Study Of Influence Factors On HBV Relapse After Nas Withdrawal In The CHB Patients Who Met Nas Cessation Criteria

objective:To explore the influence factors on HBV relapse after Nucleos(t)ide analogues (NAs) withdrawal in the chronic hepatitis B (CHB) patients who met NAs cessation criteria.Methods:78 consecutive CHB patients were treated with NAs (31 with LAM,23ADV,4LDT,14ETV,6LAM+ADV),37 of them with e antigen positive,41 with e antigen negative,64 of them with initial treatment,14 with retreatment due to resistance to NAs at baseline. They discontinued treatment after meeting therapeutic end-point criteria. HBV DNA, HBV serological markers, ALT were measured respectively at baseline,every month before HBV DNA＜1.0×103copies/ml, every 3 month after HBV DNA＜1.0×103copies/ml, every month within first 6 months and every 2 months over 6 months after drugs withdrawal. HBV genotypes were detected by nested PCR with multiple pair primers, Of 78 patients,60 discontinued treatment with liver biopsy after meeting end-point criteria or prolonging additional treatment. Intrahepatic HBVtDNA and cccDNA were measured by sensitive and specific quantitative real-time polymerase chain reaction (PCR) assays.13 probable influence factors on relapse which were sex, age, genotype, HBV family history, baseline HBV DNA, baseline HBeAg status, baseline ALT, virological responses time, total duration of treatment, duration of additional treatment, the level of HBsAg at cessation therapy, initial treatment or retreatment, drug category respectively were analyzed with univariate,multivariate COX regression modle and x2test, The cumulative relapse was calculated by the Kaplan-Meier method. Area under the receiver operating characteristics (ROC) curve was performed to assess the predictive values of HBVtDNA and cccDNA at the end of therapy for virologic relapse.Results:(1).All of them received a mean period of 31.95±7.32 months(range 24-61 months) oral antiviral therapy.48.7% of patients relapsed. (2). Sex, age, genotype, baseline HBV DNA, baseline HBeAg status, baseline ALT, total duration of treatment, duration of additional treatment, drug category are no significant differences for relapse (P>0.05). (3). The results showed that Initial treatment or retreatment (OR,4.321; 95% CI,2.020-9.240; P= 0.000), virological responses(OR,1.255; 95% CI,1.054-1.495; P= 0.011),HBV family history(OR,1.705; 95% CI,1.095-2.654; P=0.018), the level of HBsAg at the end of therapy(OR,1.471; 95% CI,1.006-2.153; P=0.047) were independent risk factors. (4). Of the 78 patients, relapse rate of retreatment was higher than that of initial treatment (85.7% vs 40.6%, P=0.002); HBV family history higher than without family history (66.7% vs 18.2%, P=0.002); virological responses> 3 months higher than<3 months (70.8% vs 38.9%; P=0.009) HBsAg>150 ng/ml at cessation therapy higher than<150 ng/ml (57.7% vs 30.8%, P=0.025). (5). Intrahepatic HBV tDNA and cccDNA at cessation therapy can be detected in 60 patients(100%),including 2 patients whose HBsAg disappearance. The cut off value of hepatocellular HBV cccDNA predicting relapse is 6.5 copies/cell (log rank test P=0.006).Conclusions:There was no difference in the age, gender ratio, genotype, HBV DNA,HBeAg status, and ALT levels at the time of starting antiviral therapy, and there was no difference in the treatment duration between the relapsers and the sustained responders.It is easy for patients with retreatment, HBV family history, late virological responses, higher HBsAg level and hepatocellular HBV cccDNA at cessation therapy to relapse after NAs withdrawal, Therefore, we considered that the end-point of treatment also should be considered as individual as the person.For these patients(retreatment, HBV family history, virological responses>3 months and HBsAg level>150ng/ml,hepatocellular HBV cccDNA>6.5 copies/cel) even meeting cessation criteria,the duration of treatment should be extended to consolidate the efficacy.