Pharmacogenomics Study on IL28B Genetic Variants in Italian Patients With HCV Infection naïve to Treatment.
Pharmacogenomics Study on IL28B Genetic Variants in Italian Patients With HCV Infection naïve to Treatment.
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.
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
Inclusion Criteria:

 -  Patients with chronic HCV infection irrespective of HCV genotype

 Exclusion Criteria:

 -  HCV infected patients previously treated with antiviral drugs; co-infected Patients
 with HIV or Hepatitis B virus (HBsAg positive)