The Effects Of Adefovir Dipivoxil On The Intrahepatic HBV CccDNA Quantification, The Liver Pathology And The Clinical Manifestation In The Patients With Chronic Hepatitis B

Objective To observe the effects of adefovir dipivoxil on the clinical efficiency, the liver pathology,and the relationship bebetween the expression of HBsAg and HBcAg in liver tissue and the changes of intrahepatic HBV DNA and HBV cccDNA quantification in the patients with chronic hepatitis B(CHB). To discuss the clinical significance of increase or decrease of intrahepatic cccDNA during the antiretroviral therapy. Hope to further improve the evaluation system of antiretroviral therapy. Methods 52 patients with CHB from Infection Disease Department of Affiliated Hospital of Ningxia Medical University during July 2007 to October 2010 aged between 16 and 60 (average age=35.39±10.14) were selected into this study. Of which the male was 41 cases and female was 11cases. And 25 cases were HBeAg positive,17 cases were HBeAg negative. These patients were treated with adefovir dipivoxil tablets 10mg / day for 48 weeks. 23 cases of 52 were selected to do liver biopsy and detect the intrahepatic HBV DNA,HBV cccDNA quantification before and after treatment.The quantity of intrahepatic HBV cccDNA and HBV DNA was assayed by FQ-PCR and the serum HBV DNA was detected by PCR. At the same time, the liver tissue inflammatory activity grading (G) and the degree of fibrosis staging (S) was determined by routine pathological staining. The expression of HBsAg and HBcAg in the liver tissue was identified by immunohistochemistry. The liver and renal function, urine, blood and HBV marks and so on were detected . The general information, serum HBV DNA, alaninea amiontransferase (ALT), liver inflammation, fibrosis, the expression of HBsAg and HBcAg in liver tissue, the changes of intrahepatic HBV DNA and HBV cccDNA quantification in CHB patients were analyzed with SPSS 11.5. Results The serum HBV DNA negative conversion rate of 25 CHB cases with HBeAg positive was (16/25)64% after 48 weeks of treatment, ALT normalization rate was (20/25)80%, HBeAg negative conversion rate was (4/25)16%, HBeAg/anti-HBe seroconversion rate was (2/25)8%, viral breakthrough rate was (2/25)8%, both virological and biochemical breakthrough were (1/25)4%; The serum HBV DNA negative conversion rate of 27 CHB cases with HBeAg positive was (18/27)62.96%, ALT normalization rate was (21/27)77.78%, virological and biochemical breakthrough were not found. 23 CHB cases by liver biopsy were treated with adefovir dipivoxil ,one year later , the liver tissue inflammatory activity grading was better than before(Z=-3.023,P=0.003<0.05), ameliorative rate was (15/23) 65.22%;No significant difference was found in the degree of fibrosis staging before and after treatment (Z=-0.893,P=0.372>0.05), ameliorative rate wa(s8/23)34.78%.There was significant difference statistically in the intensity of HBsAg expression in liver tissue before and after treatment (Z=-2.085,P=0.005<0.05); There was also significant difference statistically in the intensity of HBcAg expression in liver tissue before and after treatment (Z=-3.227,P=0.001<0.05). 23 cases(12 cases of HBeAg positive, 11cases of HBeAg-negative) with serum HBV DNA negative conversion rate was (19/23) 82.6%,The HBV DNA, HBV cccDNA in their liver tissue were found; The level of intrahepatic HBV DNA decreased 1.83log10 compared with baseline after 48 weeks treatment; The level of intrahepatic HBV cccDNA decreased 1.19log10 compared with baseline; the level of intrahepatic HBV cccDNA of 4 patients who had been achieved HBeAg negative conversion decreased significantly, approximately decreased 1.21log10;while the level of intrahepatic HBV cccDNA of 8 patients who hadn't been achieved HBeAg negative conversion approximately decreased 0.82log10. Conclusion Adefovir dipivoxil for antiviral therapy can effectively inhibit the HBV replication, increase seroconversion rates, improve liver function, ameliorate liver pathology, decrease the intensity of HBsAg and HBcAg expression in liver tissue, and had less side effects. Adefovir dipivoxil therapy last 48 week can depress the level of intrahepatic HBV DNA and HBVcccDNA. The level of intrahepatic HBVcccDNA of the patients had achieved HBeAg negative conversion was significantly lower than those hadn't achieved HBeAg negative conversion.