Early serum HBsAg drop: A strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients

Moucari, Rami; Mackiewicz, Vincent; Lada, Olivier; Ripault, Marie–Pierre; Castelnau, Corinne; Martinot–Peignoux, Michelle; Dauvergne, Agnès; Asselah, Tarik; Boyer, Nathalie; Bédossa, Pierre; Valla, Dominique; Vidaud, Michel; Nicolas–Chanoine, Marie–Hélène; Marcellin, Patrick

doi:10.1002/hep.22744

Cited by 435 publications

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“…A 1 log IU/mL drop in qHBsAg at week 24 of therapy was shown to predict SVR (NPV ¼ 97%, PPV ¼ 92%), and a low qHBsAg level at week 48 with an on-treatment decline > 1 log IU/mL was shown to be associated with sustained HBsAg clearance. 13,14 In contrast, the clinical usefulness of qHBsAg in patients receiving oral nucleos(t)ide analogues remains largely unknown; previous studies have investigated the relevance of qHBsAg in patients treated with LAM or adefovir, which are known to be less potent agents. 4,6,9 Furthermore, for the most part, the available data were not derived from independent studies but were incorporated into studies in which either a combination was used or a comparison with PEG-IFN was made.…”

Section: Discussionmentioning

confidence: 99%

“…5,13 Briefly, the assay was carried out in two steps: HBsAg present in the sample was bound to antibody to hepatitis B surface antigen (anti-HBs)-coated microparticles, and an acridinium-labeled anti-HBs conjugate was added together with pretrigger and trigger solutions. The products of the resulting chemiluminescent reaction were measured in relative light units.…”

Section: Methodsmentioning

confidence: 99%

“…8,9 To date, the potential role of qHBsAg in antiviral therapy monitoring has been studied largely in patients receiving pegylated interferon (PEG-IFN). [10][11][12] Moucari et al 13 reported that an early drop in qHBsAg was highly predictive of a sustained virological response (SVR) in HBeAg(À) patients. This was similar to the results obtained by Brunetto et al, 14 who found that an on-treatment decline of qHBsAg was significantly associated with sustained HBsAg clearance.…”

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Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir

et al. 2011

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Quantitative hepatitis B surface antigen (qHBsAg) and quantitative hepatitis B e antigen (qHBeAg) titers are emerging as useful tools for measuring viral loads and for predicting the virological response (VR) and serological response (SR) to pegylated interferon therapy. However, the clinical utility of these assays in patients taking entecavir (ETV) is largely unknown. Treatment-naive patients with chronic hepatitis B (CHB) who were taking ETV for 2 years were enrolled. The qHBsAg and qHBeAg levels were serially measured with the Architect assay. From 95 patients, 60.0% of whom were hepatitis B e antigen-positive [HBeAg(1)], 475 samples were analyzed. The median baseline log hepatitis B virus (HBV) DNA, log qHBsAg, and log qHBeAg values were 6.73 copies/mL (4.04-9.11 copies/mL), 3.58 IU/mL (1.17-5.10 IU/ mL), and 1.71 Paul Ehrlich (PE) IU/mL (20.64 to 2.63 PE IU/mL), respectively. For the prediction of VR (HBV DNA < 60 copies/mL at 24 months) in HBeAg(1) patients, baseline alanine aminotransferase (P 5 0.013), HBV DNA (P 5 0.040), and qHBsAg levels (P 5 0.033) were significant. For the prediction of VR, the area under the curve for the baseline log qHBsAg level was 0.823 (P < 0.001); a cutoff level of 3.98 IU/mL (9550 IU/mL on a nonlogarithmic scale) yielded the highest predictive value with a sensitivity of 86.8% and a specificity of 78.9%. As for SR (HBeAg loss at 24 months), the reduction of qHBeAg was significantly greater in the SR(1) group versus the SR(2) group. The sensitivity and specificity were 75.0% and 89.8%, respectively, with a decline of 1.00 PE IU/mL at 6 months. With ETV therapy, the correlation between HBV DNA and qHBsAg peaked at 6 months in HBeAg(1) patients. Conclusion: Both qHBsAg and qHBeAg decreased significantly with ETV therapy. The baseline qHBsAg levels and the on-treatment decline of qHBeAg in HBeAg(1) patients were proven to be highly useful in predicting VR and SR, respectively. The determination of qHBsAg and qHBeAg can help us to select the appropriate strategy for the management of patients with CHB. However, the dynamic interplay between qHBsAg, qHBeAg, and HBV DNA during antiviral therapy remains to be elucidated. (HEPATOLOGY 2011;53:1486-1493 C hronic infection with hepatitis B virus (HBV) is a worldwide health problem, with more than 400 million people thought to be infected.Moreover, these patients are at increased risk for disease progression to cirrhosis and hepatocellular carcinoma. 1 Large cohort studies have shown that elevated levels of Abbreviations: ALT, alanine aminotransferase; anti-HBs, antibody to hepatitis B surface antigen; AUC, area under the curve; AUROC, area under the receiver operating characteristic

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir

et al. 2011

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“…Recently, several studies have demonstrated that on-treatment HBsAg quantification is a useful tool to predict the response to Peg-IFN treatment, whereas its role during NA treatment has been scarcely investigated [15][16][17][18][19]. Gramenzi et al studied HBsAg kinetics in the sera of 42 HBeAg-negative patients treated with LAM monotherapy for a prolonged period and found that in six on-treatment responders, lamivudine was associated with a steady HBsAg decrease up to its disappearance in two cases [20].…”

Section: Discussionmentioning

confidence: 99%

HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5years

Fasano

Lampertico

Marzano

et al. 2012

Journal of Hepatology

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Background & Aims: In long-term responder patients, it is unclear whether lamivudine (LAM) monotherapy should be continued or switched to a high-genetic-barrier analogue. This study aims at assessing LAM efficacy over a 5-year period and the residual risk of drug resistance. The rate of HBsAg clearance and LAM longterm safety profile were also evaluated. Methods: One hundred and ninety-one patients with chronic HBeAg-negative hepatitis B successfully treated with LAM monotherapy for at least 5 years were included. Biochemical and virological tests were assessed every 3 months in all patients and HBsAg quantification was performed in 45/191. Reverse-transcriptase (RT) region was directly sequenced in virological breakthrough patients. Results: One hundred and ninety-one patients (148 males, median age 53 years, 72 with compensated cirrhosis) responding to 60-month LAM monotherapy continued to receive LAM monotherapy beyond the initial 5 years and were followed for an additional 36-month median period (range 1-108). Virological response was maintained in 128/191 patients (67%) and HBsAg clearance was observed in 15/128 (11.7%) after a 32-month median period (range 1-65). The 63 remaining patients (33%) showed virological breakthrough after a 15-month median treatment (range 1-78). RT region analysis was performed in 38/63 breakthrough patients and LAM resistant mutations were found in 37/38. No significant side effects were observed. Conclusions: In long-term responder patients, continuation of LAM monotherapy resulted in persistent viral suppression in most cases with undetectable HBV DNA by real-time PCR; moreover, 11.7% of these patients cleared HBsAg. Selection of LAM resistance, however, can still occur even after successful longterm therapy, thus emphasising the importance of a careful virological monitoring. Ó

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“…In the current report by Marcellin et al [11], a C10 % reduction in log HBsAg at weeks 12 and 24 was found to be the best predictor of the post-treatment response, but no absolute HBsAg level could be identified as a useful response predictor. Similarly, a small study in France also found that an early reduction of the HBsAg level by 0.5 log IU/ml, but not an absolute HBsAg level, could predict the virological response 6-month post-treatment [13]. The reason behind the conflicting observations between HBeAg-positive and HBeAg-negative patients is largely unknown.…”

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Are we ready to use the hepatitis B surface antigen level to guide peginterferon treatment in HBeAg-negative chronic hepatitis B?

Chan

2012

Hepatol Int

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In chronic hepatitis B virus (HBV) infection, hepatitis B e antigen (HBeAg) seroconversion often indicates host immune clearance. Approximately 30 % of patients, however, still have active viremia and fluctuating alanine aminotransferase (ALT) levels in the HBeAg-negative phase [1]. These patients with HBeAg-negative chronic hepatitis B probably have an immune escape by the virus; a further attempt of immune modulator therapy by interferon might be difficult and the post-treatment relapse rate is high. Early experience in Europe using 12-month interferon-alpha combined with lamivudine only yielded a sustained viral suppression (undetectable by nonpolymerase chain reaction assay) rate of approximately 15 % at 6-12 months post-treatment [2,3]. With 12-month peginterferon alfa-2a with/without lamivudine combination in the phase III international trial for HBeAg-negative chronic hepatitis B, approximately 22.6 % of patients could achieve sustained viral suppression to B10,000 copies/ml at 3-year post-treatment [4]. Owing to the inconvenient subcutaneous route of administration, potential adverse effects, and a high drug cost of peginterferon, one should select patients who have a higher chance of response to the peginterferon therapy. On the other hand, peginterferon is not preferred or should be stopped earlier if the chance of response is too low.On post hoc analysis of the phase III trial of peginterferon alfa-2a (with/without lamivudine combination), HBeAg-negative patients at a younger age and those who had lower HBV DNA at baseline had a higher chance of achieving a response, which was defined as HBV DNA B20,000 copies/ml at 24-week post-treatment [5]. Patients infected by genotype C HBV also have a better response than those infected by genotype D HBV. Nonetheless, the differences in response between patients with different baseline predictive factors were too small to guide patient selection for treatment. For example, the mean baseline HBV DNA was 7

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Early serum HBsAg drop: A strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients

Cited by 435 publications

References 16 publications

Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir

Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir

HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5years

Are we ready to use the hepatitis B surface antigen level to guide peginterferon treatment in HBeAg-negative chronic hepatitis B?

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