World Health Organization. Hepatitis A. https://www.who.int/news-room/fact-sheets/detail/hepatitis-a. Published July 9, 2019. Accessed July 9, 2019.
World Health Organization. Hepatitis D. https://www.who.int/news-room/fact-sheets/detail/hepatitis-d. Published July 8, 2019. Accessed July 9, 2019.
Ontario, Ministry of Health and Long-Term Care. Infectious Diseases Protocol. Appendix A: Disease-Specific Chapters. Hepatitis A. http://www.health.gov.on.ca/en/pro/programs/publichealth/oph_standards/docs/hep_a_chapter.pdf. Published March 2017. Updated February 2019. Accessed July 9, 2019.
Ontario, Ministry of Health and Long-Term Care. Infectious Diseases Protocol. Appendix A: Disease-Specific Chapters. Hepatitis C. http://www.health.gov.on.ca/en/pro/programs/publichealth/oph_standards/docs/hep_c_chapter.pdf. Published January 2018. Updated February 2019. Accessed July 9, 2019.
Coffin CS, Fung SK, Alvarez F, et al. Management of Hepatitis B Virus Infection: 2018 Guidelines from the Canadian Association for the Study of Liver Disease and Association of Medical Microbiology and Infectious Disease Canada. Can Liv J. 2018:1(4):156-217. doi: 10.3138/canlivj.2018-0008. Published December 1, 2018.
European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2018. J Hepatol. 2018 Aug;69(2):461-511. doi: 10.1016/j.jhep.2018.03.026. Epub 2018 Apr 9. PubMed PMID: 29650333.
European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18. PubMed PMID: 28427875.
European Association for the Study of the Liver. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol. 2018 Jun;68(6):1256-1271. doi: 10.1016/j.jhep.2018.03.005. Epub 2018 Mar 31. PubMed PMID: 29609832.
Etiology and PathogenesisTop
1. Etiologic agent: Hepatitis A virus (HAV). Viremia occurs in the incubation period and for up to 30 days of acute disease. Early manifestations are caused by hepatocyte destruction due to the direct cytopathic effect of the virus followed by a cellular response to HAV antigens.
2. Reservoir and transmission: Humans are the nearly exclusive reservoir of HAV (with rare exceptions of chimpanzees and other primates). The virus is extensively shed with feces. Infection is most commonly by the oral route, from physical contact with an infectious individual or sewage contamination in waterborne outbreaks. Sexually transmitted infection that includes direct or indirect oral-anal contact and transmission through contaminated needles are also possible (the latter mainly in injection drug users).
3. Epidemiology: The virus is present worldwide, with endemic areas in the Mediterranean countries, Eastern Europe, Russia, as well as in areas with low hygiene standards.
Risk factors: Traveling to endemic areas, close contact with infected individuals (eg, household contacts), close contact (household or professional) with children attending nursery or preschool, consumption of seafood (notably crustaceans and raw oysters), anal sex (especially men who have sex with men [MSM]), waste or sewage management, as well as maintenance of equipment used for such purposes. Epidemics caused by the consumption of contaminated food and water may also occur.
4. Incubation and contagious period: Incubation period is usually from 15 to 50 days (on average ~28 days). The virus is shed with feces for 1 to 2 weeks before and ~1 week after the onset of signs and symptoms (the contagious period). Patients are no longer contagious 7 days after jaundice occurs.
Clinical Features and Natural HistoryTop
The disease is often asymptomatic or subclinical (particularly in children). In symptomatic patients it may be icteric, anicteric (most frequently in children), or cholestatic.
Signs and symptoms: Infected patients commonly present with jaundice, fatigue, nausea, vomiting, abdominal pain, and muscle and joint pain. Skin pruritus is prominent in cholestatic disease. In the prodromal period minor liver enlargement may be observed. In icteric disease dark urine and light-colored stools are seen. Fulminant hepatitis with acute liver failure is very rare but may be observed in patients with preexisting liver disease (see Acute Liver Failure). The disease is more severe in patients >50 years and in malnourished individuals.
Acute symptoms resolve within several days and elevated aminotransferase levels persist for 3 to 4 weeks on average. Recurrences are observed within 3 months of the first episode. In patients with jaundice the disease lasts on average 6 weeks and symptoms rarely persist >3 months (cholestatic hepatitis). HAV does not cause chronic hepatitis. Patients with uncomplicated hepatitis A may be expected to return to normal daily activities and work within 6 months.
1. Serologic tests: The basis for diagnosis is the finding of positive serum anti-HAV IgM antibodies (detected using enzyme-linked immunosorbent assay [ELISA]). The antibodies confirm a recent infection. They may persist for up to 4 to 6 months and are gradually replaced by anti-HAV IgG antibodies, which persist for life.
2. Other laboratory tests: Elevated plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (with a greater increase in ALT), hyperbilirubinemia (most commonly mixed, with elevated unconjugated and conjugated bilirubin levels); in patients with cholestatic disease also elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT).
3. Liver biopsy is performed only in exceptional circumstances in case of diagnostic uncertainties.
Acute hepatitis caused by other pathogens (viruses [hepatitis virus B, D, and C; viruses causing secondary liver infections] or bacteria [leptospirosis, listeriosis, brucellosis, tularemia, bartonellosis, and tuberculosis]), exacerbation of chronic hepatitis, toxic liver injury (drug-induced, alcohol-induced, Amanita phalloides poisoning), cholelithiasis causing obstruction of the common bile duct, cirrhosis, autoimmune hepatitis, nonalcoholic fatty liver disease, Wilson disease, acute liver ischemia, acute fatty liver in pregnancy, and liver metastases.
No antiviral treatment is available. Hospital admission may be required in patients with severe or complicated disease. The goal of treatment is to maintain appropriate nutrition and volume status. The specifics of treatment reflect our pattern of practice and judgment and represent a number of suggestions.
1. Rest: Physical activity restricted to that which is easily tolerated in patients with acute disease and during the first month of convalescence.
2. Nutrition and fluid management: Adjust diet to energy requirements. A normal diet may be resumed within 6 months. In case of severe vomiting and signs of dehydration, administration of fluids and enteral nutrition (via a gastric or intestinal tube) or parenteral nutrition may be necessary. Alcohol abstinence is strongly recommended for 6 months and should be significantly restricted for up to 1 year.
3. Management of pruritus.
4. Avoidance of drugs metabolized by the liver or causing cholestasis in patients with acute disease and convalescents.
Monitor for the development of acute liver failure by following liver synthetic functions, including international normalized ratio (INR) as required (once a week with adjustments as needed). Clinical follow-up should include assessment of potential encephalopathy. After resolution of acute disease, monitor levels of aminotransferases and when relevant also of serum bilirubin until resolution.
1. Fulminant hepatitis or acute liver failure is very rare (~0.2% of patients) and more common in those aged >50 years or with chronic liver disease.
2. In rare cases patients may develop kidney injury caused by immune complexes or autoimmune hepatitis.
Vaccination is the key method of primary prevention (see Vaccines: Hepatitis A).
1. Strict hand hygiene. Avoid sharing food during the contagious period and limit food-handling activities. Symptomatic patients who are food handlers, child-care staffs, and health-care workers should be excluded from high-risk settings for 2 weeks after symptoms begin. Contacts of infected individuals should be educated and should self-monitor for symptoms. Breastfeeding may be continued throughout the disease.
2. Disease reporting is subject to local regulations.