Effect of low expression of sodium taurocholate cotransporting polypeptide on antiviral response in chronic hepatitis B patients with active inflammation / 中华传染病杂志

ABSTRACT

Objective:To investigate the relationship between the down-regulation expression of sodium taurocholate cotransporting polypeptide (NTCP) in proliferating hepatocytes and the response to antiviral therapy of chronic hepatitis B (CHB) patients.Methods:Sixty-eight hepatitis B e antigen (HBeAg)-positive CHB patients admitted to the Fifth Medical Center of PLA General Hospital from January 2011 to March 2015 were included. Basic information and laboratory data were collected. Based on the baseline (before antiviral treatment) inflammatory activity (G), the patients were divided into ≤G2 group and >G2 group. Twelve liver puncture tissue samples were selected from each group for NTCP and Ki67 immunofluorescence staining.The proportion of Ki67-positive cells was calculated, and the staining of NTCP was scored. Five pairs of tissue specimens of patients who had hepatitis B virus (HBV) infection were diagnosed with focal nodular hyperplasia (FNH) and underwent nodular resection surgery from March 2014 to March 2017 were collected.Immunohistochemical staining was used to detect the expressions of Ki67, NTCP and hepatitis B surface antigen (HBsAg) in each tissue specimen, and the proportion of staining positive cells or the staining intensity was calculated. Statistical analysis was performed by Mann-Whitney U test, chi-square test or Spearman correlation analysis. Results:The proportion of Ki67-positive cells (6.75%(6.20%, 8.16%))in five liver FNH tissues with HBV infection was significantly higher than that in adjacent non-FNH tissues (0.75%(0.66%, 1.20%)), while the immunohistochemical scores of NTCP and HBsAg (3.00 (1.00, 3.00) and 2.00 (1.00, 2.00), respectively) were both significantly lower than those in adjacent non-FNH tissues (8.00 (8.00, 9.00) and 8.00 (6.00, 8.00), respectively), the differences were all statistically significant ( Z=-2.611, -2.424 and -2.635, respectively, P=0.009, 0.015 and 0.008, respectively). There were 37 patients in >G2 group, and 31 patients in ≤G2 group. After six months of antiviral treatment, CHB patients with persistent inflammation in >G2 group obtained a better virological response, with serum HBV DNA and HBeAg showing a greater decline ((0.71±0.14) lg IU/mL and (0.92±0.13) lg IU/mL, respectively) than those in ≤G2 group ((0.54±0.30) lg IU/mL and (0.49±0.65) lg IU/mL, respectively) ( Z=-3.048 and -2.666, respectively, P=0.002 and 0.008, respectively). The proportion of Ki67-positive cells in the specimens of >G2 group (4.34%(1.84%, 8.77%)) was significantly higher than that of ≤G2 group (0.34%(0, 0.80%)) ( Z=-3.640, P<0.01), and the immunohistochemical staining score of NTCP (1.00 (0, 3.25)) was significantly lower than that of ≤G2 group (6.00 (4.00, 8.00)) ( Z=-3.012, P=0.003). Spearman correlation analysis showed that the NTCP immunohistochemical score was negatively correlated with the proportion of Ki67-positive cells ( r=-0.512, P=0.01). Conclusions:CHB patients with persistent inflammationare often accompanied by more active hepatocyte proliferation and low membrane NTCP expression, which is not conducive to HBV reinfection. It may facilitate these patients to obtain better virological response.