End of treatment HBsAg levels may predict HBV relapse
medwireNews: Hepatitis B surface antigen (HBsAg) levels at the end of treatment or prophylaxis with nucleos(t)ide analog inhibitors could be a useful indicator of hepatitis B virus (HBV) relapse, suggest two Taiwanese studies.
One study evaluated markers to predict relapse following discontinuation of tenofovir disoproxil fumarate (TDF) in chronic HBV patients who were positive or negative for hepatitis B e antigen (HBeAg), while the other focused on HBeAg-negative patients with cancer who had received TDF or entecavir prophylaxis during chemotherapy. Both analyses drew on data from patients treated at Kaohsiung Chang Gung Memorial Hospital; the first study also included patients from E-Da Hospital in Kaohsiung.
Among the 143 patients included in the first study – all of whom met the Asian Pacific Association for the Study of the Liver 2012 guidelines for treatment cessation – the cumulative incidence of virologic relapse at 104 weeks was 66.6% for the 39 HBeAg-positive patients and 72.3% for the 104 HBeAg-negative patients. Virologic relapse was defined as the presence of serum HBV levels over 2000 IU/mL at two consecutive measurements at least 3 months apart after treatment cessation.
In multivariate analysis, higher end of treatment HBsAg levels were significantly associated with virologic relapse in patients positive and negative for HBeAg, with corresponding hazard ratios per log IU/mL of 1.97 and 2.16 (p=0.036 and p<0.001, respectively).
Using time-dependent area under the receiver operating characteristic curve analysis, a cutoff for HBsAg levels of 200 IU/mL was found to be optimal for identifying HBeAg-positive patients who were likely to relapse, such that virologic relapse rates at 78 weeks were 14.3% and 69.7% for those with end of treatment levels below versus at or above this cutoff, a significant difference (p=0.017).
For HBeAg-negative patients, the optimal cutoff was 80 IU/mL; virologic relapse rates at the 78-week mark were significantly lower among participants with HBsAg levels at or below this cutoff, at 19.6%, compared with rates of 91.7%, 80.0%, and 86.1% for patients with levels of 81–200, 201–500, and over 500 IU/mL, respectively (p<0.001).
Tsung-Hui Hu, from Kaohsiung Chang Gung Memorial Hospital, and team write in the Journal of Viral Hepatitis that additional large-scale and case–control studies are required, but they believe that end of treatment HBsAg levels could be a “useful marker” for predicting virologic relapse.
The other study, by the same research group, comprised data on 122 HBeAg-negative cancer patients who received prophylactic anti-HBV therapy during and for at least 6 months after completing chemotherapy. The 3-year cumulative incidence of virologic relapse was 46.6%.
And again end of treatment HBsAg levels were significantly associated with virologic relapse (HR= 1.977 per log10 IU/mL, p<0.001), with a cutoff of 500 IU/mL considered the optimal value for predicting relapse at 3 years.
Noting that this threshold was higher than that in the study of non-cancer patients, the researchers say that they are unable to explain this discrepancy.
But they believe that “[a] higher rate of pretreatment HBV DNA<2000 IU/mL, shorter consolidation duration, and impaired immune system in cancer patients might contribute to the higher HBsAg cut-off value for HBV relapse.”
Of note, HBsAg levels of 500 IU/mL were a significant predictor of relapse only in patients with baseline HBV DNA levels below 2000 IU/mL. The 3-year relapse rate was 21.3% for those with end of treatment HBsAg levels lower than 500 IU/mL, which was significantly lower than the 46.4% rate for participants with levels equal to or higher than the cutoff (p=0.038).
As reported in the Journal of Gastroenterology and Hepatology, there was no such association among patients with baseline HBV DNA levels of 2000 IU/mL or higher.
Researcher Chien-Hung Chen, from Kaohsiung Chang Gung Memorial Hospital, and colleagues therefore “suggest that HBsAg should be checked to predict HBV relapse in patients with baseline HBV DNA <2000 IU/mL.”
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