Overview

Definition:
-Hepatitis C virus (HCV) infection in children is a chronic liver disease caused by the RNA virus HCV, primarily leading to inflammation and potential fibrosis, cirrhosis, and hepatocellular carcinoma over time
-While vertical transmission is the main route in pediatric populations, other parenteral exposures can occur.
Epidemiology:
-Globally, pediatric HCV is less common than in adults, with an estimated prevalence of 0.1-1% in developed countries
-The vast majority of pediatric cases result from vertical transmission from infected mothers, accounting for 4-8% of overall HCV transmission
-Other routes include needle-stick injuries and blood product transfusions prior to 1992.
Clinical Significance:
-Early identification and treatment of pediatric Hepatitis C are crucial to prevent long-term liver damage, including fibrosis progression, cirrhosis, and the development of potentially fatal complications like portal hypertension and hepatocellular carcinoma
-Effective treatment with DAAs offers high cure rates, improving long-term outcomes and reducing the burden of chronic liver disease.

Transmission And Risk Factors

Modes Of Transmission:
-Vertical transmission from mother to child during pregnancy, labor, or delivery is the most common route in children
-Less common routes include sharing contaminated needles, receipt of unscreened blood products or organ transplants before 1992, and sexual transmission (rare in children).
Risk Factors In Children:
-Maternal HCV infection status is the primary risk factor for vertical transmission
-Other factors include prematurity, prolonged rupture of membranes, invasive fetal monitoring during labor, and co-infection with HIV in the mother.
Screening Recommendations:
-HCV screening is recommended for all pregnant women
-Infants born to mothers with HCV should undergo HCV antibody testing at 18 months of age or later, and HCV RNA testing at 3-6 months of age to confirm infection
-Infected children should be referred to pediatric hepatology or infectious disease specialists.

Clinical Presentation

Symptoms:
-Most children with chronic HCV are asymptomatic, particularly in the early stages
-When symptoms occur, they may include fatigue, abdominal discomfort (right upper quadrant), poor appetite, nausea, and occasional jaundice
-These are often nonspecific and can be mistaken for other common childhood illnesses.
Signs:
-Physical examination findings in asymptomatic children are typically normal
-In more advanced disease, hepatomegaly, splenomegaly, and signs of chronic liver disease such as palmar erythema, spider angiomata, and ascites may be present, though these are rare in childhood.
Diagnostic Criteria:
-Diagnosis of pediatric Hepatitis C is confirmed by positive anti-HCV antibodies along with detectable HCV RNA in serum
-Children are considered chronically infected if HCV RNA is detected 6 months or more after initial diagnosis
-Genotyping is important for guiding treatment selection.

Diagnostic Approach

History Taking:
-A detailed maternal and birth history is paramount, focusing on potential exposure to HCV
-Ask about any blood transfusions before 1992, history of intravenous drug use, receipt of organ transplants, or exposure to contaminated needles
-Inquire about vague symptoms like fatigue or abdominal pain.
Physical Examination:
-A thorough physical examination should focus on the liver and spleen size, assessment for jaundice, and signs of chronic liver disease
-Palpate for hepatomegaly or splenomegaly
-Check for ascites or edema.
Investigations:
-Initial investigations include liver function tests (ALT, AST, bilirubin, albumin, PT/INR)
-Serological tests for anti-HCV antibodies are followed by quantitative HCV RNA (PCR) to confirm active infection and assess viral load
-HCV genotype determination is essential for DAA selection
-Fibrosis assessment using non-invasive methods like transient elastography (FibroScan) or biochemical markers is also recommended.
Differential Diagnosis:
-Other causes of chronic hepatitis in children must be considered, including autoimmune hepatitis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic fatty liver disease (NAFLD), and other viral hepatitis (e.g., Hepatitis B, Hepatitis A)
-Distinguishing features and specific tests are required for each.

Direct Acting Antivirals And Timing

Current Treatment Regimens:
-Direct-Acting Antivirals (DAAs) are now the standard of care for pediatric Hepatitis C, offering high cure rates (SVR >95%) with shorter treatment durations and fewer side effects compared to older interferon-based therapies
-Common regimens include sofosbuvir/ledipasvir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir, depending on the HCV genotype and prior treatment history.
Age Considerations And Dosing:
-DAA regimens are approved for children aged 3 years and older
-Dosing is weight-based for younger children and fixed for older children and adolescents
-Specific dosing regimens depend on the chosen DAA combination and HCV genotype
-For instance, sofosbuvir/ledipasvir is approved for genotypes 1, 4, 5, and 6 in children aged 12 years and older, with weight-based dosing
-Glecaprevir/pibrentasvir is approved for genotypes 1-6 in children aged 8 years and older.
Timing Of Treatment Initiation:
-Treatment is generally recommended for all children with confirmed chronic HCV infection, regardless of disease severity, to prevent long-term complications
-Treatment can be initiated once chronic infection is confirmed (HCV RNA positive for at least 6 months) and the child is deemed old enough and stable for treatment
-Decisions on immediate vs
-delayed treatment may consider the child's overall health status and potential for spontaneous clearance (though rare in children).
Treatment Duration:
-Treatment duration typically ranges from 8 to 12 weeks, depending on the specific DAA regimen, HCV genotype, and whether there is evidence of cirrhosis or prior treatment failure
-Most children achieve a sustained virologic response (SVR) with these shorter durations.

Complications

Early Complications:
-In children, early complications are uncommon and usually related to the acute phase if it occurs, which is rare
-In rare cases of severe acute hepatitis, hepatic decompensation might occur, but this is not typical for chronic pediatric HCV.
Late Complications:
-Long-term complications in untreated children include liver fibrosis progression to cirrhosis, portal hypertension, liver failure, and hepatocellular carcinoma
-These are significantly reduced with successful DAA therapy.
Prevention Strategies:
-Prevention of pediatric HCV primarily focuses on preventing vertical transmission through maternal screening and treatment, and preventing nosocomial transmission through strict adherence to infection control measures in healthcare settings
-For infected children, timely treatment with DAAs is the key to preventing long-term complications.

Prognosis

Factors Affecting Prognosis:
-The prognosis for children with Hepatitis C has dramatically improved with DAAs
-Factors influencing outcomes include the duration of infection before treatment, presence of fibrosis at diagnosis, adherence to treatment, and response to therapy
-Early diagnosis and treatment lead to excellent outcomes.
Outcomes With Treatment:
-With DAA therapy, sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion, is achieved in over 95% of children
-SVR is considered a cure, leading to cessation of viral replication and regression of liver inflammation and fibrosis, significantly reducing the risk of long-term complications.
Follow Up:
-After successful treatment and confirmation of SVR, routine follow-up is recommended
-This includes annual liver function tests and monitoring for the development of hepatocellular carcinoma, especially in children who had significant fibrosis or cirrhosis at baseline
-Counseling on preventing reinfection is also crucial.

Key Points

Exam Focus: Key points for DNB/NEET SS include: vertical transmission as the primary route, importance of HCV RNA testing at 3-6 months and antibody testing at 18 months for infants born to HCV-positive mothers, DAAs as current standard of care, approved age ranges for specific DAAs, and high SVR rates with treatment.
Clinical Pearls:
-Always consider maternal HCV status in neonates and infants presenting with liver issues
-Non-invasive fibrosis assessment is crucial before initiating DAA therapy
-Remember that most children are asymptomatic
-Ensure proper weight-based dosing for younger children on DAAs.
Common Mistakes:
-Failing to screen pregnant mothers for HCV
-Delaying treatment in infected children
-Misinterpreting serological markers in infants (antibody can persist due to maternal antibodies)
-Using outdated treatment protocols that do not include DAAs
-Not considering genotype-specific DAA regimens.