PLoS ONE (Jan 2022)

Fucosylated haptoglobin is a novel predictive marker of hepatocellular carcinoma after hepatitis C virus elimination in patients with advanced liver fibrosis.

  • Kumiko Shirai,
  • Hayato Hikita,
  • Ryotaro Sakamori,
  • Akira Doi,
  • Yuki Tahata,
  • Sadatsugu Sakane,
  • Yoshihiro Kamada,
  • Kazuhiro Murai,
  • Akira Nishio,
  • Ryoko Yamada,
  • Takahiro Kodama,
  • Yasutoshi Nozaki,
  • Naruyasu Kakita,
  • Hisashi Ishida,
  • Fumihiko Nakanishi,
  • Naoki Morishita,
  • Kazuho Imanaka,
  • Mitsuru Sakakibara,
  • Tomohide Tatsumi,
  • Eiji Miyoshi,
  • Tetsuo Takehara

DOI
https://doi.org/10.1371/journal.pone.0279416
Journal volume & issue
Vol. 17, no. 12
p. e0279416

Abstract

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BackgroundPatients with advanced fibrosis are at risk for developing hepatocellular carcinoma (HCC) even after hepatitis C virus (HCV) elimination. We previously reported that serum fucosylated haptoglobin (Fuc-Hp) levels increase as the disease progresses from chronic hepatitis to cirrhosis and then HCC. However, it remains unclear whether serum Fuc-Hp levels can stratify the risk of HCC occurrence after a sustained virological response (SVR) is achieved with direct-acting antivirals (DAAs) in patients with advanced liver fibrosis.MethodsAmong 3,550 patients with chronic hepatitis C treated with DAAs at Osaka University Hospital and related hospitals, the stored sera of 140 patients who were diagnosed with F3 or F4 by liver biopsy before DAA treatment, achieved SVR, and had no history of HCC were available at both baseline and the end of treatment (EOT). We measured the Fuc-Hp levels in these samples.ResultsThe median serum levels of Fuc-Hp at EOT were significantly lower than those at baseline. During the 54.4-month follow-up period, 16 of 140 patients developed HCC. Multivariate Cox proportional hazards analysis revealed that high Fuc-Hp at EOT, high body mass index (BMI), and low albumin at EOT were independent risk factors for HCC occurrence. Patients with all three factors-high Fuc-Hp, high BMI, and low albumin-had a higher incidence of HCC than patients without these factors.ConclusionsHigh serum Fuc-Hp levels at EOT were an independent risk factor for HCC occurrence after SVR. Combined with BMI and albumin, Fuc-Hp can stratify the risk of HCC occurrence among those with advanced fibrosis.