Doctor123.org

Viral Hepatitis, Pediatric

Basics

Description

- Hepatitis B and C (transmission: blood, body fluids, and sexual contact) - Recipients of blood or blood products - IV drug users - Multiple sexual partners - Homosexual males - Body piercing and tattoos - HIV-positive status - Infants born to a mother with hepatitis B or C - Household contacts with hepatitis B or C

- Jaundice, hepatomegaly, or tenderness over the liver may or may not be present during acute infection. - Signs and symptoms during acute infection: - Fever - Malaise and fatigue - Nausea and vomiting, anorexia - Jaundice: in hepatitis A, seen in 88% of adults but only 65% of children - Hepatomegaly - Right upper quadrant (RUQ) abdominal pain - Dark urine and pale stools - Arthralgias/arthritis - The vast majority of affected patients are minimally symptomatic or asymptomatic, especially with chronic infection.

- Biochemical markers for each virus for diagnosis, management, and monitoring - Hepatitis A - Virus (HAV) IgM: recent infection - Anti-HAV IgG: past exposure or immunization-acquired

- Hepatitis B - Surface antigen (HBsAg): current infection, acute or chronic - Surface antibody (HBsAb): immunized or resolved infection - "e " antigen (HBeAg): active viral replication; "infectious " - "e " antibody (HBeAb): end of severe infectivity (except in precore mutants). End point for many hepatitis B therapies and studies - Core antigen (HBcore) IgM: early phase of acute infection, not present in chronic HBV - Core total Ab: exposed to HBV - HBV DNA: quantification useful to assess viral load - HBV mutations: useful to assess resistance to treatment - HBV genotyping can sometimes be helpful in determining if interferon therapy would be beneficial (genotype D unfavorable for interferon use).

- Hepatitis A - Mild disease usual - Rarely results in relapsing, fulminant, or cholestatic disease - No chronic liver disease - Mortality <1% - Protective antibodies develop in response to infection and persist for life.

  • Viral hepatitis is defined as a systemic viral infection, in which the predominant manifestation is that of hepatic injury and dysfunction.
  • It is primarily caused by hepatotropic viruses, which include hepatitis A " E.
  • 10% of cases are caused by other viruses, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), rubella, parvovirus, adenovirus, enteroviruses, and others.

Epidemiology

Incidence

  • Hepatitis A: ~17,000 cases per year in the United States. 8% occur in day care centers.
  • Hepatitis B: 140,000 " 320,000 infections per year worldwide. ~40,000 U.S. cases per year
  • Hepatitis C: 20,000 infections per year in the United States
  • Hepatitis E: Common in poorly developed countries but rare in the United States.

Prevalence

  • Hepatitis B: United States has a low prevalence with <1% of the population infected; higher rates in certain subgroups such as immigrants from endemic areas, homosexuals, and parenteral drug users
  • Hepatitis C: United States has prevalence of 1.8%, representing ~3.9 million people (85% chronically infected).

Risk Factors

  • Hepatitis A (transmission: fecal " oral)Day care attendance, household exposure, travel to endemic areas, men who have sex with menMaximum infectivity 2 weeks before jaundice
  • Hepatitis B and C (transmission: blood, body fluids, and sexual contact)Recipients of blood or blood productsIV drug usersMultiple sexual partnersHomosexual malesBody piercing and tattoosHIV-positive statusInfants born to a mother with hepatitis B or CHousehold contacts with hepatitis B or C

General Prevention

  • Good sanitation, hygiene, vaccination, screening blood products, condom use, safe disposal of needles
  • Hepatitis AVaccination of all children between the ages of 1 and 18 years, especially those travelling to endemic regions or those with liver diseaseVaccine (Havrix, Vaqta): 0.5-mL dose IM and 2nd dose 6 " 12 months laterPrior to travel to an endemic region, immune globulin 0.02 mL/kg should be given to children younger than 1 year of age and considered for children who are immunocompromised or have liver disease.Infected patients should avoid return to day care center for 2 weeks after illness subsides.Postexposure prophylaxis for children >1 year of age: hepatitis A vaccinePostexposure prophylaxis for <1 year of age and immunocompromised individuals: immune globulin 0.02 mL/kg IM
  • Hepatitis BScreen all pregnant women.Hepatitis B vaccine to all infants at birth; complete 3-vaccine series 0.5-mL dose IM during infancy.Vaccine and hepatitis B immunoglobulin to high-risk infantsMother 's with previous vertical transmission should consult a high-risk obstetrician and hepatitis B expert at least 3 " 6 months prior to delivery of another infant.
  • Hepatitis CElective C-section has not been shown to reduce vertical transmission.During vaginal delivery, avoid fetal scalp monitoring and prolonged rupture of membranes >8 hours.Avoid sharing of toothbrushes, nail clippers, and razors.Breastfeeding is allowed, unless the mother has active bleeding from nipples.

Pathophysiology

  • Acute viral hepatitis tends to affect the liver parenchyma, whereas chronic viral hepatitis affects portal and periportal areas.
  • Chronic viral hepatitis (B or C) is defined by continuing viral replication and inflammation of the liver for >6 months.
  • Worsening injury leads to extensive fibrosis that occurs between portal tracts (portal bridging), nodular changes, and finally, cirrhosis.

Diagnosis

History

  • History should focus on risk factors for viral exposure, sick contacts, travel history, and high-risk behaviors.
  • Family history of liver or autoimmune disease, medications, or drug and alcohol use should also be explored.

Physical Exam

  • Jaundice, hepatomegaly, or tenderness over the liver may or may not be present during acute infection.
  • Signs and symptoms during acute infection:FeverMalaise and fatigueNausea and vomiting, anorexiaJaundice: in hepatitis A, seen in 88% of adults but only 65% of childrenHepatomegalyRight upper quadrant (RUQ) abdominal painDark urine and pale stoolsArthralgias/arthritisThe vast majority of affected patients are minimally symptomatic or asymptomatic, especially with chronic infection.

Diagnostic Tests & Interpretation

Lab

  • Liver testsMarked elevation of aspartate aminotransferase/alanine aminotransferase (AST/ALT) during acute infectionMay be normal to mildly elevated in chronically infected individualsBilirubin from mild to marked elevationIn severe hepatitis, monitor PT/INR, albumin, electrolytes, glucose, and CBC.
  • Biochemical markers for each virus for diagnosis, management, and monitoringHepatitis AVirus (HAV) IgM: recent infectionAnti-HAV IgG: past exposure or immunization-acquiredHepatitis BSurface antigen (HBsAg): current infection, acute or chronicSurface antibody (HBsAb): immunized or resolved infection "e " antigen (HBeAg): active viral replication; "infectious " "e " antibody (HBeAb): end of severe infectivity (except in precore mutants). End point for many hepatitis B therapies and studiesCore antigen (HBcore) IgM: early phase of acute infection, not present in chronic HBVCore total Ab: exposed to HBVHBV DNA: quantification useful to assess viral loadHBV mutations: useful to assess resistance to treatmentHBV genotyping can sometimes be helpful in determining if interferon therapy would be beneficial (genotype D unfavorable for interferon use).Hepatitis CHCV Ab: exposure to HCVHCV RNA: Quantitative, assess viral load; qualitative, assess presence/absence of virus.HCV genotype: useful to determine duration of treatment and likelihood of responseHepatitis DHDV Ab: exposure to hepatitis D

Diagnostic Procedures/Other

Liver biopsy is often needed to determine type and extent of liver damage. It is usually indicated prior to initiation of antiviral therapy in children with hepatitis B or C.

Pathologic Findings

A wide array of histologic features is possible on liver biopsy, including inflammation, necrosis, and fibrosis, based on the severity and chronicity of disease.

Differential Diagnosis

  • Many disorders give rise to elevated transaminases, and clues to a viral origin are based on the history, serology, and histologic findings.
  • The diagnosis of "non A " E hepatitis " is often used when the cause is almost certainly viral, but no virus is isolated.
  • Other possibilities include drug-induced, ischemic, alcoholic, autoimmune hepatitis, as well as Wilson disease orα1-antitrypsin deficiency.

Treatment

Medication

  • Hepatitis ANo specific therapy is necessary for previously immunized or infected patients.Postexposure prophylaxis is recommended for nonimmunized patients household contacts, intimate exposure contacts, and children and staff in nursery or day care centers with outbreaks.Hepatitis A vaccine for children >1 year of age. Children <1 year of age or immunocompromised individuals should receive immune globulin 0.02 mL/kg IM 1.
  • Hepatitis BPostexposure prophylaxis with hepatitis B vaccine and hepatitis B immunoglobulin (HBIG) is indicated for neonates born to mothers who are hepatitis B carriers and for unvaccinated individuals after sexual contact with carriers or accidental exposure to infected blood products.Persons previously vaccinated with known titer >10 mIU/mL do not require any intervention, and children vaccinated with low titer need only a booster HBV vaccine.There is no treatment for acute hepatitis B, although lamivudine is reported to be effective in fulminant HBV hepatitis.Treatment is not usually considered when patients are immune tolerant (normal ALT, (HBeAg) positive, with high HBV DNA).Children should be monitored every 6 " 12 months with ALT, HBeAg, and HBeAb. When ALT is elevated, treatment is considered by hepatitis B experts.Some pediatric studies suggest that antiviral therapy hastens but does not increase the rate of HBeAg seroconversion.Medications that have been used for chronic hepatitis B include the following: interferon, peginterferon, lamivudine, adefovir, tenofovir, or entecavir.Lamivudine is no longer routinely recommended in chronic HBV due to a high rate of resistance with prolonged treatment.Adefovir dipivoxil and tenofovir are approved for children >12 years of age and entecavir for children >16 years of age.The factor most predictive of treatment response in children with chronic hepatitis B is an elevated pretreatment ALT.Each year, approximately 5% of children spontaneously clear HBeAg, at which point the disease usually becomes inactive, although a few will later reactivate.
  • Hepatitis CFor acute hepatitis C, treatment with interferon in first 3 months after acquiring infection has been quite successful in adults and should be considered in children.Antiviral therapy for chronic infection can be initiated at any time after 3 years of age, and is indicated for children with progressive or advanced diseasePegylated interferon and ribavirin is currently the treatment of choice for chronic hepatitis C in children >3 years of age.Treatment duration depends on genotype:Genotypes 1 and 4: 1 year (type 1 most common in United States)Genotypes 2 and 3: 6 months (types more likely to respond to therapy)Several protease inhibitors, telaprevir and boceprevir, have recently been approved for treatment of chronic HCV in adults in combination with peginterferon and ribavirin.

General Measures

  • Most cases of acute hepatitis do not require hospitalization.
  • Dehydration, coagulopathy, or severe cases need inpatient care; monitor and correct coagulation defects and fluid, electrolyte, and acid " base imbalances.
  • Report acute cases to public health department.
  • Patients with acute liver failure should be transferred to a pediatric transplant center.

Ongoing Care

Follow-up Recommendations

  • For hepatitis B and C, serial measurement of serum AST/ALT, viral markers,α-fetoprotein, and ultrasound of the liver
  • Liver biopsy pretreatment and for evaluation of disease progression

Prognosis

  • Hepatitis AMild disease usualRarely results in relapsing, fulminant, or cholestatic diseaseNo chronic liver diseaseMortality <1%Protective antibodies develop in response to infection and persist for life.
  • Hepatitis BFulminant hepatitis 1 " 2%Mortality 0.8%Chronic sequelae: Rate of chronicity is inversely proportional to age of acquisition: 90% in infants, 25% in ages 1 " 5 years, and 6 " 10% in older children; cirrhosis <5%, hepatocellular carcinoma
  • Hepatitis CFulminant hepatitis 1%Chronic sequelae: Infants infected via vertical transmission have 60 " 80% chance of chronic infection. Cirrhosis is uncommon, and hepatocellular carcinoma is rare in children and adolescents. If untreated, HCV can lead to advanced liver disease in adults.HCV is the most common indication for liver transplantation in adults.

Complications

  • Patients with advanced liver disease due to chronic hepatitis B or C are at risk of complications associated with cirrhosis and portal hypertension.
  • Patients with chronic hepatitis B or with cirrhosis due to hepatitis C are at increased risk of hepatocellular carcinoma.
  • Hepatitis BHepatitis D coinfection: Acute hepatitis B and D virus infection occur simultaneously.Hepatitis D superinfection: Acute hepatitis D occurs in a chronic carrier of hepatitis B.

Pregnancy Considerations

Hepatitis E: mortality of 20% caused by acute liver failure in pregnant women

Additional Reading

  • Daniels D, Grytdal S, Wasley A, Centers for Disease Control and Prevention. Surveillance for acute viral hepatitis " United States, 2007. MMWR Surveill Summ. 2009;58(3):1 " 27. [View Abstract]
  • Haber BA, Block JM, Jonas MM, et al. Recommendations for screening, monitoring, and referral of pediatric chronic hepatitis B. Pediatrics. 2009;124(5):e1007 " e1013. [View Abstract]
  • Mack CL, Gonzalez-Peralta RP, Gupta N, et al. NASPGHAN practice guidelines: diagnosis and management of hepatitis C infection in infants, children, and adolescents. J Pediatr Gastroenterol Nutr. 2012;54(6):838 " 855. [View Abstract]
  • Mohan N, Gonz ‘lez-Peralta RP, Fujisawa T, et al. Chronic hepatitis C infection in children. J Pediatr Gastroenterol Nutr. 2010;50(2):123 " 131. [View Abstract]
  • Murray KF, Shah U, Mohan N, et al. Chronic hepatitis. J Pediatr Gastroenterol Nutr. 2010;47(2):225 " 233. [View Abstract]

Codes

ICD09

  • 070.9 Unspecified viral hepatitis without mention of hepatic coma
  • 070.30 Viral hepatitis B without mention of hepatic coma, acute or unspecified, without mention of hepatitis delta
  • 70.51 Acute hepatitis C without mention of hepatic coma
  • 070.1 Viral hepatitis A without mention of hepatic coma
  • 070.54 Chronic hepatitis C without mention of hepatic coma
  • 070.32 Chronic viral hepatitis B without mention of hepatic coma without mention of hepatitis delta

ICD10

  • B19.9 Unspecified viral hepatitis without hepatic coma
  • B19.10 Unspecified viral hepatitis B without hepatic coma
  • B19.20 Unspecified viral hepatitis C without hepatic coma
  • B15.9 Hepatitis A without hepatic coma
  • B18.2 Chronic viral hepatitis C
  • B18.1 Chronic viral hepatitis B without delta-agent

SNOMED

  • 3738000 Viral hepatitis (disorder)
  • 66071002 Type B viral hepatitis (disorder)
  • 50711007 Viral hepatitis C (disorder)
  • 40468003 viral hepatitis, type A (disorder)
  • 61977001 chronic type B viral hepatitis (disorder)
  • 128302006 chronic hepatitis C (disorder)

FAQ

  • Q: Why do infants who acquire HBV at birth have a higher incidence of chronicity?
  • A: The immaturity of the neonatal immune system contributes to the higher incidence of chronicity in this population.
  • Q: Should a mother with HCV positivity breastfeed?
  • A: Transmission of HCV via breast milk is unlikely.