Monitoring HBcrAg levels could help optimise PEG-IFN therapy

By Shreeya Nanda, Senior medwireNews Reporter

Serum hepatitis B core-related antigen (HBcrAg) could serve as a quantitative marker of response to pegylated interferon (PEG-IFN) therapy in patients with chronic hepatitis B virus (HBV) infection positive for hepatitis B e antigen (HBeAg), findings indicate.

Baseline and post-treatment HBcrAg levels correlated closely with intrahepatic covalently closed circular DNA (cccDNA), the template of viral replication, report Pisit Tangkijvanich, from Chulalongkorn University in Bangkok, Thailand, and team.

Writing in Liver International, they suggest that “[m]onitoring HBcrAg levels during PEG-IFN therapy may help identify some patients with a very low probability of treatment response”, but add that their results need to be validated in large-scale prospective studies.

In this chart review, a virological response, defined as HBeAg clearance plus HBV DNA level <2000 copies/mL, was achieved by 32.6% of 46 patients with HBeAg-positive chronic HBV 24 weeks after 48 weeks of treatment with either PEG-IFNα-2a or PEG-IFNα-2b.

Among 30 patients with available pre- and post-treatment liver biopsy samples, baseline levels of HBcrAg correlated significantly with cccDNA levels at the same timepoint (r=0.564; p=0.001).

The authors also evaluated baseline hepatitis B surface antigen (HBsAg), which they explain has previously shown clinical utility in monitoring PEG-IFN therapy, and found a similar significant correlation with baseline levels of cccDNA (r=0.424; p=0.020).

Moreover, reduction in HBcrAg and HBsAg levels during treatment correlated with the decrease in cccDNA (r=0.503; p=0.005 and r=0.579; p=0.001, respectively).

But in a multivariate analysis adjusting for various baseline and on-treatment factors, HBcrAg, but not HBsAg, levels at week 12 were significantly associated with virological response (p=0.007).

And at a cutoff of log₁₀ 8.0 U/mL, serum HBcrAg levels predicted virological response at week 12 with a sensitivity of 93.3%, a specificity of 54.8%, a positive predictive value of 50.0% and a negative predictive value (NPV) of 94.4%, while the corresponding values at week 24 were 100.0%, 35.5%, 42.9% and 100.0%.

By contrast, using HBsAg levels greater than 20,000 IU/mL to identify non-responders was “somewhat inadequate” at week 12, with an NPV of 80.0%, say the researchers. But at week 24, the HBsAg algorithm performed equally well (NPV=100.0%).

When the markers were used in combination, the NPV at 12 weeks was 88.9%, which was lower than that for HBcrAg alone, but higher than for HBsAg alone.

Tangkijvanich et al speculate that the difference “could be partly explained by the patterns of HBcrAg and HBsAg decline induced by PEG-IFN. Among responders, more rapid decline of HBcrAg levels was observed in an early stage of therapy, while HBsAg levels tended to have a late decline after week 12.

“Consequently, an early decrease in HBcrAg at week 12 could possibly be a predictor of treatment response comparable to, if not better than, quantitative HBsAg”, they conclude.

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