Prospective Cohort Study Of Chronic Hepatitis B Patients Treated With Adefovir Dipivoxil And Interferon-α

BackgroundHepatitis B virus (HBV) infection is a major health problem in China. Hepatitis B surface antigen (HBsAg) carriers accout for9.09%of the total population. Carriers of HBV have increased the risk of developing cirrhosis, liver decompensation and hepatocellular carcinoma (HCC).It brings great burden to the society and families. To overcome this difficult problem, we must take both preventions and treatments methods. For the uninfected, our main preventive measure is the application of vaccination, especially for the newborn. The rate of hepatitis B infection has decreased rapidly since our country began to promote hepatitis B vaccine and disposable syringes, especially for the children under10years old. For the infected, receiving the antiviral treatment under the direction of professional doctors in regular hospitals is the fundamental means of inhibiting the progression of hepatitis B. In recent years, antiviral drugs are emerging and the treatment measures are being improved.Interferon-a(IFN-a)and adefovir dipivoxil (ADV)were approved at domestic and abroad and have been widely used to treat chronic hepatitis B for years.Besides,their formulations have been made in China. Due to the relatively inexpensive price, they are easily accepted by grassroots hospitals patients. To further consolidate the basis for the prevention and treatment of hepatitis B in Shandong Province, the project "Scale field epidemiology and intervention research in the hepatitis B prevention and treatment comprehensive demonstration zones in Shandong Province" is approved. The emphasizes of the project are to complete the capacity building of the hepatitis B prevention and control, hepatitis B prevention strategies of community study and community intervention research mission of HBV infected patients. Our research is one part of the project, community intervention research, and we choose domestic Interferon-a and adefovir dipivoxil to interrupt the patients with HBV in the demonstration zones Shouguang and Zhangqiu to determine the effects of the two antiviral therapies.ObjectiveTo research the efficacy, safety, compliance, ADV-resistant mutations of domestic Adefovir dipivoxil (ADV) and Interferona-2b(IFNa-2b) in the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B(CHB)patients and domestic Adefovir dipivoxil (ADV) in the hepatitis B e antigen (HBeAg)-negative chronic hepatitis B(CHB)patients for48weeks.To investigate the baseline correlation factors of affecting the efficacy.Methods98patients who were screened from the hepatitis B prevention and treatment comprehensive demonstration zones Shouguang and Zhangqiu of Shandong Province were enrolled in this prospective open cohort study.68patients with hepatitis B e antigen-positive received antiviral treatment with IFNa-2b (33cases, IFN group), ADV (35cases, ADV(+) group)randomly. The other30patients with hepatitis B e antigen-negative received ADV(ADV(-) group). The biochemical, virological, serological response of the three groups, toxicity and compliance were observed for48weeks and correlation factors analysis was investigated.At the same time, ADV-resistant mutations were detected.Results(1)At48weeks, normalization rates of ALT in IFN and ADV(+) groups were24.2%and85.7%(ITT analysis),57.1%and88.2%(PP analysis); HBV DNA undetectable rates were24.2%and88.6%(ITT analysis),57.1%and91.2%(PP analysis),normalization rate of ALT and HBV DNA undetectable rate in ADV(+) group were higher than those in IFN group, the difference had statistical significance (P<0.05). The rates of HBeAg loss were12.1%and31.4%(ITT analysis),28.6%and32.4%(PP analysis), HBeAg seroconversion rates were6.1%and2.9%(ITT analysis),14.3%and2.9%(PP analysis), the differences of both had no statistical significance (P>0.05). The normalization rates of ALT in ADV(-) group were76.7%(ITT analysis)and85.2%(PP analysis);HBV DNA undetectable rates were73.3%(ITT analysis)and81.5%(PP analysi),the difference had no statistical significance compared to ADV(+) group (P>0.05)②The univariate analysis found that HBV DNA undetection in the IFNa-2b and ADV(+) groups was associated with baseline AST and no factors were related to HBeAg loss,what’s more, HBsAg was also related to HBV DNA undetection in ADV(+) group; multi-factor analysis showed that ADV and baseline AST level were predictive factors for HBV DNA undetection, the independent predictive factor of HBeAg loss was ADV. The univariate analysis of ADV(-) group found that baseline AST and HBV DNA level were predictive factors related to HBV DNA undetection; multi-factor analysis of ADV(+) and ADV(-) groups showed that baseline AST and HBeAg level were predictive factors for HBV DNA undetection.③The toxicity of IFN group was common, fever (30cases,90.9%), abnormalities of white blood cells (20cases.60.6%), abnormalities of platelet(2cases,6.1%), Thyroid dysfunction(3cases9.1%). There was no toxicity in the two ADV groups.④The drop-out rates of IFN and ADV(+) groups were18.2%and2.9%, the drop-out rate in IFN group was much higher than that in ADV(+) group (.P=0.044). The drop-out rate of ADV(-) group was10%. the difference had no statistical significance compared to ADV(+) group (P=0.340).⑤No resistant mutation was detected in ADV(+) and ADV(-) groups during48weeks.ConclusionsBoth domestic ADV and IFNa-2b can treat chronic hepatitis B (CHB) patients effectively. What’s more, the efficacy, safety and compliance of domestic ADV are inferior to IFNa-2b. Domestic ADV can treat whether HBeAg-positive or negative chronic hepatitis B effectively and has no significant difference in efficacy. Baseline AST is predictive factor of IFNa-2b in the antiviral treatment of hepatitis B e antigen-positive chronic hepatitis B for48weeks. Baseline AST and HBeAg level are predictive factors of domestic ADV in the antiviral treatment of chronic hepatitis B for48weeks.No resistant mutation occurred during one year therapy of domestic ADV.