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Genomic Testing for HCV

Genotype testing helps enhance efficacy of Hepatitis C treatment

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Vol. 22 • Issue 11 • Page 24

Molecular Diagnostics

Hepatitis C (HCV) is finally gaining significant public awareness, thanks to the CDC and other organizations. Earlier this year, CDC issued a recommendation that Baby Boomers (people born between 1945 and 1965) be tested for exposure to HCV. It is believed that many in that generation could be harboring the virus without knowing it.

The long-term impact of HCV infection is highly variable, ranging from minimal effects to chronic hepatitis, extensive fibrosis, cirrhosis, and hepatocellular carcinoma.1 Increased awareness of HCV should prompt more patients to talk to their doctors about the disease and inquire about testing. As a result, it is expected that physicians will diagnose and treat more patients who may have had asymptomatic HCV for many years, even decades. Treatment should help lower the incidence of downstream complications, such as liver cancer.

Active Infection

While the CDC's action is motivating primary care doctors to be more proactive in testing for HCV, what should they do when a patient tests positive for the virus? A positive HCV antibody result only establishes that the individual has been exposed to Hepatitis C virus. To confirm an active HCV infection, viral replication should be confirmed with the use of highly sensitive real-time PCR tests for HCV RNA. Upon diagnosis and confirmation of an active HCV infection, laboratories should counsel their physicians to order additional tests aimed at better understanding both the patient's clinical status and the nature of the virus causing the infection. An essential tool used to guide physicians in the management of patients with HCV infection is the HCV genotype assay, which determines the specific viral genotype present in the blood of an HCV-infected individual.

HCV is highly variable genetically, with six major genotypes described that share 70-80% nucleotide identity with one another, along with more than 80 subtypes, which share 80-90% nucleotide identities within these genotypes.2 HCV genotype 1 accounts for about 60% of infections worldwide and subtype 1a is the most common cause of infection in the United States.

First Available Assay

On June 20, Abbott announced it received FDA approval for the first commercially available test to identify specific genotypes of HCV. The HCV genotype test is an in vitro reverse transcription-polymerase chain reaction (RT-PCR) assay performed on Abbott's fully automated m2000 system. It provides qualitative identification of HCV genotypes 1, 1a, 1b, and 2-5 in plasma or serum from individuals chronically infected with HCV. The assay is approved as an aid in the management of HCV-infected individuals and in guiding the selection of therapies for specific genotypes. It should be ordered for patients who are chronically infected with HCV, considered for antiviral treatment, and positive for HCV RNA. Results from the HCV genotyping test should be evaluated in conjunction with other clinical and laboratory findings.

Clinical Value

Why is HCV genotype testing clinically valuable? Understanding the HCV strain infecting an individual enables physicians to tailor the course and duration of anti-viral therapies to the specific patient. For example, patients with genotype 2 and 3 HCV infections have much better response to interferon and ribavirin therapy, and patients infected with these viral genotypes may benefit from truncated treatment duration (24 weeks vs. 48 weeks), thereby minimizing their exposure to these toxic and expensive therapy regimens while maintaining high cure rates. Newer direct acting antiviral agents (the protease inhibitors boceprevir or telaprevir), given in combination with interferon and ribavirin are only indicated for treatment of HCV genotype 1 infections and should not be given to patients with genotype 2-6 infections.3,4

Within genotype 1, patients with subtype 1a infections have experienced a higher rate of drug resistance and viral breakthrough than subtype 1b. Studies identified that HCV subtype 1a naturally harbors one of the two mutations associated with the development of drug-resistance to these new protease inhibitors at a significantly higher frequency than subtype 1b. This confers HCV subtype 1b with a higher barrier (requiring two mutations) to anti-viral drug resistance than subtype 1a (which requires only one mutation). In recent updated guidelines, the American Society for the Study of Liver Diseases recommends that patients treated with boceprevir or telaprevir in combination with interferon and ribaviron who continue to have detectable viral RNA should discontinue treatment because of the high likelihood for developing viral resistance.5

Even though in the U.S. genotypes 1a and 1b are predominant, it should not be assumed by clinicians that every HCV infection is genotype 1. Increasing ethnic diversity in the U.S. population and widespread international travel have increased the possibility that other HCV genotypes may be present. For example, an American who contracts HCV in India could have genotype 3 or an infection occurring in Egypt could be genotype 4.

Though significant progress has occurred in diagnosing and treating HCV and in generating better awareness about the dangers of untreated HCV, success in combating the disease is enhanced when clinicians and laboratorians collaborate to understand the complete clinical picture, including host and viral genetic factors, and use this information to determine appropriate therapies.

Dr. Cloherty is director, global scientific affairs, infectious diseases, molecular diagnostics, Abbott.


1. The Global Burden of Hepatitis C Working Group. The Global Burden of Hepatitis C. J Clinical Pharmacology 2004;44:20-29].

2. Kuiken C, Simmonds P. Nomenclature and numbering of the hepatitis C virus. Methods Mol Biol 2009; 510: 33-53.

3. Merck Sharp & Dohme Corporation. VICTRELIS (boceprevir) Capsules for oral use: Highlights of Prescribing Information.

4. Vertex Pharmaceuticals Incorporated. INCIVEK (telaprevir) Film Coated Tablets, for oral use: Highlights of Prescribing Information.

5. Ghany M, et al. An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases.


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