Efficacy Of Sequential Add-on Pegylated Interferon A-2a In Combination With Adefovir Dipivoxil In Chronic Hepatitis B With Low Serum HBeAg Titer

ObjectiveAt present, the most commonly antiviral treatment used for chronic hepatitis B (HBV) is nucleoside analogues (acid) or interferon. There are many difficult problems in the treatment process,such as virus resistant,the end point of treatment and relapse.Especially after long-term nucleotide analogues monotherapy, the chronic hepatitis B (CHB) patients with low serum hepatitis B e antigen(HBeAg)titer, and difficult to achieve seroconversion.. The treatment of pegylated interferon alfa-2a for CHB patients, with a short course of treatment and can obtain more HBeAg seroconversion opportunity characteristics.The aim of this study is to investigate the efficacy of sequential add-on of pegylated interferon alpha-2a for48weeks in CHB patients with low serum HbeAg titer after long term adefovir dipivoxil(ADV)monotherapy, expect to obtain higher HBeAg serological conversion rates and the decrease of HBV covalently closed circular DNA(cccDNA) loads.MethodsThis study evaluated55CHB patients who had accepted antiviral therapy from October of2011to of September2012in the Provincial Hospital affiliated to Shandong University, whoes diagnostic conforms to the chronic hepatitis B prevention guide (2010edition).There were some inclusion criterias for the patients, ages from18to60, accepted ADV monotherapy for72to144weeks, obtained the Serum virological response of HBVDNA (Serum HBVDNA<1000copy/ml), low HBeAg titer(5s/co<HBeAg<50S/CO)and serum hepatitis B surface antigen (HBsAg)<5000IU/mL,with no contraindications of interferon or liver biopsy. The patients were categorized into ADV monotherapy group and ADV plus pegylated interferon alpha-2a combination therapy group by random number table. Patients in ADV group continued ADV monotherapy and patients in combination therapy group added pegylated interferon alpha-2a to ADV for48weeks. The ADV monotherapy group acceived follow-up visit once every12weeks, inclouding liver function, routine blood, kidney function, biochemistry index, serum virology markers. The requirements of follow-up visit Of combination therapy group was according to the chronic hepatitis b prevention guide,AST, ALTand TBil times a month after starting treatment, after3times in a row once every3months; Routine blood began to check1time every1～2weeks. For four after review1times a month; HBeAg, HBsAg and HBV DNA review every3months1time; Assess mental status of patients once every3months. The liver function was detected by completely automatic biochemistry analyzer.The serum virology markers were measured by Abbott Achitect. CccDNA in liver sample were detected by Roche light-cycle FQ-PCR. Analyzed the research data by SPSS17.0software.Performed measurement data by mean±standard deviation. Pre-and post-treatment results were compared by paired samples t test. Comparison between groups was performed using indepedent samples t test. Comparison of rates between groups was performed using x2test. After the treatment, efficacy of the two therapies were assessed by comparing the reduction of serum HBeAg reduction, HBeAg loss rate,HBeAg seroconversion rate,and reduction of intrahepatic HBV DNA and cccDNA.Results1. Fifty CHB patiernts were evaluated, Male47cases and female8cases,ages from22to37, average29.08±3.29years old. Every group had2patients excluded， monotherapy group is in12th and22th weeks, combination therapy group was in36th and38th weeks. Baseline characteristics including age distribution,sex ratio,alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil), serum HBeAg and HBsAg, hepatic HBVDNA and HBV cccDNA were all comparable(all P>0.05). After the treatment,monotherapy group had3cases, and4cases of group B refused to receive liver puncture again,so monotherapy group puncture22patients and so as combination therapy group..2. HBeAg loss rates in the two groups were16.0%(4/25) and46.15%(12/26). Combination therapy group was higher than monotherapy group (x2=5.38, P<0.05). HBeAg seroconversion conversion rate was12.0%(3/25)and38.5%(10/26), combination therapy group was higher than monotherapy group (X2=4.69, P<0.05).3. HBeAg titers of both groups were significantly lower than those of baseline(t=8.43and8.50, respectively, both P<0.05). HBeAg of combination therapy group was lower than monotherapy group after treatment (t=5.60,P<0.01); There was no statistical difference of serum HBsAg loads (P>0.05).4. The HbeAg titers of the two groups were decreased, the rate of combination therapy group was higher than monotherapy group. The HBeAg titers of combination therapy group was less than monotherapy group since12weeks (P<0.05), until the end of treatment.5.HBV DNA and HBV cccDNA in liver tissue of combination therapy group were both lower than baseline(t7.12,6.67, respectively, both P<0.01). HBV DNA in liver tissue of monotherapy group was lower than baseline(t=2.67,P=0.02), but there was no statistical difference of cccDNA (P>0.05).HBV cccDNA in liver tissue of combination therapy group was lower than that of monotherapy group(t=2.87,P<0.01).ConclusionsCompared with adefovir monotherapy, adefovir plus Peg-IFN a-2a combination therapy can achieve higher serum HBeAg loss rates and seroconversion rates, and improve the clearance of HBVDNA and cccDNA in liver tissue.