Early Serum HBsAg Kinetics as Predictor of HBsAg Loss in Patients with HBeAg-Negative Chronic Hepatitis B after Treatment with Pegylated Interferonα-2a

Abstract

Hepatitis B surface antigen (HBsAg) loss is an ideal treatment endpoint for patients with chronic hepatitis B (CHB). We investigated the predictive value of on-treatment HBsAg levels for HBsAg loss in hepatitis B e antigen (HBeAg)-negative CHB patients who received 120-week PEG-IFNa-2a treatment. Serum HBV DNA, HBsAg, and anti-HBs levels were assayed at baseline and every 3 months during the treatment. Of 81 patients, 12 achieved HBsAg loss, 20 achieved HBsAg \ 100 IU/mL, and 49 maintained HBsAg C 100 IU/mL. HBsAg loss rate was only 3.7% at 48 weeks, while it reached to 11.1% and 14.8% after treatment of 96 weeks and 120 weeks. The cutoff HBsAg levels at 12 weeks predicting HBsAg loss at 96 weeks and 120 weeks of treatment were 400 IU/mL and 750 IU/mL, with AUC 0.725 and 0.722, positive predictive value (PPV) 29.41% and 30.56%, and negative predictive value (NPV) 93.75% and 97.78%, respectively. The cutoff HBsAg levels at 24 weeks predicting HBsAg loss at 96 weeks and 120 weeks of treatment were 174 IU/mL and 236 IU/mL respectively, with AUC 0.925 and 0.922, PPV 40.0% and 46.15%, and both NPV 100%. The predictive ability of the cutoff HBsAg levels at 24 weeks was better than that at 12 weeks for HBsAg loss at either 96 or 120 weeks (v 2 = 3.880, P = 0.049 and v 2 = 4.412, P = 0.036). These results indicate that extended therapy is critical to HBsAg loss in HBeAg-negative CHB patients during PEG-IFN treatment, and the HBsAg level at 24 weeks can be used to predict HBsAg loss during tailoring PEG-IFN therapy.

Dynamic Changes of Cytokine Profiles and Virological Markers Associated With HBsAg Loss During Peginterferon Alpha-2a Treatment in HBeAg-Positive Chronic Hepatitis B Patients

“…NA treatment cannot effectively reduce viral antigen, so it is difficult to achieve clinical cure ( 7 ). Interferon can reduce the production of viral antigens and restore the function of damaged immune cells, resulting in a higher HBsAg disappearance rate than NA treatment ( 12 , 13 , 21 , 35 ). Our study showed that the baseline IL-10, IL-6 and TGF-β2 levels were not different in the two groups, but after 24 weeks of interferon treatment, the level of IL-10 in the clinical cure group was significantly lower than that in the non-clinical-cure group, and the clinical cure group had a greater decline range of IL-10 and TGF-β2.…”

“…Our previous studies found that changes of virological and serological indexes could predict the disappearance of HBsAg in CHB patients treated with interferon ( 10 , 11 ). If patients were given consolidation treatment of interferon for 12-24 weeks after functional cure, it was not easy to relapse ( 10 , 12 , 13 ). We also found that incidence of hepatitis B was positively correlated with IFN-α, and negatively correlated with transforming growth factor-beta (TGF-β) and interleukin- 10 (IL-10) ( 14 , 15 ).…”

Case Report: Both Mother and Child With Chronic HBV Infection Were Clinically Cured After PEG-IFN Treatment

“…Our study also shows that in patients treated with nucleoside analogues for viral suppression, a higher rate of surface antigen disappearance can be achieved by combination therapy with interferon [8] . Because of the research which highlighted the importance of extension treatment to the maintenance of HBsAg vanishing in CHB patients [9,10] , we extended the treatment for another 24 weeks after the patient had achieved the disappearance of the surface antigen, in order to better maintain the state of functional healing.…”

Immune Mechanisms Underlying Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B Patients With Viral Coinfection

“…Functional cure occurs at an average annual rate of 0.22% in CHB patients during first-line oral NAs antiviral treatment ( 42 ). PEG-IFN treatment can acquire an average HBsAg clearance annual rate of 3% ( 43 – 45 ), 5-year cumulative rate of 14% and 10-year cumulative rate of 32% ( 46 ) in CHB patients. But in inactive HBsAg carriers, the HBsAg clearance rate can reach to 47% after 48 weeks of PEG-IFN treatment ( 47 ).…”