Pediatric Hepatitis C Workup

Both acute and chronic hepatitis C virus (HCV) infections are often asymptomatic; therefore, the diagnosis often relies on the identification of a potential risk factor and on subsequent screening for HCV-directed antibodies. Obtaining serum alanine aminotransferase (ALT) levels may be helpful.

Genotyping of HCV has proven to be a useful clinical tool, as the response to therapy and prognosis is influenced by the viral genotype. Genotype 1 is less than half as likely as other genotypes to respond to therapy, and combination therapy regimens vary depending on the different genotypes. In addition, early work by one group suggests that alpha-fetoprotein may have a prognostic significance, at least for genotypes 1 and 4; the likelihood of treatment failure was 6 times higher for patients with serum AFP above the median value (5.7 ng/ml).^[4]

Imaging studies are not generally warranted to establish the etiology of hepatitis. However, ultrasonography is useful to monitor for HCV-related complications.

See also Pediatric Hepatitis A and Pediatric Hepatitis B.

Hepatitis C virus–directed antibodies may be detected. Antibody screening using enzyme immunoassay (EIA) is inexpensive and reliable; generally, this is the screening test of choice for diagnosis. Recombinant immunoassay (RIBA) can then be used to confirm positive EIA results.

The US Food and Drug Administration (FDA) has approved OraQuick HCV Rapid Antibody Test, which uses a venipuncture whole blood sample and provides results in approximately 20 minutes.^[5] The test can be used for persons at risk for hepatitis or for those with signs or symptoms of hepatitis.

Hepatitis C virus RNA may be detected with the polymerase chain reaction (PCR) test. Several FDA-approved test kits that can be used for blood product screening or diagnostic testing are currently available. (Kits are not usually approved for both uses.) Hepatitis C virus RNA is usually detectable within 1-2 weeks of exposure. Quantitative assays are available, but hepatitis C viral load has not been definitively shown to be useful in predicting outcome (unlike HIV viral load). It may be useful in predicting risk of recurrence in transplant recipients.

PCR testing is useful to confirm positive EIA results in the setting of indeterminate RIBA test results and to distinguish between resolved and chronic HCV infection in patients with positive EIA and RIBA results.

Other viral serologic tests may be useful in ruling out other causes of hepatitis, which can be present alone or in combination with hepatitis C virus.

• Hepatitis A virus immunoglobulin M (IgM) and immunoglobulin G (IgG)
• Hepatitis B virus surface antigen and antibody, core antibody
• Cytomegalovirus (CMV) IgM and IgG (and/or CMV in urine cultures)
• Epstein-Barr virus IgM and IgG
• HIV IgG enzyme-linked immunoassay (ELISA)

Acute infections

The peak serum ALT level is less than 2000 IU/mL in most patients with acute HCV infection, and 50% have a peak serum ALT level of less than 800 IU/mL. Overall, this peak is generally less than that seen in hepatitis A or B infections.

HCV-directed antibodies are generally detectable approximately 6-8 weeks after exposure; however, as many as 5% of infected patients do not produce antibodies.

Chronic infections

Many patients have normal serum ALT levels, although these levels may significantly fluctuate over time. Once present, HCV-directed antibodies generally persist.

Congenital infections

Infants born to mothers with HCV infection deserve special consideration.^[6] Definitive serology cannot be obtained until age 9-15 months. Most experts recommend waiting until after age 12 months to obtain antibody levels, with follow-up testing for any positives at that time.

Testing with real time PCR (RT-PCR) for HCV RNA is sensitive after the first 1-2 months of life; 95% of infants exposed will be uninfected and a negative result at this early point can be reassuring for the family. An argument can be made for not testing for HCV RNA because of cost considerations, however, and because even if the child is infected, treatment is rarely needed until the second decade of life.

Spontaneous clearance can occur (up to 30% of infected infants) but is rare beyond age 3 years. Children who clear infection are negative for HCV RNA but remain antibody-positive.

Liver biopsy is generally not used to diagnose hepatitis C virus. However, it is the most accurate method of evaluating the extent of hepatitis C virus–related liver disease. Liver biopsy is recommended for all patients before they start antiviral therapy.

In patients with chronic HCV infection, inflammatory cells accumulate in the portal tracts. They may also have foci of inflammation accompanied by necrosis in the parenchyma. Subsequently, the margins of the parenchyma and liver tracts become inflamed, and liver cell necrosis results.

Ultimately, if the infection progresses, inflammation and necrosis may lead to fibrosis. Mild fibrosis is confined to the portal tracts and adjacent parenchyma, whereas severe fibrosis is associated with bridging between the portal tracts and hepatic veins.

Eventually, fibrosis can progress to cirrhosis, when the fibrous septa separate the liver into nodules.