Genetic Variants May Control Hepatitis C After Childbirth

Researchers in a new study may have identified genes that may boost immunity to hepatitis C virus in women after childbirth.

Women with genetic variations of interferon lambda 3 (IFNL3) and human leukocyte antigen (HLA)-DPB1 genes had a sharp decline in viral levels in the blood 3 months postpartum, according to the study published by the Proceedings of the National Academy Services.

However, mothers who did not carry the genetic variations did not see similar changes in viral levels after giving birth, which researchers believe suggests an association between the genetic variants and lowered viral levels.

“Immunity is normally exhausted in people who have chronic hepatitis C,” said study author Jonathan R. Honegger, MD. “The liver produces about a trillion viruses per day, and the T cells that should attack the virus don't work.”

Researchers were originally examining hepatitis C virus transmission from mother-to-child, but they observed something strange. They discovered that some women had a significant decline in viral levels as much as 10 to 1000-fold.

“These initial observations really piqued our interest,” Dr Honegger said. “There's a lot of effort underway to find ways to turn on exhausted T cells, and the months following pregnancy appeared to provide a unique opportunity to study this.”

Of the 34 women included in the study, 5 had consecutive pregnancies, according to the researchers. They noticed similar decreases in viral load with each pregnancy.

“The postpartum viral load decline was very similar with each consecutive pregnancy, which made you think it wasn't just a random event—that some stable factor was controlling how viremia fell after delivery,” Dr Honegger said.

IFNL3 is a signaling protein known to affect control of hepatitis C virus in individuals who are not pregnant. In the study, researchers discovered that a common genetic variant of this protein increases control of the virus after pregnancy.

HLA molecules give small protein pieces to CD4+ T cells, which allows them to recognize and fight foreign pathogens. The researchers found that women who had a particular variant of HLA-DBP1 had better T cell recovery and viral control compared with women who did not have the variants.

“This finding was important because helper T cells are thought to be particularly dysfunctional in chronic hepatitis C,” Dr Honegger said. “These findings suggest that HCV-specific helper T cells may regain function after delivery. This is now an active line of investigation for us.”

Despite the focus on hepatitis C virus, researchers said that their findings, especially regarding T cell exhaustion, may serve as a model to identify factors that can be used to restore immunity to patients with other chronic infections like hepatitis C virus and HIV, the study concluded.