www.hivandhepatitis.com

Viral Load, HIV Status, but not IL28B Predict Perinatal HCV Transmission

Women with higher HCV viral load and those coinfected with HIV were more likely to transmit HCV to their babies in a recent Spanish study. IL28B gene pattern did not affect transmission directly, but babies with the favorable CC pattern more often spontaneously cleared HCV.

It is well known that mothers with hepatitis C virus (HCV) can transmit the disease to their babies during pregnancy, delivery, or breast-feeding but the timing and risk factors for vertical transmission are not fully understood.

As described in the March 16, 2011, advance online edition of Hepatology, Ángeles Ruiz-Extremera from San Cecilio University Hospital in Granada and colleagues analyzed the role of HCV viral load, IL28B, and other factors in mother-to-child HCV transmission.

Researchers first reported in 2009 that variations in the human genome near the IL28B gene can help predict outcomes among people with hepatitis C. Each individual carries 2 copies of every gene, 1 from each parent. People with 2 copies of the protective "C" gene variant at the rs12979860 location (known as CC) are more likely to spontaneously clear HCV and respond better to interferon-based therapy. People with the TT pattern have the worst outcomes, while those with the CT pattern fall in between.

In the present analysis, investigators enrolled 145 pregnant women between 1991 and 2009; 112 women (who collectively gave birth to 142 children) had detectable HCV RNA viral load, while 33 women (who had a total of 43 children) were HCV antibody positive -- indicating prior infection -- but had undetectable HCV viral load.

IL28B gene patterns were determined for both mothers and children. Children were tested for HCV RNA at birth and at regular intervals until age 6 years. HCV vertical transmission was assumed if a child tested positive for HCV RNA in 2 subsequent blood samples.

Results

• 19 of the 31 mothers (61%) with the IL28B CC pattern had detectable HCV viral load, compared with 56 of 68 mothers (82%) with non-CC (that is, either CT or TT) patterns.
• 26 of 128 infants (20%) born to HIV negative women with detectable HCV RNA acquired HCV infection, but only 9 (7%) became chronically infected.
• The rate of HCV vertical transmission was higher among mothers with higher HCV viral load.
• No HCV vertical transmission was observed from women with undetectable HCV RNA.
• Women coinfected with HIV were much more likely to transmit HCV to their babies, with a transmission rate of 43%
• Neither the mother's nor the child's IL28B status was associated with an increased likelihood of HCV vertical transmission.
• Children with the CC pattern, however, were more likely to clear HCV without treatment, as were those with HCV genotypes other than 1.
• In a multivariate analysis, a child having the favorable CC pattern was the only predictor of clearance of genotype 1 HCV.

Based on these findings, the study authors concluded, "High maternal viral load is the only predictive factor of HCV vertical transmission."

"IL28B plays no role in HCV vertical transmission," they continued, "but IL28B CC child polymorphism is associated independently with the spontaneous clearance of HCV genotype 1 among infected children."

"Our data are the first to account for HCV virus clearance and may provide important information about protective immunity to HCV," Ruiz-Extremera said in a press release issued by Hepatology publisher Wiley Blackwell. "Further investigation is needed to understand the mechanisms involved with this genetic variation and the clinical impact of the IL28B variant on HCV infection."

Investigator affiliations: San Cecilio University Hospital, Granada, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (Ciberehd), Granada, Spain; La Paz Hospital, Madrid, Spain; Department of Medicine, Granada University, Spain.

4/29/11

Reference
A Ruiz-Extremera, J Munoz-Gámez, MA Salmerón-Ruiz, et al. Genetic variation in IL28B with respect to vertical transmission of hepatitis C virus and spontaneous clearance in HCV infected children. Hepatology (abstract). March 16, 2011 (Epub ahead of print).

Other Source
Wiley Blackwell. Severity of hepatitis C and HIV co-infection in mothers contribute to HCV transmission to child. Media advisory. April 27, 2011.