation criteria of2008APASL CHB guideline after HBV DNA,undetectale (<1000copies/ml by domestic reagents),these patients had ahigh risk to relapse;(3) Serum2.24copies/ml of low-load HBV DNA could beas the predictive value of relapse.