Preliminary study on the efficacy of sequential therapy with nucleotide analogues followed by interferon alpha in chronic hepatitis B patients with low HBsAg level / 中国感染与化疗杂志

ABSTRACT

Objective To investigate the efifcacy of interferon alpha (IFNα) followed by nucleotide analogues (NAs) treatment in patients with negative hepatitis B e antigen (HBeAg), undetectable serum HBV-DNA and low hepatitis B surface antigen (HBsAg) levels.Methods The enrolled HBeAg-negative chronic hepatitis B patients had undetectable HBV-DNA level (HBV-DNA<1000 copies/mL for at least 12 months) and low HBsAg level (HBsAg≤2000 U/mL) with long-term NAs treatment. These patients switched their therapy sequentially from NAs regimens to IFNα for 48 weeks. The treatment response was evaluated in terms of serum HBV DNA load, serological HBV markers, liver function tests and routine blood test before treatment and 12, 24 and 48 weeks of treatment. The patients were followed up for 24 weeks after treatment. The primary endpoint was HBsAg loss or seroconversion and HBsAg<10 U/mL. Logistic regression analysis was conducted to examine relevant predictive factors. Receiver operating characteristic curve was used to evaluate the value of prior HBeAg seroconversion and on-treatment HBsAg dynamics in predicting HBeAg seroconversion than in HBsAg persistence group (χ2=9.527,P=0.002). HBsAg loss was more likely in the patients who had HBsAg decline at least 0.5 log U/mL from baseline at week 12 of treatment (χ2=16.576,P<0.001). The area under the ROC curve for prediction of HBsAg loss was 0.810 (95 %CI, 0.686 to 0.935,P<0.001).Conclusions The HBeAg-negative chronic hepatitis B patients with positive virological response and low HBsAg level after NAs treatment are more likely to achieve HBsAg clearance when switched to IFNα treatment. Prior HBeAg seroconversion and on-treatment HBsAg dynamics are useful in predicting and guiding IFNα sequential therapy.