Many patients with interleukin 28B genotypes associated with response to therapy are ineligible for treatment because of comorbidities

Clin Gastroenterol Hepatol. 2014 Feb;12(2):327-333.e1. doi: 10.1016/j.cgh.2013.08.034. Epub 2013 Aug 23.

Abstract

Background & aims: Interleukin (IL)-28B (interferon-λ 3) genotype is the strongest predictor of response of patients with hepatitis C virus (HCV) infection to antiviral therapy. However, patients with HCV infection often have physical or mental comorbidities that contraindicate or complicate treatment, regardless of their genotype. The potential role of IL28B genotype within the context of patients' clinical and social environment is therefore unclear.

Methods: We characterized the IL28B genotype (for rs12980275 and rs8099917) in 308 patients (mean age, 56 y; 25% African American; 38% with advanced-stage fibrosis) with genotype 1 HCV infection seen at the Michael E. DeBakey Veterans Administration Medical Center in Houston, Texas, from May 1, 2009, through April 1, 2012. We evaluated their eligibility for antiviral treatment based on clinical and social factors such as physical or mental health comorbidity, ongoing alcohol or drug use, and noncompliance with treatment evaluation.

Results: Of the 308 subjects, 40% were homozygous for rs12980275 (associated with response to therapy), 46% were heterozygous, and 15% were homozygous for alleles associated with reduced response to therapy. Overall, 36% of patients were considered to be ineligible for treatment; of these, 40% had the rs12980275 genotype. More than half of the patients with rs12980275 who were ineligible for treatment were excluded because of mental health comorbidities; one-third of these patients had advanced fibrosis. The reason(s) for treatment exclusion resolved in only 8% of patients during a mean 1.5 years of follow-up evaluation.

Conclusions: In a well-characterized cohort of patients with HCV, a large proportion (40%) with IL28B polymorphisms associated with response to therapy is ineligible for treatment because of contraindications. One potential role of IL28B genotype analysis could be to identify patients who, although not currently eligible for antiviral treatment, could become so by modifying fixable exclusions to treatment.

Keywords: DAA; Genetics; HCV; Interferon Lambda 3; Liver Disease; SNP; SVR; direct acting antiviral; hepatitis C virus; single-nucleotide polymorphism; sustained virologic response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antiviral Agents / therapeutic use
  • Black or African American / genetics
  • Comorbidity
  • Contraindications
  • Drug Therapy
  • Gene Frequency
  • Genotype
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / epidemiology
  • Hepatitis C, Chronic / genetics*
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / epidemiology
  • Liver Cirrhosis / genetics*
  • Male
  • Middle Aged
  • Patient Selection
  • Polymorphism, Single Nucleotide
  • White People / genetics

Substances

  • Antiviral Agents
  • IFNL3 protein, human
  • Interleukins
  • Interferons