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INTRODUCTION — 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 Hepatovirus in the family Picornaviridae. 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'.)
EPIDEMIOLOGY — 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) .
Hepatitis A can occur sporadically or in an epidemic form . Outbreaks have been described, including healthcare-associated outbreaks [17,18] and community outbreaks due to contaminated water or food (including shellfish and vegetables) [19-24]. Cooked foods can transmit HAV if the temperature during food preparation is inadequate to kill the virus or if food is contaminated after cooking, as occurs in outbreaks associated with infected food handlers . International outbreaks have occurred via importation of contaminated food from areas where HAV is endemic [21,22,25]. In some circumstances, seemingly sporadic occurrences may reflect cases from geographically distant outbreaks. In one report, for example, 213 cases of hepatitis A were detected from 23 schools in Michigan and 29 cases from 13 schools in Maine; all were related to contaminated frozen strawberries from a common source .
Fulminant hepatic failure develops in less than 1 percent of patients with hepatitis A ; it occurs most commonly among patients with underlying liver disease, particularly chronic hepatitis C virus infection [13,28,29]. In one study including 163 patients with chronic hepatitis B and 432 patients with chronic hepatitis C followed prospectively, hepatitis A superinfection occurred in 27 patients . Among 17 patients with hepatitis C who acquired hepatitis A, fulminant hepatic failure developed in 7 cases, of whom 6 died. Among 10 patients with hepatitis B who acquired hepatitis A, 9 had uncomplicated infection; one patient developed marked cholestasis in the setting of preexisting cirrhosis.
PATHOGENESIS — Hepatic injury occurs as a result of the host immune response to hepatitis A virus (HAV). Viral replication occurs in the hepatocyte cytoplasm; hepatocellular damage and destruction of infected hepatocytes is mediated by human leukocyte antigen–restricted, HAV-specific CD8+ T lymphocytes and natural killer cells [30-32]. Interferon-gamma appears to have a central role in promoting clearance of infected hepatocytes . An excessive host response (denoted by a marked reduction of circulation HAV RNA during acute infection) is associated with severe hepatitis .
Typical manifestations — Acute hepatitis A virus (HAV) infection in adults is usually a self-limited illness; fulminant hepatic failure occurs in less than 1 percent of cases. The incubation period of hepatitis A infection averages 28 days (range 15 to 50 days) .
More than 70 percent of adults with HAV have symptomatic illness, which begins with abrupt onset of nausea, vomiting, anorexia, fever, malaise, and abdominal pain (figure 4) . Within a few days to a week, dark urine (bilirubinuria) appears; pale stools (lacking bilirubin pigment) may also be observed. These are followed by jaundice and pruritus (40 to 70 percent of cases). The early signs and symptoms usually diminish when jaundice appears, and jaundice typically peaks within two weeks.
Physical findings include fever, jaundice, scleral icterus, hepatomegaly (80 percent of cases), and abdominal pain [16,36]. Less common findings include splenomegaly and extrahepatic manifestations such as skin rash and arthralgias. (See 'Extrahepatic manifestations' below.)
Laboratory abnormalities include elevations of serum aminotransferases (often >1000 international units/dL), serum bilirubin (typically ≤10 mg/dL), and alkaline phosphatase (up to 400 U/L) . The serum aminotransferase elevations precede the bilirubin elevation. Serum alanine aminotransferase (ALT) is commonly higher than the serum aspartate aminotransferase (AST). Serum aminotransferases peak approximately one month after exposure to the virus and then decline by approximately 75 percent per week . The serum bilirubin concentration usually declines within two weeks of peak levels . Other laboratory abnormalities include elevations of acute-phase reactants and inflammatory markers.
Infected individuals are contagious during the incubation period and remain so for about a week after jaundice appears . HAV replicates in the liver and is shed in the stool in high concentrations from two to three weeks before to one week after onset of clinical illness (figure 4) .
Full clinical and biochemical recovery is observed within two to three months in 85 percent of patients, and complete recovery is observed by six months in nearly all patients . HAV infection does not become chronic, and individuals cannot become reinfected after recovering from infection.
Fulminant hepatic failure refers to the development of severe acute liver injury with encephalopathy and impaired synthetic function (international normalized ratio [INR] ≥1.5). It occurs most commonly in individuals >50 years of age and individuals with other liver diseases such as hepatitis B or C . (See "Acute liver failure in adults: Etiology, clinical manifestations, and diagnosis".)
Extrahepatic manifestations — A number of extrahepatic manifestations associated with hepatitis A virus infection have been described. Extrahepatic manifestations occur most commonly in patients who have protracted illness such as relapsing or cholestatic hepatitis [40,41]. (See 'Cholestatic hepatitis' below and 'Relapsing hepatitis' below.)
The most common extrahepatic manifestations include evanescent rash and arthralgias (occurring in 10 to 15 percent of patients). Other conditions related to immune complex disease and vasculitis also occur, including [40-45]:
●Leukocytoclastic vasculitis (most often apparent on the legs and buttocks; biopsy demonstrates anti-HAV immunoglobulin (Ig)M and complement in the blood vessel walls)
●Toxic epidermal necrolysis
●Red cell aplasia
Complications — Complications of acute hepatitis A infection include cholestatic hepatitis, relapsing hepatitis, and autoimmune hepatitis .
Cholestatic hepatitis — Prolonged cholestasis is characterized by a protracted period of jaundice (lasting >3 months); it occurs among fewer than 5 percent of patients with acute hepatitis A infection [46,47].
The course of cholestatic hepatitis is usually characterized by marked jaundice, pruritus, fever, weight loss, diarrhea, and malaise [36,42,46,48]. Laboratory findings include markedly elevated serum bilirubin (often >10 mg/dL) and alkaline phosphatase, modest elevation of serum aminotransferases, and elevated serum cholesterol. Peak bilirubin levels may be reached in the eighth week or later.
In general, cholestatic hepatitis resolves spontaneously with no sequelae; recognition is important to avoid unnecessary testing. Ultrasonography is appropriate to exclude biliary obstruction; cholangiography or liver biopsy are usually not necessary .
Relapsing hepatitis — Up to 10 percent of patients experience a relapse of symptoms during the six months after acute illness [39,42,49-53]. The duration of clinical relapse is generally less than 3 weeks, although biochemical relapse may last as long as 12 months . The cause of relapsing hepatitis is unknown, and no predisposing factors for relapse have been identified .
The clinical course usually consists of apparent clinical recovery after acute infection with near normalization of the serum aminotransferases, followed by biochemical (and, in some cases, clinical) relapse; clinical manifestations of relapse are often milder than the initial episode . Serum aminotransferases may exceed 1000 international units/dL, and serum anti-hepatitis A virus IgM antibodies typically persist throughout the course of the disease [49,54]. HAV can be recovered from stool during relapse episodes, so such patients should be considered infectious . (See 'Diagnosis' below.)
Multiple relapses can occur. In one series including 297 adults with acute hepatitis A infection, relapse was observed in 13 percent of patients (of whom 22 percent had more than one relapse); approximately half of patients were asymptomatic during the relapses . Development of extrahepatic manifestations (such as arthritis, vasculitis, nephritis, and cryoglobulinemia) during relapse has been described [40,43]. (See 'Extrahepatic manifestations' above.)
In general, patients with relapsing hepatitis have complete recovery; recognition is important to avoid unnecessary testing. Ultrasonography is appropriate to exclude biliary obstruction in patients with significant jaundice; cholangiography or liver biopsy are usually not necessary.
Autoimmune hepatitis — Rarely, HAV infection may serve as a trigger for development of autoimmune hepatitis in susceptible individuals [55,56]. Autoimmune hepatitis is a chronic hepatitis characterized by hyperglobulinemia, the presence of circulating autoantibodies (such as anti-nuclear, anti-smooth muscle, and/or anti-actin antibodies), and inflammatory changes on liver histology.
Issues related to autoimmune hepatitis are discussed separately. (See "Autoimmune hepatitis: Clinical manifestations and diagnosis".)
DIAGNOSIS — The diagnosis of acute hepatitis A virus (HAV) infection should be suspected in patients with abrupt onset of prodromal symptoms (nausea, anorexia, fever, malaise, or abdominal pain) and jaundice or elevated serum aminotransferase levels, particularly in the setting of known risk factors for hepatitis A transmission (table 1) .
The diagnosis is established by detection of serum immunoglobulin (Ig)M anti-HAV antibodies. Serum IgM antibodies are detectable at the time of symptom onset, peak during the acute or early convalescent phase of the disease, and remain detectable for approximately three to six months (figure 4). Among patients with relapsing hepatitis, serum IgM antibodies persist for the duration of this pattern of disease. (See 'Relapsing hepatitis' above.)
Detection of serum IgM antibodies in the absence of clinical symptoms may reflect prior hepatitis A infection with prolonged persistence of IgM, a false-positive result, or asymptomatic infection (which is more common in children <6 years of age than older children or adults) .
Serum IgG antibodies appear early in the convalescent phase of the disease, remain detectable for decades, and are associated with lifelong protective immunity (figure 4). Detection of anti-HAV IgG in the absence of anti-HAV IgM reflects past infection or vaccination rather than acute infection.
Imaging studies are generally not needed for diagnosis of HAV infection. Ultrasonography is appropriate to alternate diagnoses (such as biliary obstruction); cholangiography or liver biopsy are usually not necessary.
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of hepatitis A virus infection includes other viruses that can cause hepatitis, all of which may be distinguished via serology:
●Hepatitis B, C, D, and E – Hepatitis A and E are acute infections transmitted by the fecal-oral route, whereas hepatitis B, C, and D can present acutely or chronically and are transmitted by body fluids. (See related topics.)
●Epstein-Barr and cytomegalovirus – Both Epstein-Barr and cytomegalovirus may present with liver function abnormalities as well as fever, fatigue, and lymphadenopathy. (See "Infectious mononucleosis in adults and adolescents" and "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults".)
●Yellow fever virus – Yellow fever virus is transmitted by mosquitoes in endemic regions; initial manifestations consist of malaise and other nonspecific symptoms, followed by acute illness with fever and gastrointestinal manifestations. (See "Yellow fever".)
●Herpes simplex virus – Hepatitis is a rare complication of herpes simplex virus infection. It may present fulminantly, most commonly in immunocompromised hosts. (See "Clinical manifestations and diagnosis of herpes simplex virus type 1 infection", section on 'Hepatitis'.)
●Adenovirus – Adenovirus infection typically involves the respiratory and gastrointestinal tracts; hepatitis may be a complication of adenovirus infection in immunocompromised hosts. (See "Epidemiology and clinical manifestations of adenovirus infection", section on 'Gastrointestinal tract'.)
●HIV infection – Patients with acute HIV infection may have nausea, diarrhea, and anorexia. More serious gastrointestinal manifestations such as hepatitis can occur though are rare. (See "Acute and early HIV infection: Clinical manifestations and diagnosis".)
Other infectious causes of fever and jaundice include:
●Malaria – Malaria is a mosquito-borne parasitic infection characterized by fever, anemia, and parasitemia; clinical manifestations include jaundice due to hemolysis. The diagnosis may be established by examination of the peripheral blood smear. (See "Clinical manifestations of malaria in nonpregnant adults and children".)
●Leptospirosis – Leptospirosis is a bacterial infection characterized by fever, myalgia, headache, and conjunctival suffusion. Modest elevation of hepatic transaminases may be observed. The diagnosis is established by serology. (See "Epidemiology, microbiology, clinical manifestations, and diagnosis of leptospirosis".)
●Syphilis – Syphilis is sexually transmitted infection; secondary syphilis consists of a number of clinical manifestations including elevated serum alkaline phosphatase, often with normal or only slightly abnormal transaminases. The diagnosis is established by serology. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients", section on 'Clinical manifestations'.)
●Q fever – Q fever occurs as a result of infection with Coxiella burnetii; hepatic involvement includes transaminitis, hepatomegaly without jaundice, and granulomas on liver biopsy. The diagnosis is established by serology. (See "Clinical manifestations and diagnosis of Q fever".)
Noninfectious entities with presentations similar to hepatitis A infection include:
●Drug-induced liver injury (DILI) – Liver injury can be associated with many drugs (table 2). Patients with DILI may be asymptomatic with abnormal liver function tests or have malaise, anorexia, nausea, vomiting, right upper quadrant pain, dark urine, acholic stools, jaundice, and pruritus. The diagnosis may be established via liver biopsy. (See "Drug-induced liver injury".)
●Budd-Chiari syndrome – Budd-Chiari syndrome is defined as hepatic venous outflow tract obstruction. Patients with Budd-Chiari syndrome may present with acute or subacute liver disease or acute liver failure. The diagnosis is established via ultrasonography. (See "Budd-Chiari syndrome: Epidemiology, clinical manifestations, and diagnosis".)
●Autoimmune hepatitis – Autoimmune hepatitis may be asymptomatic or present with nonspecific symptoms, such as malaise, anorexia, nausea, abdominal pain, itching, and arthralgia. The diagnosis is established via serologic testing and histology. (See "Autoimmune hepatitis: Clinical manifestations and diagnosis".)
●Wilson disease – Wilson disease is a genetic disorder characterized by excess copper; it can present as acute hepatitis, jaundice, abdominal pain, and elevated transaminase levels (typically <2000 international units/dL with an aspartate aminotransferase/alanine aminotransferase ratio >2). The diagnosis is based on serum ceruloplasmin and copper levels and ocular slit-lamp examination for Kayser-Fleisher rings. (See "Wilson disease: Clinical manifestations, diagnosis, and natural history".)
TREATMENT — Hepatitis A virus infection is usually self-limited, and treatment consists of supportive care. Medications that might cause liver damage or are metabolized by the liver should be used with caution. Full clinical and biochemical recovery is observed within three months in 85 percent of patients, and complete recovery is observed by six months in nearly all patients .
Patients with fulminant hepatic failure require aggressive supportive therapy and should be transferred to a center capable of performing liver transplantation. (See "Acute liver failure in adults: Management and prognosis".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topics (see "Patient education: Hepatitis A (The Basics)")
●Beyond the Basics topics (see "Patient education: Hepatitis A (Beyond the Basics)")
●Hepatitis A infection is caused by the hepatitis A virus (HAV) that occurs worldwide. Hepatitis A is usually a self-limited illness that does not become chronic. (See 'Introduction' above.)
●HAV is typically 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). (See 'Epidemiology' above.)
●The incubation period of HAV averages 28 days (range 15 to 50 days). Most adults with HAV infection have symptomatic illness which begins with abrupt onset of nausea, anorexia, fever, malaise, and abdominal pain. Within a few days to a week, dark urine and acholic stools appear, followed by jaundice and pruritus. The early clinical manifestations usually diminish when jaundice appears, and jaundice typically peaks within two weeks. (See 'Clinical manifestations' above.)
●Laboratory abnormalities include elevations of serum aminotransferases (often >1000 international units/dL), followed by elevations of serum bilirubin (up to 10 mg/dL). Serum aminotransferases peak approximately one month after exposure to the virus and then decline by approximately 75 percent per week. The serum bilirubin concentration usually declines within two weeks of peak levels. (See 'Clinical manifestations' above.)
●The diagnosis of acute HAV infection should be suspected in patients with abrupt onset of gastrointestinal signs and symptoms and jaundice or elevated serum aminotransferase levels, particularly in the setting of known risk factors for hepatitis A transmission (table 1). The diagnosis is established by detection of serum immunoglobulin (Ig)M anti-HAV antibodies. (See 'Diagnosis' above.)
●Extrahepatic manifestations include evanescent rash, arthralgias, and other conditions related to immune complex disease and vasculitis. Complications of acute hepatitis A infection include cholestatic hepatitis, relapsing hepatitis, and autoimmune hepatitis. (See 'Extrahepatic manifestations' above and 'Complications' above.)
●HAV infection is usually self-limited, and treatment consists of supportive care. Medications that might cause liver damage or are metabolized by the liver should be used with caution. Full clinical and biochemical recovery are observed within two to three months in most patients, and complete recovery is observed by six months in nearly all patients. HAV infection confers lifelong immunity. (See 'Clinical manifestations' above and 'Treatment' above.)
●Fulminant hepatic failure occurs in less than 1 percent of patients with HAV infection. It consists of severe acute liver injury with encephalopathy and impaired synthetic function and occurs most commonly in individuals >50 years of age and individuals with other liver diseases such as hepatitis B or C. Patients with fulminant hepatic failure should be transferred to a center capable of performing liver transplantation. (See 'Clinical manifestations' above and "Acute liver failure in adults: Etiology, clinical manifestations, and diagnosis".)
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Dr. Catherine Cheney, who contributed to earlier versions of this topic review.
- 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.