A report published online in the August 6, 2009, issue of the journal Nature suggests that the reason for the disparity in responses to the standard hepatitis C (HCV) treatment, a combination therapy of interferon and ribavirin, may lie in a specific variation in a patient’s genetics. The study was led by David B. Goldstein, PhD, Professor of Molecular Genetics & Microbiology, Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University in Durham, NC.
Although the interferon/ribavirin combination effectively treats many chronic HCV patients, nearly 50% do not respond to it. Further, patients who do respond to it often experience debilitating side effects that can last the duration of the treatment—either 24 or 48 weeks. Interferon side effects include severe flulike symptoms, depression, fatigue and insomnia. Ribavirin can cause anemia, skin rash and itching, fatigue and birth defects. It would be beneficial to be able to predict in which patients the therapy will work.
Goldstein and his team used a genetic test known as a genome-wide association study, to screen the three billion sites of the human genome from 1,671 patients with HCV genotype 1. They found that a specific site, the one near the gene (IL28B) responsible for a protein called “interferon-lambda-3,” contains genetic coding that could play a decisive role in HCV therapy response. Interferons are natural proteins manufactured by human cells to fight viral infections.
Investigators believe that the combination of DNA units a person inherits at IL28B determines the level of interferon production and subsequent ability to battle infections such as HCV. Since a person inherits two copies of the genome at IL28B (one from each parent), either a “T” or a “C” unit, three possibilities occur: CC, TT or CT. Individuals with the CC version respond much better to interferon/ribavirin. In this study, their sustained viral response rate (ability to clear the virus) was 80% compared to 30% in the subjects with the other versions. While C versions are more prevalent in East Asians and Europeans, they are far less common in people of African ancestry. C versions are most common among East Asians.
A comparison of the HCV therapy success rates in each of the three groups highlights the disparity. Approximately 75% of East Asians respond favorably to combination therapy, compared to 55% of Americans of European ancestry. In stark contrast, only an approximate 25% of African-Americans experience a successful round of HCV therapy.
The report, “Genetic Variation in IL28B Predicts Hepatitis C Treatment-induced Viral Clearance,” was published August 16, 2009, on the Nature Web site.
Source: The New York Times, August 17, 2009