Genetics are probably to blame for why some patients have significant intestinal side effects from Roferon-A (interferon alfa-2a, recombinant – Roche) while others do not, according to a new French investigation reported in issue of Cellular and Molecular Gastroenterology and Hepatology.

The “interindividual heterogeneity of response to [interferon] IFN-alfa in noninflammatory conditions could be related to interindividual differences in the genetic background,” said investigators led by Anne Jarry, MD, of the University of Nantes (Cell Mol Gastroenterol Hepatol 2016. doi: 10.1016/j.jcmgh.2016.09.007).

They cultured intestinal wall samples taken from 20 colon cancer patients when they had surgery; none of them had been exposed to chemotherapy, radiation, or immunosuppressives. The team bathed the cells in IFN-alfa 2a and other biochemicals to see how they reacted. It was bench work, but the findings could eventually be useful if the team identifies the genetic risk factors for Roferon intestinal side effects and finds better options for patients at risk. Roferon is widely used for blood cancer, melanoma, viral hepatitis, and renal and hepatocellular carcinomas.

“IFN-alfa 2a elicited a rapid (24 hours) disruption of surface and crypt colonic epithelial cells via apoptosis that was variable in intensity among the 20 individuals studied. This apoptotic effect was dependent on the initiation of an IFN-gamma response … expressed in T cell–positive lamina propria cells,” the investigators said.

“IFN-alfa impairs human intestinal mucosa homeostasis by eliciting epithelial barrier disruption via apoptosis … The IFN-alfa–elicited impairment of intestinal mucosa homeostasis is heterogeneous among individuals,” Dr. Jarry and her associates wrote.

“This ex vivo finding parallels clinical observations of the interpatient variability of Roferon therapy side effects. … It has been reported that approximately 60% of patients with chronic hepatitis or cancer treated with Roferon have intestinal disorders, especially diarrhea,” they said.

The authors had no conflicts of interest. The work was funded by the University of Nantes.