Routine nucleos(t)ide analogs (NUCs) have not yet been recommended for patients with immune-tolerant (IT) phase in chronic hepatitis B virus (HBV) infection. We aimed to evaluate prognosis of patients in untreated IT-phase (UIT group), compared to those in immune-active phase who achieved virological response by NUCs according to guidelines (VR group). Between 2006 and 2012, patients in UIT or VR groups were included. Cumulative risks of HCC and liver-related events (LREs) development were assessed. Furthermore, propensity-score was calculated based upon age, gender, diabetes and liver stiffness. UIT group (n = 126) showed younger age, lower proportion of male gender and lower LS than VR group (n = 641). UIT group had similar 10-year cumulative risks of HCC (2.7% vs. 2.9%, p = 0.704) and LRE (4.6% vs. 6.1%, p = 0.903) development, compared to VR group. When we re-defined UIT group by the lower ALT cut-offs, 10-year cumulative risks of HCC and LRE development were 2.9% and 4.8%, respectively. Using propensity-score matching and inverse probability treatment weighting analysis, similar results were reproduced. UIT group consistently had similar prognosis compared to VR group. Therefore, further large-scale prospective studies in order to verify rationales of routine NUCs in UIT group are still required.
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