Hepatitis C in Children - Pediatric Nursing - 2 of 2

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Hepatitis C in Children - continued

Diagnostic Tests

Children complaining of abdominal symptoms, jaundice, or with a history of

risk factors for hepatitis C should have a screening panel of blood work

done including a complete blood count (CBC), sedimentation rate, amylase and

lipase levels, and liver function tests (LFTs). LFTs determine the serum

transaminases, which rise with any hepatocellular inflammation; the serum

bilirubin levels that may increase if the hepatocytes are not able to

metabolize bilirubin normally; the synthetic function of the liver as

indicated by the serum albumin; the coagulation profile as reflected in the

prothromin and partial thromboplastin times; and the metabolic functions of

the liver as indicated by the serum glucose level (see Table 1). LFTs are

usually normal in hepatitis C infections except for mild elevations of serum

transaminase levels.

Specific screening test for HCV can be done in a child with known exposure

or to determine the cause of elevated LFTs. The time from exposure to onset

of viremia is generally 1 to 2 weeks, but there are no direct tests for the

serum viral antigen of HCV. The two major types of tests available to detect

for HCV infection are antibody assays for immunoglobulin (Ig) G anti-HCV

(Alter, Kuhnert, & Finelli, 2003) (see Table 2). The initial screening for

HCV is usually performed through an anti-HCV screening enzyme immunoassay

(EIA) (USPSTF, 2004). Positive results should be confirmed by a recombinant

immunoblot assay (RIBA). Both third generations of these tests are 97%

sensitive and 99% specific (USPSTF, 2004). False negative results can occur

early in the course of infection due to the possible long interval between

exposure and seroconversion, and repeat testing may be indicated in children

with high risk factors. At this time, the USPSTF recommends against routine

screening for HCV infection in asymptomatic adults who are not at increased

risk for infection. In addition, there is insufficient evidence to recommend

for or against routine screening for HCV infection in adults at high risk

for infection (USPSTF, 2004). These screening tests are unable to

discriminate between persistent infection and resolved infection. No

recommendations have been made for children regarding screening for HCV

infection.

The Food and Drug Administration (FDA) has approved diagnostic Nucleic Acid

Tests (NATs) for quantitative detection and genotyping of HCV RNA using

reverse transcriptase-polymerase chain reaction (RT-PCR) (AAP, 2003). This

test determines the presence of active viremia. HCV RNA can be detected in

serum within 1-2 weeks of exposure and before anti-HCV tests are effective

or abnormalities in LFTs occur. Genotyping and quantifying viral load are

important when assessing the possible value of antiviral therapy.

In infants born to anti-HCV-positive mothers, passively acquired maternal

antibodies can persist for up to 18 months; therefore, infants must be

retested after 18 months of age with either of these tests to determine

active anti-HCV status. Consequently, HCV RNA testing is used to identify

infection in infants early in life when maternal serum antibodies can

interfere with other test results. Viral RNA may be detected intermittently

early in the infection, so false negative results can occur.

Treatment

Children with acute HCV infection usually require only supportive care at

home. Supportive care for the child with hepatitis includes rest, a healthy

diet, avoidance of hepatotoxic drugs like acetaminophen and alcohol, and

prevention of additional liver disease through active immunization against

hepatitis A and B. Children with HCV should be followed every 6 to 12 months

with serial LFTs to assess the degree of inflammation and measurement of

serum alphafetoprotein (AFP) along with an abdominal ultrasound to screen

for hepatocellular carcinoma. If the LFTs begin to rise, the viral load

should be reassessed with a repeat RT-PCR. Children should not be excluded

from daycare if they have HCV, but standard precautions regarding bloodborne

pathogens should be practiced both in school and at home. Transmission among

family members is uncommon but can occur from direct or inapparent

percutaneous or mucosal exposure to blood (AAP, 2003). Adolescents should be

educated about the risk of transmission of the infection to their sexual

partners, the use of alcohol, and the hazard of parenteral drug use.

Most children infected with HCV will not have long-term complications. As

stated before, only 50%-60% of children with HCV infection will develop

persistent infection. Of these, less than 10% will develop chronic

hepatitis, and fewer than 5% will develop cirrhosis. Therefore, the benefit

of additional antiviral therapy is questionable at this time.

There are two specific therapies currently approved by the FDA for chronic

hepatitis C infections in adults and recently approved for use in children

with hepatitis C age 3 years and older.

Interferon Therapy (Interferon-Alfa, Pegylated Interferon Alfa-2a, Alfa-2b)

Interferons are antiviral and immunomodulatory proteins. They are naturally

produced by leucocytes in response to infectious agents and tumors. In

virus-infected cells, interferons can produce antiviral proteins, inhibit

synthesis of viral RNA, and allow recognition of the infected hepatocytes by

cytotoxic T lymphocytes. It is manufactured by the recombinant method. The

disadvantages of this drug are its parenteral route of administration and

tolerable but frequent side effects (see Table 3). Its longer acting

formulation, called pegylated interferon, requiring once weekly infusion, is

now available for adult use only (AAP, 2003; Hochman & Balistreri, 2003;

Strader, , , & Seeff, 2004). Given by itself, interferon-alfa

only resulted in a sustained decrease in viral load in 10%-20% of the adults

treated. Use of the pegylated interferon resulted in sustained response in

25%-39% of treated adults and lower rates for adults with genotype-1, the

most common genotype found in the United States (Fried et al., 2002).

Treatment protocols require at least weekly infusions for 12 months.

Ribavirin Therapy

Ribavirin is a guanosine analogue. Although monotherapy showed no beneficial

effects in the treatment of hepatitis C, it has a synergistic effect when

used with interferon alfa-2b for the therapy of chronic hepatitis C. This

combination therapy resulted in sustained response in 33% of adults with

genotype 1 and approximately 80% of adults with genotypes 2 or 3 (AAP,

2003). An oral liquid formulation (Rebetol ®), to be used in conjunction

with interferon alfa-2b, has recently been approved by the FDA

(Schering-Plough, 2004). Treatment for HCV genotype-1 virus requires 48

weeks and 24 weeks for genotype-2 virus.

To Treat or Not to Treat

There are several factors that make treatment of HCV in children

controversial. In a follow-up study conducted in 460 children who underwent

cardiac surgery before 1991 when blood donor screening was initiated, it was

found that 15% of the children became anti-HCV positive (Vogt et al., 1999).

Fifty-five percent of these positive children remained HCV RNA-positive

indicating continued virus production, but only one child had abnormal liver

enzymes. Forty-five percent of the children cleared the infection

spontaneously. This study showed that over a 20-year time interval almost

half the children had cleared the virus. In those who remained infected, the

disease had a benign course. As stated before, the treatment is long (6-12

months) and involves the use of parenteral medications with frequent side

effects that have to be closely monitored via blood tests.

There have been studies conducted recently that show that early treatment

may give the best chance of eradicating the virus and preventing chronic

hepatitis. In a small cohort of children with chronic hepatitis C, early

initiation of antiviral treatment was associated with a sustained response

rate independent of treatment type (Hartman, Berkowitz, Rimon, & Shamir,

2003). In a study of 44 adults treated with interferon, 42 of 43 patients

treated within 3 months of acquiring infection or within 1 month of being

symptomatic were able to eliminate the virus (Jaeckel, et al., 2001).

Although this study did not include children, it highlights the importance

of early diagnosis and referral of children to a pediatric hepatologist for

potential treatment.

Conclusion

There is no vaccine or universally effective treatment available for HCV.

The prevalence of long-term complications of HCV acquired during childhood

is unknown. Additional insults to the liver must be prevented whenever

possible in children infected with hepatitis C. Due to the lack of effective

treatment and the virus's ability to mutate, universal screening is not

currently recommended. Education against high-risk activities is the only

available protection. Research into the management of HCV in children is

currently active and should result in a better understanding of the risks

associated with each virus genotype, the best practice guidelines for

treatment, and, hopefully, an effective means of prevention. Combination

therapies for hepatitis C that have improved treatment efficacy in adults

should be tested in controlled clinical trials in children. Protease

inhibitors, antisense oligonucleotides, and ribosomes are some of the

alternative treatment modalities being explored.

's adoptive parents were told that given the maternal history of

Hepatitis C infection should be screened for the presence of HCV

infection with LFTs and an anti-HCV screening enzyme immunoassay (EIA). If

the EIA test is positive, she will be further screened with the RT-PCR to

detect the level of viremia and genotype. When the results of these tests

are known, should be referred to a hepatologist for long-term

follow-up. In the meantime, her parents should be reassured that there is

minimal risk of contagion in the family or daycare setting, although

universal bloodborne pathogen precautions are recommended. The parents were

also told that the frequency of long-term complications from HCV in children

is thought to be low and careful follow-up will be instituted with these

complications in mind. HCV does not alter a child's growth or development.

The Primary Care Approaches section focuses on physical and developmental

assessment and other topics specific to children and their families. If you

are interested in author guidelines and/or assistance, contact L.

at pat.jacksonallen@...