Association Between IgG Antibody Against The C-terminal Region Of The Pres1 Protein Of Hepatitis B Virus And The Capacity Of Early Response To Interferon Therapy In Chronic Hepatitis B

Background Alpha-Interferon (IFN-alpha) is the only agent with an established long-term beneficial effect on the natural history of chronic hepatitis B (CHB). Several controlled clinical trials using IFN-alpha have shown that approximately 20–30% of treated patients with CHB, regardless of ethnic background, will lose HBV DNA and HBeAg and normalise transaminases. This response has been shown to have beneficial long-term effects on disease outcome, in addition the risk of developing hepatocellular carcinoma is reduced in IFN-alpha-treated patients with CHB. Because of the therapeutic benefit experienced by the group of patients with the capacity to respond to IFN-alpha therapy, identification of pretreatment factors predicting response is needed.Objective To determine the relationship between IgG antibody against the C-terminal region of the preS1 protein of hepatitis B virus and the capacity of early response to interferon therapy in chronic hepatitis B.Methods 69 patients with chronic hepatitis B virus (genotype B) infection were recruited in this study. 42 patients were treated with interferon-α-1b orα-2b, and 27 patients were treated with PEG interferon (α-2a). Peptide mimicking the C-terminal region of the preS1 protein(94-117aa) of genotype B HBV were synthesised, and the IgG antibody against this peptide was measured by enzymelinked immunosorbent assay (ELISA), and the early response to IFN-alpha therapy was judged by the effect on the viral kinetics, transaminase and the status of HBeAg at 12th week after the treatment.Results 21 patients were positive for anti-preS1 antibody, and 48 patients were negative for anti-preS1 antibody. The average decrease in viral levels was 3.37lg copies/ml and 0.33lg copies/ml in anti-PreS1 positive patients and anti-preS1 negative patients, respectively 12 weeks after the treatment, the difference between the two groups was significant (Z = -3.658, P = 0.000 ); the average decrease in ALT levels was 92 U/L and 30.5 U/L in two groups, respectively (Z = -2.132, P = 0.033). The rate of hepatitis B e antigen (HBeAg) loss was 41.2% (7/17) and the rate of anti-HBe seroconversion was 5.9% (1/17) in anti-PreS1 positive group, however, the rate of hepatitis B e antigen loss were only 12.8% (5/39) and none of the patients in anti-PreS1 negative group showed anti-HBe seroconversion, difference between the two groups was significant (Z = -5.110, P = 0.000). The rates of response were 71.4% (15/21) and 16.7% (8/48) , respectively in anti-PreS1 positive group and anti-PreS1 negative group. The rates of complete response were 23.8% (5/21) and 6.25% (3/48) , respectively in these two groups. The positive predictive value (PPV) of anti-C-terminal region of preS1 (94-117aa) antibody in predicting early response was 71.6% and the negative predictive value (NPV) was 83.3%.Conclusions Detection of anti-C-terminal region of preS1 (94-117aa) antibody may help to improve the efficacy of INF-alpha therapy for chronic hepatitis B (CHB).