Update on Pediatric HCV: Screening, Treatment, and Other Considerations

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Vertical HCV infection is the most common route of transmission in children.
Vertical HCV infection is the most common route of transmission in children.

Of approximately 200 million people infected with hepatitis C virus (HCV) worldwide, children comprise 0.05% to 0.4% of individuals in developed countries and 2% to 5% in resource-limited regions.1 Vertical HCV infection is the most common route of transmission in children. Chronic infection occurs in an estimated 5% of children born to mothers with HCV, increasing the risk of cirrhosis and liver failure, along with impaired cognitive function and overall health.2

Adverse fetal outcomes such as fetal growth restriction and low birth weight have been linked to HCV infection during pregnancy.3 While universal HCV screening is not currently recommended, it is recommended for children born to HCV-infected mothers, especially because children with HCV infection are typically asymptomatic. However, a recent study found that only 16% of children born to HCV-infected mothers underwent testing, and the investigators called for improvements in screening practices in pregnant women and their children.2

To learn more about screening, treatment, and other considerations for pediatric HCV, Infectious Disease Advisor spoke with 2 experts: Wikrom Karnsakul, MD, associate professor of pediatrics at Johns Hopkins University School of Medicine in Baltimore, Maryland, and director of the Pediatric Liver Center in the division of pediatric gastroenterology, hepatology and nutrition at Johns Hopkins Children's Center in Baltimore, Maryland; and Catherine Chappell, MD, MsC, OB/GYN and assistant professor in the department of obstetrics, gynecology, and reproductive sciences at Magee-Womens Hospital of the University of Pennsylvania Medical Center in Philadelphia.

Infectious Disease Advisor: How important are screenings for preventing the perinatal and parenteral transmission of HCV?

Dr Karnsakul: Since 1992, blood units transfused have mostly been free of HCV, which is estimated to be less than 0.01 percent per transfusion.4 Therefore, perinatal transmission has been the major mode of HCV transmission in children in the United States. In other regions of the world, parenteral transmission is still significant. The role of HCV screenings is essential, particularly in children at high risk for acquiring HCV. 

Screening tests for HCV are usually recommended in children and adolescents with clinical signs of hepatitis or unexplained elevation of serum aspartate and alanine aminotransferase; HIV infection; a history of illicit injection drug use, sexual assault, or multiple sexual partners; and mothers who are known or suspected to be infected with HCV or have a history of intravenous (IV) drug use. In addition, screening tests are recommended in children who are international adoptees or refugees from countries or regions with high prevalence rates of HCV infection including Africa, China, Russia, Eastern Europe, and Southeast Asia. 

Dr Chappell: Screening for HCV can identify patients at risk of transmission either from IV drug use or perinatal transmission. Currently, the American Congress of Obstetrics and Gynecology recommends only screening pregnant women with risk factors for hepatitis C, such as a history of or current IV drug use, a history of blood transfusion before July 1992, or hepatitis C exposure. Therefore, adequate screening requires pregnant women to disclose drug use, which is extremely difficult and stigmatizing. Some health centers with a high incidence of HCV have moved to adopt universal testing for HCV in pregnancy — similar to HIV — so that no cases of perinatal exposure are missed. I think this is wise, and more health centers should consider universal screening to identify children at risk for perinatal HCV infection.

Infectious Disease Advisor: What are the available treatment options in pediatric patiens with HCV, and what are some challenges in treating this population?

Dr Karnsakul: No data are available on treating children with acute HCV infection. For chronic hepatitis C infection, the current US Food and Drug Administration (FDA)-approved standard of care for children age 3 to 18 is a once-weekly injection of pegylated interferon (PEG-IFN)-alpha-2a or PEG-IFN-alpha-2b plus ​daily ribavirin for 24 weeks for HCV genotypes 2 and 3, and for 48 weeks for HCV genotypes 1 and 4. The response in children with HCV genotype 2 and 3 is much higher for a shorter period. In children with HCV genotype 1, the response is poorer and requires a longer treatment period.5 

Direct-acting antiviral agents (DAAs) have fundamentally changed the treatment of HCV infection, particularly for HCV genotype 1. The FDA recently approved supplemental applications of Sovaldi® (sofosbuvir) taken with [ribavirin], and Harvoni® — a combination of ledipasvir and sofosbuvir — to treat HCV in children age 12 to 17. These will be great options for those children. However, the cost is high, and the treatment may not be available and financially affordable for every child. The challenges will be the availability of the oral form of these drugs in young children.

Dr Chappell: The new DAAs are orally administered, more effective, and better tolerated than peg-interferon/ribavirin. Currently these superior drugs are only approved for children 12 or older, although studies in younger children are ongoing. Therefore, children with perinatal HCV infection have to wait until age 12 to receive the most effective treatment, and a few of those children progress to having liver disease before age 12. The biggest challenge in the treatment of children with HCV is that many children who are perinatally exposed to HCV are not tested for the virus. Therefore, many children will not be followed or treated for HCV until they show evidence of liver damage.

Infectious Disease Advisor: What are some of the medical conditions commonly associated with HCV infection in children, and how are they managed?

Dr Karnsakul: The accumulative duration of HCV infection since birth theoretically makes children with vertical/perinatal transmission of HCV at risk for cirrhosis and hepatocellular carcinoma by the time of transition to adulthood. ​HCV infection may cause cryoglobulinemia and other autoimmune or immune-mediated conditions, which should also be improved with clearance of the virus.

Infectious Disease Advisor: What should be next steps in terms of research in this area? 

Dr Karnsakul: Prevention of perinatal transmission and clinical trials using DAAs.

Dr Chappell: Further research into interventions to improve screening and detection of HCV in individuals at greatest risk for transmission, such as active intravenous drug users (IVDUs) and pregnant women. Then, further interventions to facilitate treatment in those groups will be most effective to prevent further transmission of HCV.

Currently there are no interventions that are proven to prevent perinatal transmission of HCV. OB/GYNs avoid artificial rupture of membranes and the use of fetal scalp electrodes, which may be associated with increased maternal-to-child blood exchange. Cesarean delivery before the onset of labor also does not reduce transmission of HCV, although this practice does reduce transmission of HIV. Administration of antibiotics to mothers is common to prevent perinatal transmission of bacteria (like group B strep) as well as viruses (HIV and herpes simplex virus). With the recent development of potent antivirals for HCV, we now have the tools to prevent perinatal transmission of HCV. Ledipasvir/sofosbuvir (Harvoni) is a one-pill-once-a-day medication used for 12 weeks that has a >95% cure rate outside of pregnancy. We are doing the first study of the use of ledipasvir and sofobuvir in pregnant women (ClinicalTrials.gov identifier: NCT02683005). Our hope is that this medication will not only cure the maternal HCV infection, but also prevent transmission to the infant.

Summary

Although recommended for all infants born to HCV-infected mothers, HCV screening occurs in only a small percentage of cases, preventing many patients from receiving timely treatment.

References

  1. Tovo PA, Calitri C, Scolfaro C, Gabiano C, Garazzino S. Vertically acquired hepatitis C virus infection: Correlates of transmission and disease progression. World J Gastroenterol. 2016;22(4):1382-1392.
  2. Kuncio DE, Newbern EC, Johnson CC, Viner KM. Failure to test and identify perinatally infected children born to hepatitis C virus-infected women. Clin Infect Dis. 2016;62(8):980-985.
  3. Hughes BL, Page CM, Kuller JA; Society for Maternal-Fetal Medicine (SMFM). Hepatitis C in pregnancy: screening, treatment, and management [published online August 4, 2017]. Am J Obstet Gynecol. doi:10.1016/j.ajog.2017.07.039
  4. Karnsakul W, Schwarz KB. Hepatitis B and C. Pediatr Clin North Am. 2017;64(3):641-658.
  5. Schwarz KB, Karnsakul W. Treatment of hepatitis C in children. Current Hepatology Reports. 2017;16(1):18-25.

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