Hepatitis B virus surface antigen levels: A guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B # †

Abstract

We investigated the relationship between hepatitis B virus surface antigen (HBsAg) serum level decline and posttreatment response in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B from a large multinational study of pegylated interferon alfa-2a (peginterferon alfa-2a), with or without lamivudine, versus lamivudine alone. Serum HBsAg was quantified using the Architect assay (Abbott Diagnostics) at pretreatment, end of treatment (week 48), and 6 months after the end of treatment (week 72) in sera from 386 of the 537 patients who participated in the multinational study (peginterferon alfa-2a, 127; peginterferon alfa-2a plus lamivudine, 137; lamivudine monotherapy, 122). Pretreatment HBsAg levels varied according to genotype, with the highest levels present in patients infected with genotypes A (median, 4.11 log 10 IU/mL) and D (median, 3.85 log 10 IU/mL). Significant on-treatment decline in HBsAg was observed during treatment with peginterferon alfa-2a (alone or combined with lamivudine; mean decline at week 48, ؊0.71 and ؊0.67 log 10 IU/mL, respectively, P < 0.001), but not during treatment with lamivudine alone (؊0.02 log 10 IU/mL). Significantly more patients treated with peginterferon alfa-2a (21%) or peginterferon alfa-2a plus lamivudine (17%) achieved HBsAg levels <100 IU/mL at the end of treatment compared with lamivudine (1%) (both P < 0.001 versus lamivudine). End-of-treatment HBsAg level correlated strongly with HBV DNA suppression to <400 copies/mL 6 months posttreatment. An HBsAg level <10 IU/mL at week 48 and on-treatment decline >1 log 10 IU/mL were significantly associated with sustained HBsAg clearance 3 years after treatment (both P < 0.0001). Conclusion: On-treatment quantification of HBsAg in patients with HBeAg-negative chronic hepatitis B treated with peginterferon alfa-2a may help identify those likely to be cured by this therapy and optimize treatment strategies. C hronic hepatitis B is a global health problem accounting for 1 million deaths each year. 1 Ageadjusted death rates are 3 to 3.6 times higher in carriers of hepatitis B virus (HBV) surface antigen (HBsAg) than in persons without HBV infection. 2 The aim of treatment for patients with chronic hepatitis B (CHB) is to decrease progression of liver disease to cirrhosis and hepatocellular carcinoma, with the ultimate aim of improving survival. This can be pursued by maintaining constant inhibition of viral replication through a longterm treatment with nucleos(t)ide analogs or by inducing, through the combined antiviral and immunomodulatory Abbreviations: ALT, alanine aminotransferase; CART, classification and regression tree; CHB, chronic hepatitis B; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B virus surface antigen; HBV, hepatitis B virus;

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

“…[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.…”

“…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.…”

“…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. 7,[10][11][12]14,29 Therefore, the data in this study are valuable because the clinical significance of serial qHBsAg was systematically analyzed in patients treated with ETV as a first-line therapy for CHB.…”

“…Although this was greater than the drop achieved with 1 year of LAM (À0.02 log IU/mL), it was less than that reported with PEG-IFN (À0.71 log IU/mL). 14 There are several potential explanations for this modest decline of qHBsAg. First, the mechanism of action of oral nucleos(t)ide analogues is the suppression of viral replication through inhibition of HBV polymerase; because HBsAg production proceeds by a pathway distinct from that of HBV DNA, the effect of ETV on qHBsAg is possibly less prominent.…”

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

“…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].…”