HBsAg may persist in chronic HBV patients beyond seroclearance

By Shreeya Nanda, Senior medwireNews Reporter

The use of a highly sensitive assay for the detection of hepatitis B surface antigen (HBsAg) suggests that HBsAg negativity as evaluated by the conventional test may not be indicative of seroclearance in patients with chronic hepatitis B virus (HBV) infection.

The study authors explain that the highly sensitive assay, which couples a chemiluminescent enzyme immunoassay with an immune complex transfer method, is 100 times more sensitive than the conventional assay, with respective lower limits of detection of 0.5 mIU/mL and 50.0 mIU/mL.

Among 109 chronic HBV patients, the rate of HBsAg positivity as assessed by the highly sensitive assay was 80.7% at baseline (ie, the date of so-called conventional HBsAg seroclearance) and 55.0% at 6–12 months. And at 3–5 years from baseline, the highly sensitive test detected HBsAg in 21.3% of the 94 patients with available follow-up data.

Man-Fung Yuen, from the University of Hong Kong, and co-workers believe that the assay could be useful for differentiating chronic HBV patients with HBsAg seroclearance as detected by conventional methods from individuals previously exposed to HBV but who are not carriers. They add that it is important to identify the former group because of the continued risk of hepatocellular carcinoma as well as HBV transmission and reactivation.

Serum anti-HBsAg antibodies (anti-HBs) were detected in 11.1% of study participants at baseline and in half the patients after 3 to 5 years.

A comparison of patients positive for anti-HBs at one or more timepoints with those persistently negative showed a significant difference in the detectability of the highly sensitive HBsAg test at 6–12 months and 3–5 years, at 44.4% versus 72.5% (p=0.007) and 7.4% versus 40.0% (p<0.001), respectively.

The low detection rate among patients positive for anti-HBs suggests that additional markers, such as hepatitis B core-related antigen, or the improved detection of HBV DNA, for instance via ultracentrifugation, would “likely be needed for the identification of [chronic HBV] after conventional HBsAg seroclearance”, say the researchers.

They also found a significant difference in the rate of anti-HB–positivity at 3–5 years between patients with genotype B and those with genotype C, at 63.2% versus 41.1% (p=0.036).

“This could imply different HBV genotypes have different risk of reactivation during immunosuppressive therapy with the risk among HBV genotype C possibly higher because of their comparably smaller proportion of anti-HBs positive patients”, Yuen et al conclude in Liver International.

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