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 level:47 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.
ABSTRACT
BACKGROUND: Clinical observations have shown that patients infected with chronic hepatitis B virus (HBV) genotype C versus genotype B had a higher load of the virus, more serious illness, and poorer responses to antiviral therapy and prognosis. However, the disparity between the two has not been clarified. OBJECTIVES: To explore possible relationship between HBV genotypes B and C and peripheral blood follicular helper T cells (Tfh) and its significance in treating chronic hepatitis B (CHB) patients. PATIENTS AND METHODS: One hundred and fifty CHB patients were enrolled into this study, including 70 cases infected with HBV genotype C and 79 cases with genotype B. One patient had suffered from both genotypes B and C. The levels of Tfh, also known as interleukin-21 (IL-21), HBV specific cytotoxic T lymphocytes (CTL), HBV DNA and alanine transaminase (ALT) were evaluated and compared in patients infected with genotype B and C. RESULTS: Levels of Tfh, IL-21 and HBV specific CTL of patients infected with HBV genotype C were significantly lower than those of patients infected with HBV genotype B, P < 0.01. Levels of HBV DNA and ALT of patients infected with genotype C were significantly higher than those of the patients infected with HBV genotype B, P < 0.01. CONCLUSIONS: Compared with chronic hepatitis B (CHB) patients infected with genotype B, higher levels of serum HBV DNA, ALT and TBil of patients infected with HBV genotype C may be related to their lower level of peripheral blood Tfh, which may result in lower IL-21, and it may result in lower HBV specific CTL.
ABSTRACT
BACKGROUND: It is difficult to predict what type of chronic hepatitis B (CHB) progresses to chronic severe hepatitis B. OBJECTIVES: This study aimed to observe changes in the HBV-specific and -nonspecific cellmediated immune responses after CHB deteriorates into severe hepatic disease and explore the significance of such changes. PATIENTS AND METHODS: This study aimed to observe changes in the HBV-specific and -nonspecific cell-mediated immune responses after CHB deteriorates into severe hepatic disease and explore the significance of such changes. RESULTS: In 49 of 255 CHB patients (19.22%), the disease developed into chronic severe hepatitis (early stage) an average of 10.06 ± 1.73 days after admission. CD4+ and NK cells levels in Group A were lower after progression into severe hepatitis than on the second day of admission (baseline) (P < 0.01). CD8+ cells and nonspecific CTL levels in Group A were higher after progression than at baseline (P < 0.01), and latter was higher than in Group B at baseline (P < 0.01); the levels of CD8+ cells and nonspecific CTLs in Group A after progression were significantly higher than those of Group B 10 days after admission (P < 0.01). There were no significant differences in HBV-specific CTL levels in Group A before and after progression to severe hepatitis (P > 0.05). CONCLUSIONS: Our results suggest that the immunological pathogenesis of chronic severe hepatitis B is related to significant rises in CD8+ and nonspecific CTL levels and that such increases predict that the disease will deteriorate into severe hepatitis.
