Hepatology
Hepatitis Types
Five viruses, five biologies — fecal-oral A and E, blood-borne B and C, and the defective satellite D
Five viruses share the name "hepatitis" and almost nothing else. A and E spread fecal-oral and resolve. B and C spread by blood and persist. D is a defective satellite that needs B. HCV is cured in 95%+ of patients with 8–12 weeks of direct-acting antivirals.
- HAV / HEV routeFecal-oral, acute, no chronic
- HBV / HCV routeBlood, sex, perinatal — chronic
- HBV perinatal chronicity~90% (5% in adult-acquired)
- HCV cure rate95%+ with 8–12 weeks of DAAs
- HEV in pregnancy~20% mortality (genotype 1)
- HDV requirementNeeds HBsAg to assemble
Interactive visualization
Five panels, one per hepatitis virus — route in, virology inside, treatment out.
Watch the 60-second explainer
A condensed visual walkthrough — narrated, captioned, under a minute.
Five viruses, one liver
The hepatitis viruses share clinical biology (hepatocyte tropism, inflammatory injury with ALT/AST elevation, jaundice) and nothing else. They are not related taxonomically. The clinically useful grouping is by route of transmission and chronicity, which determines what test to send and what to do next.
Hepatitis A — picornavirus, fecal-oral, acute
Non-enveloped ssRNA picornavirus. Fecal-oral via contaminated food (shellfish, undercooked produce) and water; common in travelers, daycare, men who have sex with men. Incubation 15–50 days. Clinical: acute hepatitis — fever, malaise, anorexia, RUQ pain, jaundice, dark urine, light stools. ALT often >1000. No chronic carrier state. Vaccine (inactivated, 2-dose) is universal childhood immunization in the US since 2006. Post-exposure prophylaxis: HepA vaccine within 14 days; add Ig if older, immunocompromised, or with chronic liver disease.
Hepatitis B — hepadnavirus, blood/sex/perinatal, can become chronic
Partial dsDNA hepadnavirus that replicates via a reverse transcriptase. Transmits via blood (needles, transfusions before 1972 screening, occupational sharps), sex, and — most consequentially globally — perinatally (mother-to-infant). Chronicity rate depends sharply on age at infection: ~90% if acquired perinatally, ~25% in young children, ~5% in adults. Serology is the lingua franca:
- HBsAg. Present = currently infected (acute or chronic).
- Anti-HBs. Immune — from vaccine or recovered infection.
- HBcAb (anti-HBc). Exposure ever; IgM in acute; IgG forever after.
- HBeAg / Anti-HBe. Replicative state — HBeAg positive with high DNA = more infectious; anti-HBe with low DNA = inactive carrier.
- HBV DNA. Quantitative viral load — drives treatment.
Treatment: oral nucleos(t)ide analogues (entecavir, tenofovir alafenamide/disoproxil) suppress viral replication; rarely curative — the cccDNA template persists in hepatocyte nuclei. Treatment indications are based on ALT, DNA, fibrosis, and special situations (pregnancy, immunosuppression, HCC family history). Vaccine: recombinant HBsAg, 3 doses or 2-dose Heplisav-B for adults — prevents not just HBV but also HDV.
Hepatitis C — flavivirus, blood-borne, curable
Enveloped ssRNA flavivirus. Blood-borne — historically transfusion before screening (1992 US), now overwhelmingly injection drug use. Sexual and perinatal transmission less efficient. ~75% of acute infections become chronic — opposite of HBV. Once chronic, ~20–30% develop cirrhosis over 20–30 years; cofactors (alcohol, HIV, fatty liver) accelerate. The 2014–2017 revolution: direct-acting antivirals (DAAs) targeting NS3/4A protease, NS5A protein, and NS5B polymerase. Pan-genotypic combinations — sofosbuvir/velpatasvir (Epclusa) and glecaprevir/pibrentasvir (Mavyret) — achieve sustained virologic response at 12 weeks (SVR12, the cure endpoint) in 95–98% of patients in 8–12 weeks, oral pills, well tolerated. Reinfection is possible; sterile cure doesn't grant immunity. No vaccine has yet been licensed.
Hepatitis D — the satellite virus
Defective ssRNA virus that encodes a single protein (HDAg) and can't make its own envelope. It hijacks HBsAg from HBV. Two clinical patterns:
- Co-infection. Simultaneous HBV + HDV acquisition. Acute illness more severe than HBV alone; chronicity rare because HBV usually self-clears in adults.
- Superinfection. HDV layered onto pre-existing chronic HBV. ~80% chronicity. Most aggressive viral hepatitis known — cirrhosis in years, not decades.
Diagnosis: anti-HDV antibody, then HDV RNA. Test all chronic HBV patients at least once. Treatment: pegylated interferon alfa for 48 weeks (modest response); bulevirtide (entry inhibitor blocking the NTCP bile-acid receptor) approved in Europe 2020 — emerging standard of care. Best prevention: HBV vaccination.
Hepatitis E — hepevirus, fecal-oral, severe in pregnancy
Non-enveloped ssRNA hepevirus. Genotypes 1 and 2 are obligate human pathogens — water-borne outbreaks in Asia, Africa, Mexico. Genotypes 3 and 4 are zoonotic in developed countries — undercooked pork, wild boar, deer, shellfish. Clinical: acute self-limited hepatitis like HAV. Pregnant women in the third trimester with genotype 1 have ~20% mortality (fulminant hepatic failure, mechanism poorly understood). Chronic HEV occurs in immunocompromised hosts (solid organ transplant) and is treated with ribavirin. A vaccine (Hecolin) is licensed only in China.
Worked clinical example — the asymptomatic HBV screen
A 34-year-old immigrant from a high-prevalence country has a routine screen at a primary care visit. Labs: HBsAg positive, anti-HBs negative, anti-HBc positive (IgG), HBeAg negative, anti-HBe positive, HBV DNA 4,200 IU/mL, ALT 28 (normal), platelet count 215k, INR 1.0. Pattern: HBeAg-negative chronic HBV infection in the inactive carrier phase. No fibrosis surrogate evidence (normal platelets, ALT) — FibroScan ordered for elastography. Plan: monitor ALT and HBV DNA every 6 months, AFP + ultrasound every 6 months (HBV is HCC-causing even without cirrhosis if family history or African origin), HDV antibody (one-time test), test household and sexual contacts, vaccinate susceptibles. No antiviral therapy yet — initiate if DNA >2000 with ALT elevation, fibrosis F2+, or HCC family history. This is a classic, common encounter — global HBV prevalence ~3.5% means it walks into clinic often.
Hepatitis A through E at a glance
| Virus | Genome | Route | Chronic? | Vaccine | Treatment |
|---|---|---|---|---|---|
| HAV | ssRNA, picornavirus | Fecal-oral | No | Yes (inactivated, 2 doses) | Supportive |
| HBV | Partial dsDNA, hepadnavirus | Blood, sex, perinatal | Yes (~5% adult, ~90% perinatal) | Yes (recombinant HBsAg) | Entecavir, tenofovir (suppress, rarely cure) |
| HCV | ssRNA, flavivirus | Blood | Yes (~75%) | No | DAAs, 8–12 wk, 95%+ cure |
| HDV | ssRNA, defective satellite | Blood (needs HBV) | ~80% in superinfection | HBV vaccine prevents | Peg-IFN, bulevirtide |
| HEV | ssRNA, hepevirus | Fecal-oral (genotypes 1–2); zoonotic (3–4) | Only in immunocompromised | Yes in China only | Supportive; ribavirin in chronic |
Common misconceptions
- "Anti-HBc positive means chronic infection." No — it means exposure ever. Anti-HBc IgM = recent acute. Anti-HBc IgG with anti-HBs = recovered. Anti-HBc IgG with HBsAg = chronic.
- "HCV cure = immunity." Wrong — reinfection occurs, especially with ongoing risk behavior. Continue harm-reduction counseling and periodic re-testing.
- "Vaccinated against HAV protects against HBV." Different viruses, different vaccines. Combination (Twinrix) covers both.
- "HEV is rare and tropical." Genotype 3 HEV is widespread in developed countries via pork — under-diagnosed acute hepatitis in Western Europe and US.
- "HBV needs cirrhosis for HCC." Unique among hepatitis viruses, HBV can cause HCC without cirrhosis — viral DNA integration is directly oncogenic.
Frequently asked questions
What's the difference between hepatitis A and E?
Both are non-enveloped ssRNA viruses, fecal-oral transmission, no chronic carrier state. HAV (picornavirus) — global, contaminated food and water, travel exposure. Incubation 15–50 days. Vaccine highly effective; post-exposure prophylaxis with vaccine ± Ig within 14 days. HEV (hepevirus) — genotypes 1 and 2 obligate human pathogens; genotypes 3 and 4 zoonotic (pork, deer). Pregnant women with HEV genotype 1 have ~20% mortality (fulminant hepatic failure). Chronic HEV occurs in immunocompromised hosts — treated with ribavirin.
How do you interpret hepatitis B serology?
HBsAg — present = active infection. HBsAg positive >6 months = chronic. Anti-HBs — immunity (vaccine or recovered). HBcAb — exposure; IgM in acute, IgG persists for life. HBeAg — high replication/infectivity. Anti-HBe with low DNA = inactive carrier. HBV DNA quantifies viral load. After vaccine: anti-HBs alone. Past recovered: anti-HBs and anti-HBc. Chronic carrier: HBsAg and anti-HBc, no anti-HBs.
Is hepatitis C really curable?
Yes. Sustained virologic response (SVR) at 12 weeks after finishing therapy is the cure endpoint. Direct-acting antivirals target NS3/4A protease, NS5A, NS5B polymerase. Pan-genotypic regimens — sofosbuvir/velpatasvir (Epclusa) and glecaprevir/pibrentasvir (Mavyret) — cure 95–98% in 8–12 weeks regardless of HCV genotype. Treatment is recommended for all hepatitis C-infected patients. Reinfection is possible — sterile cure doesn't grant immunity. No vaccine yet.
Why does hepatitis D need hepatitis B?
HDV is a defective satellite — only a single-stranded circular RNA encoding the delta antigen. It can't make its own envelope. To assemble new virions, HDV must hijack HBV's surface antigen. Co-infection: simultaneous HBV + HDV usually resolves with HBV. Superinfection: HDV layered onto chronic HBV — much worse; ~80% become chronic, with the most aggressive viral hepatitis. Treatment: pegylated interferon alfa; bulevirtide (entry inhibitor) approved in Europe 2020. HBV vaccination prevents HDV.
Who needs hepatitis B vaccine?
All infants (US universal recommendation since 1991). All adults 19–59 (ACIP universal in 2022); adults ≥60 with risk factors. Risk factors: healthcare workers, dialysis, HIV, household/sexual contacts of HBsAg+, MSM, injection drug users, travelers. Three-dose series (0, 1, 6 months) for standard; Heplisav-B is a two-dose adjuvanted vaccine. Post-vaccine anti-HBs ≥10 mIU/mL = protection. The hepatitis B vaccine was the first vaccine to prevent a cancer (HCC).
When does acute hepatitis become fulminant?
Acute liver failure (ALF) = INR ≥1.5 + hepatic encephalopathy in someone without pre-existing liver disease, within 8–26 weeks of symptom onset. Viral causes: HBV (especially with HDV), HEV genotype 1 (notably in pregnancy), rarely HAV. Markers of severe disease: rising INR, falling factor V (<20% poor prognosis), bilirubin >18 mg/dL, encephalopathy progression, ammonia >150. King's College Criteria identify candidates for emergent transplant. Mortality without transplant historically 50–80%.
What's the connection between hepatitis and liver cancer?
Chronic HBV and HCV cause ~80% of global hepatocellular carcinoma (HCC). HBV is uniquely oncogenic — viral DNA integrates into host genome; cirrhosis isn't required for HCC in HBV. HCV drives HCC via cirrhosis. Screening: AFP + ultrasound every 6 months in cirrhotics with HBV/HCV; in HBV-related cirrhosis annual risk ~3%. Successful HCV cure with DAAs reduces but doesn't eliminate HCC risk in cirrhotics — surveillance continues.