Changes In Serum HBsAg And HBV DNA Level In Chronic Hepatitis B Patients During Adefovir Dipivoxil Therapy

Background and Aim:Hepatitis B virus (HBV) infection is a challenging global health problem, affecting an estimated 2 billion people worldwide. Of those infected with HBV,400 million remain chronically infected and an estimated 1 million die of HBV-related liver diseases annually. Most carriers of chronic HBV including Asians, Africans, and a proportion of persons in Mediterranean countries acquire the infection at birth or within the first 1 to 2 years after birth. It is estimated that 50% of male carriers and 14% of female carriers will eventually die of the complications of cirrhosis and hepatocellular carcinoma (HCC). HBV continues to be a major cause of significant morbidity and mortality despite the availability of effective vaccines and improved therapeutic options. Complications of CHB including liver failure and hepatocellular carcinoma result in 1.2 million deaths per year, making CHB the 10th leading cause of mortality worldwide.HBsAg levels were shown to correlate with HBV DNA in different studies among patients and asymptomatic carriers. A significant reduction in serum HBsAg titer has been observed with antiviral therapy, which correlated with changes in cccDNA, total intracellular HBV DNA and serum HBV DNA. Sustained inhibition of HBV replication has been shown to be associated with normalization of aminotransferases and histological improvement, while HBsAg seroconversion is the best surrogate marker for viral clearance. Therefore, this study aimed at the quantitative assay of serum HBs Ag and HBV DNA concentration in HBeAg positive and Negative CHB patients during Adefovir Dipivoxil therapy. Methods:A total of 37 Chronic Hepatitis B patients,19 HBeAg Positive and 18 HBeAg Negative, were treated with ADV (Shanghai Rui Guang Biochemical Technology Company) for 48 weeks and ADV (Gilead Science, Forster City, CA, USA) 10 mg orally once daily for 104 weeks, respectively. All the patients were signed an informed consent form and ethical clearance was obtained from Jilin University First Hospital.Blood samples were collected sequentially during the course of treatment at baseline, weeks 12, 24 and 48 for HBeAg positives and at baseline,12,24,36,52,65,78,92 and 104 weeks of treatment for HBeAg negative CHB patients. Serum HBV DNA levels were measured by the central laboratory of Second Shanghai Medical University, Rui Jin Hospital (Roche Light Cycler, MDS assay, lower limit of detection 5000 copies per milliliter for HBeAg positive and 3000 copies/ml for HBeAg negative CHB patients) and the values were log-transformed with use of a base 10 scale. HBsAg quantitation was performed by automated chemiluminescent microparticle immunoassay (Architect quantitative HBsAg, Abbott, IL).The collected data was entered to computer and analysis was done using SPSS for windows version 17. The correlation between HBsAg and HBV DNA was analyzed. All analyses were tested at a 2-sided a level of 0.05. P<0.05 was accepted as significant.All serum HBV DNA results below the lower limit of detection (<5000 copies per milliliter for HBeAg positives and <3000 for HBsAg negatives) were analyzed as being 5000 and 3000 copies per milliliter.ResultsHBeAg positive CHB patientsAt the end of treatment, no patient had HBsAg loss. Only 10.5% of HBeAg positive CHB patients had undetectable serum levels of HBV DNA (<5000 copies/ml) at the 48th week of treatment. The mean HBV DNA levels and the corresponding mean HBsAg concentration measured at baseline,12,24 and 48 weeks of treatment were 8.33,6.63,5.93 and 5.62 logarithmic copies/ml and 29,750.3,20,760.0,14,527.9 and 13,409.6 IU/ml, respectively. HBsAg levels were significantly decreased within the first 12 weeks of treatment in 57.9% (n= 11) of patients, P= 0.038). After six months (24th week) of treatment the changes in serum HBsAg level and serum HBV DNA level had showed a significant relationship (P=0.01).Figure 1. Concentration curves of hepatitis B surface antigen (HBsAg) quantitation and hepatitis B virus (HBV) DNA levels in HBeAg Positive CHB patients.HBeAg negative CHB patientsAt the end of treatment no patient had HBsAg loss.83.3% of the total patients had undetectable serum HBV DNA levels (<3000 copies/ml) at the 104th week of treatment.After six months (24th week) of treatment the changes in serum HBsAg level and serum HBV DNA level had showed a significant relationship (P=0.01). At treatment weeks 24,52,78 and 104 the mean log HBV DNA and mean HBsAg reduction from baseline were -2.24,-2.46,-2.63 and -2.35 and -1482.22,-1501.44,-1616.94 and -1693.61 IU/ml, respectively (P= 0.01).In the treatment group all the patients showed viral load reduction within the initial 12 weeks of treatment (P=0.014). Figure 2. Concentration curves of Hepatitis B surface Antigen (HBsAg) quantitation and hepatitis B virus (HBV) DNA levels in all HBeAg Negative CHB patients.Conclusion:The mean reduction of serum HBsAg had a good correlation with the corresponding logarithmic HBVDNA. Quantitative determination of HBsAg provides additional information and can be used as a surrogate marker for monitoring the viral load reduction during the management of chronic HBV infection.