Clinical

Gene mutations linked with response to HCV therapy

Last Updated: 2006-12-13 16:21:59 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - Patients with hepatitis C virus infection (HCV) who carry HFE mutations have increased iron stores within the liver, but they also seem to have increased rates of response to interferon and ribavirin therapy.

"Our results," lead investigator Dr. Herbert L. Bonkovsky told Reuters Health, "emphasize the importance of iron as a comorbid factor in chronic HCV. We and others have pointed this out recently for several liver diseases, including chronic viral hepatitis B and C, alcoholic liver disease, and non-alcoholic fatty liver disease."

Mutations in the HFE gene can increase iron stores and influence liver disease, Dr. Bonkovsky of the University of Connecticut Health Center, Farmington and colleagues note. To investigate further, the researchers studied 1051 HCV patients and found that 35% carried at least one HFE gene mutation.

Nevertheless, compared to those without these mutations, carriers had a significantly higher end of treatment response (40% versus 29%) and virological response (20% versus 14%).

"The striking finding," continued Dr. Bonkovsky "is that although HFE mutations -- especially the H63D genetic variation --led to more iron in the livers and blood of the subjects, they also were associated with improved responses to the current best therapy for chronic hepatitis C."

"Thus," he concluded, "the presence of these genetic variations is a two-edged sword."

In an accompanying editorial, Drs. Kris V. Kowdley and Jacob Alexander of the University of Washington, Seattle conclude that this "important study" has provided "unique insights into the role of iron and HFE mutations in response to treatment in chronic hepatitis virus C."

Gastroenterology 2006;131:1440-1451,1635-1638.