Effect of pioglitazone on outcome following curative treatment for hepatocellular carcinoma in patients with hepatitis C virus infection: A prospective study

Sumie,Shuji; Kawaguchi,Takumi; Kawaguchi,Atsushi; Kuromatsu,Ryoko; Nakano,Masahito; Satani,Manabu; Yamada,Shingo; Okamura,Shusuke; Yonezawa,Yuko; Kakuma,Tatsuyuki; Torimura,Takuji; Sata,Michio

doi:10.3892/mco.2014.435

Effect of pioglitazone on outcome following curative treatment for hepatocellular carcinoma in patients with hepatitis C virus infection: A prospective study

Authors:
- Shuji Sumie
- Takumi Kawaguchi
- Atsushi Kawaguchi
- Ryoko Kuromatsu
- Masahito Nakano
- Manabu Satani
- Shingo Yamada
- Shusuke Okamura
- Yuko Yonezawa
- Tatsuyuki Kakuma
- Takuji Torimura
- Michio Sata
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Affiliations: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Biostatistics Center, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Graduate School of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
Published online on: October 6, 2014 https://doi.org/10.3892/mco.2014.435
Pages: 115-120

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Abstract

Pioglitazone is an insulin sensitizer used for the treatment of diabetes mellitus (DM). DM with insulin resistance is a risk factor for hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection. We aimed to investigate the effects of pioglitazone on HCC recurrence following treatment in HCV‑infected patients. Between 2009 and 2011, 85 HCV‑infected HCC patients who underwent curative treatment were enrolled in this prospective study. Among 45 patients with type 2 DM, 27 were administered pioglitazone (pioglitazone group) following treatment. The remaining 58 patients were assigned to the control group. The primary outcome was recurrence‑free survival. Changes in insulin resistance and serum adiponectin levels resulting from pioglitazone treatment were also assessed. In the whole analysis (n=85), no significant difference in recurrence‑free survival was observed between the pioglitazone and control groups. However, in a spline model analysis of DM patients, a decreased risk of HCC recurrence was associated with increased body weight in patients with a body mass index (BMI) ≥23; this association became significant at BMI ≥24 (hazard ratio=0.17; 95% confidence interval: 0.03‑0.95). In addition, significantly decreased homeostasis model assessment for insulin resistance values (P=0.002) and significantly increased serum high‑molecular‑weight adiponectin levels (P<0.001) were observed following pioglitazone treatment. Although pioglitazone did not suppress HCC recurrence in the whole analysis, it inhibited HCC recurrence in overweight HCV‑infected diabetic patients. Moreover, pioglitazone improved insulin resistance and adipocytokine levels. Thus, pioglitazone may suppress HCC recurrence, which is associated with glucose and fat metabolism disorders.

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