Methodology-dependent performance of serum HBV RNA in predicting treatment outcomes in chronic hepatitis B patients

Whether different serum HBV RNA detection assays can consistently predict treatment outcomes in patients with chronic hepatitis B remains controversial.

We enrolled 188 patients who had stopped nucleos(t)ide analogues (NAs) (STOP cohort-1, -2) and 78 receiving entecavir (ETV) therapy (ETV cohort) and used double-target (targeting both 5' and 3' ends of the HBV pregenome RNA [DT-RNA]) and three single-target (targeting the S-region [S-RNA], X-region [X-RNA], and poly-A tail of HBV RNA [PolyA-RNA]) assays to predict treatment outcomes.

In STOP cohorts, DT-RNA, S-RNA and X-RNA at NAs cessation showed higher predictive powers for clinical relapse (time-dependent areas under the curve [AUCs] for years 1, 2, 3, and 4 ranged between 0.724 and 0.772 in cohort-1, and between 0.741 and 0.824 in cohort-2) than the PolyA-RNA (AUCs between 0.604 and 0.611 in cohort-1; and between 0.530 and 0.584 in cohort-2). The predictive power for 2-year HBeAg loss of the four targeted RNAs in the ETV cohort at 6 months were similar (AUCs, 0.848, 0.838, 0.825, and 0.801), and superior to that of the HBV DNA level at 6 months (AUC, 0.721).

The outcome prediction performance of serum HBV RNAs is methodology-dependent. PolyA-RNA detection was not recommended to predict off-treatment relapses.