Changes of programmed death receptor-1 in patients with different baseline hepatitis B virus DNA levels after treatment with adefovir dipivoxil / 中华传染病杂志

ABSTRACT

Objective To explore the changes of programmed death receptor-1 (PD-1) in chronic hepatitis B (CHB) patients with different baseline of hepatitis B virus (HBV) DNA levels after treatment with adefovir dipivoxil (ADV).Methods One hundred CHB patients with positive hepatitis B e antigen (HBeAg),1 × 104 copy/mL≤HBV DNA≤1 × 107 copy/mL,and positive human leukocyte antigen-A2 were divided into two groups according to the baseline HBV DNA level47 cases in low virus load group whose HBV DNA level was ≤1 × 105 copy/mL; 53 cases in high virus load group whose HBV DNA level was＞1 × 105 copy/mL.Both groups were treated with ADV 10 mg/d.Serum HBV DNA,HBeAg seroconversion rate,alanine aminotransferase (ALT) and total bilirubin (TBil) levels of both groups before treatment and 12 months after treatment were compared.Flow cytometry was used to test peripheral blood HBV-specific cytotoxic T lymphocyte (CTL) surface PD-1 and peripheral blood HBV-specific CTL level.Categorical data were tested by x2 test; quantitative data was compared with t-test.Results Peripheral blood HBV-specific CTL surface PD-1 of CHB patients in low virus load group was 20.17 ％±1.69％,which was lower than that in high virus load group (41.38％±2.30％,t =53.02,P＜0.01) ; peripheral blood HBV specific CTL levels in two groups were 0.37％±0.02％ and 0.17％± 0.02％,respectively (t=50.47,P＜0.01) ; ALT and TBil levels in low virus load group were both lower than those of high virus load group (t=13.07,P＜0.01; t=5.06,P＜0.01).Twelve months after treatment,HBV DNA of 25 cases (53.2％) in low virus load group and 10 cases (18.9％) in high virus load group were lower than the detectable level (HBV DNA＜500 copy/mL,x2 =12.89,P＜0.01);HBeAg seroconversion was achieved in 15 cases(31.9％) and 1 case (1.9％),respectively (x2 =16.72,P＜0.01) ; peripheral blood HBV-specific CTL surface PD-1 expression levels were 9.00 ％ ±1.38 ％ and 29.40 ％ ± 3.76 ％,respectively (t =36.80,P＜ 0.01) ; peripheral blood HBV-specific CTL levels were 0.65％±0.10％ and0.48％±0.07％,respectively (t=9.61,P＜0.01).Conclusions After treatment with ADV,along with the decrease of HBV DNA load,HBV-specific CTL surface PD-1 expression decreases,while HBV-specific CTL level increases.The changes in low virus load group are much more remarkable.