Risk factors for recurrence after drug withdrawal in HBeAg-positive chronic hepatitis B patients completing pharmacotherapy with nucleos(t) ide analogues

Objective To investigate the risk factors for recurrence after drug withdrawal in HBeAg- positive chronic hepatitis B( CHB)patients completing the treatment with nucleos( t) ide analogues( NAs). Methods A total of 60 HBeAg- positive CHB patients who visited and were treated in The First Hospital Affiliated to Guangxi Medical University from May 2004 to December 2014 were enrolled. The drugs were withdrawn after the patients reached the criteria for drug withdrawal in related guidelines. The univariate and multivariate Cox proportional hazards regression model analyses were performed for 15 factors which might influence recurrence,i. e.,sex,age,a family history of HBV infection,baseline HBV DNA load,baseline total bilirubin( TBil) level,baseline alanine aminotransferase( ALT) level,baseline aspartate aminotransferase( AST) level,duration of virologic response,time to disappearance of HBeAg,time from the start of medication to the development of HBeAg seroconversion,duration of consolidation therapy after HBeAg seroconversion,total course of the treatment,prolonged course of the treatment,HBs Ag level at drug withdrawal,and drug type. The Kaplan- Meier method was used for calculating the cumulative recurrence rate. Results The mean course of the treatment was 37. 36 ± 12. 67 months,the prolonged course of the treatment was 7. 0( 2. 0 ~ 13. 0) months,and 56. 7% of all patients experienced recurrence. Sex,age,baseline HBV DNA load,baseline TBil level,baseline ALT level,baseline AST level,duration of virologic response,duration of consolidation therapy,total course of the treatment,prolonged course of the treatment,and drug type were not significantly associated with recurrence after drug withdrawal in patients who met the criteria for drug withdrawal( all P > 0. 05). A family history of HBV infection( RR = 1. 583,P = 0. 047),time to HBeAg seroconversion( RR = 1. 205,P = 0. 015),and HBs Ag level at drug withdrawal were independent risk factors for recurrence after drug withdrawal. The patients with time to HBeAg seroconversion > 12 months had a significantly higher recurrence rate than those with time to HBeAg seroconversion < 12 months( 80. 0% vs 48. 9%,P < 0. 001). Conclusion A family history of HBV infection,delayed HBeAg seroconversion,and high HBs Ag level at drug withdrawal are major risk factors for recurrence after drug withdrawal in HBeAg- positive CHB patients who have met the criteria for drug withdrawal in the treatment with NAs. If HBeAg- positive CHB patients can acquire immune control,recurrence after withdrawal of NAs will be reduced.