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Overview of hepatitis A virus infection in children
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Overview of hepatitis A virus infection in children
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Literature review current through: Sep 2017. | This topic last updated: Mar 31, 2016.

INTRODUCTION — Although the reported cases of hepatitis A virus (HAV) infection have decreased over the past decade, HAV infection is still a frequently reported disease in the United States [1]. HAV is a 27 nm single-stranded, icosahedral, nonenveloped RNA virus that belongs to the Heparnavirus genus of the Picornaviridae. Four well-defined genotypes of HAV have been described in humans, yet they belong to a single serotype [2]. The virus is stable at low pH and moderate temperature, but it is inactivated by high temperature, chlorine, and formalin. These characteristics are relevant for preventive measures.

EPIDEMIOLOGY — Hepatitis A virus (HAV) infection occurs worldwide (figure 1). Although it remains one of the most commonly reported vaccine-preventable diseases in the United States and among American travelers [1,3], the incidence in the United States has declined substantially since vaccination was recommended for persons at increased risk (in 1996), for children living in states with the highest incidence of HAV (in 1999), and for all children (in 2006) [4]. The incidence of acute HAV infection in the United States has declined from 12 cases per 100,000 in 1995 to about 0.4 case per 100,000 in 2011 [5,6]. Declines were greatest in states in which routine vaccination of children for HAV was initiated in 1999. In 2013, a total of 1781 cases of hepatitis A were reported in the United States to CDC (0.6 cases per 100,000), a 14 percent increase from 2012, indicating that hepatitis A infection is still an important issue in the United States. This increase is believed to be due to a large hepatitis A outbreak from imported pomegranate arils consumed by people in several southwestern states and Hawaii [1,7]. (See "Hepatitis A virus infection in adults: An overview", section on 'Epidemiology'.)

A similar decline in the incidence of HAV infection was seen in Israel following a universal immunization program for toddlers that was initiated in 1999 [8-10]. The incidence declined from 50.4 cases per 100,000 in 1993 to 1998 to 2.2 to 2.5 cases per 100,000 in 2002 to 2004, and outbreaks in school and day care settings were essentially eliminated.

To what extent the observed reductions in the incidence of HAV infection in these reports can be attributed to improved environmental and hygienic conditions or variation in the epidemic cycle is difficult to evaluate [11]. Nonetheless, the above reports highlight the potential for "herd protection" through the immunization of toddlers or children [4,8,10].

HAV is spread via the fecal-oral route. The majority of patients who acquire the illness have had personal contact with an infected person. In the childcare setting, spread of HAV usually takes place before the index case has been recognized. Outbreaks are usually recognized only after childcare staff members develop symptoms, such as jaundice, since most of the children are asymptomatic or have nonspecific symptoms [3,12]. The potential for broad exposure is compounded in childcare centers that include children who have not yet been toilet-trained [13]. (See 'Clinical manifestations' below.)

Community, restaurant, and school outbreaks due to contaminated water or food have been described. In the United States, clusters of cases have been seen around international adoptions, more than half of which occurred in non-travelling contacts of adoptees [14]. In a report of 288 international adoptees, 1 percent had acute HAV infection [15].

Nosocomial spread of HAV is rare [16-18]. Among these reports include outbreaks in neonatal intensive care units where newborns were infected through blood-product transfusions and later transmitted the virus to other neonates and the units' staff members [16].

The incubation period for HAV is 15 to 50 days. HAV RNA can be detected in stools at least one week before the onset of histological and biochemical evidence of hepatitis [19], and it can be detected for at least 33 days after the onset of disease (figure 2) [20]. In neonates and younger children, HAV RNA can be detected in stools for several months [18].

PATHOGENESIS — The degree of hepatic injury during HAV infection depends upon the host's immune response. HAV infection traditionally has been considered a biphasic process [21]. In the first phase, a non-cytopathic stage, viral replication occurs exclusively within the cytoplasm of the hepatocyte. This phase is followed by a second phase, a cytopathic stage, with florid portal zone infiltration, necrosis, and erosion of the limiting plate. Hepatocellular damage and destruction is not the result of a direct cytopathic effect by HAV but a process mediated by HLA-restricted, HAV-specific, CD8 lymphocytes, and natural killer cells [22-24].

Interferon gamma appears to have a central role in promoting clearance of infected hepatocytes [22]. An excessive host response, reflected by a marked reduction in HAV RNA during acute infection, is associated with severe hepatitis and a possible fulminant course [25].

CLINICAL MANIFESTATIONS — Hepatitis A virus (HAV) infection in children is typically an acute, self-limited illness associated with general, nonspecific symptoms, such as fever, malaise, anorexia, vomiting, nausea, abdominal pain or discomfort, and diarrhea. During the prodromal period, aminotransferases are typically elevated. Jaundice (conjugated hyperbilirubinemia) usually occurs one week after onset of symptoms, along with choluria (bilirubin in the urine) and mild hepatomegaly [26].

Symptomatic hepatitis occurs in approximately 30 percent of infected children younger than six years, some of whom become jaundiced. When it does occur, jaundice usually lasts for less than two weeks. Conjugated bilirubin and aminotransferases return to normal within two to three months [27].

In contrast, older children and adults with HAV infection are usually symptomatic for several weeks. Approximately 70 percent are jaundiced, 80 percent have hepatomegaly, and 40 percent are hospitalized [5,21,26]. Symptoms lasting for up to six months have been described [28].

Acute liver failure is rare, occurring in fewer than 1 percent of cases. However, the case-fatality for HAV infection varies with age. In 2001, the case fatality rate was 0.3 percent in children younger than 14 years, 0.1 percent in adolescents and young adults (15 to 39 years), 0.4 percent in older adults (40 to 59 years), and 1.7 percent in people older than 60 years [29]. This case fatality rate has remained fairly stable. In 2013 case-fatality estimates ranged from 0.3 to 0.6 percent for most age groups, and up to 1.8 percent among adults aged >50 years [30]. From 2009 to 2013, the overall mortality rate also remained approximately steady at 0.02 deaths per 100,000 population each year [1]. Acute liver failure secondary to HAV infection is more common in those with underlying liver disease such as hepatitis C [31]. HAV is responsible for no more than one percent of acute liver failure in children in the United States [32], and up to 60 percent of liver failure in Latin America [33,34] or other countries in which HAV infection is endemic [35]. (See "Acute liver failure in adults: Etiology, clinical manifestations, and diagnosis".)

The most common extrahepatic manifestations of HAV infection include an evanescent rash (11 percent) and arthralgias (14 percent) [36]. Much less common extrahepatic manifestations include vasculitis, arthritis, optic neuritis, transverse myelitis, encephalitis, and bone marrow suppression [37].

HAV rarely is associated with a relapsing pattern. It may also trigger autoimmune hepatitis in genetically predisposed hosts [38-40]. (See "Hepatitis A virus infection in adults: An overview", section on 'Extrahepatic manifestations'.)

DIAGNOSIS — The diagnosis of acute HAV infection is made by the detection of anti-HAV IgM in a patient with the typical clinical presentation. Serum IgM anti-HAV is the gold standard for the detection of acute illness. This antibody is positive at the onset of symptoms, peaks during the acute or early convalescent phase of the disease, and remains positive for approximately four to six months (figure 2).

The serologic detection of antibodies is simpler, easier, and less expensive than other techniques, such as HAV detection in stool and body fluids by electron microscopy and HAV RNA detection in stool, body fluids, serum, and liver tissue. IgG anti-HAV appears early in the convalescent phase of the disease, and remains detectable for decades.

There may be special considerations when assessing anti-HAV antibodies. In adults, antibodies become detectable two weeks after HAV vaccination, but titers are 10- to 100-fold lower than levels induced by wild-type infection [41,42]. Similar data are not available in children. Anti-HAV IgM may persist at a low titer for 12 to 14 months in patients with a relapsing or protracted course [43]. (See "Hepatitis A virus infection in adults: An overview", section on 'Diagnosis'.)

PREVENTION AND PROPHYLAXIS

General measures — Since hepatitis A virus (HAV) is transmitted predominantly by the fecal-oral route, prevention can be aided by improved sanitary conditions, adherence to sanitary practices (eg, handwashing), heating foods appropriately, and avoidance of water and foods from endemic areas. Handwashing is highly effective in preventing the transmission of the virus, since HAV may survive for up to four hours on the fingertips. Chlorination and certain disinfecting solutions (household bleach 1:100 dilution) are sufficient to inactivate the virus. (See "Hepatitis A virus infection: Prevention", section on 'Hygienic practices'.)

Vaccination — In January, 2006, Hepatitis A vaccine was added to the recommended childhood and adolescent immunization schedule in the United States [3]. Hepatitis A vaccine is administered in a two-dose schedule and is recommended for all children at one year of age (ie, 12 to 23 months) [3]. It also is recommended for specific high-risk groups, such as international travelers, close contacts of newly arriving international adoptees, persons with clotting factor disorders, patients with chronic liver disease, men who have sex with men, injecting/noninjecting drug users, and people living in communities with HAV outbreaks [3,44]. By 2009, 74 percent of adolescents in states that have been practicing universal hepatitis A vaccination since 1999 had received at least one dose of the vaccine; in states practicing hepatitis A vaccination since 2006, coverage for adolescents was only 28 percent [45]. (See "Hepatitis A virus infection: Prevention".)

A compelling argument for universal vaccination of children is the observation that the disease tends to be more severe when acquired at older ages. In a report from the Centers of Disease Control and Prevention, for example, hospitalization was required in 13 percent of children younger than five years compared to 31 percent of older children and adults [29]. Because humans are the only known reservoir for HAV, universal immunization strategies could hypothetically eradicate HAV.

Immune globulin — Polyclonal serum immune globulin (IgG) pre- and post-HAV exposure has been available since the 1940s and can decrease the incidence of HAV infection by more than 90 percent. Passive immunity lasts for up to six months depending upon the IgG dose used but is only effective if administered within two weeks post-exposure. (See "Hepatitis A virus infection: Prevention".)

Post-exposure prophylaxis — Indications for and detailed recommendations about postexposure prophylaxis are discussed separately. (See "Hepatitis A virus infection: Prevention".)

TREATMENT

General principles — Treatment is supportive. Hepatitis A virus (HAV) infection in children is usually a minor and self-limited infection; as mentioned above, HAV is often asymptomatic or associated only with symptoms indistinguishable from nonspecific viral gastrointestinal infections. The usual supportive measures for fever and diarrhea may be undertaken. (See "Acute viral gastroenteritis in children in resource-rich countries: Management and prevention" and "Fever in infants and children: Pathophysiology and management", section on 'Management of fever'.)

No particular diet has had a major impact on outcomes of patients with acute hepatitis A. As a result, no specific diet is recommended unless patient has severely compromised hepatic function (ie, fulminant hepatic failure).

Patients rarely require hospitalization except for those who develop fulminant hepatic failure. The following criteria were proposed by the Pediatric Acute Liver Failure Study Group (PALF SG) to identify such patients [32,46]:

Absence of known chronic liver disease

Evidence of hepatic injury

PT>15 and/or INR>1.5 with encephalopathy

PT>20 and/or INR>2.0 with or without encephalopathy

These criteria should be fulfilled within eight weeks from the onset of illness, and the above-described coagulopathy (prolonged prothrombin time and/or INR) should be unresponsive to vitamin K therapy.

These patients require aggressive supportive therapy, and should be transferred to a center capable of performing liver transplantation. (See "Acute liver failure in adults: Etiology, clinical manifestations, and diagnosis".)

Return to school or daycare — Children should not return to school or daycare until one week after onset of the illness, the prophylaxis program for contacts is completed, or directed by the responsible health department [47]. In addition, adherence to universal precautions is crucial, since HAV may be present in stool for several months after the initial onset of disease [18,20]. Post-exposure prophylaxis and universal precautions are discussed separately. (See "Hepatitis A virus infection: Prevention" and "Infection prevention: Precautions for preventing transmission of infection".)

SUMMARY AND RECOMMENDATIONS

Hepatitis A virus (HAV) infection occurs worldwide (figure 1). HAV is spread via the fecal-oral route. The majority of patients who acquire the illness have had personal contact with an infected person. (See 'Epidemiology' above.)

The incubation period for HAV is 15 to 50 days. HAV RNA can be detected in stools at least one week before the onset of histological and biochemical evidence of hepatitis, and it can be detected for at least 33 days after the onset of disease. In neonates and younger children, HAV RNA can be detected in stools for several months. In the childcare setting, spread of HAV usually takes place before the index case has been recognized. (See 'Epidemiology' above.)

HAV infection in children is typically an acute, self-limited illness associated with nonspecific symptoms, such as fever, malaise, anorexia, vomiting, nausea, abdominal pain or discomfort, and diarrhea. During the prodromal period, aminotransferases are typically elevated. Jaundice (conjugated hyperbilirubinemia) usually occurs one week after onset of symptoms, along with choluria (bilirubin in the urine) and mild hepatomegaly. (See 'Clinical manifestations' above.)

HAV disease tends to be more severe when acquired at older ages. Among younger children (under six years of age) with HAV infection, only one third develop symptomatic hepatitis, and this often lasts less than two weeks. In contrast, most older children and adults with HAV infection are jaundiced and have hepatomegaly, and they are usually symptomatic for several weeks. Acute liver failure is rare, occurring in less than 1 percent of cases. (See 'Clinical manifestations' above.)

The diagnosis of acute HAV infection is made by the detection of anti-HAV IgM in a patient with the typical clinical presentation. Serum IgM anti-HAV is the gold standard for the detection of acute illness. This antibody is positive at the onset of symptoms, peaks during the acute or early convalescent phase of the disease, and remains positive for approximately four to six months (figure 2). (See 'Diagnosis' above.)

Hepatitis A vaccine is part of the recommended childhood and adolescent immunization schedule in the United States. It is recommended for all children at one year of age (ie, 12 to 23 months), and also for specific high-risk groups, including international travelers and patients with chronic liver disease. (See 'Vaccination' above.)

Post-exposure prophylaxis for individuals with recent exposure to HAV may be accomplished with the HAV vaccine or immune globulin. Indications for and detailed recommendations about postexposure prophylaxis are discussed separately. (See "Hepatitis A virus infection: Prevention".)

HAV infection in children is usually a minor and self-limited infection requiring no specific therapy. The usual supportive measures for fever and diarrhea may be undertaken. Patients rarely require hospitalization except for those who develop fulminant hepatic failure. Children with HAV-related hepatic failure are candidates for liver transplantation. (See 'Treatment' above.)

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REFERENCES

  1. Centers for Disease Control and Prevention. Surveillance for Viral Hepatitis – United States, 2013. Available at: http://www.cdc.gov/hepatitis/statistics/2013surveillance/ (Accessed on February 26, 2016).
  2. Lemon SM, Jansen RW, Brown EA. Genetic, antigenic and biological differences between strains of hepatitis A virus. Vaccine 1992; 10 Suppl 1:S40.
  3. Advisory Committee on Immunization Practices (ACIP), Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006; 55:1.
  4. Wasley A, Samandari T, Bell BP. Incidence of hepatitis A in the United States in the era of vaccination. JAMA 2005; 294:194.
  5. Division of Viral Hepatitis. Hepatitis Surveillance Report - United States, 2011. United States Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, GA 2011.
  6. Daniels D, Grytdal S, Wasley A, Centers for Disease Control and Prevention (CDC). Surveillance for acute viral hepatitis - United States, 2007. MMWR Surveill Summ 2009; 58:1.
  7. Collier MG, Khudyakov YE, Selvage D, et al. Outbreak of hepatitis A in the USA associated with frozen pomegranate arils imported from Turkey: an epidemiological case study. Lancet Infect Dis 2014; 14:976.
  8. Dagan R, Leventhal A, Anis E, et al. Incidence of hepatitis A in Israel following universal immunization of toddlers. JAMA 2005; 294:202.
  9. Belmaker I, Dukhan L, Yosef Y, et al. Elimination of hepatitis a infection outbreaks in day care and school settings in southern Israel after introduction of the national universal toddler hepatitis a immunization program. Pediatr Infect Dis J 2007; 26:36.
  10. Barkai G, Belmaker I, Givon-Lavi N, Dagan R. The effect of universal toddlers-only hepatitis A virus vaccination program on seropositivity rate in unvaccinated toddlers: evidence for reduced virus circulation in the community. Pediatr Infect Dis J 2009; 28:391.
  11. Van Damme P, Van Herck K. Effect of hepatitis A vaccination programs. JAMA 2005; 294:246.
  12. Hadler SC, Webster HM, Erben JJ, et al. Hepatitis A in day-care centers. A community-wide assessment. N Engl J Med 1980; 302:1222.
  13. Vernon AA, Schable C, Francis D. A large outbreak of hepatitis A in a day-care center: association with non-toilet-trained children and persistence of IgM antibody to hepatitis A virus. Am J Epidemiol 1982; 115:325.
  14. Fischer GE, Teshale EH, Miller C, et al. Hepatitis A among international adoptees and their contacts. Clin Infect Dis 2008; 47:812.
  15. Abdulla RY, Rice MA, Donauer S, et al. Hepatitis A in internationally adopted children: screening for acute and previous infections. Pediatrics 2010; 126:e1039.
  16. Noble RC, Kane MA, Reeves SA, Roeckel I. Posttransfusion hepatitis A in a neonatal intensive care unit. JAMA 1984; 252:2711.
  17. Klein BS, Michaels JA, Rytel MW, et al. Nosocomial hepatitis A. A multinursery outbreak in Wisconsin. JAMA 1984; 252:2716.
  18. Rosenblum LS, Villarino ME, Nainan OV, et al. Hepatitis A outbreak in a neonatal intensive care unit: risk factors for transmission and evidence of prolonged viral excretion among preterm infants. J Infect Dis 1991; 164:476.
  19. Pinto MA, Marchevsky RS, Baptista ML, et al. Experimental hepatitis A virus (HAV) infection in Callithrix jacchus: early detection of HAV antigen and viral fate. Exp Toxicol Pathol 2002; 53:413.
  20. Bruisten SM, van Steenbergen JE, Pijl AS, et al. Molecular epidemiology of hepatitis A virus in Amsterdam, the Netherlands. J Med Virol 2001; 63:88.
  21. Lemon SM. Type A viral hepatitis. New developments in an old disease. N Engl J Med 1985; 313:1059.
  22. Vallbracht A, Fleischer B, Busch FW. Hepatitis A: hepatotropism and influence on myelopoiesis. Intervirology 1993; 35:133.
  23. Fleischer B, Fleischer S, Maier K, et al. Clonal analysis of infiltrating T lymphocytes in liver tissue in viral hepatitis A. Immunology 1990; 69:14.
  24. Baba M, Hasegawa H, Nakayabu M, et al. Cytolytic activity of natural killer cells and lymphokine activated killer cells against hepatitis A virus infected fibroblasts. J Clin Lab Immunol 1993; 40:47.
  25. Rezende G, Roque-Afonso AM, Samuel D, et al. Viral and clinical factors associated with the fulminant course of hepatitis A infection. Hepatology 2003; 38:613.
  26. Lednar WM, Lemon SM, Kirkpatrick JW, et al. Frequency of illness associated with epidemic hepatitis A virus infections in adults. Am J Epidemiol 1985; 122:226.
  27. Tong MJ, el-Farra NS, Grew MI. Clinical manifestations of hepatitis A: recent experience in a community teaching hospital. J Infect Dis 1995; 171 Suppl 1:S15.
  28. Gordon SC, Reddy KR, Schiff L, Schiff ER. Prolonged intrahepatic cholestasis secondary to acute hepatitis A. Ann Intern Med 1984; 101:635.
  29. Centers for Disease Control and Prevention. Hepatitis Surveillance Report. United States Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, GA 2011.
  30. Epidemiology and prevention of vaccine-preventable diseases. In: The Pink Book: Course Textbook, 13th ed, Centers for Disease Control and Prevention (Ed), United States Department of Health and Human Services, Atlanta, GA 2015. p.136.
  31. Vento S, Garofano T, Renzini C, et al. Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. N Engl J Med 1998; 338:286.
  32. Squires RH Jr, Shneider BL, Bucuvalas J, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr 2006; 148:652.
  33. Ciocca M, Moreira-Silva SF, Alegría S, et al. Hepatitis A as an etiologic agent of acute liver failure in Latin America. Pediatr Infect Dis J 2007; 26:711.
  34. Ciocca M, Ramonet M, Cuarterolo M, et al. Prognostic factors in paediatric acute liver failure. Arch Dis Child 2008; 93:48.
  35. Shah U, Habib Z, Kleinman RE. Liver failure attributable to hepatitis A virus infection in a developing country. Pediatrics 2000; 105:436.
  36. Terrault NA, Wright TL. Viral hepatitis A through G. In: Gastrointestinal and Liver Disease, Feldman M, Scharschmidt BF, Sleisenger MH (Eds), WB Saunders, Philadelphia 1998. p.1129.
  37. Schiff ER. Atypical clinical manifestations of hepatitis A. Vaccine 1992; 10 Suppl 1:S18.
  38. Vento S, Garofano T, Di Perri G, et al. Identification of hepatitis A virus as a trigger for autoimmune chronic hepatitis type 1 in susceptible individuals. Lancet 1991; 337:1183.
  39. Skoog SM, Rivard RE, Batts KP, Smith CI. Autoimmune hepatitis preceded by acute hepatitis A infection. Am J Gastroenterol 2002; 97:1568.
  40. Vento S, Cainelli F. Is there a role for viruses in triggering autoimmune hepatitis? Autoimmun Rev 2004; 3:61.
  41. Ashur Y, Adler R, Rowe M, Shouval D. Comparison of immunogenicity of two hepatitis A vaccines--VAQTA and HAVRIX--in young adults. Vaccine 1999; 17:2290.
  42. Jilg W, Bittner R, Bock HL, et al. Vaccination against hepatitis A: comparison of different short-term immunization schedules. Vaccine 1992; 10 Suppl 1:S126.
  43. Kao HW, Ashcavai M, Redeker AG. The persistence of hepatitis A IgM antibody after acute clinical hepatitis A. Hepatology 1984; 4:933.
  44. Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices. Updated recommendations from the Advisory Committee on Immunization Practices (ACIP) for use of hepatitis A vaccine in close contacts of newly arriving international adoptees. MMWR Morb Mortal Wkly Rep 2009; 58:1006.
  45. Dorell CG, Yankey D, Byrd KK, Murphy TV. Hepatitis a vaccination coverage among adolescents in the United States. Pediatrics 2012; 129:213.
  46. Narkewicz MR, Dell Olio D, Karpen SJ, et al. Pattern of diagnostic evaluation for the causes of pediatric acute liver failure: an opportunity for quality improvement. J Pediatr 2009; 155:801.
  47. American Academy of Pediatrics. Hepatitis A. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.391.
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