Kinetics of hepatitis B surface antigen decline during 3 years of telbivudine treatment in hepatitis B e antigen-positive patients

Abstract

The impact of prolonged direct antiviral therapy on hepatitis B surface antigen (HBsAg) levels in patients with chronic hepatitis B is poorly understood. We quantitatively assessed serum HBsAg levels during 3 years of telbivudine treatment, as well as their relationship with virologic and biochemical characteristics in 162 hepatitis B e antigen–positive patients who maintained undetectable serum hepatitis B virus (HBV) DNA long‐term. Telbivudine treatment progressively reduced serum HBsAg levels (mean ± SD) from baseline (3.8 ± 0.6 log10 IU/mL) to treatment week 24 (3.4 ± 0.7 log10 IU/mL), treatment year 1 (3.3 ± 0.8 log10 IU/mL), and treatment year 3 (3.0 ± 1.4 log10 IU/mL) (P <0.0001). In this patient population, HBsAg loss was observed in nine (6%) of 162 patients through year 3. During the first year of treatment, three patterns of HBsAg decline were observed: rapid (≥1 log10 IU/mL) in 32 patients, slow (0‐1 log10 IU/mL) in 74 patients, and steady levels in 56 patients. These findings were associated with different likelihoods of HBsAg loss during long‐term telbivudine therapy. Eight of 32 patients with rapid HBsAg decline versus none of 56 patients with steady HBsAg levels achieved HBsAg loss at year 3 (P = 0.0024). HBV genotype was a significant determinant for HBsAg kinetics, with the fastest decline in genotype A patients. In patients with subsequent HBsAg loss, viral antigens were already undetectable in liver biopsy samples after 1 year of treatment. This was associated with markedly enhanced antiviral T cell reactivity. Conclusion: In patients who have effective suppression of viral replication during telbivudine treatment, a rapid decline in serum HBsAg levels during the first year may identify those with a greater likelihood of achieving HBsAg clearance. (HEPATOLOGY 2010

Multicenter Evaluation of the Elecsys Hepatitis B Surface Antigen Quantitative Assay

“…A number of recent studies have suggested that monitoring HBsAg levels during treatment with a finite course of PEG-IFN may help identify those patients who are most likely to achieve a sustained response to therapy and go on to clear HBsAg (3,4,14,17,19) or identify those who may relapse following treatment (17). Recent data have also suggested that HBsAg levels may help predict response to therapy with NAs (9,25). For example, in analyses of patients treated as part of the pivotal trials of PEG-IFN alfa-2a in HBV, a decline of Ն10% in HBsAg levels from baseline at weeks 12 and 24 of treatment in HBeAg-negative patients (18) or HBsAg levels of Ͻ1,500 IU/ml at weeks 12 and 24 of treatment in HBeAg-positive patients (19) were found to be associated with high rates of sustained immune control and HBsAg loss posttreatment.…”

“…A number of studies have shown that the degree and timescale of reductions in HBsAg levels during pegylated interferon (PEG-IFN)-based therapy may predict a sustained response in both HBeAg-positive and HBeAg-negative CHB infection (3,11,13,14,17,19) and may also predict the response to treatment with some nucleos(t)ide analogs (NAs) (9,25). There is also evidence that HBsAg levels, particularly in combination with HBV DNA levels, can be used to identify patients who are in the inactive carrier phase of HBV infection compared with patients with active disease and so distinguish those patients who do not require therapy from those who would benefit from treatment (2,10,15).…”

Response-Guided Therapy Based on the Combination of Quantitative HBsAg and HBV DNA Kinetics in Chronic Hepatitis B Patients

“…An HBsAg decline more than 1 log 10 IU/mL after 1 year of oral antiviral treatment in HBeAg-positive CHB patients have been shown to predict the HBsAg loss [32].…”

“…Moreover, there is a variability of the quantitative HBsAg across different viral genotypes [3]. Patients with genotype A and D have the highest mean value of serum HBsAg (4.5 log 10 IU/mL) compared to genotypes B and C (4.3 log 10 IU/mL and 3.8 log 10 IU/mL, respectively) [32,39].…”

Comparison of Three Luminescent Immunoassays for Hepatitis B Virus Surface Antigen Quantification during the Natural History of Chronic Hepatitis B Virus Infection

“…Recently, evidence has suggested that the HBsAg levels change during the natural course of chronic HBV infection (8,9), and a rapid decline in HBsAg levels indicates a strong response to therapy, regardless of the treatment approach. Monitoring HBsAg levels can help identify nonresponders to therapy (peginterferon [PEG-IFN] or nucleoside analogues) and determine the best management strategy for many patients (10)(11)(12)(13)(14)(15).…”