Introduction to Congenital Hepatitis C Infections

Congenital Hepatitis C Virus (HCV) infection occurs when an HCV-infected mother transmits the virus to her infant during pregnancy or childbirth. This vertical transmission is a significant global health concern, affecting approximately 5% of infants born to HCV-positive mothers worldwide.

• HCV is an RNA virus of the Flaviviridae family
• Globally, an estimated 71 million people have chronic HCV infection
• Vertical transmission is the primary route of HCV infection in children

Understanding the mechanisms of transmission, clinical course, and management of congenital HCV is crucial for healthcare providers to prevent long-term complications and improve outcomes for affected infants.

Transmission of Congenital Hepatitis C

The risk of vertical transmission of HCV from mother to infant is approximately 5-10%, but can vary based on several factors:

Factors Influencing Transmission

• Maternal HCV viral load: Higher viral loads increase transmission risk
• HIV co-infection: Can increase transmission risk to 10-20%
• Mode of delivery: No clear evidence that cesarean section reduces transmission
• Breastfeeding: Not contraindicated unless nipples are cracked or bleeding
• Invasive procedures during pregnancy or delivery
• Premature rupture of membranes

Timing of Transmission

Transmission can occur:

• In utero (transplacental): Less common
• Intrapartum (during delivery): Most common route
• Postpartum: Rare, usually through infected breast milk

Prevention Strategies

• Universal screening of pregnant women for HCV
• Antiviral treatment of women before pregnancy when possible
• Avoiding invasive procedures during pregnancy and delivery
• Proper management of HIV co-infection

Clinical Manifestations of Congenital Hepatitis C

The clinical course of congenital HCV infection can vary significantly among infected infants:

Neonatal Period

• Most infants are asymptomatic at birth
• Rare cases may present with:
  • Hepatomegaly
  • Jaundice
  • Failure to thrive

Infancy and Early Childhood

• Spontaneous clearance occurs in 25-40% of infected infants by 4-5 years of age
• Persistent infection may lead to:
  • Elevated liver enzymes (ALT, AST)
  • Hepatomegaly
  • Splenomegaly
• Most children remain asymptomatic or have mild, non-specific symptoms

Long-term Complications

• Chronic hepatitis: Develops in 60-75% of infected children
• Fibrosis progression: Generally slower in children compared to adults
• Cirrhosis: Rare in childhood, but can occur in adolescence or early adulthood
• Hepatocellular carcinoma: Extremely rare in children, but a long-term risk
• Extrahepatic manifestations: Less common in children, but may include:
  • Cryoglobulinemia
  • Glomerulonephritis
  • Thyroid dysfunction

Diagnosis of Congenital Hepatitis C

Diagnosing congenital HCV infection requires a systematic approach due to the presence of maternal antibodies in infants:

Maternal Screening

• Universal HCV antibody screening recommended for all pregnant women
• If positive, confirm with HCV RNA testing

Infant Testing

• HCV RNA PCR:
  • Can be performed as early as 2-3 months of age
  • Two positive tests at least 3 months apart confirm infection
• HCV antibody testing:
  • Not reliable before 18 months due to maternal antibodies
  • Positive test after 18 months confirms infection
• Liver function tests: Monitor ALT and AST levels

Additional Investigations

• HCV genotyping: Important for treatment decisions
• Liver biopsy: Rarely needed in children, but may be considered for assessing fibrosis
• Non-invasive fibrosis assessment:
  • Transient elastography (FibroScan)
  • Serum fibrosis markers (e.g., APRI, FIB-4)

Differential Diagnosis

Consider other causes of neonatal hepatitis, including:

• Other congenital infections (e.g., CMV, toxoplasmosis)
• Metabolic disorders
• Biliary atresia
• Alpha-1 antitrypsin deficiency

Management of Congenital Hepatitis C

Management of congenital HCV infection focuses on monitoring, supportive care, and timely initiation of antiviral therapy:

Monitoring

• Regular clinical assessments
• Periodic liver function tests and HCV viral load measurements
• Assessment of growth and development
• Screening for complications (e.g., liver fibrosis)

Antiviral Therapy

• Direct-acting antivirals (DAAs) are the mainstay of treatment
• Treatment considerations:
  • Age: FDA-approved DAAs available for children as young as 3 years
  • HCV genotype: Influences choice of regimen
  • Presence of cirrhosis
  • Prior treatment history
• Common DAA regimens:
  • Ledipasvir/sofosbuvir
  • Glecaprevir/pibrentasvir
  • Sofosbuvir/velpatasvir
• Treatment duration: Usually 8-12 weeks
• High cure rates: >95% sustained virological response (SVR)

Supportive Care

• Nutritional support
• Vaccination against hepatitis A and B
• Avoidance of hepatotoxic medications
• Psychosocial support for patients and families

Long-term Follow-up

• Continued monitoring after SVR to ensure no relapse
• Screening for long-term complications in those with advanced fibrosis
• Education about liver health and risk factors for HCV transmission

Future Directions

• Development of pan-genotypic DAA regimens for younger children
• Research on the long-term outcomes of children treated with DAAs
• Potential for HCV vaccine development