Comparison between chronic hepatitis B patients with untreated immune-tolerant phase vs. those with virological response by antivirals

Hye Won Lee,Kwang-Hyub Han,Oidov Baatarkhuu,Jun Yong Park,Do Young Kim,Beom Kyung Kim,Sang Hoon Ahn,Seung Up Kim

doi:10.1038/s41598-019-39043-2

Hye Won Lee, Kwang-Hyub Han + Show 6 more

Open Access

https://doi.org/10.1038/s41598-019-39043-2

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Abstract

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.

Highlights

Routine nucleos(t)ide analogs (NUCs) have not yet been recommended for patients with immunetolerant (IT) phase in chronic hepatitis B virus (HBV) infection
There has been the lack of evidence that NUCs might be beneficial in terms of improving overall prognosis in untreated IT-phase patients
Normal serum ALT level does not always indicate minimal or no hepatic inflammation and disease may progress with active HBV replication, despite persistently normal serum ALT level[8,9,24]

Summary

Introduction

Routine nucleos(t)ide analogs (NUCs) have not yet been recommended for patients with immunetolerant (IT) phase in chronic hepatitis B virus (HBV) infection. Among the natural history of chronic HBV infection, “Immune-tolerant (IT)” phase is characterized by the presence of serum HBeAg, very high serum HBV-DNA level and persistently normal serum alanine aminotransferase (ALT)[2] During this clinical phase, there is minimal or no hepatic necro-inflammation or fibrosis and the overall risk of disease progression might be low[2]. Higher serum HBV-DNA levels are associated with a higher risk of disease progression including development of hepatocellular carcinoma (HCC) and liver cirrhosis, even in a subgroup with normal serum ALT level[8,9] This phenomenon might pose the question whether IT-phase patients would benefit from earlier antiviral therapy. In the current study, we aimed to compare long-term clinical outcomes including HCC development between patients in the untreated IT-phase vs patients in the immune-active phase who achieved virological response (VR) by NUCs therapy according to the current treatment guidelines

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