Pharmacogenomics Study on IL28B Genetic Variants in Italian Patients With HCV Infection naïve to Treatment.
Condition: Liver Disease
MeSH terms: Liver Diseases
Study type: Observational

Summary: 
      More than 1.5 millions individuals are infected with HCV in Italy. They are at risk to
      develop related morbidity and mortality from cirrhosis and hepatocellular carcinoma, unless
      the evolution of their disease is halted by treatment-induced HCV RNA clearance. Indeed, it
      is well recognized that a curative antiviral treatment, leading to HCV RNA undetectability 24
      weeks after the end of therapy, may prevent the occurrence of complications of HCV chronic
      liver disease.

      Several pre-treatment host and viral factors have been associated with the outcome of
      pegylated Interferon and Ribavirin treatment. These predictors are relevant as the ability to
      identify patients with the highest likelihood of achieving HCV RNA clearance may increase the
      number of patients who agree to be treated and who maintain their adherence to treatment.

      Several pre-treatment predictors as HCV genotype, HCV viral load, age, gender, body mass
      index, stage of fibrosis and race are very well recognized and have been used for many years
      during the treatment decision-making process. Based on studies of viral kinetics, HCV RNA
      undetectable at week 4 on treatment has been shown to represent the best on treatment
      predictor of response. In addition to these well known factors, very recently, a single
      nucleotide polymorphism (SNP) upstream of the gene IL28B on chromosome 19, coding for
      IFN-lambda 3 has been identified as associated with both spontaneous and treatment induced
      HCV RNA clearance.

      We have developed the molecular technique needed to evaluate this polymorphism in our
      laboratory. This technical process was a consequence of the genetics expertise of our
      research Institute. We have also performed a valuable comparison of the different methods to
      evaluate this polymorphism. Comparison of different technologies allow us to know the rate of
      variability between the different assays used.

      With this methodology we have evaluated "a posteriori" patients previously enrolled in
      Randomized Controlled Trial. The results of these studies confirmed the association between
      IL28B CC allele and a favorable outcome of HCV infection in our geographic area (Mangia et al
      Gastroenterology 2010; Mangia et al Hepatology 2010, AASLD presentation). We are now
      interested in prospective evaluation of patients referring to our center at the aim of
      understanding whether there are differences in the rates of IL28B frequencies in patients
      with different HCV genotypes.

      In fact, we hypothesize that the frequency of IL28B might be different according with
      different HCV genotypes and that this difference may explain the different rates of response
      to antiviral treatment reported in patients with HCV infection.

      Since we lead a collaborative group of hepatologists named AL-LIVER operating in Puglia,
      Lazio, Basilicata, Sicilia and Campania regions in Italy we would like to extend this
      evaluation to our collaborative group to explore in a large number of patients whether the
      prevalence of CC, CT and TT genotypes is inversely associated with HCV G1, 4, 3 and 2.
    

Detailed description: 
      This study is a prevalence study involving naïve patients and without links with treatment.
      Five hundred patients with HCV infection consecutively observed during 2011 will be requested
      to sign an informed consent at the aim to be tested for genetics. The study will be evaluated
      and approved by the Central Ethic Committee. It will have a planned duration of 12 months and
      will involve 15 centers.

      All the HCV infected patients previously untreated can be enrolled once they have signed the
      Informed consent for genetic testing.

      Each patient enrolled at the single center will be evaluated for demographical, virological,
      biochemical, histological and genetic (IL28B) characteristics. In case of unavailable liver
      biopsy at least APRI score and Fibroscan evaluation should be used to assess the severity of
      the underlying liver disease. All the blood specimens will be stored and evaluated by a
      pre-developed TaqMan allelic discrimination assay (Applied Biosystem) or by direct sequencing
      for IL28B genetic variation. A serum sample will be also stored to evaluate HCV genotype and
      HCV RNA levels.

      Data will be collected in a database that can be used in the future to select patients
      needing antiviral treatment.

      The association between IL28B variants and the other predictors will be explored by means of
      descriptive statistical analyses. Number of patients, mean, standard deviation, median will
      be calculated for continuous variables. Absolute frequencies and per cent will be used to
      describe frequencies parameters
    

Intervention name(s): genotyping and/or sequencing
Intervention type(s): Genetic
Intervention description(s): genotyping and/or sequencing DNA for IL28
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        HCV infected patients previously untreated
      
Biospecimen description: 
      DNA from blood sample
    
Keywords: Possible association; between severity; IL28B genetic variants; patients; different HCV genotypes