Dynamic HBsAg measurements predict HBV inactivity

By Shreeya Nanda

In patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection, repeated measurement of hepatitis B surface antigen (HBsAg) during long-term follow-up can help identify those with inactive virus, suggests a chart review.

"HBsAg levels seem to better reflect the natural history [of infection] and a revision of the definitions including HBsAg levels may ease the management of HBeAg negative [chronic HBV]", say Willem Brouwer, from Erasmus MC in Rotterdam, the Netherlands, and team.

Among 292 treatment-naïve noncirrhotic chronic HBV patients with baseline HBV DNA levels below 20,000 IU/mL, 189 were deemed inactive carriers - HBV DNA of 2000 IU/mL or less and persistently normal serum alanine aminotransferase concentrations as per the current criteria - after a year of follow-up, while the remaining 103 had HBV activity.

When participants were stratified by baseline HBsAg levels, those with low HBsAg levels (ie <100 IU/mL) had significantly lower 5- and 10-year cumulative probabilities of HBV activity than patients with intermediate (100-1000 IU/mL) or high (>1000 IU/mL) levels of HBsAg (p=0.009).

And patients with low HBsAg levels were significantly more likely to remain in the inactive carrier phase in the following year (p<0.001), with a probability of 97% compared with 85% for patients with intermediate levels and 74% for those with high levels.

The researchers assessed the diagnostic performance of various combinations of HBsAg and HBV DNA levels, and found that a cutoff of HBsAg levels no higher than 100 IU/mL and HBV DNA levels no higher than 2000 IU/mL predicted inactive carrier status in the next year with a specificity of 98% and a positive predictive value of 97%.

Moreover, a combination of HBV DNA levels of 5000 IU/mL or less and a decline in HBsAg levels of at least 0.5 log IU/mL identified patients likely to become inactive carriers in the following year with a specificity of 99%, a sensitivity of 16%, a positive predictive value of 83% and a negative predictive value of 72%.

These patients have a high probability of becoming inactive carriers and "may therefore not require antiviral therapy", say Brouwer et al.

Based on their findings, the study authors propose that inactive carriers be defined "as those with both an HBV DNA ≤2000 IU/mL and HBsAg <100 IU/mL".

And those who fulfil the current criteria for inactive status but have HBsAg levels between 100 and 1000 IU/mL "should be defined as 'HBV remission patients' and should be kept under close surveillance for at least 1 more year to confirm [inactive carrier] status", they write in Clinical Gastroenterology and Hepatology.

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