IL-28B variant as a predictor in patients with advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy

J Gastroenterol Hepatol. 2020 Oct;35(10):1813-1820. doi: 10.1111/jgh.15035. Epub 2020 Apr 1.

Abstract

Background and aim: Single-nucleotide polymorphisms (SNPs) of the interleukin-28B (IL-28B) gene are associated with the effectiveness of interferon therapy for chronic hepatitis C infection. Whether the IL-28B genotype affects the course of treatment and the outcomes of patients with advanced hepatocellular carcinoma (HCC) is unknown.

Methods: We detected the IL-28B SNP (rs8099917) using TaqMan PreDesigned SNP Genotyping Assays to assess the effects of the IL-28B genotype on treatment efficacy and prognosis of patients with advanced HCC treated with hepatic arterial infusion chemotherapy (HAIC) between September 2003 and January 2015.

Results: The study included 154 patients who received HAIC to treat advanced HCC, among which 27 (17.5%) had the minor genotype, IL-28B rs8099917 TG or GG, and the others had the major genotype, IL-28B rs8099917 TT. The objective response rates of patients with the minor or major genotype were 51.9% and 29.1% (P = 0.022), respectively. Multivariate analysis revealed that the minor genotype remained associated with the response to HAIC (odds ratio, 2.620; P = 0.026). The median overall survival of patients with major or minor genotypes was 14.1 and 16.9 months, respectively, and the overall survival of patients with the major genotype was significantly shorter than that of patients with the minor genotype (P = 0.027). Multivariate analysis revealed that the major genotype was an independent, unfavorable prognostic factor (hazard ratio, 1.720; P = 0.024). Consistent results were obtained in selected populations after propensity score matching analysis.

Conclusions: The IL-28B SNP (rs8099917) will serve as a useful predictor of the outcomes of patients with advanced HCC treated with HAIC.

Keywords: Hepatic arterial infusion chemotherapy, predictive factor, prognostic factor; Hepatocellular carcinoma; IL-28B genotype.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Cisplatin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Forecasting
  • Genotype
  • Hepatic Artery
  • Humans
  • Infusions, Intra-Arterial
  • Interferon alpha-2 / administration & dosage
  • Interferon-alpha / administration & dosage
  • Interferons / genetics*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Propensity Score
  • Recombinant Proteins / administration & dosage
  • Survival Rate
  • Treatment Outcome

Substances

  • interferon-lambda, human
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Interferons
  • peginterferon alfa-2b
  • Cisplatin
  • Fluorouracil