Genetic test predicts who will respond to hepatitis C treatment

Researchers report in Nature that they have identified a gene that predicts response to treatment for hepatitis C with pegylated interferon and ribavirin.

“Advanced knowledge of host genotype of patients with hepatitis C virus could in the future become an important component of the clinical decision to initiate treatment", comment the investigators.

It is estimated that 170 million individuals are infected with hepatitis C virus around the world. Treatment is available that can clear this infection, but it can cause unpleasant side-effects and does not always work.

A better understanding of the factors associated with responses to therapy for hepatitis C is therefore needed.

Investigators looked at the contribution human genes make to the efficacy of treatment for hepatitis C. Their study sample included 1,137 individuals infected with hepatitis C virus genotype-1 (the hardest strain of hepatitis C to treat). These patients were involved in the IDEAL study, a clinical trial investigating the safety and effectiveness of pegylated interferon-based therapy for hepatitis C infection.

The investigators found that a specific gene was strongly associated with a sustained virological response to treatment. This association was most pronounced in individuals of European ancestry, with the patients who carried this gene having a significantly increased chance of a response to treatment with anti-hepatitis C drugs than patients who did not (odds ratio [OR], 7.3; 95% CI: 5.1-10.4). The gene also increased the chances of treatment working in African-Americans and Hispanics, but to a lesser degree than in whites.

Furthermore, the investigators found that the gene was more strongly associated with response to treatment in European-Americans than either baseline hepatitis C viral load or liver fibrosis, the usual predictors of hepatitis C treatment response.

However, in African-Americans and Hispanics, both of these traditional risk factors were a better guide to treatment response than the presence of the gene.

The investigators believe that their identification of this gene could be an explanation of the better responses to hepatitis C therapy observed in white patients than African-Americans.

Several new anti-hepatitis C drugs are in development. These include protease inhibitors, and the investigators note that research is needed to see if the gene also affects responses to this class of drug. They also suggest that studies should be undertaken to determine if the gene plays a role in responses to therapy in patients infected with other hepatitis C genotypes.

As the gene also appears to be associated with natural clearance of hepatitis C as well as treatment response, they suggest “it seems likely that the gene product is involved in innate control of hepatitis C virus.”

The research involved individuals mono-infected with hepatitis C, so it remains to be seen if the gene can also predict treatment response in HIV-positive patients who are co-infected with the virus.