Study Of Relationship Between HBV Relapse And Liver Histology Status In CHB Patients Met Nas Cessation Criteria

Objective:To explore relationship between HBV relapse and liver histology status in CHB patients who met NAs treatment for 2008 Asian-Pacific cessation criteria.Method:Liver biopsies were percutaneous needle biopsies in 97 CHB and compensated cirrhosis patients who reached the NAs therapy endpoint or extended treatment duration. The liver tissue were stained with the hematoxylin-eosin and reticular fibrosis.HAI and Fibrosis of liver tissue were scored with Ishak’s scoring system.These were also subjected to immunohistochemistry for expression of HBsAg and hepatitis B core antigen (HBcAg).The scores of inflammation and fibrosis were compared with Non-parameter test in CHB and compensated cirrhosis patients. The cumulative relapse rate in 71 patients stopped NAs was calculated with Chi-square test and Kaplan-Meier.The cumulative relapse rates in 71 patients stopped NAs were compared among 4 subgroups of different scores of inflammation and fibrosis and 3 subgroups of different expression of the HBcAg and HBsAg with Log-rank test. Results:(1) The average scores of inflammation activities and fibrosis of 82 CHB patients were all lighter than the 15 compensated cirrhosis patients who had reached therapy endpoint criteria(2.80±1.88 vs.4.40±1.92, Z=-2.987 P= 0.003,1.87±1.21 vs.4.27±1.94, Z=-4.320 P<0.001); Scores of histology of 56.10% of CHB patients were HAI<4 and Fibrosis<3 and that of 43.90% patients were HAI≧4 and/Fibrosis≧3. Only scores of histology of 6.7% the cirrhosis patients were HAI<4 and Fibrosis<3 and that of 93.3% them were HAI≧4 and/Fibrosis≧3.The scores of inflammation in age≧40 years old in CHB patients were similary to that of age<40 years old (2.97±1.45vs2.69±2.15,Z=-1.567 P= 0.117),but the scores of the fibrosis (2.24±1.23) were higher than that of age <40 years old (1.60±1.13 Z=-2.245 P= 0.025);(2) In CHB and cirrhosis patients,on the liver tissue expression mode of HBsAg and HBcAg,28.9% patients were HBsAg (-) and HBcAg (-), and 71.1% were HBsAg (+) and/HBcAg (+). (3) For the 71 CHB patients stopped NAs,the cumulative relapse rate of scores of histology of patients with HAI<4 was lower than patients with HAI≧4(34.0% vs 61.9%,X2= 4.720 P= 0.030),the cumulative relapse rate of scoers of histology patients with Fibrosis <3 was lower than patients with Fibrosis≧3(32.65% vs 63.64% X2=5.973 P=0.015);the cumulative relapse rate in group with HAI<4 and Fibrosis<3 was lower than the group with HAI≧4 and/Fibrosis≧3(30.95% vs 58.62% X2=5.382 P=0.020).The subgroups analysis shew:the cumulative relapse rate of group A (HAI <4 and Fibrosis <3) was lower than groups B (HAI≧4 and Fibrosis <3), group C (HAI <4 and Fibrosis≧3) and group D (HAI≧4 and Fibrosis≧3)(P- 0.016);the histology scores of 6 cirrhosis patients were HAI≧4 and /Fibrosis≧3 and HBV relapsed from 2 to 10 months (mean 7.50±3.56 months) after stopping NAs.(4)The cumulative relapse rate of CHB patients with HBcAg(-) and HBsAg(-) was lower than the patients with HBsAg (+) and/ HBcAg (+)(20.83% vs 53.19% X2= 6.818 P= 0.009);the subgroups analysis shew:the cumulative relapse rate of group A [HBsAg (-) and HBcAg (-)] was lower than group B [HBsAg(+) and HBcAg(-)] and group C [(HBsAg (+) and HBcAg(+)] (P= 0.018).Conclusion:Even though the patients had met the NAs cessation criteria of the 2008 Asian-Pacific guideline,the liver histological improvement were not still satisfied and the expression of HBsAg and/HBcAg in liver tissue were positive in some patients, there was high risk of relapse for these patients.Therefore, as a supplement parameter of NAs cessation criteria, if histology scores are still HAI≧4 and/Fibrosis≧3 and expression of HBsAg and/HBcAg was positive, these patients should prolong additional treatment even if they had met cessation criteria.