Viral Hepatitis

Viral hepatitis is systemic infection predominantly affecting the liver, caused by five hepatotropic viruses (A, B, C, D, E). NEET PG loves the serological markers of HBV, the chronicity profile of each virus, and the coinfection vs superinfection contrast of HDV. Get the markers right and you have already banked most of the marks.

Classification & basic virology

The five hepatotropic viruses differ in genome, route of transmission, incubation, and tendency to chronicity. Memorise the table below — it is the single most examined slide in hepatology.

Virus	Genome	Family	Route	Incubation	Chronicity	Vaccine
HAV	ssRNA	Picornavirus	Faeco-oral	15–45 d (avg 28)	Never	Yes (killed)
HBV	dsDNA (partial)	Hepadnavirus	Parenteral / sexual / vertical	30–180 d	Yes (5–10% adults, 90% neonates)	Yes (recombinant HBsAg)
HCV	ssRNA	Flavivirus	Parenteral	15–160 d	Yes (highest, 50–85%)	None
HDV	ssRNA (defective)	Deltavirus	Parenteral (needs HBV)	30–180 d	Variable	HBV vaccine protects
HEV	ssRNA	Hepevirus	Faeco-oral	15–60 d	Usually no*	Yes (HEV 239, China only)

*HEV genotype 3 can cause chronic hepatitis in transplant/immunosuppressed patients.

High-yield: "Vowels hit the bowels" — A and E are faeco-oral and do not cause chronic disease. The consonant viruses B, C, D are blood-borne and can become chronic.

High-yield: HBV is the only DNA virus among the hepatotropic viruses. All the rest are RNA viruses.

Hepatitis A (HAV)

• Picornavirus, faeco-oral, contaminated water/shellfish; commonest acute viral hepatitis in India in children.
• Self-limiting; never chronic, no carrier state.
• Children mostly subclinical; severity increases with age. Fulminant hepatic failure is rare (<0.1%).
• Diagnosis: anti-HAV IgM = acute infection; anti-HAV IgG = past infection / immunity.
• A relapsing and a cholestatic variant exist but resolve.
• Prevention: killed vaccine; post-exposure prophylaxis with vaccine ± immunoglobulin within 2 weeks.

Hepatitis E (HEV)

• Hepevirus, faeco-oral, water-borne epidemics; the commonest cause of acute viral hepatitis in adults in India and the commonest cause of fulminant hepatic failure in pregnancy.
• Genotype 1 & 2 — epidemic, faeco-oral, humans (India). Genotype 3 & 4 — zoonotic (pig), sporadic, can be chronic in immunosuppressed.
• Diagnosis: anti-HEV IgM.

High-yield: HEV in pregnancy (third trimester) carries a mortality up to 20% with high risk of fulminant hepatic failure. This is the single most repeated HEV fact.

Hepatitis B (HBV) — the marker workhorse

HBV (Dane particle) is a partially double-stranded DNA hepadnavirus. Its serological markers are tested every year, so understand each one.

The antigens and antibodies

Marker	Meaning
HBsAg	Surface antigen — first to appear; ongoing infection (acute or chronic). >6 months = chronic
Anti-HBs	Recovery + immunity; the only marker after vaccination
HBeAg	High infectivity / active replication
Anti-HBe	Lower replication; seroconversion = better prognosis
Anti-HBc IgM	Acute infection; only marker positive in the window period
Anti-HBc IgG	Past or chronic infection (never appears after vaccination)
HBV DNA	Best quantitative marker of viral load / replication

High-yield: In the window period, HBsAg has disappeared and anti-HBs has not yet appeared — the only positive marker is anti-HBc IgM. A donor in the window period can still transmit HBV.

High-yield: Vaccinated person → anti-HBs positive, everything else negative. Natural immunity → anti-HBs and anti-HBc IgG positive. This single discriminator (anti-HBc) separates vaccination from past infection.

Interpreting common serological patterns

HBsAg	Anti-HBc	Anti-HBs	Interpretation
+	IgM	–	Acute hepatitis B
+	IgG	–	Chronic hepatitis B
–	IgM	–	Window period
–	IgG	+	Past infection, recovered, immune
–	–	+	Vaccinated, immune
–	IgG	–	Distant past infection / low-level / false

HBeAg-negative chronic HBV

A pre-core / core-promoter mutant causes chronic disease with high HBV DNA but HBeAg negative and anti-HBe positive. Do not be fooled into calling it inactive — check HBV DNA and ALT.

Natural history & outcomes

Acute HBV in adults → >90% clear the virus; only ~5–10% become chronic. In neonates the figures invert — ~90% become chronic because of immune tolerance. Chronic HBV → cirrhosis → hepatocellular carcinoma (HCC).

High-yield: HBV can cause HCC even without cirrhosis because the viral DNA integrates into the host genome (it is directly oncogenic). HCV causes HCC almost always via cirrhosis.

Extrahepatic manifestations: polyarteritis nodosa (PAN) and membranous glomerulonephritis are classically HBV-associated.

Hepatitis C (HCV)

• Flavivirus, RNA, parenteral (IV drug use, transfusion); commonest cause of post-transfusion hepatitis historically and the virus most likely to cause chronicity.
• Acute infection usually silent; 50–85% progress to chronic infection → cirrhosis → HCC over decades.
• Diagnosis flow: Anti-HCV antibody (screening) → if positive → HCV RNA (confirms active infection). Anti-HCV alone cannot distinguish active from cleared infection.
• Genotype determines treatment regimen/duration (genotype 1 commonest worldwide; genotype 3 common in India).
• Extrahepatic: mixed essential cryoglobulinaemia, membranoproliferative GN, porphyria cutanea tarda, lichen planus.

High-yield: HCV → highest chronicity (the "C = Chronic" mnemonic). No vaccine exists for HCV because of high genomic variability (hypervariable E2 region).

Hepatitis D (HDV) — coinfection vs superinfection

HDV is a defective RNA virus requiring the HBsAg coat of HBV to replicate. Therefore HDV cannot infect a person who is not HBV-infected, and the HBV vaccine protects against HDV.

Feature	Coinfection	Superinfection
Timing	HBV + HDV acquired together	HDV on established chronic HBV
Anti-HBc	IgM positive	IgG positive
Chronicity of HDV	Low (~2–5%)	High (up to 80%)
Severity	Usually self-limiting	Severe; rapid progression to cirrhosis
Marker tip	Both acute	Acute-on-chronic

High-yield: Distinguish the two by anti-HBc class — IgM = coinfection, IgG = superinfection. Superinfection is the more dangerous (more chronicity, faster cirrhosis).

Clinical features (common to all)

Four classic phases:

1. Incubation / pre-icteric (prodromal): anorexia, nausea, malaise, low-grade fever, distaste for smoking, RUQ discomfort, serum-sickness-like syndrome (arthralgia, urticaria) in HBV.
2. Icteric phase: jaundice, dark urine (bilirubinuria), pale stools, tender hepatomegaly.
3. Convalescence: symptoms resolve, jaundice fades.
4. Recovery (or progression to chronic in B/C/D).

Stepwise diagnostic approach: clinical jaundice → LFT (raised ALT > AST, conjugated bilirubin) → viral serology panel → if HBsAg/anti-HCV positive, quantify DNA/RNA → assess fibrosis (FibroScan/biopsy) → screen for HCC if cirrhotic.

Investigations

• Liver enzymes: ALT and AST markedly raised (often >1000 IU/L in acute), ALT > AST (reverse of alcoholic hepatitis where AST:ALT > 2:1).
• Bilirubin: conjugated (direct) predominant; bilirubinuria.
• Prothrombin time / INR: the best marker of hepatic synthetic function and prognosis; prolonged PT signals impending fulminant failure.
• Viral markers as above.
• Fibrosis assessment: transient elastography (FibroScan), APRI, FIB-4; biopsy is gold standard but rarely needed now.

High-yield: A rising / prolonged PT-INR with falling transaminases and encephalopathy in acute hepatitis means acute liver failure — not improvement. Falling enzymes here are ominous (hepatocyte exhaustion).

Management & drug of choice

Acute hepatitis (A, E, most acute B)

Supportive — rest, hydration, avoid hepatotoxins/alcohol/paracetamol overdose. Most acute HBV in adults needs no antiviral. Acute HCV may be treated to prevent chronicity.

Chronic hepatitis B

First-line oral agents (high barrier to resistance):

• Tenofovir (TDF or TAF) — drug of choice; TAF preferred if renal/bone concerns.
• Entecavir — drug of choice, especially in decompensated cirrhosis.
• Pegylated interferon-alfa — finite course, good for young patients with high ALT, low DNA, HBeAg-positive; contraindicated in decompensated cirrhosis and pregnancy.

High-yield: Tenofovir is the antiviral of choice for HBV in pregnancy (third trimester, to prevent vertical transmission) and the DOC for preventing mother-to-child transmission alongside HBIG + vaccine to the neonate. Lamivudine has a high resistance rate and is no longer first line.

Chronic hepatitis C

• Direct-acting antivirals (DAAs) — cure rate >95%, all-oral, 8–12 weeks.
• Sofosbuvir (NS5B inhibitor) backbone, combined with velpatasvir (NS5A inhibitor) — pangenotypic regimen. Others: ledipasvir, daclatasvir, glecaprevir/pibrentasvir.
• Interferon and ribavirin are now largely obsolete for HCV.

High-yield: Sofosbuvir-based DAA = HCV (curable, no vaccine). Tenofovir/Entecavir = HBV (suppressible, has vaccine). Do not mix these up — a favourite distractor pairing.

HDV

Treat the underlying HBV; pegylated interferon-alfa is the only established option. Bulevirtide (entry inhibitor) is a newer agent.

Prevention

• HBV vaccine (recombinant HBsAg) — birth dose + schedule; protects against HBV and HDV.
• HAV vaccine and HEV vaccine (HEV 239, licensed in China) available.
• HBV post-exposure: HBIG + vaccine (e.g. needlestick from HBsAg-positive source, or neonate of HBsAg-positive mother within 12 h of birth).

Complications

• Fulminant hepatic / acute liver failure — encephalopathy + coagulopathy within 8 weeks; HEV in pregnancy, HBV±HDV are top causes.
• Chronic hepatitis → cirrhosis → portal hypertension, varices, ascites.
• Hepatocellular carcinoma — HBV (with or without cirrhosis), HCV (via cirrhosis).
• Cholestatic hepatitis, relapsing hepatitis (HAV).
• Extrahepatic: PAN, membranous GN (HBV); cryoglobulinaemia, MPGN, PCT, lichen planus (HCV); aplastic anaemia (rare, post-hepatitis).

Key differentials

• Alcoholic hepatitis — AST:ALT > 2:1, GGT up, history of alcohol.
• Drug-induced liver injury — paracetamol, anti-TB drugs, herbal.
• Autoimmune hepatitis — ANA/anti-smooth muscle/anti-LKM, raised IgG, young women.
• Leptospirosis (Weil disease) — jaundice + AKI + conjunctival suffusion + myalgia.
• Obstructive jaundice — raised ALP/GGT, dilated ducts on USG, pale stools persistently.
• Wilson disease — young patient, low ceruloplasmin, KF rings, Coombs-negative haemolysis.

Recently asked / exam angle

• Window period marker identification (anti-HBc IgM) — repeated across NEET PG, INI-CET.
• Differentiate vaccinated vs naturally immune using anti-HBc — high-frequency one-liner.
• Coinfection vs superinfection of HDV by anti-HBc class — classic two-statement question.
• "Which hepatitis is most likely to become chronic?" → HCV.
• "Commonest cause of FHF in pregnancy?" → HEV.
• "DOC for HBV in pregnancy?" → Tenofovir.
• "Hepatitis virus causing HCC without cirrhosis?" → HBV (DNA integration).
• DAA matching: sofosbuvir → HCV; entecavir/tenofovir → HBV.
• Image/serology grid interpretation tables are increasingly common — practise reading the marker matrix fast.
• HBeAg-negative chronic HBV (pre-core mutant) appearing as a clinical vignette.

Rapid revision

1. Vowels hit the bowels — HAV & HEV are faeco-oral, never chronic; B, C, D are blood-borne and can chronify.
2. HBV is the only DNA virus among hepatitis viruses.
3. HCV = highest chronicity (50–85%); HBV chronicity 90% in neonates, 5–10% in adults.
4. Anti-HBc IgM is the sole marker positive in the window period.
5. Anti-HBs alone = vaccinated; anti-HBs + anti-HBc IgG = naturally immune/recovered.
6. HBeAg = high infectivity; HBV DNA = best quantitative replication marker.
7. HDV needs HBV to replicate → HBV vaccine protects against HDV.
8. Coinfection = anti-HBc IgM; superinfection = anti-HBc IgG (superinfection more chronic/severe).
9. HEV in third-trimester pregnancy → up to 20% mortality, commonest FHF in pregnancy.
10. Tenofovir / Entecavir for chronic HBV; Sofosbuvir-based DAAs cure HCV (>95%); Peg-IFN for HDV.
11. PT/INR = best prognostic marker in acute hepatitis; rising INR + encephalopathy = acute liver failure.
12. HBV → HCC even without cirrhosis (DNA integration, directly oncogenic); HBV linked to PAN, HCV to cryoglobulinaemia.