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 agents: Hepatitis B virus (HBV). The surface of HBV contains glycoprotein S (HBs antigen [HBsAg]), while the DNA core contains HBc antigen (HBcAg) (undetectable in serum, in contrast to HBV core antigen, which is found in serum or plasma). The infected hepatocyte releases noninfectious HBsAg particles and complete infectious virions. Blood, body fluids, and secretions also contain HBe antigen (HBeAg), sharing a part of the common protein structure with HBcAg (some mutant strains do not produce HBeAg). HBeAg and HBV DNA are markers of intense viral replication and high infectivity of the patient.
Symptoms of hepatocyte damage result from a strong immune response (cytotoxic and cytokine-mediated), whereas the development of chronic hepatitis is caused by a poor immune response to viral antigens. Some of the extrahepatic symptoms and complications of hepatitis B (eg, polyarteritis nodosa, glomerulonephritis, as well as serum sickness–like symptoms observed in the prodromal period) are caused by the formation of immune complexes (particularly those formed by HBsAg and anti-HBs antibodies).
2. Reservoir and transmission: The only HBV reservoir is individuals with active disease or carriers. Routes of transmission include parenteral (contact with infected blood and blood-contaminated instruments), sexual, and perinatal transmission.
3. Epidemiology: The virus is present worldwide, with endemic (high-risk) areas in Eastern Europe, southeast Asia, China, Russia, the former Soviet republics in Asia, Africa, Latin America, South America, and the Pacific islands.
Risk factors, depending on the local conditions, are found in ~70% of patients and include close contact with a person with HBV infection (household contacts, sexual contacts), invasive diagnostic or therapeutic procedures, treatment with blood products, hemodialysis, multiple sexual partners, IV drug use, occupational exposure to blood and body fluids (health-care professionals), employment in long-term care facilities, and being a prison inmate. The risk of vertical mother-to-child transmission without interventions (see Chronic Hepatitis B) is ~90% for HBeAg-positive mothers and ~10% for HBeAg-negative HBsAg-positive mothers.
4. Incubation and contagious period: The incubation period is from 28 to 160 days (average, 70-80 days). Patients with positive serum HBeAg tend to be more contagious because of the presence of high levels of HBV DNA in the blood.
Clinical Features and Natural HistoryTop
Clinical manifestations of acute hepatitis B are similar to those of acute hepatitis A, but the development of signs and symptoms is generally slower while the course of the disease is more severe. In 5% to 15% of patients clinical manifestations of the prodromal period may resemble serum sickness, including persistent muscle and joint pain, which resolve with the onset of jaundice. An asymptomatic course is also possible.
Hyperbilirubinemia usually lasts ~4 weeks and elevated alanine aminotransferase (ALT) levels persist for up to 8 to 16 weeks. In patients with cholestatic disease symptoms persist for up to 24 weeks. In some patients, particularly the elderly, several flares of subacute hepatitis may be observed in the first 3 months of the disease.
Viral hepatitis is suspected in patients with jaundice or elevated plasma aminotransferase levels (or both).
1. Identification of HBV DNA is the first detectable indicator of infection, occurring on average around week 12 after infection.
2. Serologic tests: Depending on the time from infection and phase of the disease, HBV antigens (HBsAg, HBeAg) and specific antibodies (anti-HBc IgM and IgG, anti-HBe, anti-HBs) can be detected in serum in variable combinations, with anti-HBc IgM positivity being an important marker of acute hepatitis B in the “window period” (the period between disappearance of HBsAg and appearance of anti-HBs antibodies). Assuming there is no progression to chronic hepatitis B, serum HBeAg remains positive for up to ~10 weeks and HBsAg for up to 3 months. As their levels gradually decrease, anti-HBe IgG and anti-HBc IgG appear. Anti-HBs are observed during convalescence. Over time, the antibodies gradually disappear, beginning from anti-HBe and followed by anti-HBs. Anti-HBc IgG persist for life.
3. Laboratory tests: Serum ALT levels become elevated within several days or weeks after the appearance of HBV antigens in serum. Elevation of bilirubin may follow. Mixed hyperbilirubinemia may be present.
4. Liver biopsy is generally not required for the diagnosis of acute hepatitis B but may be needed if it progresses to chronic hepatitis B or in case of diagnostic uncertainty.
As in acute hepatitis A.
Supportive therapy as in acute hepatitis A. Glucocorticoids are generally contraindicated due to the increased risk of developing chronic hepatitis. Adult patients in most instances do not require hepatitis B therapy, given the high rates of spontaneous HBV clearance. However, in patients with fulminant hepatitis B treatment should be focused on the management of acute liver failure; use of nucleoside analogues (NAs), such as entecavir or tenofovir, may be of benefit.
As in hepatitis A. Perform follow-up serologic tests at 6 months to exclude chronic hepatitis even in patients with normal ALT levels.
1. Fulminant hepatitis is the most serious complication (~1% of patients, more frequently in young women and in 30%-40% of patients with hepatitis D virus [HDV] coinfection; the risk is also higher in patients with preexisting hepatitis C virus [HCV] infection).
2. Extrahepatic complications (caused by immune complexes) include systemic vasculitides (eg, polyarteritis nodosa), polymyalgia rheumatica, erythema nodosum, glomerulonephritis and nephritic syndrome (more common in children), mixed cryoglobulinemia, myocarditis, and Guillain-Barré syndrome.
Acute hepatitis B may progress to chronic hepatitis B in 90% of neonates and infants, ~30% of children aged 1 to 5 years, and in 2% to 5% (according to some authors <10%) of older children and adults. Risk factors include perinatal or early childhood infection, high exposure to the virus, anicteric acute hepatitis, mild acute hepatitis, low ALT levels during acute disease, male sex, advanced age, immunosuppression, and use of glucocorticoids. Mortality is <1% and is mainly due to fulminant liver failure. The course is more severe in patients with HCV or HDV coinfection.
1. Vaccination is the key method of primary prophylaxis.
2. Passive immunoprophylaxis with hepatitis B immunoglobulin (HBIG) is used mostly to prevent vertical transmission to the newborn.
1. Strict adherence to the principles of infection prevention, both in health-care and other facilities (hair salons, tattoo parlors). This involves the use of disposable equipment and appropriate handling of materials contaminated with blood or other body fluids, use of condoms, as well as testing of blood donors and limiting indications for transfusion.
2. No isolation precautions are required in HBV-infected patients. Educate patients and carriers about reducing the risk of transmitting the infection to other persons by preventing contact with the patient’s personal belongings that may be contaminated with infected blood (eg, toothbrushes, razors, as well as needles and syringes in the case of IV drug users). Sexual abstinence is recommended until the elimination of HBV infection or until the partner completes the vaccination cycle.
3. Disease reporting is subject to local regulations.