On-treatment decrease of NKG2D correlates to early emergence of clinically evident hepatocellular carcinoma after interferon-free therapy for chronic hepatitis C

Hakusyo Cho, Nobuhiro Nakamoto, Nobuhito Taniki, Keisuke Ojiro, Takeru Amiya, Yuko Makita, Hiroko Murata, Akihiro Yamaguchi, Shunsuke Shiba, Rei Miyake, Tadashi Katayama, Aya Yoshida, Akihiko Ikura, Karin Takeda, Hirotoshi Ebinuma, Hidetsugu Saito, Takanori Kanai

Research output: Contribution to journalArticle

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Abstract

Background and aims Interferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs. Methods We conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i.e., during the 6-month surveillance period following treatment.) recurrence or occurrence of clinically evident HCC. We also analyzed the peripheral blood mononuclear cells, both before treatment and at end of treatment (EOT), of 24 of the patients who received IFN-free DAAs, and 16 who received IFN-combined protease inhibitor. Results We found early emergence of clinically evident HCC after IFN-free DAAs in 12 (12%) patients. Higher pre-treatment NKG2D expression, higher FIB-4 score, previous HCC history and failure to achieve sustained viral response were significant factors correlating to early HCC emergence. After IFN-free DAAs, a rapid decrease of NKG2D at EOT correlated with early HCC emergence in the IFN-free DAA-treated patients, but not in patients treated with the IFN-combined regimen. The decrease of NKG2D until EOT was predictive of early HCC emergence at a cut-off of -52% (AUC = 0.92). Conclusions On-treatment decrease of NKG2D may be a useful predictor of early emerging HCC in patients treated with IFN-free DAAs.

Original languageEnglish
Article numbere0179096
JournalPLoS One
Volume12
Issue number6
DOIs
Publication statusPublished - 2017 Jun 1

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chronic hepatitis C
antiviral agents
Chronic Hepatitis C
interferons
hepatoma
Interferons
Hepatocellular Carcinoma
Antiviral Agents
therapeutics
Therapeutics
Recurrence
observational studies
mononuclear leukocytes
proteinase inhibitors
Protease Inhibitors
Area Under Curve
Observational Studies
Blood Cells
Blood
pretreatment

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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On-treatment decrease of NKG2D correlates to early emergence of clinically evident hepatocellular carcinoma after interferon-free therapy for chronic hepatitis C. / Cho, Hakusyo; Nakamoto, Nobuhiro; Taniki, Nobuhito; Ojiro, Keisuke; Amiya, Takeru; Makita, Yuko; Murata, Hiroko; Yamaguchi, Akihiro; Shiba, Shunsuke; Miyake, Rei; Katayama, Tadashi; Yoshida, Aya; Ikura, Akihiko; Takeda, Karin; Ebinuma, Hirotoshi; Saito, Hidetsugu; Kanai, Takanori.

In: PLoS One, Vol. 12, No. 6, e0179096, 01.06.2017.

Research output: Contribution to journalArticle

Cho, Hakusyo ; Nakamoto, Nobuhiro ; Taniki, Nobuhito ; Ojiro, Keisuke ; Amiya, Takeru ; Makita, Yuko ; Murata, Hiroko ; Yamaguchi, Akihiro ; Shiba, Shunsuke ; Miyake, Rei ; Katayama, Tadashi ; Yoshida, Aya ; Ikura, Akihiko ; Takeda, Karin ; Ebinuma, Hirotoshi ; Saito, Hidetsugu ; Kanai, Takanori. / On-treatment decrease of NKG2D correlates to early emergence of clinically evident hepatocellular carcinoma after interferon-free therapy for chronic hepatitis C. In: PLoS One. 2017 ; Vol. 12, No. 6.
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abstract = "Background and aims Interferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs. Methods We conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i.e., during the 6-month surveillance period following treatment.) recurrence or occurrence of clinically evident HCC. We also analyzed the peripheral blood mononuclear cells, both before treatment and at end of treatment (EOT), of 24 of the patients who received IFN-free DAAs, and 16 who received IFN-combined protease inhibitor. Results We found early emergence of clinically evident HCC after IFN-free DAAs in 12 (12{\%}) patients. Higher pre-treatment NKG2D expression, higher FIB-4 score, previous HCC history and failure to achieve sustained viral response were significant factors correlating to early HCC emergence. After IFN-free DAAs, a rapid decrease of NKG2D at EOT correlated with early HCC emergence in the IFN-free DAA-treated patients, but not in patients treated with the IFN-combined regimen. The decrease of NKG2D until EOT was predictive of early HCC emergence at a cut-off of -52{\%} (AUC = 0.92). Conclusions On-treatment decrease of NKG2D may be a useful predictor of early emerging HCC in patients treated with IFN-free DAAs.",
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T1 - On-treatment decrease of NKG2D correlates to early emergence of clinically evident hepatocellular carcinoma after interferon-free therapy for chronic hepatitis C

AU - Cho, Hakusyo

AU - Nakamoto, Nobuhiro

AU - Taniki, Nobuhito

AU - Ojiro, Keisuke

AU - Amiya, Takeru

AU - Makita, Yuko

AU - Murata, Hiroko

AU - Yamaguchi, Akihiro

AU - Shiba, Shunsuke

AU - Miyake, Rei

AU - Katayama, Tadashi

AU - Yoshida, Aya

AU - Ikura, Akihiko

AU - Takeda, Karin

AU - Ebinuma, Hirotoshi

AU - Saito, Hidetsugu

AU - Kanai, Takanori

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Background and aims Interferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs. Methods We conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i.e., during the 6-month surveillance period following treatment.) recurrence or occurrence of clinically evident HCC. We also analyzed the peripheral blood mononuclear cells, both before treatment and at end of treatment (EOT), of 24 of the patients who received IFN-free DAAs, and 16 who received IFN-combined protease inhibitor. Results We found early emergence of clinically evident HCC after IFN-free DAAs in 12 (12%) patients. Higher pre-treatment NKG2D expression, higher FIB-4 score, previous HCC history and failure to achieve sustained viral response were significant factors correlating to early HCC emergence. After IFN-free DAAs, a rapid decrease of NKG2D at EOT correlated with early HCC emergence in the IFN-free DAA-treated patients, but not in patients treated with the IFN-combined regimen. The decrease of NKG2D until EOT was predictive of early HCC emergence at a cut-off of -52% (AUC = 0.92). Conclusions On-treatment decrease of NKG2D may be a useful predictor of early emerging HCC in patients treated with IFN-free DAAs.

AB - Background and aims Interferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs. Methods We conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i.e., during the 6-month surveillance period following treatment.) recurrence or occurrence of clinically evident HCC. We also analyzed the peripheral blood mononuclear cells, both before treatment and at end of treatment (EOT), of 24 of the patients who received IFN-free DAAs, and 16 who received IFN-combined protease inhibitor. Results We found early emergence of clinically evident HCC after IFN-free DAAs in 12 (12%) patients. Higher pre-treatment NKG2D expression, higher FIB-4 score, previous HCC history and failure to achieve sustained viral response were significant factors correlating to early HCC emergence. After IFN-free DAAs, a rapid decrease of NKG2D at EOT correlated with early HCC emergence in the IFN-free DAA-treated patients, but not in patients treated with the IFN-combined regimen. The decrease of NKG2D until EOT was predictive of early HCC emergence at a cut-off of -52% (AUC = 0.92). Conclusions On-treatment decrease of NKG2D may be a useful predictor of early emerging HCC in patients treated with IFN-free DAAs.

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