title: Many patients with interleukin 28B genotypes associated with response to therapy are ineligible for treatment because of comorbidities.
abstract: OBJECTIVE
  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.
authors: Clinical Epidemiology and Outcomes Program, Houston VA Health Services Research and Development Center of Excellence, Houston, Texas; Department of Medicine, Baylor College of Medicine, Houston, Texas; Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas. Electronic address: kanwal@bcm.edu.
authors: Fasiha
authors: F
authors: Kanwal
authors: Clinical Epidemiology and Outcomes Program, Houston VA Health Services Research and Development Center of Excellence, Houston, Texas; Department of Medicine, Baylor College of Medicine, Houston, Texas.
authors: Donna L
authors: DL
authors: White
authors: Department of Medicine, Baylor College of Medicine, Houston, Texas; Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors: Shahriar
authors: S
authors: Tavakoli-Tabasi
authors: Clinical Epidemiology and Outcomes Program, Houston VA Health Services Research and Development Center of Excellence, Houston, Texas; Department of Medicine, Baylor College of Medicine, Houston, Texas.
authors: Li
authors: L
authors: Jiao
authors: Department of Medicine, Baylor College of Medicine, Houston, Texas.
authors: Derek
authors: D
authors: Lin
authors: Clinical Epidemiology and Outcomes Program, Houston VA Health Services Research and Development Center of Excellence, Houston, Texas; Section of Health Services Research, Baylor College of Medicine, Houston, Texas.
authors: David J
authors: DJ
authors: Ramsey
authors: Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors: Andrew
authors: A
authors: Spiegelman
authors: Clinical Epidemiology and Outcomes Program, Houston VA Health Services Research and Development Center of Excellence, Houston, Texas; Section of Health Services Research, Baylor College of Medicine, Houston, Texas.
authors: Jill
authors: J
authors: Kuzniarek
authors: Clinical Epidemiology and Outcomes Program, Houston VA Health Services Research and Development Center of Excellence, Houston, Texas; Department of Medicine, Baylor College of Medicine, Houston, Texas; Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors: Hashem B
authors: HB
authors: El-Serag
mesh_terms: D001741:Black or African American / Q000235:genetics; D000998:Antiviral Agents / Q000627:therapeutic use; D015897:Comorbidity; D000075202:Contraindications; D004358:Drug Therapy; D005787:Gene Frequency; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: DAA; Genetics; HCV; Interferon Lambda 3; Liver Disease; SNP; SVR; direct acting antiviral; hepatitis C virus; single-nucleotide polymorphism; sustained virologic response
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