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

NCT01437969 | Completed

• 1 other identifier: EPAT-IL28B
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Possible association; between severity; IL28B genetic variants; patients; different HCV genotypes

Interventions

genotyping and/or sequencing GENETIC

genotyping and/or sequencing DNA for IL28

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

HCV infected patients previously untreated

You may qualify if:

• Patients with chronic HCV infection irrespective of HCV genotype

You may not qualify if:

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

Sponsors & Collaborators

• Casa Sollievo della Sofferenza IRCCS: lead
• INMI L Spallanzani IRCCS Roma: collaborator
• IRCCS Azienda Ospedaliero-Universitaria di Bologna: collaborator
• Azienda Ospedaliera San Camillo Forlanini: collaborator
• Fondazione IRCCS Policlinico San Matteo di Pavia: collaborator
• Azienda ospedaliera Garibaldi Nesinma Catania: collaborator
• Azienda Ospedaliero-Universitaria Careggi: collaborator
• University of Milan: collaborator
• Catholic University, Italy: collaborator
• Ospedale Francesco Ferrari: collaborator
• Ospedale di Canosa di Puglia: collaborator
• Ospedale di Venosa: collaborator
• Clinica Santa Rita Bari: collaborator
• Ospedale SS. Annunziata, Taranto: collaborator
• Ospedali Riuniti di Foggia: collaborator

Study Sites (1)

IRCCS "Casa Sollievo della Sofferenza"

San Giovanni Rotondo, Foggia, 71013, Italy

Location

Related Publications (6)

• Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009 Sep 17;461(7262):399-401. doi: 10.1038/nature08309. Epub 2009 Aug 16.

  PMID: 19684573 BACKGROUND

• Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, Bassendine M, Spengler U, Dore GJ, Powell E, Riordan S, Sheridan D, Smedile A, Fragomeli V, Muller T, Bahlo M, Stewart GJ, Booth DR, George J. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet. 2009 Oct;41(10):1100-4. doi: 10.1038/ng.447. Epub 2009 Sep 13.

  PMID: 19749758 BACKGROUND

• Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, Korenaga M, Hino K, Hige S, Ito Y, Mita E, Tanaka E, Mochida S, Murawaki Y, Honda M, Sakai A, Hiasa Y, Nishiguchi S, Koike A, Sakaida I, Imamura M, Ito K, Yano K, Masaki N, Sugauchi F, Izumi N, Tokunaga K, Mizokami M. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009 Oct;41(10):1105-9. doi: 10.1038/ng.449. Epub 2009 Sep 13.

  PMID: 19749757 BACKGROUND

• Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, Urban T, Afdhal NH, Jacobson IM, Esteban R, Poordad F, Lawitz EJ, McCone J, Shiffman ML, Galler GW, Lee WM, Reindollar R, King JW, Kwo PY, Ghalib RH, Freilich B, Nyberg LM, Zeuzem S, Poynard T, Vock DM, Pieper KS, Patel K, Tillmann HL, Noviello S, Koury K, Pedicone LD, Brass CA, Albrecht JK, Goldstein DB, McHutchison JG. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology. 2010 Jul;139(1):120-9.e18. doi: 10.1053/j.gastro.2010.04.013. Epub 2010 Apr 24.

  PMID: 20399780 BACKGROUND

• Mangia A, Thompson AJ, Santoro R, Piazzolla V, Tillmann HL, Patel K, Shianna KV, Mottola L, Petruzzellis D, Bacca D, Carretta V, Minerva N, Goldstein DB, McHutchison JG. An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response. Gastroenterology. 2010 Sep;139(3):821-7, 827.e1. doi: 10.1053/j.gastro.2010.05.079. Epub 2010 Jun 2.

  PMID: 20621700 BACKGROUND

• Afdhal NH, McHutchison JG, Zeuzem S, Mangia A, Pawlotsky JM, Murray JS, Shianna KV, Tanaka Y, Thomas DL, Booth DR, Goldstein DB; Pharmacogenetics and Hepatitis C Meeting Participants. Hepatitis C pharmacogenetics: state of the art in 2010. Hepatology. 2011 Jan;53(1):336-45. doi: 10.1002/hep.24052.

  PMID: 21254181 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

DNA from blood sample

MeSH Terms

Conditions

Liver Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Officials

• Alessandra Mangia, MD

  Liver Unit, Casa Sollievo della Sofferenza

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 20, 2011
• First Posted: September 21, 2011
• Study Start: September 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2022
• Last Updated: August 30, 2023

Record last verified: 2023-08

Locations

IT (1)