hepatitis%20-%20viral%20(pediatric)
HEPATITIS - VIRAL (PEDIATRIC)
The majority of acute viral hepatitis infections are asymptomatic or they can cause an anicteric illness that may not be diagnosed as hepatitis.
Hepatitis A generally causes minor illness in childhood with >80% of infections being asymptomatic. Jaundice and intestinal symptoms usually resolve 2-3 weeks after onset. A patient is infectious 1-2 weeks prior to the clinical illness.
Hepatitis B, C, & D may be symptomatic depending on the mode and time of transmission.
Hepatitis A is predominantly transmitted through oral-fecal by person-person direct transmission and contaminated material or food.
Hepatitis B is transmitted perinatal, horizontal spread, percutaneous, sexual, close person-to-person contact.
Majority of hepatitis C infections are identified in children with repeated exposure to blood products.
Hepatitis D is route of transmission is through sexual, percutaneous especially IV drug use.
Hepatitis E is transmitted primarily through contaminated drinking water and oral-fecal transmission.

History

Important points in the clinical history for patients with suspected viral hepatitis

  • Contacts with jaundiced patients
  • Intravenous (IV) drug use
  • History of blood transfusion
  • Surgery or hospitalizations
  • Family history of chronic liver disease
  • Maternal history of hepatitis infection

Laboratory Tests

Serological Tests for Viral Hepatitis

Hepatitis A

  • Anti-hepatitis A virus immunoglobulin M (IgM) has high sensitivity & specificity
    • This test remains positive for ≥6 months

Hepatitis B

  • Hepatitis B is usually characterized by the presence of hepatitis B surface antigen (HBsAg)
    • Recommended tests for HBsAg-positive pediatric patients:
      • HBeAg/anti-HBe status
      • HBV DNA
      • Anti-HBc IgM
      • Anti-HCV
      • Anti-HIV
      • Anti-HAV
      • Anti-HDV
  • In the Asia-Pacific region, HBV infection is commonly found on routine blood testing
  • Anti-HBc is the 1st antibody to appear in the serum & is a marker of natural infection
    • Presence of anti-HBc IgM (anti-core antibody) is diagnostic for acute hepatitis B virus (HBV) infection but may occur during a flare of chronic hepatitis B
    • Its presence indicates an immune response against HBV within liver cells & is a specific marker of acute hepatitis B infection
  • Hepatitis B e antigen (HBeAg) is a marker of active viral replication
    • This may be negative at the time that the patient is evaluated for acute hepatitis B since viral replication may have already ceased
  • Anti-HBs is usually produced following a resolved infection & is the only HBV antibody marker present after immunization
  • Patients with seropositive HBsAg for >6 month may be classified to have chronic HBV infection, & these patients should be tested for coinfection with hepatitis C virus (HCV), hepatitis D virus (HDV) & human immunodeficiency virus (HIV), if they are at risk for these infections
  • Depending on local health services, the following groups should be tested for chronic HBV infection:
    • Persons born in hyperendemic areas, infants born to mothers with chronic HBV, with multiple sexual partners or history of STDs, intravenous (IV) drug users, dialysis patients, patients undergoing chemotherapy or immunosuppression, HIV positive individuals, & family members, household members & sexual contacts of HBV-infected persons
      • Individuals who are seronegative should be vaccinated against HBV
      • HBsAg positive patients should be evaluated to assess progression of liver disease & need for antiviral therapy
      • Anti-HBs positive patients have developed natural immunity & do not need to be vaccinated
      • All pregnant women should be screened for HBsAg with appropriate treatment of newborn & immunization of infants

Hepatitis C

  • Generally in clinical practice, acute hepatitis C is not commonly recognized & the majority of patients already have chronic hepatitis C
  • Acute hepatitis C cannot be reliably diagnosed by antibody tests since these often do not become positive until 3 months after infection
  • Anti-HCV antibody
    • First-line serologic test for patients infected with acute Hepatitis C
    • Patients with positive anti-HCV antibody should be tested for HCV RNA
      • If results show negative HCV RNA even with a positive anti-HCV result, patient should be retested after 3 months to confirm infection
    • A reactive HCV antibody & positive HCV RNA is conclusive of current Hepatitis C infection
  • HCV RNA
    • If the clinical suspicion is high, the patient should be tested for HCV RNA to establish the diagnosis
    • Reverse-transcriptase polymerase chain reaction detects small amounts of HCV RNA within days of infection
    • Quantitative measurement of HCV RNA may be useful in prognosis or evaluating response to therapy
    • Both HCV RNA & anti-HCV antibody are needed to conclude diagnosis of chronic hepatitis C
  • Recombinant immunoblot assay (RIBA) may be used to establish the cause of a positive anti-HCV test in a person with undetectable HCV RNA
    • A negative RIBA indicates that a positive anti-HCV immunoassay result showed a false positive result & no further testing is necessary
    • A positive RIBA & ≥2 subsequent tests in which HCV RNA cannot be detected suggests that HCV infection has resolved & no further testing is indicated
  • HCV genotype should be determined, if possible, in all HCV-infected persons prior to treatment to determine duration of therapy & chances of response
    • Genotypes 2 & 3 are easier to treat, require shorter duration of therapy & a lower Ribavirin dose
  • Liver biopsy may be done if it is thought that the results will influence clinical decision, but biopsy is not mandatory to start therapy in patients with genotypes 2 & 3
    • Liver biopsy may be obtained to provide prognostic information
  • Depending on local health services, the following pediatric groups should be tested for HCV infection:
    • Persons who have in the recent or remote past used illicit IV drugs
    • Persons with conditions associated with high prevalence of HCV infection
      • Positive HIV, history of hemodialysis, unexplained abnormal aminotransferase levels
    • Persons who received blood/blood products or organ transplants prior to 1992, children born to HCV infected mothers, patients who had sexual encounters with HCV-infected persons 
    • Infants born to HCV mothers who are HCV antibody positive & HCV RNA negative do not need to be tested
      • An HCV antibody test must be performed at 12 months of age & thereafter to determine the majority of children who are not infected
      • Children born to mothers who are co-infected with HIV, & infants who are HCV antibody (positive) at 12 months of age should have HCV RNA determination which must be confirmed, if positive, on a second sample
      • An HCV RNA test & repeat tests can be done at 2 months of age in infants whose risk of HCV infection must be known before 12 months of age
    • Children with chronically elevated transaminase
    • Children coming from regions with reported high incidence of HCV infection

Hepatitis D

  • Confirmed by positive anti-HDV antibody or HDV RNA test
  • Hepatitis D only occurs as coinfection with Hepatitis B

Hepatitis E

  • Diagnosis is made in endemic populations by clinical symptoms & exclusion of other infectious agents like Hepatitis A, B, C, Epstein-Barr virus & cytomegalovirus
  • Definitive diagnosis can be made by detection of IgM anti-HEV, immunoglobulin G (IgG) anti-HEV
  • Hepatitis E virus (HEV) RNA from serum & stool of infected patients

Other laboratory tests that are recommended in patients suspected to have viral hepatitis:

  • Liver Function Tests (LFTs)
    • Aspartate aminotransferase (AST) & alanine aminotransferase (ALT) are usually increased (1.5-10 x)
    • Serum bilirubin, total bilirubin, alkaline phosphatase (ALP)
    • Complete blood count (CBC)
  • Prothrombin time (PT), international normalized ratio (INR)
  • Liver biopsy
    • Reserved for pediatric patients suspected of having Hepatitis B infection, with HBV DNA of >2000 IU/ml, ALT ≥30 IU//L for boys & ≥19 IU/L for girls obtained twice & done 3 months apart
  • Tests for hepatocellular carcinoma (HCC), including liver ultrasound, alpha fetoprotein (AFP) for HBV-suspected pediatric patients

Evaluation

  • For Hepatitis A & B virus, the following are clues that hepatic decomposition may be present:
    • Mental dullness
    • Bilateral asterixis
    • Ascites
    • Hepatic encephalopathy
    • Clinical deterioration
    • Prothrombin time (PT) is 3 seconds longer than control
    • International normalized ratio (INR) >1.5
    • Serum bilirubin >2.5x ULN

Acute Hepatitis B

  • History & physical exam
  • Measure HBeAg, anti-HBe, HBV DNA & ALT
  • Complete blood count (CBC), PT
  • Screen for hepatocellular carcinoma (HCC) in high-risk patients

If patient meets criteria for chronic hepatitis B

  • Liver biopsy to grade stage of liver disease
    • The decision to perform biopsy in children should be guided by all factors considering its necessity & its benefits to the patient
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