Chief, Department of Laboratory Medicine
St. Joseph’s Healthcare & Hamilton Health Sciences
St. Joseph’s Hospital, L301-2
50 Charlton Avenue East
Hamilton, Ontario L8N 4A6
Director for Laboratory Genetics, HRLMP
Professor, Dept of Pathology & Molecular Medicine, McMaster University
1200 Main Street W Room 3N20 HSC
Hamilton, Ontario L8N 3Z5
Dr. M. Crowther, Director
Tel: (905) 522-1155, ext. 33841
Fax: (905) 521-6090 e-mail: crowthrm@mcmaster.ca
R. Carter, PhD, FCCMG, FACMG
Tel: (905)-521-5085
Fax: (905)-521-2651 e-mail: rcarter@mcmaster.ca
TO:
FROM:
DATE:
RE:
Infectious Disease Specialists
Dr. Mark Crowther and Ron Carter
August 24, 2011
IL28B Genotyping Test for Resistance to Hepatitis C Virus
The HRLMP has a new test that will be useful in the management of patients with Hepatitis C infection. This pharmacogenetic test is based upon analysis of patient DNA ( not Hepatitis C viral
DNA). The test assays 3 DNA sequence variants in the region of the IL28B gene, which codes for an interleukin protein with a central role in the development of a response to HCV infection. These variants have a strong correlation with: a) spontaneous clearance of the virus in the acute phase of infection, and/or b) achieving sustained viral clearance after therapy for chronic HCV hepatitis. The test therefore helps clinicians to explain and more accurately predict outcomes from management for
HCV infection. This test is useful in management of HCV-infected patients in several ways; for example, it may help identify patients who are more likely to complete therapy successfully despite co-morbidities, or may help to differentiate the potential causes of poor treatment outcomes (e.g. non-compliance versus susceptibility).
Information about test ordering is available through the Laboratory Reference Centre (LRC). Refer to http://www.lrc.hrlmp.ca/ . Results will be provided directly to the ordering physician.
For your reference, an article describing clinical significance and utility of the test is attached.
Questions about the IL28B genotyping test should be directed to Dr. Ron Carter at
905-979-0250.
Sincerely,
Mark Crowther, MD, MSc, FRCPC Ron Carter, PhD, FCCMG, FACMG

Genotyping For Resistance to Hepatitis C Infection
Submitted by R. Carter, PhD, and Christine Lee, MD, FRCPC
Dept. of Pathology & Molecular Medicine, McMaster University, the Hamilton Regional
Laboratory Medicine Program, and the Bay Area Genetic Laboratory
Hepatitis C Virus (HCV) infects thousands of Canadians every year through contact with infected blood and body fluids. About 80% of those infected (over 200,000 people) become chronically infected carriers, and the virus causes chronic liver inflammation (hepatitis), leading to cirrhosis, liver cancer, and other morbidities over time if not successfully treated. When chronic HCV infection is diagnosed, patients are usually advised to complete a 48-week treatment regimen that includes pegylated interferon and other medications. Treatment is expensive, time-consuming, and difficult to tolerate. Unfortunately, many patients respond poorly and fail to achieve sustained viral clearance despite completion of treatment. Major goals in management of patients with chronic HCV infection are to improve the adherence of patients to treatment and increase the number of patients cured of infection. Understanding why some patients are poor responders and others are cured has been a key objective for researchers. Now, laboratories around the world have shown that the genetics of our body's defense mechanisms have an important role in how well patients respond to the virus.
As initially reported by D. Ge and colleagues in 2009 (Nature 461:1-3), our DNA code for a type of defensive protein called an interleukin is a critical component of the body's resistance to
HCV. Genome scanning studies showed that genetic variations in the region of a specific interleukin gene, IL28B, are very strongly associated with ability to clear the virus after treatment. People who originate from areas with high rates of endemic HCV infection (e.g. Asia) are more likely to carry protective IL28B genotypes than people from areas that traditionally did not have endemic HCV (e.g. continental Africa), explaining in large part how they selected for a

protective mechanism over time and became resistant to HCV infection. The predicted difference in clinical outcomes is substantial; inheritance of favourable IL28B genotypes brings approximately 4 times better odds of responding to treatment for chronic HCV infection compared to non-resistance genotypes. It is important to note that other factors also determine response to treatment, including viral strain, compliance with treatment, history of previous treatment, stage of liver failure, and co-morbidities like diabetes or alcoholism, and that genotype data have to be interpreted in the context of the whole clinical picture.
Using funding made available by the Dept of Pathology and Molecular Medicine at McMaster
University and the Bay Area Genetic Laboratory, Drs. Christine Lee and Ron Carter have developed a clinical genetic test for IL28B-associated HCV resistance and susceptibility. In related research, an initial aim has been to confirm the predicted frequencies of genotypes in
Ontario, but availability of this test also opens up the possibility of answering interesting new questions. For example, how do IL28B genotypes correlate with outcomes of initial medical management prior to referral to specialty clinics in Ontario? How can knowledge of IL28B genotypes aid in the development of more effective management strategies for patients predicted to have difficulty clearing infection? This test will provide useful information for patients and clinicians when they consider approaches to clinical management, and both researchers and clinicians are looking forward to determining how genotyping results can help explain to patients their clinical history and progress in managing infection with HCV.