A study of seroconversion of HBsAg in chronic hepatitis B patients with HBeAg positive by combination treatment with interferon and nucleoside analogue / 中华传染病杂志

ABSTRACT

Objective To study clinical features and mechanism in patients suffered from chronic hepatitis B achieving seroconversion of HBsAg by combination treatment with interferon (IFN) and nucleoside analogue (NA). Methods Thirty-two cases with chronic HBV hepatitis were enrolled into this retrospective study. All of them received combination treatment with IFN and Lamivudine/Adefovir, as well as achieved seroconversion of HBsAg from June, 2001 to May, 2007. All the cases in this study were followed up. Results Generally, serum HBV DNA fell below the detection limit 3 to 6 months after starting combination treatment. Virological breakthrough/relapse or new clinical resistant had not been found in all enrolments after combination treatment, including patients with previous resistant to Lamivudine, although the average length of treatment was over 2 years. The average period of following up after seroconversion of HBsAg was 13.2 months. Two cases transfered back to HBsAg positive, one of them achieved seroconversion of HBsAg again by the anti-virus treatment, and the other one gave up treatment and remained anti-HBe positive and HBeAg negative.The other 30 eases kept at the stage of seroconversion of HBsAg. Seven patients underwent liver biopsy after seroconversion of HBsAg, and 3 of them had taken liver biopsy before combination therapy too. Biopsy specimens were scored for fibrosis and neeroinflammation according to the Knodell histological activity index. Six cases showed HBsAg and HBcAg negative by immunohistochemistry,and only 1 case with HBsAg positive in liver tissue experienced relapse. Inflammation and fibrosis grade of the 3 cases who had taken liver biopsy twice were lowered after HBsAg seroconversion,although the ALT level of 1 case who had turned from G2S4 to GIS2-3 remained abnormal after HBsAg seroconversion. According to the sequence and character of HBsAg seroconversion, there were three models of HBsAg conversion. The sequence of transition was HBV DNA→HBeAg→HBsAg,which was dominant one, accounting for 59%(19/32 cases). HBV DNA negative, and the titer of HBeAg wandering at a low level, after then HBeAg and HBsAg change to negative in the same time,31% (10/32 cases). The titer of HBsAg decreased rapidly after the HBV DNA clearance, and the HBsAg clearance was earlier than HBeAg, 9% (3/32 cases). After 1 year of combination therapy,there were 15 of 21 cases (71.4%) whose titer HBsAg showed less than 100 COI by agent from Roche, and 7 of 11 cases (63.6%) whose titer HBsAg showed less than 250 IU/L by agent from Abbott. The frequency of adverse reaction was similar with that induced by IFN monotherapy, and no new adverse reaction was found. Conclusions Combination therapy and long course treatment might be the key to achieve the HBsAg seroconversion. Those with HBsAg in liver tissue and (or) low serum anti-HBs are more likely to relapse. The titer of HbsAg<100 COI (Roche, Germany) or<250 IU/L (Abbott, USA) after one year treatment may be regarded as a predict index of HBsAg seroconversion.