Hepatitis A virus infection in adults: An overview
- Michelle Lai, MD, MPH
Michelle Lai, MD, MPH
- Assistant Professor, Harvard Medical School
- Beth Israel Deaconess Medical Center
- Sanjiv Chopra, MD, MACP
Sanjiv Chopra, MD, MACP
- Editor-in-Chief — Gastroenterology/Hepatology
- Section Editor — General Hepatology
- Section Editor — Gallbladder and Biliary Tract Disease
- Professor of Medicine
- Harvard Medical School
- Senior Consultant in Hepatology
- James Tullis Firm Chief
- Beth Israel Deaconess Medical Center
Hepatitis A infection is caused by the hepatitis A virus (HAV). Humans are the only known reservoir. HAV infection is usually a self-limited illness that does not become chronic. Fulminant hepatic failure occurs in less than 1 percent of cases. Infection confers lifelong immunity and is preventable via vaccination.
HAV is a member of the genus Heparnavirus in the family Picornaviridae family. Two clinical forms of hepatitis were recognized in 1947 and designated hepatitis A and hepatitis B ; subsequently, the virus that causes hepatitis A was identified in 1973 . Other terms previously used for hepatitis A virus infection include epidemic jaundice, acute catarrhal jaundice, and campaign jaundice.
The epidemiology, clinical manifestations, diagnosis, and treatment of HAV infection in adults are reviewed here. Issues related to HAV vaccination are presented separately, as are issues related to HAV in children and pregnant women. (See "Hepatitis A virus infection: Prevention" and "Overview of hepatitis A virus infection in children" and "Intercurrent hepatobiliary disease during pregnancy", section on 'Hepatitis A'.)
Hepatitis A virus (HAV) infection occurs worldwide. Globally, an estimated 1.4 million cases occur each year . HAV is usually transmitted by the fecal-oral route (either via person-to-person contact or consumption of contaminated food or water). Risk factors for HAV transmission include residence in or travel to areas to poor sanitation, household or sexual contact with another person with hepatitis A, homosexual activity in men, exposure to daycare centers, exposure to residential institutions, and illicit drug use (table 1) [4-6]. Bloodborne transmission can occur but is uncommon . Maternal-fetal transmission has not been described.
The incidence of HAV has declined substantially since implementation of vaccination among children. In the United States, since vaccination was recommended for individuals at increased risk for infection (in 1996), children living in states with the highest incidence of HAV (in 1999) and for all infants (in 2006), the incidence of acute hepatitis A has declined from 6 to 0.4 cases per 100,000 between 1999 and 2014; an estimated 2500 cases of hepatitis A occurred in 2014 (figure 1 and figure 2) [4,8-14]. Similarly, in China, the incidence among individuals age ≤19 years in one province declined to a historically low rate in 2014, while the highest incidence rate was observed in those aged ≥20 years . In addition, improvement of living conditions in developing countries has been associated with fewer child infections, leading to a larger population of adults who lack protective antibodies and are at risk for outbreaks (figure 3) .
- MacCallum FO. Homologous serum jaundice. Lancet 1947; 2:691.
- Feinstone SM, Kapikian AZ, Purceli RH. Hepatitis A: detection by immune electron microscopy of a viruslike antigen associated with acute illness. Science 1973; 182:1026.
- World Health Organization. Global Alert and Response (GAR): Hepatitis A. http://www.who.int/csr/disease/hepatitis/whocdscsredc2007/en/index4.html#estimated (Accessed on July 13, 2016).
- 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.
- Klevens RM, Miller JT, Iqbal K, et al. The evolving epidemiology of hepatitis a in the United States: incidence and molecular epidemiology from population-based surveillance, 2005-2007. Arch Intern Med 2010; 170:1811.
- Bohm SR, Berger KW, Hackert PB, et al. Hepatitis A outbreak among adults with developmental disabilities in group homes--Michigan, 2013. MMWR Morb Mortal Wkly Rep 2015; 64:148.
- Bower WA, Nainan OV, Han X, Margolis HS. Duration of viremia in hepatitis A virus infection. J Infect Dis 2000; 182:12.
- Wasley A, Samandari T, Bell BP. Incidence of hepatitis A in the United States in the era of vaccination. JAMA 2005; 294:194.
- 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.
- Mutsch M, Spicher VM, Gut C, Steffen R. Hepatitis A virus infections in travelers, 1988-2004. Clin Infect Dis 2006; 42:490.
- Ly KN, Klevens RM. Trends in disease and complications of hepatitis A virus infection in the United States, 1999-2011: a new concern for adults. J Infect Dis 2015; 212:176.
- Centers for Disease Control and Prevention. Hepatitis A Questions and Answers for Health Professionals. http://www.cdc.gov/hepatitis/hav/havfaq.htm#general (Accessed on July 13, 2016).
- Centers for Disease Control and Prevention. Viral Hepatitis Surveillance: United States, 2013. US Department of Health and Human Services, Atlanta, GA 2015. http://www.cdc.gov/hepatitis/statistics/2013surveillance/pdfs/2013hepsurveillancerpt.pdf (Accessed on April 28, 2016).
- Murphy TV, Denniston MM, Hill HA, et al. Progress Toward Eliminating Hepatitis A Disease in the United States. MMWR Suppl 2016; 65:29.
- Wang Z, Chen Y, Xie S, Lv H. Changing Epidemiological Characteristics of Hepatitis A in Zhejiang Province, China: Increased Susceptibility in Adults. PLoS One 2016; 11:e0153804.
- Cuthbert JA. Hepatitis A: old and new. Clin Microbiol Rev 2001; 14:38.
- Chodick G, Ashkenazi S, Lerman Y. The risk of hepatitis A infection among healthcare workers: a review of reported outbreaks and sero-epidemiologic studies. J Hosp Infect 2006; 62:414.
- Wiseman R, Weil LM, Lozano C, et al. Notes from the Field: Health Care-Associated Hepatitis A Outbreak - Texas, 2015. MMWR Morb Mortal Wkly Rep 2016; 65:425.
- De Serres G, Cromeans TL, Levesque B, et al. Molecular confirmation of hepatitis A virus from well water: epidemiology and public health implications. J Infect Dis 1999; 179:37.
- Dentinger CM, Bower WA, Nainan OV, et al. An outbreak of hepatitis A associated with green onions. J Infect Dis 2001; 183:1273.
- Wheeler C, Vogt TM, Armstrong GL, et al. An outbreak of hepatitis A associated with green onions. N Engl J Med 2005; 353:890.
- Donnan EJ, Fielding JE, Gregory JE, et al. A multistate outbreak of hepatitis A associated with semidried tomatoes in Australia, 2009. Clin Infect Dis 2012; 54:775.
- Tang YW, Wang JX, Xu ZY, et al. A serologically confirmed, case-control study, of a large outbreak of hepatitis A in China, associated with consumption of clams. Epidemiol Infect 1991; 107:651.
- Halliday ML, Kang LY, Zhou TK, et al. An epidemic of hepatitis A attributable to the ingestion of raw clams in Shanghai, China. J Infect Dis 1991; 164:852.
- Jacobsen KH, Wiersma ST. Hepatitis A virus seroprevalence by age and world region, 1990 and 2005. Vaccine 2010; 28:6653.
- Hutin YJ, Pool V, Cramer EH, et al. A multistate, foodborne outbreak of hepatitis A. National Hepatitis A Investigation Team. N Engl J Med 1999; 340:595.
- Kemmer NM, Miskovsky EP. Hepatitis A. Infect Dis Clin North Am 2000; 14:605.
- Taylor RM, Davern T, Munoz S, et al. Fulminant hepatitis A virus infection in the United States: Incidence, prognosis, and outcomes. Hepatology 2006; 44:1589.
- 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.
- Vallbracht A, Fleischer B, Busch FW. Hepatitis A: hepatotropism and influence on myelopoiesis. Intervirology 1993; 35:133.
- 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.
- 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.
- 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.
- Lemon SM. Type A viral hepatitis. New developments in an old disease. N Engl J Med 1985; 313:1059.
- 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.
- 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.
- Koff RS. Clinical manifestations and diagnosis of hepatitis A virus infection. Vaccine 1992; 10 Suppl 1:S15.
- Richardson M, Elliman D, Maguire H, et al. Evidence base of incubation periods, periods of infectiousness and exclusion policies for the control of communicable diseases in schools and preschools. Pediatr Infect Dis J 2001; 20:380.
- Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
- Inman RD, Hodge M, Johnston ME, et al. Arthritis, vasculitis, and cryoglobulinemia associated with relapsing hepatitis A virus infection. Ann Intern Med 1986; 105:700.
- Dan M, Yaniv R. Cholestatic hepatitis, cutaneous vasculitis, and vascular deposits of immunoglobulin M and complement associated with hepatitis A virus infection. Am J Med 1990; 89:103.
- Schiff ER. Atypical clinical manifestations of hepatitis A. Vaccine 1992; 10 Suppl 1:S18.
- Ilan Y, Hillman M, Oren R, et al. Vasculitis and cryoglobulinemia associated with persisting cholestatic hepatitis A virus infection. Am J Gastroenterol 1990; 85:586.
- Lavine J, Bull F, Millward-Sadler G. Acute viral hepatitis. In: Wright's Liver and Biliary Disease, Millard-Sadler G, Wright R, Arthur M (Eds), WB Saunders, London 1992. p.681.
- Shenoy R, Nair S, Kamath N. Thrombocytopenia in hepatitis A--an atypical presentation. J Trop Pediatr 2004; 50:241.
- Gordon SC, Reddy KR, Schiff L, Schiff ER. Prolonged intrahepatic cholestasis secondary to acute hepatitis A. Ann Intern Med 1984; 101:635.
- Jung YM, Park SJ, Kim JS, et al. Atypical manifestations of hepatitis A infection: a prospective, multicenter study in Korea. J Med Virol 2010; 82:1318.
- Schiraldi O, Modugno A, Miglietta A, Fera G. Prolonged viral hepatitis type A with cholestasis: case report. Ital J Gastroenterol 1991; 23:364.
- Glikson M, Galun E, Oren R, et al. Relapsing hepatitis A. Review of 14 cases and literature survey. Medicine (Baltimore) 1992; 71:14.
- Kassas AL, Telegdy L, Méhesfalvi E, et al. Polyphasic and protracted patterns of hepatitis A infection: a retrospective study. Acta Med Hung 1994; 50:93.
- Bornstein JD, Byrd DE, Trotter JF. Relapsing hepatitis A: a case report and review of the literature. J Clin Gastroenterol 1999; 28:355.
- Grünhage F, Spengler U, Fischer HP, Sauerbruch T. Autoimmune hepatitis--sequel of a relapsing hepatitis A in a 75-year-old woman. Digestion 2004; 70:187.
- Sjogren MH, Tanno H, Fay O, et al. Hepatitis A virus in stool during clinical relapse. Ann Intern Med 1987; 106:221.
- Rachima CM, Cohen E, Garty M. Acute hepatitis A: combination of the relapsing and the cholestatic forms, two rare variants. Am J Med Sci 2000; 319:417.
- 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.
- Skoog SM, Rivard RE, Batts KP, Smith CI. Autoimmune hepatitis preceded by acute hepatitis A infection. Am J Gastroenterol 2002; 97:1568.
- Centers for Disease Control and Prevention (CDC). Positive test results for acute hepatitis A virus infection among persons with no recent history of acute hepatitis--United States, 2002-2004. MMWR Morb Mortal Wkly Rep 2005; 54:453.