Hepatitis Viruses: Genome, Transmission, and Chronicity
The hepatitis viruses (HAV, HBV, HCV, HDV, HEV) all cause liver inflammation but differ in the features that matter most for the exam: genome type, route of transmission, capacity to establish chronic infection, and whether a vaccine exists. A useful framework is that the fecal-oral viruses (HAV, HEV) generally cause acute, self-limited disease, whereas the blood/body-fluid viruses (HBV, HCV, HDV) are the ones that classically go chronic. One exception worth knowing is that HEV (genotype 3) can become chronic in immunocompromised hosts. Vaccination is available for HAV, HBV, and HEV (the last not in the US), and preventing HBV also prevents HDV.
Hepatitis A Virus (HAV)
HAV is an RNA virus transmitted by the fecal-oral route. It causes an acute infection that does not become chronic. A vaccine is available. As a fecal-orally spread virus, it groups with HEV as a cause of self-limited acute hepatitis rather than persistent liver disease.
Hepatitis B Virus (HBV)
HBV is the only DNA virus among the hepatitis viruses. It is transmitted through blood, sexual contact, and vertically (mother to child). It can progress to chronic infection in roughly 5–10% of infected adults, but the risk is much higher in perinatally infected infants. A vaccine is available and is central to prevention. Because HDV depends on HBV, HBV vaccination also protects against HDV.
Hepatitis C Virus (HCV)
HCV is an RNA virus transmitted primarily through blood. It has the highest rate of chronicity of the hepatitis viruses—about 80% of infections become chronic. There is no vaccine, making it distinct from HAV and HBV. Its blood-borne route and high chronicity make it a major cause of persistent liver disease.
Hepatitis D Virus (HDV)
HDV is a defective RNA virus that requires HBV (specifically HBsAg) to replicate and cause infection. Coinfection (acquired with HBV) tends to be acute, whereas superinfection (HDV on top of chronic HBV) carries a higher risk of severe, chronic disease and fulminant hepatitis. There is no specific HDV vaccine, but the HBV vaccine prevents HDV by preventing the HBV infection it depends on.
Hepatitis E Virus (HEV)
HEV is an RNA virus transmitted by the fecal-oral route, similar to HAV. In immunocompetent hosts it usually causes acute, self-limited disease. However, HEV (genotype 3) can progress to chronic infection in immunocompromised patients—classically solid organ transplant recipients, patients on chemotherapy, and HIV patients with low CD4 counts. HEV is also notorious for causing high mortality (fulminant hepatitis) in pregnant women. A vaccine exists but is not available in the US.
High-yield
- HBV is the only DNA hepatitis virus; all others are RNA.
- Fecal-oral transmission: HAV and HEV.
- Blood-borne transmission: HBV, HCV, and HDV (via HBV).
- Chronic infection is classically seen with HBV (5–10% of adults), HCV (80%), and HDV; HAV never becomes chronic, and HEV is usually acute EXCEPT genotype 3 in immunocompromised hosts.
- HCV has the highest chronicity rate (~80%) and no vaccine.
- HEV causes fulminant hepatitis with high mortality in pregnant women.
- Vaccines exist for HAV, HBV, and HEV (HEV vaccine not available in the US).
- HBV vaccine also prevents HDV because HDV cannot replicate without HBV.
- HDV is a defective virus that needs HBV (HBsAg) to establish infection; superinfection is more severe than coinfection.
Pitfalls
- Assuming all hepatitis viruses are RNA—HBV is DNA.
- Forgetting there is no HCV vaccine, despite HCV having the highest chronicity.
- Mixing up chronicity rates: HBV is ~5–10% in adults, whereas HCV is ~80%.
- Thinking HDV has its own vaccine—prevention relies on the HBV vaccine.
- Assuming fecal-oral viruses are always acute—HEV (genotype 3) can become chronic in immunocompromised hosts.
- Overlooking that HEV causes high-mortality fulminant hepatitis in pregnant women.
- Believing HEV vaccination is available everywhere—it exists but is not in the US.
Clinical pearls
- "Vowels hit your bowels": HAV and HEV spread fecal-orally and are usually acute.
- HEV in a transplant or immunosuppressed patient can go chronic (genotype 3).
- HEV is especially dangerous in pregnancy—high mortality from fulminant hepatitis.
- HBV = DNA; think of it as the odd one out among RNA hepatitis viruses.
- No HBV, no HDV—prevent one and you prevent both.
- HCV: high chronicity, no vaccine—a double threat for chronic liver disease.
Frequently asked
Which hepatitis virus is a DNA virus?
HBV is the only DNA virus among the hepatitis viruses; HAV, HCV, HDV, and HEV all have RNA genomes.
Which hepatitis viruses are transmitted by the fecal-oral route?
HAV and HEV. Both typically cause acute, self-limited hepatitis, though HEV (genotype 3) can become chronic in immunocompromised patients.
Which hepatitis virus most often becomes chronic?
HCV, with about 80% of infections becoming chronic. In contrast, HBV becomes chronic in roughly 5–10% of infected adults.
Can hepatitis E become chronic?
Usually no—HEV causes acute, self-limited disease in immunocompetent hosts. However, HEV genotype 3 can establish chronic infection in immunocompromised patients such as solid organ transplant recipients and HIV patients with low CD4 counts. HEV is also associated with fulminant hepatitis and high mortality in pregnant women.
Why does HBV vaccination also protect against HDV?
HDV is a defective virus that cannot replicate or cause infection without HBV (it requires HBsAg). Preventing HBV infection therefore prevents HDV.
Which hepatitis viruses have available vaccines?
HAV, HBV, and HEV have vaccines, though the HEV vaccine is not available in the US. There is no vaccine for HCV, and HDV is prevented via the HBV vaccine.
How is HBV transmitted?
HBV spreads through blood, sexual contact, and vertically from mother to child.
How is HCV transmitted, and is there a vaccine?
HCV is transmitted primarily through blood, has a high rate of chronic infection (~80%), and has no vaccine.
Turn this into reasoning you can use on exam day — practice Hepatitis Viruses on branching cases where your decisions shape the patient.