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MI4.7-9 | Viral Hepatitis — SDL Guide (Part 2)

Hepatitis B Virus (HBV) — Structure & Markers

A three-panel medical diagram shows HBV virion structure, meanings of major viral markers, and key serological interpretations. — **Panel A:** HBV outer envelope, HBsAg surface antigen spikes, nucleocapsid/core, HBcAg core antigen, partially double-stranded circular DNA, DNA polymerase/reverse transcriptase.. **Panel B:** HBsAg as diagnostic and vaccine antigen, HBeAg as active replication and high infectivity marker, HBcAg as core antigen not detectable in serum, DNA polymerase as antiviral target for tenofovir and entecavir.. **Panel C:** HBsAg current infection, anti-HBs immunity/vaccination, IgM anti-HBc acute or recent infection, IgG anti-HBc past exposure, HBeAg high infectivity, anti-HBe reduced infectivity..

HBV is a partially double-stranded DNA hepadnavirus with a complex structure:
- Outer envelope: contains HBsAg (surface antigen) — the basis of both diagnosis and vaccine
- Core: HBcAg (core antigen, not detectable in serum); HBeAg (soluble secreted form — marker of active replication and high infectivity)
- DNA polymerase (reverse transcriptase activity) — target for antivirals (tenofovir, entecavir)

Key serological markers:

Marker	What it means
HBsAg	Active infection (acute or chronic); carrier state
Anti-HBs (HBsAb)	Immunity (vaccination or recovery)
Anti-HBc IgM	Acute HBV infection ('window period' marker)
Anti-HBc IgG	Past infection or chronic carrier
HBeAg	Active viral replication, high infectivity
Anti-HBe	Declining replication (seroconversion — good sign)
HBV DNA	Gold standard for viral load; guides antiviral therapy

Timeline graph of acute hepatitis B serological markers over 6 months showing HBsAg, HBeAg, anti-HBc IgM, anti-HBe, anti-HBs, and the window period. — **Panel A:** Main acute HBV timeline graph showing HBsAg, HBeAg, anti-HBc IgM, anti-HBe, anti-HBs, incubation phase, acute hepatitis symptoms, and the shaded window period.. **Panel B:** Clinical interpretation sidebar with marker key and callouts for early infection, window period, and recovery..

HBV Pathogenesis & Chronicity

Three-panel diagram showing HBV virion structure, meanings of major viral markers, and serological patterns distinguishing resolved acute infection from chronic HBV infection. — **Panel A:** HBV outer envelope, HBsAg surface antigen spikes, nucleocapsid/core, HBcAg core antigen, partially double-stranded relaxed circular DNA, DNA polymerase/reverse transcriptase.. **Panel B:** HBsAg as current infection and vaccine antigen, HBeAg as active replication and high infectivity marker, HBcAg as core antigen not detectable in serum, HBV DNA/DNA polymerase as viral load marker and antiviral target for tenofovir and entecavir.. **Panel C:** Serology timeline showing HBsAg, HBeAg, anti-HBc IgM, anti-HBc IgG, anti-HBs, HBV DNA, acute resolved infection, chronic infection, and persistence of HBsAg beyond 6 months..

Transmission: Parenteral (blood, needles), sexual, vertical (mother-to-neonate) — most important route in India; neonates infected at birth have 90% risk of chronicity.

Pathogenesis: HBV itself is not directly cytopathic; injury is CTL-mediated (CD8+ T cells kill infected hepatocytes). In chronic infection, immune tolerance → insufficient CTL response → persistent viraemia without adequate clearance.

Natural history:
1. Acute HBV (adults): 90–95% recover fully with seroconversion; 5–10% become chronic
2. Chronic HBV phases:
- Immune tolerance (high HBeAg, high DNA, minimal inflammation)
- Immune clearance (HBeAg positive hepatitis — active necroinflammation)
- Immune control (HBeAg seroconversion → anti-HBe; low DNA; inactive carrier)
- Immune escape (HBeAg-negative hepatitis — pre-core mutations)
3. Complications: Cirrhosis (20%), hepatocellular carcinoma (risk 100× higher than general population)

Treatment: Oral antivirals — tenofovir or entecavir (suppress HBV DNA; rarely achieve cure = HBsAg clearance)

Hepatitis C & D — Key Points

Three-panel medical diagram comparing hepatitis C virology, transmission and diagnosis, and hepatitis D dependence on hepatitis B surface antigen. — **Panel A:** HCV envelope glycoproteins, lipid envelope, core protein, positive-sense ssRNA genome, acute infection, chronic hepatitis, cirrhosis, hepatocellular carcinoma, no vaccine, direct-acting antivirals.. **Panel B:** Blood-borne transmission, injection drug use or needle sharing, transfusion or unsafe medical procedures, anti-HCV antibody screening, HCV RNA confirmation.. **Panel C:** HDV circular RNA, delta antigen, HBsAg envelope, HBV requirement, coinfection, superinfection, chronic HBV carrier, severe chronic liver disease risk..

Hepatitis C (HCV):
- Enveloped ssRNA(+) flavivirus; 6 major genotypes; genotype 1 dominant globally, genotype 3 common in India
- Parenteral only: IV drug use (#1 risk in India), unsafe injections, transfusions (pre-NAT screening), needlestick, sexual (lower risk)
- Chronicity: 70–85% — HCV is the most likely hepatitis virus to become chronic
- No vaccine available; NS5B RNA polymerase and NS3 protease are antiviral targets
- Treatment revolution: Direct-acting antivirals (DAAs — sofosbuvir, ledipasvir/sofosbuvir) → >95% cure rates, 12-week oral regimens
- Diagnosis: Anti-HCV ELISA (screening) → HCV RNA PCR (confirmatory + quantitative)

Hepatitis D (HDV):
- Unique 'virusoid' — defective virus requiring HBsAg as its envelope; cannot infect without HBV
- Two patterns:
- Co-infection (simultaneous HDV + HBV): fulminant hepatitis risk high; but both resolve together
- Super-infection (HDV in chronic HBV carrier): rapidly accelerates cirrhosis
- Prevention: HBV vaccination prevents HDV
- Diagnosis: Anti-HDV antibodies; HDV RNA PCR

SELF-CHECK

A blood donor's sample tests positive for HBsAg. Further testing shows: Anti-HBc IgM negative, Anti-HBc IgG positive, HBeAg negative, Anti-HBe positive, HBV DNA 500 IU/mL. What is the most likely interpretation?

A. Acute HBV infection

B. Inactive HBV carrier state (past seroconversion from HBeAg to anti-HBe)

C. Vaccinated individual (anti-HBs positive)

D. Window period of acute HBV infection

Reveal Answer

Answer: B. Inactive HBV carrier state (past seroconversion from HBeAg to anti-HBe)

This pattern — HBsAg positive, anti-HBc IgG positive (past/chronic), anti-HBc IgM negative (not acute), HBeAg negative, anti-HBe positive (seroconverted), low HBV DNA — is classic for an inactive HBsAg carrier (previously called healthy carrier). This person had HBeAg-positive chronic HBV but has seroconverted and now has suppressed viral replication. Window period would show anti-HBc IgM positive; vaccination shows anti-HBs but NOT anti-HBc (no natural infection).