Interferon-λ-related genes and therapeutic response in Chinese hepatitis C patients

World J Gastroenterol. 2015 Apr 7;21(13):4006-13. doi: 10.3748/wjg.v21.i13.4006.

Abstract

Aim: To determine the association between rapid viral response and IL28B, IL28RA, IL10RB and MxA polymorphisms in the Chinese Han population.

Methods: The study cohort consisted of 238 chronic hepatitis C patients treated with interferon (IFN)-α-2b and ribavirin. Six single nucleotide polymorphisms were genotyped using the ABI TaqMan allelic discrimination assay. Biochemical indices were measured at baseline. Serum hepatitis C virus (HCV) RNA was detected at weeks 0, 4, 12 and 24 of therapy.

Results: Only IL28B rs12980275 was associated with treatment response in the Chinese Han population. Patients carrying AG/GG genotypes had a reduced rapid viral response compared with patients carrying the AA genotype (additive model: adjusted OR = 0.43, 95%CI: 0.24-0.75). It took less time for patients with the AA genotype to achieve a viral load < 500 copies/mL (log-rank test, P = 0.004). In addition, the protective effect of genotype AA was independent of baseline viral load. HCV genotype, and baseline white blood cell count, α-fetoprotein and viral load might also help predict treatment response. The area under the receiver-operating characteristic curve was 0.726.

Conclusion: IL28B rs12980275 AA genotype is a strong predictor of positive response to IFN therapy in Chinese Han patients with hepatitis C.

Keywords: Chinese population; Hepatitis C virus; IL28B; Interferon; Rapid viral response.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Area Under Curve
  • Asian People / genetics*
  • Biomarkers / blood
  • Chi-Square Distribution
  • China / epidemiology
  • Drug Therapy, Combination
  • Female
  • Gene Frequency
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / ethnology
  • Hepatitis C, Chronic / genetics*
  • Humans
  • Interferon Lambda
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukin-10 Receptor beta Subunit / genetics
  • Interleukins / genetics
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myxovirus Resistance Proteins / genetics
  • Odds Ratio
  • Pharmacogenetics
  • Phenotype
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide*
  • Predictive Value of Tests
  • RNA, Viral / blood
  • ROC Curve
  • Receptors, Cytokine / genetics*
  • Receptors, Interferon
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • Biomarkers
  • Interferon alpha-2
  • Interferon-alpha
  • Interferons
  • Interleukin-10 Receptor beta Subunit
  • Interleukins
  • Myxovirus Resistance Proteins
  • Polyethylene Glycols
  • RNA, Viral
  • Receptors, Cytokine
  • Receptors, Interferon
  • Recombinant Proteins
  • Ribavirin
  • interferon-lambda, human
  • Interferon Lambda
  • IFNLR1 protein, human
  • IL10RB protein, human
  • MX1 protein, human
  • peginterferon alfa-2b