Overview of viral hepatitides

Viral hepatitides comprise the infectious diseases hepatitis A, B, C, D, and E, which have various routes of transmission (e.g., fecal-oral, sexual, parenteral, and perinatal transmission). Most patients are either asymptomatic or experience mild symptoms, which usually resolve spontaneously within weeks to months. However, patients with hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, or hepatitis D virus (HDV) infection may experience a chronic disease course, increasing the risk of cirrhosis and hepatocellular carcinoma (HCC). Pregnant individuals with hepatitis E virus (HEV) infection have an increased risk of developing fulminant hepatic failure. Diagnostic studies include liver function tests, viral serologic testing, and measurement of viral load. Treatment of acute hepatitis primarily involves supportive care. HCV infection can be effectively treated with early direct-acting antivirals. Treatment of chronic hepatitis involves antivirals to reduce viral replication and infectivity. Vaccination is available against hepatitis A and hepatitis B.

This article contains an overview of viral hepatitides as well as hepatitis D and hepatitis E. See also “Hepatitis A,” “Hepatitis B,” and “Hepatitis C.”

Vowels (A and E) are transmitted via the bowels (fecal-oral) and usually only cause AcutE hepatitis.

• Pathogen: hepatitis D virus (HDV)
  • Belongs to the Deltaviridae family and the genus Deltavirus
  • Defective, circular, single-stranded RNA virus
  • Incomplete viral particle resembling a viroid
  • Comprises an outer lipoprotein envelope made of the hepatitis B surface antigen (HBsAg) for entry into host cells and an inner ribonucleoprotein structure in which the HDV genome resides
• Epidemiology: 5% of all patients with chronic HBV infection carry HDV.
• Route of transmission: sexual, parenteral, perinatal
• Risk factors
  • Men who have sex with men
  • History of STIs
  • Multiple sexual partners
  • Sex workers
  • Injection drug use
  • Multiple blood transfusions
  • Individuals born in countries with a high prevalence of HDV infection
• Incubation period
  • Acute coinfection (acute HBV and HDV infection): 1–6 months
  • Acute HDV superinfection (HDV after HBV): 2–8 weeks
• Clinical features: similar to acute HBV infection
• Clinical course
  • Acute coinfection with HBV usually leads to severe acute hepatitis.
    • Two peaks of ALT and AST elevation may be observed. ^[3]
    • Approximately 5% of patients with coinfection progress to chronic HDV infection. ^[4]
  • HDV superinfection in patients with chronic hepatitis B increases the risk of liver cirrhosis and HCC.
    • More than 80% of patients with superinfection progress to chronic HDV infection. ^[4]
    • The development of chronic HDV infection can exacerbate hepatic injury caused by HBV.
• Diagnostics: The presence of HBsAg is necessary for the diagnosis because of the dependence of HDV on HBV.
  • Confirmatory testing
    • Presence of HBsAg and IgM anti-HBc
    • Anti-HDV antibodies
    • Serum HDV RNA
  • Liver biopsy (not routinely indicated): See “Pathology of viral hepatitis.”
• Treatment
  • Acute hepatitis D: supportive care
  • Chronic hepatitis D
    • Pegylated interferon alfa (PEG-IFN-α)
    • Indicated in patients with active liver disease and detectable HDV RNA
• Complications: same as complications of hepatitis B
• Prevention
  • HBV vaccination
  • Measures to prevent HBV transmission
• Prognosis
  • Patients with superinfection have a poor prognosis.
  • While most patients with acute coinfection successfully recover from both HBV and HDV infection, coinfection presents a greater risk of acute liver failure compared to acute HBV infection alone.

Remember the 3 Ds of hepatitis D: Defective Deltavirus Dependent on HBV HBsAg coat for entry.

• Pathogen: hepatitis E virus (HEV)
  • Belongs to the Hepeviridae family and the genus Orthohepevirus
  • Small (34 nm in diameter), nonenveloped virus with single-stranded, positive-sense RNA
  • HEV genotypes 1 and 2 are found only in humans; genotypes 3 and 4 are zoonotic diseases with reservoirs in both humans and animals such as pigs, monkeys, and dogs. ^[7]
• Epidemiology
  • Uncommon in the US
  • An important cause of endemic viral hepatitis in developing countries and equatorial regions (e.g., India, western and northern Africa, Middle East, Mexico)
• Route of transmission
  • Fecal-oral: contaminated water and food (e.g., uncooked meat)
  • Parenteral: blood transfusions
  • Perinatal: vertical transmission
• Incubation period: 2–8 weeks
• Clinical features
  • Similar to clinical features of acute hepatitis A
  • In the majority of cases, the disease is self-limited.
  • Symptoms resolve after 2–4 weeks.
• Diagnostics
  • Confirmatory testing
    • Anti-HEV IgM antibodies: active infection
    • Anti-HEV IgG antibodies: past infection
    • PCR: can detect HEV RNA in stool and serum samples
  • Liver biopsy (not routinely indicated): See “Pathology of viral hepatitis.”
• Treatment
  • Acute: supportive care
  • Chronic: ribavirin
• Complications
  • Chronic HEV infection in immunosuppressed individuals (e.g., due to transplantation, HIV infection) ^[8][9]
  • Fulminant hepatic failure
• Prevention
  • Advise all travelers to follow primary preventive measures such as food and water safety.
  • No HEV vaccine is available.
• Prognosis
  • In most cases, HEV infection is self-limited; patients should make a full recovery.
  • High mortality risk in pregnant individuals with fulminant hepatitis

Women who are Expecting a child should be FULly aware of the risks: Hepatitis E can lead to FULminant hepatitic failure.

A fulminant course occurs in up to 20% of pregnant individuals with HEV infection; it is life-threatening for both the mother and fetus.