Hepatitis A


Article Author:
Natalya Iorio


Article Editor:
Savio John


Editors In Chief:
Dustin Constant
Donald Kushner


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
4/20/2019 10:05:05 PM

Introduction

The hepatitis A virus (HAV) is a common infectious etiology of acute hepatitis worldwide. HAV is most commonly transmitted through the oral-fecal route via exposure to contaminated food, water, or close physical contact with an infectious person. According to the World Health Organization (WHO), infection rates in developed countries are low. However, high-risk groups include injection-drug users, men who have sex with men, people traveling to endemic areas, and isolated communities. HAV does not cause chronic liver disease unlike hepatitis B or C. Acute hepatitis as an infection usually presents as a self-limited illness; development of fulminant hepatitis is rare. Typical symptoms of acute infection include nausea, vomiting, abdominal pain, fatigue, malaise, poor appetite, and fever; management is with supportive care. Alternate clinical patterns include cholestatic, prolonged, and relapsing disease. Vaccination against HAV is recommended for children 12 months or older and adults with the risk of exposure including travelers to endemic countries, men who have sex with men, illicit drug users, potential occupational exposure, and/or chronic liver disease.[1][2][3][4]

Etiology

HAV is one of the most common causes of acute hepatitis infection worldwide. The WHO estimates that approximately 1.5 million people are infected with HAV each year. Endemic rates are high in developing countries with low socioeconomic conditions and poor sanitation and hygiene practices. Exposure in these developing countries usually occurs in childhood. Infection rates are low in developed countries such as the United States, Canada, and Western Europe. High-risk groups in low endemicity countries have been identified as injection-drug users, men who have sex with men, people traveling to endemic areas, and isolated communities such as nursing homes and even day-care centers. The incidence of HAV in a given population correlates with socioeconomic properties such as income, the density of housing, sanitation, and water quality. With the implementation of vaccination, the incidence of HAV in the United States has significantly decreased. The incidence of acute HAV infection has decreased by 92% from 12 cases per 100,000 in 1995 to 1 case per 100,000 in 2007.[5]

Epidemiology

Improved sanitation has resulted in a shift in the age group that acquires hepatitis A. In recent years there has been a decline in the incidence of new infection.

The United States has a low endemicity. Mexico has a high prevalence of individuals with the anti-HAV antibody indicating a previous infection. The frequency of acute hepatitis is higher in those U.S. states that are adjacent to Mexico.

The reported hepatitis A incidence has declined by 90% to as low as 1.2 cases per 100,000 population. The greatest reductions are seen in children and in those states where routine vaccination was started in 1999. Over the last 4 decades, the average age of hepatitis A infected individuals has increased.

Individuals in high-risk populations account for most cases of HAV infection. These groups include foreign travelers to developing nations, gays, childcare workers, institutionalized individuals, and those living in poverty.

Food handlers are an infrequent source of outbreaks in the United States. Virtually any food may be contaminated with HAV.

International

HAV is highest in resource-poor regions such as Africa, Asia, and South America, where evidence of past infection is nearly universal. Acquisition often occurs in childhood, and it is usually asymptomatic. 

Sex

There is no sexual predilection. It is most common in aid workers, gays, and around sewage.

Age

With increasing age symptomatic disease and adverse sequelae increases. Mortality from fulminant hepatic failure increases with increasing age.

Pathophysiology

HAV, first identified in 1973 by Feinstone et al., is classified in the family Picornaviridae and genus Hepatovirus. It is a positive-sense, single-stranded RNA virus which replicates primarily within hepatocytes. Animal studies showing HAV antigen in the epithelial cells of intestinal crypts and cells of the lamina propria in the small intestine suggest replication might also occur at these sites. Once ingested orally, the virus is taken up from the gastrointestinal tract and the HAV particles are carried to the basolateral membrane of the hepatocyte via portal circulation. The hepatocellular injury in acute HAV infection is mediated by various immune mechanisms. It has been shown that patients with acute HAV infection have the virus-specific T-cell mediated release of cytotoxic interferon gamma. Additionally, recent mice-models have demonstrated HAV-induced hepatocellular apoptosis and inflammation associated with the innate immune response.  The humoral immune response is responsible for the diagnostic serologic assays. Following replication in the liver, HAV is excreted in bile and released into the stool. The concentration of the virus is highest in the stool during the 2 weeks before onset of jaundice, at which point the individual is most infectious. Most people are no longer infectious 1 week after jaundice appears at which time stool shedding and viremia are decreased.

History and Physical

Acute HAV infection is typically a self-limited illness characterized by nausea, vomiting, right upper quadrant abdominal discomfort, malaise, anorexia, myalgia, fatigue, and fever. Patients may develop dark urine and pale stools within a week, followed by jaundice, icteric (yellow-tinted) sclera, and pruritus. Patients usually have elevated levels of serum alanine aminotransferase, aspartate aminotransferase, bilirubin, alkaline phosphatase, and lambda-glutamyl transpeptidase. These lab abnormalities typically resolve within 1 to 6 weeks following the onset of symptoms. The incubation period usually ranges from 14 to 28 days but can last up to 50 days. The severity of symptoms varies with age and comorbidities, particularly underlying chronic liver disease. Most children with acute HAV infection are asymptomatic.

Extra-hepatic manifestations rarely occur but may include pancreatitis, rash, acute kidney injury with interstitial nephritis or glomerular nephritis, pneumonitis, pericarditis, hemolysis, and acute cholecystitis. Neurologic complications have also been reported such as mononeuritis, Guillan-Barre, encephalitis and central myelitis. There were two reported cases in 1991 of autoimmune hepatitis triggered by acute HAV infection. Lemon et al. describe five clinical patterns: 

  1. Asymptomatic infection
  2. Symptomatic infection with jaundice, dark urine, and clay-colored stool
  3. Cholestatic hepatitis with prolonged alkaline phosphatase and bilirubin elevation and pruritus
  4. Relapsing infection
  5. Fulminant hepatitis.

Evaluation

Acute hepatitis A is diagnosed by serologic testing to detect HAV-specific immunoglobulin (IgM) antibodies in the blood. Additional testing can include reverse transcriptase polymerase chain reaction to detect the viral RNA. Immunoglobulin G (IgG) anti-HAV emerges soon after infection and remains present for the person’s lifetime.

Treatment / Management

No specific treatment is needed for most patients with acute, uncomplicated HAV infection beyond supportive care. Complete recovery from symptoms may take several weeks to months. In the rare case of fulminant hepatitis from HAV infection, liver transplantation may be a life-saving measure. Extrahepatic complications are managed routinely.[5][6][7]

According to the WHO, the most effective way to prevent HAV infection is to improve sanitation, food safety, and immunization practices. In the United States, vaccination against hepatitis A is available as inactivated, single-antigen vaccines (HAVRIX and VAQTA) or in combination with hepatitis B (TWINRIX). The Centers for Disease Control and Prevention recommends vaccination for children 12 months or older, travelers to endemic countries, gays, illegal drug users, individuals with occupational risk exposure, persons with clotting factor disorders or chronic liver disease. Standard adult dosing recommends administration of two doses of the vaccine 6 to 12 months apart. These vaccines are highly efficacious were seroconversion rates approaching 100%.

Until more recently, immunoglobulin was the only treatment for post-exposure prophylaxis again HAV. However, animal studies and clinical trials demonstrated the efficacy of post-exposure immunization with an inactivated HAV vaccine has led the CDC to recommend the vaccine instead of immunoglobulin for exposure to HAV in healthy individuals aged 1 to 40 years. For individuals 41 years and older, immunoglobulin administration is preferred due to the risk of more severe clinical presentation and limited evidence of vaccine efficacy in this age group. Children less than 12 months, individuals with chronic liver disease, and immunocompromised persons should also receive immunoglobulin.[8][9][10]

Enhancing Healthcare Team Outcomes

Hepatitis A infection is usually managed by a multidisciplinary team that includes an infectious disease expert, emergency department physician, nurse specialist, primary care provider and the internist. There is no specific treatment for thsi infection. Supportive care helps recovery in most patients. For people who travel to endemic areas, the primary care providers should educate the patient on the hepatitis A Vaccine. In addition, the patient should maintain good personal hygiene, wash all fruits and vegetables, drink boiled water and avoid sexual encounters with strangers.

The prognosis for most patients with hepatitis A is excellent.[11][12]

 


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Hepatitis A - Questions

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Which of the following is transmitted by the fecal-oral route?



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Hepatitis A is acquired by which method of transmission?



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How is hepatitis A typically acquired?



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What is the most common route of acquiring hepatitis A?



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After acquiring hepatitis A, what is the single most important factor for determining illness severity?



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How is acute hepatitis A infection most commonly diagnosed?



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A 13-month-old child attending daycare is brought in by his mother. The child is healthy, but his mother is concerned because another child of 2 1/2 years who attends the same daycare center was diagnosed with hepatitis A infection about one week ago. What is not an appropriate way to manage the child?



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After exposure to hepatitis A, immunoglobulin for IM administration should be given within what time period?



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A 2-year-old boy is brought in with a 4-day history of fever followed by decreased appetite. His mother denies vomiting or diarrhea, but she thinks that he may be nauseated after eating or drinking. She also indicates that his stool pattern has changed in that for the past 3 days he has only had two stools. The last stool was firm in consistency. The child has attended daycare for the past 8 weeks. His immunizations, including the pneumococcal conjugate vaccine (Prevnar) have been documented to be complete. On physical examination the child appears to be ill. The temperature is 101.8°F (38.8°C). The child's weight is 0.1 kg less than when seen approximately 2 months ago for a physical examination prior to entering daycare. There is no rash. The examination of the lungs and heart is normal. There is epigastric fullness and mild right upper quadrant pain with examination of the abdomen. What is the diagnostic test most likely to be helpful in establishing the diagnosis in this child?



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Hepatitis A infection is identified in an employee of a day care center. This is the second out-break of hepatitis A in the center in the past year. What is the most appropriate management of a 3-year-old child who also attends the day care center?



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How long should an employee with hepatitis A be excluded from the daycare center in relation to the onset of the illness?



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Hepatitis A is acquired by what method of transmission?



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Which of the following is most likely to be positive in a patient who has recently traveled to South America and presents with signs of jaundice, hepatomegaly, elevated liver enzymes, bilirubinemia, and normal alkaline phosphatase?



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By what route is hepatitis A transmitted?



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What is the best method to prevent hepatitis A transmission?



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Which of the following statements about hepatitis A infection is TRUE?



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What type of virus is hepatitis A?



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Which of the following is true about hepatitis A?



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A 17-year-old male was diagnosed with hepatitis A one month ago by anti-hepatitis A virus IgM. He made a full recovery but returns with nausea, vomiting, malaise, and anorexia. Transaminases and bilirubin are again elevated. Select the most likely scenario.



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A young child presents with right upper quadrant pain and jaundice. Which of the following tests is most appropriate?



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Which type of hepatitis poses the least risk to health care workers?



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Hepatitis A is spread via the:



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What measure has had the greatest impact on the incidence of hepatitis A?



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Which of the following infections is transmitted through the fecal-oral route?



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Which of the following is the predominant route of transmission for hepatitis A?



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Acalculous cholecystitis is known to occur in pregnancy as a complication of which infection?



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Which is true regarding hepatitis A?



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Which of the following is not generally seen with hepatitis A?



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Which of the following can be prevented by passive immunization?



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A patient recovered from hepatitis A one year ago. What will a liver biopsy show?



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How is hepatitis A spread?



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When do the IGM titers disappear after acute hepatitis A infection?



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A 17-year-old female with asthma presents to the emergency department with right upper quadrant abdominal pain, nausea, and jaundice for two weeks. Laboratory analysis shows alanine aminotransferase of 1048, aspartate aminotransferase of 1120, alkaline phosphatase of 212, and bilirubin of 4.1. INR is 2.1. She appears slightly confused and lethargic. Hepatitis C RNA by polymerase chain reaction (PCR) is not detected, HCV antibody is negative, hepatitis A IgM is positive, hepatitis B core antibody IgM is negative, hepatitis B core antibody IgG is positive, and hepatitis B surface antigen is negative. What is the next step in management?



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Which is not a potential clinical pattern of hepatitis A infection?



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Which is not a reported extraintestinal manifestation of acute hepatitis A infection?



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Which of the following statements suggests the client needs more education regarding their diagnosis of hepatitis A infection? Select all that apply.



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Hepatitis A - References

References

Alberts CJ,Boyd A,Bruisten SM,Heijman T,Hogewoning A,Rooijen MV,Siedenburg E,Sonder GJB, Hepatitis A incidence, seroprevalence, and vaccination decision among MSM in Amsterdam, the Netherlands. Vaccine. 2019 Apr 13;     [PubMed]
Johnson KD,Lu X,Zhang D, Adherence to hepatitis A and hepatitis B multi-dose vaccination schedules among adults in the United Kingdom: a retrospective cohort study. BMC public health. 2019 Apr 15;     [PubMed]
Brennan J,Moore K,Sizemore L,Mathieson SA,Wester C,Dunn JR,Schaffner W,Jones TF, Notes from the Field: Acute Hepatitis A Virus Infection Among Previously Vaccinated Persons with HIV Infection - Tennessee, 2018. MMWR. Morbidity and mortality weekly report. 2019 Apr 12;     [PubMed]
Wilson E,Hofmeister MG,McBee S,Briscoe J,Thomasson E,Olaisen RH,Augustine R,Duncan E,Bamrah Morris S,Haddy L, Notes from the Field: Hepatitis A Outbreak Associated with Drug Use and Homelessness - West Virginia, 2018. MMWR. Morbidity and mortality weekly report. 2019 Apr 12;     [PubMed]
Tan EM,Marcelin JR,Virk A, Pre-travel counseling for immunocompromised travelers: A 12-year single-center retrospective review. Infection, disease     [PubMed]
Nelson NP,Link-Gelles R,Hofmeister MG,Romero JR,Moore KL,Ward JW,Schillie SF, Update: Recommendations of the Advisory Committee on Immunization Practices for Use of Hepatitis A Vaccine for Postexposure Prophylaxis and for Preexposure Prophylaxis for International Travel. MMWR. Morbidity and mortality weekly report. 2018 Nov 2;     [PubMed]
Gervasi G,Biticchi M,Zaratti L,Franco E, [Epidemics of Hepatitis A and opportunities for vaccination: a focus on the category of men who practice sex with men (MSM)]. Igiene e sanita pubblica. 2018 May-Jun;     [PubMed]
Waszczuk K,Waszczuk E,Szenborn L, Can we better protect patients with inflammatory bowel disease against infections - patient attitude and personal immunization knowledge. Acta gastro-enterologica Belgica. 2018 Apr-Jun;     [PubMed]
O'Leary ST,Kimberlin DW, Update From the Advisory Committee on Immunization Practices. Journal of the Pediatric Infectious Diseases Society. 2018 Aug 17;     [PubMed]
Singh V,Crosby RA,Gratzer B,Gorbach PM,Markowitz LE,Meites E, Disclosure of Sexual Behavior Is Significantly Associated With Receiving a Panel of Health Care Services Recommended for Men Who Have Sex With Men. Sexually transmitted diseases. 2018 Dec;     [PubMed]
Doshani M,Weng M,Moore KL,Romero JR,Nelson NP, Recommendations of the Advisory Committee on Immunization Practices for Use of Hepatitis A Vaccine for Persons Experiencing Homelessness. MMWR. Morbidity and mortality weekly report. 2019 Feb 15;     [PubMed]
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The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Surgery-Podiatry Cert Medicine. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

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Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Surgery-Podiatry Cert Medicine. When it is time for the Surgery-Podiatry Cert Medicine board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Surgery-Podiatry Cert Medicine.