Serum miR-192-5p levels predict the efficacy of pegylated interferon therapy for chronic hepatitis B.

Yoshihito Nagura ,Eiji Tanaka ,Jae-Heon Kang ,Tsunamasa Watanabe ,Kiyotaka Matsuura ,Chiaki Okuse ,Masao Tateyama ,Hiromi Kataoka ,Shuhei Nishiguchi ,Masataka Tsuge ,Akihiro Matsumoto ,Etsuko Iio ,Koji Fujita ,Masaru Enomoto ,Hiroki Ikeda ,Tomoyuki Inoue ,Takeshi Matsui ,Masanori Atsukawa ,Yasuhito Tanaka

doi:10.1371/journal.pone.0263844

Abstract

We examined the association between serum miRNA (-192-5p, -122-3p, -320a and -6126-5p) levels and the efficacy of pegylated interferon (Peg-IFN) monotherapy for chronic hepatitis B (CHB) patients. We enrolled 61 CHB patients treated with Peg-IFNα-2a weekly for 48 weeks, of whom 12 had a virological response (VR) and 49 did not VR (non-VR). A VR was defined as HBV DNA < 2,000 IU/ml, hepatitis B e antigen (HBeAg)-negative, and nucleos(t)ide analogue free at 48 weeks after the end of treatment. The non-VR group showed a significantly higher HBeAg-positivity rate, ALT, HBV DNA, and serum miR-192-5p levels at baseline (P = 0.024, P = 0.020, P = 0.007, P = 0.021, respectively). Serum miR-192-5p levels at 24-weeks after the start of treatment were also significantly higher in the non-VR than the VR group (P = 0.011). Multivariate logistic regression analysis for predicting VR showed that miR-192-5p level at baseline was an independent factor (Odds 4.5, P = 0.041). Serum miR-192-5p levels were significantly correlated with the levels of HBV DNA, hepatitis B core-related antigen, and hepatitis B surface antigen (r = 0.484, 0.384 and 0.759, respectively). The serum miR-192-5p level was useful as a biomarker for the therapeutic efficacy of Peg-IFN in CHB treatment.

Highlights

Hepatitis B virus (HBV) infection is a global public health problem, with approximately 240 million people, or 6% of the world’s population, chronically infected with HBV [1]
We compared clinical characteristics between the virological response (VR) and non-VR groups among hepatitis B e antigen (HBeAg)-negative patients, which showed that there was no significant difference in ALT and HBV DNA levels, while miR-192-5p levels tended to be higher in the non-VR group (S1 Table)
Several factors have been reported to be associated with VR in the treatment of chronic hepatitis B (CHB), for instance patients with HBeAg-negative CHB who show decreased Hepatitis B core-related antigen (HBcrAg) levels during treatment with pegylated interferon (Peg-IFN) combination therapy with or without nucleos(t) ide analogues (NAs) were more likely to succeed with anti-viral treatment [21, 22]

Summary

Introduction

Hepatitis B virus (HBV) infection is a global public health problem, with approximately 240 million people, or 6% of the world’s population, chronically infected with HBV [1]. The long-term goal of antiviral therapy for chronic hepatitis B (CHB) has been to eliminate hepatitis B surface antigen (HBsAg). The current standard therapies using nucleos(t) ide analogues (NAs) or pegylated interferon (Peg-IFN) are difficult to achieve the elimination of HBsAg [3]. Peg-IFN has the advantage of maintaining a drug-free therapeutic effect without additional drug administration after treatment in CHB patients who exhibit a therapeutic response [7, 8]. The levels of ALT and HBV DNA, and HBV genotype at baseline, have been reported to significantly affect the response to Peg-IFN therapy after 24-weeks of treatment [8–10]. Along these lines, a reliable marker for the efficacy of Peg-IFN therapy in CHB is needed [11]

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Results

Conclusion