STEPTRACKERGASTROINTESTINAL | PATHOLOGY + MICROBIOLOGY + IMMUNOLOGY | HIGH-YIELD REVIEW

Viral Hepatitis

Five viruses, two routes, very different outcomes — and the hepatitis B serology timeline that every exam asks about.

FOCUS ON
A and E: fecal-oral, acute only (E is dangerous in pregnancy). B, C, D: blood/sexual/perinatal, can go chronic → cirrhosis, HCC. HBV is a DNA virus with reverse transcriptase; chronicity depends on age at infection. HCV goes chronic most often; cured by direct-acting antivirals. HDV needs HBsAg.
VIRUS
STRUCTURE · SPREAD
COURSE
CLUE
Hepatitis A
Picornavirus, ssRNA; fecal-oral (travel, shellfish, daycare)
Acute, self-limited; no carrier state; rarely fulminant
IgM anti-HAV = acute · vaccine
Hepatitis B — virus
Hepadnavirus, partially dsDNA, replicates by reverse transcriptase; blood, sex, perinatal
Chronic in ~90% of neonates, < 5% of adults
HCC even without cirrhosis (DNA integration)
Hepatitis B — extrahepatic
Immune complexes containing HBsAg
Polyarteritis nodosa, membranous nephropathy, serum sickness-like prodrome (rash, arthralgia)
Ground-glass hepatocytes (HBsAg)
Hepatitis B — treatment
Suppress replication
Tenofovir, entecavir (nucleos(t)ide analogs); peginterferon-α
Vaccine (recombinant HBsAg) → anti-HBs only
Hepatitis C
Flavivirus, ssRNA, no proofreading (antigenic variation); IV drug use, transfusion before 1992
Chronic in most (~75%) → cirrhosis, HCC; often silent
Anti-HCV antibody, confirm with HCV RNA · no vaccine
Hepatitis C — extrahepatic
B-cell stimulation, immune complexes
Mixed cryoglobulinemia, MPGN, porphyria cutanea tarda, lichen planus, B-cell lymphoma, insulin resistance
Purpura + arthralgia + low complement
Hepatitis C — treatment
Direct-acting antivirals
NS5B polymerase inhibitor (sofosbuvir) + NS5A inhibitor (ledipasvir, velpatasvir) or NS3/4A protease inhibitor (glecaprevir)
Cure rates > 95%
Hepatitis D
Defective RNA virus; needs HBsAg for its envelope
Coinfection (with acute HBV) or superinfection of chronic HBV (worse, fulminant)
HBV vaccine prevents HDV
Hepatitis E
Hepevirus, ssRNA; fecal-oral, contaminated water, undercooked pork
Usually acute; fulminant in pregnant women; chronic in transplant patients
Outbreaks in South Asia, Africa
Histology
Cytotoxic T cells kill infected hepatocytes
Acute: ballooning, Councilman bodies (apoptosis), lobular inflammation · chronic: portal inflammation, interface hepatitis, fibrosis
HCV: lymphoid aggregates + steatosis

Mechanism — HBV replication and outcomes

Partially dsDNA
→
cccDNA in nucleus
→
RNA transcripts
→
Reverse transcriptionNew DNA genomes
Strong T-cell response
→
Acute hepatitis → clearanceAdults
Weak response (neonate)Tolerance → chronic carrier
→
Cirrhosis, HCC

Reading HBV serology

STATE
HBsAg
ANTI-HBs
ANTI-HBc
Acute infection
⁺
−
IgM ⁺
Window period
−
−
IgM ⁺
Chronic infection
⁺ (> 6 months)
−
IgG ⁺
Recovered
−
⁺
IgG ⁺
Vaccinated
−
⁺
−

HBeAg and HBV DNA mark active replication and high infectivity; anti-HBe signals lower infectivity.

How it's tested

COMMON CONFUSIONAnti-HBs alone = vaccinated. Anti-HBs plus IgG anti-HBc = past infection that cleared. Only natural infection makes anti-HBc.
THE TRAPIn the window period both HBsAg and anti-HBs are negative. IgM anti-HBc is the only positive marker — don't call it "no infection."
YOUR APPROACHRoute (fecal-oral vs blood) → acute or chronic → serology pattern → extrahepatic clues → treatment or prevention (vaccine, DAAs).

If you see… think…

Hepatitis after eating raw oysters abroad, IgM anti-HAV → hepatitis A
Pregnant woman in South Asia with fulminant hepatitis → hepatitis E
HBsAg⁺ for over 6 months → chronic hepatitis B
Only IgM anti-HBc positive → window period
Only anti-HBs positive → vaccinated
HBV with polyarteritis nodosa → immune complex vasculitis
Former IV drug user, palpable purpura, low C4, ↑ ALT → HCV cryoglobulinemia
Blistering on sun-exposed hands + HCV → porphyria cutanea tarda
Chronic HBV carrier suddenly much worse → HDV superinfection
Drug that inhibits HCV NS5B polymerase → sofosbuvir