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Hepatitis A vs B vs C vs D vs E

Five viruses that all damage the liver but split sharply on transmission, genome, chronicity, and pregnancy risk. The pivot is the route plus whether you can go chronic.

Mechanism

The vowels (A and E) are fecal-oral and do not go chronic in immunocompetent hosts. The consonants (B, C, D) are blood/sexual and can go chronic.

Differentiator Table

HAVHBVHCVHDVHEV
GenomeRNA (+ssRNA)DNA (partial dsDNA)RNA (+ssRNA)RNA (-ssRNA, circular)RNA (+ssRNA)
FamilyPicornavirusHepadnavirusFlavivirusDeltavirusHepevirus
TransmissionFecal-oralBlood, sexual, perinatalBlood (IVDU, transfusion pre-1992)Requires HBV — same routesFecal-oral (often contaminated water)
ChronicityNo5–10% adults, >90% perinatal50–80%Yes (worse with HBV)No (except immunocompromised)
Pregnancy riskStandard acuteVertical transmission to neonateLower vertical riskAs HBVFulminant hepatic failure (~20% mortality)
VaccineYesYes (HBsAg)NoIndirect via HBV vaccineLimited (available in some countries)
HCC riskNoYesYesYes (with HBV)No
TreatmentSupportiveEntecavir, tenofovirDAAs (e.g. sofosbuvir + ledipasvir) — curativeTreat underlying HBVSupportive (ribavirin in chronic)

The Pivot

Two questions usually settle it:

  1. How was it transmitted? Fecal-oral → HAV or HEV. Blood/sexual → HBV, HCV, HDV.
  2. Acute self-limited or chronic? Acute, kids, no chronic carriage → HAV. Acute, pregnant woman, fulminant → HEV. Chronic carrier with risk of cirrhosis/HCC → HBV or HCV. Acute-on-chronic worsening of a known HBV → consider HDV superinfection.

For HBV, learn the serology pattern (HBsAg, anti-HBs, IgM/IgG anti-HBc, HBeAg) cold — NBME asks it constantly.

NBME-Style Stem

A 26-year-old woman in her third trimester of pregnancy presents with jaundice, malaise, and acute liver failure. She returned from rural South Asia two months ago, where she drank well water. Hepatitis A IgM is negative. Hepatitis B surface antigen is negative. Hepatitis C antibody is negative. Which of the following is the most likely cause?
Concept Anchor
The vowels (A, E) come in through the mouth and leave the body without staying; the consonants (B, C, D) get in through blood or sex and can move in for life — with HBV and HCV driving cirrhosis and HCC, and HDV only existing as HBV's parasite.

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