Pretreatment serum HBsAg-to-HBV DNA ratio predicts a virologic response to entecavir in chronic hepatitis B

Abstract

Background/AimsDecay of hepatitis B surface antigen (HBsAg) titers has previously been shown to be predictive of a virologic response (VR), especially during peginterferon-alpha therapy. However, the role of HBsAg levels in predicting a VR to nucleos(t)ide analog therapy has not yet been established. In this study we sought to determine whether the VR can be predicted from HBsAg titers in nucleos(t)ide-naïve chronic hepatitis B (CHB) patients treated with entecavir.MethodsCHB patients who started entecavir as an initial antiviral therapy were enrolled in this study. Serum hepatitis B virus (HBV) DNA, HBsAg, and alanine aminotransferase levels were measured every 3 months during treatment. A VR was defined as undetectable serum HBV DNA titer by real-time PCR assay (<60 IU/mL).ResultsFifty-two patients were enrolled, and the median duration of treatment was 26 months (range 7-35 months). Forty-five patients achieved a VR; the cumulative VR rates at 3, 6, 12, and 24 months were 40%, 71.2%, 81.5%, and 88%, respectively. Baseline HBV DNA levels were significantly lower in patients with VR, whereas the HBsAg levels did not differ significantly between patients with or without VR. In a univariate analysis the cumulative VR rate was significantly higher in HBeAg negative patients and patients with an HBsAg/HBV DNA ratio above 0.56. However, in a multivariate analysis only an HBsAg/HBV DNA ratio above 0.56 was an independent predictor of VR (P=0.003). The area under the receiver operating characteristic curve was larger for the HBsAg/HBV DNA ratio than for either HBV DNA or HBsAg.ConclusionsPretreatment HBsAg/HBV DNA ratio can predict a long-term VR to entecavir therapy in nucleos(t)ide-naïve CHB patients.

Hepatitis B surface antigen seroclearance in patients with chronic hepatitis B infection: A clinical study

“…26 Another paper reported that HBeAgnegative patients usually had a longer HBV infection history, and were expected to have more extensive HBV DNA integration, compared with HBeAg-positive patients. 27 While the serum HBsAg to HBV DNA ratio in patients not achieving HBsAg seroclearance in our study (0.58) was similar to that observed by others (0.5-0.6), it was significantly lower in patients achieving HBsAg seroclearance (0.35). This may be due to enhanced host immunity in relation to the control of subviral production, or because fewer HBV integration events occurred in patients achieving HBsAg seroclearance than in those not achieving HBsAg seroclearance, as the proportion of HBeAg negative patients was significantly higher in the latter group, in our study.…”

Quantitative Hepatitis B Surface Antigen Analysis in Hepatitis B E Antigen-Positive Nucleoside-Naive Patients Treated with Entecavir

“…In three previous ETV studies no baseline factor predictive of HBeAg loss or HBeAg seroconversion could be identified [24,26,29]; however, in another ETV study, baseline qHBsAg was a predictor of HBeAg loss/ seroconversion in HBeAg-positive patients after 24 months of ETV treatment [25]. In a previous study with lamivudine, elevated baseline ALT was found to be a significant predictor of HBeAg loss or HBsAg loss [43].…”

“…In interferona-based anti-HBV therapy, an on-treatment decline in qHBsAg has been shown to be a predictor of a sustained virological suppression and HBsAg clearance in HBeAg-positive and HBeAg-negative patients [10,20,23]. With nucleoside/nucleotide analogue (NUC) HBV therapy, the clinical utility of qHBsAg as a potential predictor of response to treatment remains unclear [24][25][26][27][28][29].…”

Short-term spontaneous fluctuations of HBV DNA levels in a Senegalese population with chronic hepatitis B

“…Confirming immune control over viral replication was the first step of immune clearance. This ratio has been shown to be higher during the low-replicative phase, compared to immune-tolerant, immune-clearance and HBeAg negative hepatitis phase and to be repeatable regardless to ethnicity or genotype [ 19 - 21 ]. Nevertheless, in our study, the HBsAg / HBV DNA ratio was higher in samples with low HBV DNA values than in those with high HBV DNA values, as reported by others [ 22 ].…”