Hepatitis A is an infectious liver disease caused by the hepatitis A virus which is transmitted through contaminated food and water. The disease is thus associated with poor sanitation and hygiene.
It is often a self-limiting disease that does not result in chronic infection and is rarely fatal.
Most of the adults have a resolution of symptoms within two months of the infection.
Antibodies once produced, through infection offer lifelong protection.
Hepatitis A is can be prevented by vaccination.
It is one of the most common foodborne infections.
Hepatitis A virus persists in the environment and can withstand food-production processes routinely used to inactivate and/or control bacterial pathogens.
The disease is common in countries with poor sanitary conditions and hygienic practices. About 90% of children are infected, often asymptomatically, with the hepatitis A virus before the age of 10 years making older children and adults generally immune.
In developed nations with good sanitary practices, the rates of infection are low and the disease may affect high-risk adolescents and adults. Following are considered high-risk groups
- Persons who inject drugs
- Men who have sex with men
- Persons traveling to endemic areas
- Isolated populations like cult groups
In countries where sanitary conditions are variable, children often are not infected leading to a susceptible pool of adults.
Transmission of Hepatitis A Virus and Pathophysiology
The primary route of transmission for hepatitis A virus is feco-oral. This could happen when a person ingests food or water contaminated with the feces of an infected person. Hence the role of hygiene and sanitation in the prevention of the disease.
Another method of transmission is close physical contact with an infected person. Oral-anal sex is responsible in some people.
Casual contact between the persons, however, is not responsible for the spread. Transmission through blood products has been described.
Hepatitis A virus is the enterovirus of the Picornaviridae family. It is quite a resilient virus that often escapes the usual food processing methods. It can survive a temperature range of 56 to -20 degrees.
The virus can survive for many years. Boiling, chlorine, and iodine are effective methods of sterilization.
There appears to be only 1 serotype.
In humans, viral replication is said to occur exclusively in the liver though some recent reports have demonstrated the virus in the saliva as well.
The virus itself is responsible for minimal cellular changes in the liver. Hepatocyte injury is thought to be due to an immune response by the body.
The incubation period lasts for about 2-6 weeks and the quantum of virus determines the time taken for symptoms to appear.
The maximum virus is shed by the infected patient before jaundice develops. The virus is shed even after jaundice but the quantity falls rapidly.
In young children and adolescents, the infection is often without symptoms [subclinical] or mild and the time taken for the onset of symptoms may be dose-related. The disease is more symptomatic in adults and elders with symptoms often being proportional to age.
Severe disease, including fulminant hepatic failure, is known to occur.
Person-to-person contact is the most common means of transmission and is generally limited to close contacts. Transmission through blood products can occur.
Most of the patients have no defined risk for hepatitis A. Poor sanitation and lack of safe water generally lead to a higher number of infections.
However, the following people have a higher risk of getting hepatitis A.
- Personal contacts of the infected person
- Institutional residents
- Foreign travelers
- Homosexuality male [oro anal sex]
- Illicit parenteral drug use
Clinical Presentation
The incubation period is the time between the entry of the organism and the manifestation of the disease. It is 2-6 weeks in case of hepatitis. Shorter incubation periods may result from a higher total dose of the viral inoculum.
Symptoms of hepatitis A vary in severity from mild to severe. The symptoms are more pronounced in older patients. Only 10 percent of the infected children less than 6 years develop jaundice whereas 70% of adolescents and adults develop it.
The following are the symptoms that are found in hepatitis A. The symptoms are non-specific and vary from person to person and not everyone who is infected will have all of the symptoms. These are
- Fever
- Malaise
- Loss of appetite
- Diarrhea
- Nausea
- Abdominal discomfort
- Dark-colored urine
- Jaundice
Clinically, the disease has 3 phases
Prodrome
- Mild flu-like symptoms
- Loss of appetite
- Nausea and vomiting
- Fatigue
- Malaise
- Low-grade fever
- Muscle pain
- Mild headache.
- Smokers often lose their taste for tobacco, like persons presenting with appendicitis.
Icteric phase
- In the icteric phase, dark urine appears first (bilirubinuria)
- Pale stool may occur in some
- Jaundice
- Abdominal pain
- Itching or pruritis
Joint pains and skin rash are infrequent.
The patient should be enquired for
- Source of exposure
- Look for high-risk behavior
- Look for other causes of liver disease
On examination, hepatomegaly is common. Jaundice or scleral icterus may be seen.
Differential Diagnoses
- Budd-Chiari Syndrome
- Cytomegalovirus infection
- Viral Hepatitis other than Hepatitis A virus
- Other causes of acute liver disease
Lab Studies
Complete blood count
- Mild lymphocytosis
- Rarely pure red cell aplasia and pancytopenia seen
- Indices of low-grade hemolysis are not uncommon.
Prothrombin time
- Usually normal
- Derangement calls for closer watch on the patient as it could indicate fulminant nature of the disease
Liver Function Tests
Liver function tests include liver enzymes estimation, serum bilirubin levels, and serum protein levels.
Deranged values of these parameters indicate an insult to the liver.
Liver function tests can become deranged in any liver disease.
In hepatitis A, enzymes levels could be markedly increased depending upon the damage to liver tissue.
[Read more on liver function tests]
Liver enzymes in hepatitis A could go very high with ALT levels often more than AST levels.
The enzymes start rising in acute disease.
Bilirubin levels, which follow enzyme levels, can remain increased for long. A persistence of more than 3 months indicates cholestatic HAV infection. Cholestasis refers to either decreased bile flow from the liver or obstruction to bile flow.
Serum proteins may be normal or fall slightly.
Modest falls in serum albumin level may accompany the illness.
Anti-hepatitis A virus IgG and IgM
These measure IgG and IgM antibodies against the hepatitis A virus.
IgM is the first to appear and is soon followed by IgG antibodies. IgM is acute and the results remain positive for 3-6 months [up to 12 months in some].
In contrast, IgG persists for years and in absence of IgM indicates an old infection. It is responsible for protective immunity.
Treatment of Hepatitis A
Hepatitis A is a self-limiting disease and there is no specific treatment for hepatitis A. Recovery may take several weeks or months.
Rest and supportive care with the treatment of specific complications as appropriate is the mainstay of the treatment.
It is important to administer fewer drugs so that the load on the liver is not increased. Some drugs like paracetamol and anti-vomiting drugs should not be given.
Patients mostly can be treated at home with OPD visits but monitoring may necessitate hospitalization. Adequate nutrition and fluid levels need to be maintained.
Liver transplantation may be required in cases of fulminant hepatic failure.
The role of antivirals is being studied.
The risk of transmission remains for up to about 10 days after the onset of jaundice.
Prevention of Hepatitis A and Vaccination
Improved sanitation, food safety, and immunization are the most effective ways to combat hepatitis A.
The spread of hepatitis A can be reduced by:
- Safe drinking water
- Proper sewage disposal
- Personal hygiene
Vaccination is very effective in preventing HAV disease.
For people visiting endemic areas frequently, both the vaccination and intramuscular immunoglobulin can provide long-term immunity.
The vaccination is considered in high-risk groups.
Nearly 100% of people develop protective levels of antibodies to the virus within 1 month after the injection of a single dose of vaccine. However, two doses are recommended and they ensure the protection of about 5 to 8 years after vaccination.
The vaccine can be given as part of the regular childhood immunization program. Some authors recommend vaccination for all.
Others are of the view that universal immunization of children should be done in areas of endemicity whereas those areas with low endemicity may consider vaccinating high-risk adults only.
In countries with high endemicity, most adults are naturally immune.
Postexposure prophylaxis of hepatitis A can be achieved by infusion of immunoglobulins and is recommended for nonimmunized close contacts of those recently diagnosed with acute HAV infection.
Some countries recommend the vaccine for people at increased risk of hepatitis A, including:
- Users of recreational drugs
- Travelers to countries where the virus is endemic
- Men who have sex with men
- People with chronic liver disease (because of their increased risk of serious complications if they acquire hepatitis A infection).
Complications
Complications are rare. These include
- Prolonged cholestasis
- Risk increases with age
- Jaundice persists more than 3 months
- Protracted period of jaundice
- Acute renal failure
- Interstitial nephritis
- Pancreatitis
- Red blood cell aplasia
- Agranulocytosis
- Bone marrow aplasia
- Transient heart block
- Guillain-Barré syndrome
- Acute arthritis
- Still disease
- Lupus-like syndrome
- Sjögren syndrome
- Relapsing infection
Prognosis
The prognosis is excellent. The disease is self-limiting and often recurrence does not occur and provides long-term immunity.
Death is rare. It is often seen in elderly patients and in those with underlying liver disease.
The single most important determinant of illness severity is age. Adverse effects also increase with increasing age.
References
- Longatti A. The dual role of exosomes in hepatitis A and C virus transmission and viral immune activation. Viruses. 2015 Dec 17. 7(12):6707-15.
- Ansaldi F, Bruzzone B, Rota MC, et al. Hepatitis A incidence and hospital-based seroprevalence in Italy: a nation-wide study. Eur J Epidemiol. 2008. 23(1):45-53.
- Aggarwal R, Goel A. Hepatitis A: epidemiology in resource-poor countries. Curr Opin Infect Dis. 2015 Oct. 28(5):488-96.
- Kodani M, Mixson-Hayden T, Drobeniuc J, Kamili S. Rapid and sensitive approach to simultaneous detection of genomes of hepatitis A, B, C, D and E viruses. J Clin Virol. 2014 Oct. 61(2):260-4.
- Costas L, Vilella A, Trilla A, et al. Vaccination strategies against hepatitis A in travelers older than 40 years: an economic evaluation. J Travel Med. 2009 Sep-Oct. 16(5):344-8.
- Irving GJ, Holden J, Yang R, Pope D. Hepatitis A immunization in persons not previously exposed to hepatitis A. Cochrane Database Syst Rev. 2012 Jul 11. 7:CD009051.
- Linder KA, Malani PN. Hepatitis A. JAMA. 2017 Dec 19. 318(23):2393.