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

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.

Conditions

• Liver Disease

Interventions

GENETIC

genotyping and/or sequencing

genotyping and/or sequencing DNA for IL28

Sponsors & Collaborators

• INMI L Spallanzani IRCCS Roma

  collaborator UNKNOWN

• IRCCS Azienda Ospedaliero-Universitaria di Bologna

  collaborator OTHER

• Azienda Ospedaliera San Camillo Forlanini

  collaborator OTHER

• Fondazione IRCCS Policlinico San Matteo di Pavia

  collaborator OTHER

• Azienda ospedaliera Garibaldi Nesinma Catania

  collaborator UNKNOWN

• Azienda Ospedaliero-Universitaria Careggi

  collaborator OTHER

• University of Milan

  collaborator OTHER

• Catholic University, Italy

  collaborator OTHER

• Ospedale Francesco Ferrari

  collaborator OTHER

• Ospedale di Canosa di Puglia

  collaborator UNKNOWN

• Ospedale di Venosa

  collaborator UNKNOWN

• Clinica Santa Rita Bari

  collaborator UNKNOWN

• Ospedale SS. Annunziata, Taranto

  collaborator UNKNOWN

• Ospedali Riuniti di Foggia

  collaborator OTHER

• Casa Sollievo della Sofferenza IRCCS

  lead OTHER

Principal Investigators

• Alessandra Mangia, MD · Liver Unit, Casa Sollievo della Sofferenza

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-09-30

Primary Completion

2012-09-30

Completion

2022-09-30

Countries

• Italy

Study Locations