Basics
Description
- 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 men
- Maximum infectivity 2 weeks before jaundice
- 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
General Prevention
- Good sanitation, hygiene, vaccination, screening blood products, condom use, safe disposal of needles
- Hepatitis A
- Vaccination of all children between the ages of 1 and 18 years, especially those travelling to endemic regions or those with liver disease
- Vaccine (Havrix, Vaqta): 0.5-mL dose IM and 2nd dose 6 " 12 months later
- Prior 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 vaccine
- Postexposure prophylaxis for <1 year of age and immunocompromised individuals: immune globulin 0.02 mL/kg IM
- Hepatitis B
- Screen 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 infants
- Mother '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 C
- Elective 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:
- 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.
Diagnostic Tests & Interpretation
Lab
- Liver tests
- Marked elevation of aspartate aminotransferase/alanine aminotransferase (AST/ALT) during acute infection
- May be normal to mildly elevated in chronically infected individuals
- Bilirubin from mild to marked elevation
- In severe hepatitis, monitor PT/INR, albumin, electrolytes, glucose, and CBC.
- 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 C
- HCV Ab: exposure to HCV
- HCV RNA: Quantitative, assess viral load; qualitative, assess presence/absence of virus.
- HCV genotype: useful to determine duration of treatment and likelihood of response
- Hepatitis D
- HDV 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 A
- No 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 B
- Postexposure 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 C
- For 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 disease
- Pegylated 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 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.
- Hepatitis B
- Fulminant 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 C
- Fulminant 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 B
- Hepatitis 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.