Gene Variant Predicts HCV Treatment Success

Gene Variant Predicts HCV Treatment Success
By Michael Smith, North American Correspondent, MedPage Today
Published: August 18, 2009
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Earn CME/CE credit
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A small genetic change near the gene for interferon-lambda-3 doubles the chance of successful hepatitis C treatment, researchers said.

The variant -- a cytosine for thymine switch on chromosome 19 -- is the first genetic marker that predicts response to treatment for genotype 1 hepatitis C, according to David Goldstein, PhD, of Duke University, and colleagues.

The alteration is also more common among people of European ancestry than those of African background, which may explain much of the difference in treatment response between the two ethnic groups, Goldstein and colleagues wrote online in Nature.

"This is what personalized medicine is all about," Goldstein said in a statement. "This discovery enables us to give patients valuable information that will help them and their doctors decide what is best for them."
Action Points

* Explain to interested patients that treatment for hepatitis C is not uniformly successful.


* Note that this study found a small genetic variation that explains much of the difference in treatment success rates, which may allow for better prognostic assessments.

The finding comes from a genome-wide association study of more than 1,600 patients involved in the so-called IDEAL trial, which compared three treatment regimens for the disease. (See Head-to-Head Trial Finds HCV Regimens Equal)

Across all ethnic groups, the polymorphism was significantly associated (at P=1.37x10-28) with sustained virological response (SVR), defined as the absence of detectable virus at the end of follow-up.

In patients of European ancestry who carry two copies of the C variant, the genotype was associated with a twofold greater rate of SVR than the TT genotype.

The ratios were similar in both the African-American and the Hispanic populations in the study – threefold and twofold, respectively, the researchers said.

Interestingly, African-Americans with two copies of the C allele had a 53.3% SVR rate, significantly higher (at P<0.05) than the 33.3% seen in Europeans with two copies of the T allele.

That finding, Goldstein and colleagues said, "emphasizes the greater importance of individual genotype compared with ethnicity in predicting treatment response."

In a random, multi-ethnic sample, whose hepatitis C status was not known, the C allele appeared in about 40% of African-Americans, compared with between 70% and 80% for European-Americans and Hispanics, Goldstein and colleagues said.

East Asians, who are known to have even better SVR rates than Europeans, had the C allele more than 90% of the time, the researchers found.

The researchers said they were struck by the finding that the CC genotype was beneficial to all subgroups, Goldstein said.

"But because it appears significantly more often among Caucasian populations than it does among African populations, we feel it explains much of the difference in response rates we see between African-Americans and those of European ancestry," he said.

He and colleagues cautioned that the finding only applies to genotype 1 hepatitis C, which is the most common form. They said more research is needed to see if it applies to less common forms of the disease.

The study was supported by the Schering-Plough Research Institute.

Goldstein reported financial links with Schering-Plough, and several authors are employees of the company.

Goldstein and other authors are inventors of a patent application based on this finding.

Primary source: Nature
Source reference:
Ge D, et al "Genetic variation in IL28B predicts hepatitis C
treatment-induced viral clearance" Nature 2009; DOI: 10.1038/nature08309.