Q3 LONG ANSWER 10M ★ High-yield

Describe the viruses causing hepatitis. Explain the morphology of acute and chronic hepatitis and the interpretation of hepatitis B serology.

Pathology · 2nd Professional — Para-Clinical

The Hepatitis Viruses

Virus	Genome	Transmission	Incubation	Chronicity	Vaccine
HAV	RNA picornavirus	Faeco-oral — contaminated water and food	2–6 weeks	Never	Yes
HBV	DNA hepadnavirus	Parenteral, sexual, vertical	1–6 months	5–10% of adults; 90% of neonates	Yes
HCV	RNA flavivirus	Parenteral — transfusion, injecting drug use	4–20 weeks	Up to 80% — the highest	NO
HDV	Defective RNA virus — requires HBsAg	Parenteral	Variable	High with superinfection	Prevented by HBV vaccine
HEV	RNA hepevirus	Faeco-oral — water-borne epidemics	2–8 weeks	Rare (in the immunosuppressed)	Available in some countries

The faeco-oral viruses (A and E) do not cause chronic disease; the blood-borne viruses (B, C, D) do. This single rule organises the whole subject
HEV in pregnancy carries a mortality of about 20% from fulminant hepatic failure, particularly in the third trimester — a major concern in India, where waterborne epidemics are common
HDV — CO-infection with HBV usually resolves; superinfection of a chronic HBV carrier causes severe, rapidly progressive disease

Clinicopathological Syndromes

Syndrome	Features
Asymptomatic infection	Detected only serologically or by raised transaminases
Acute hepatitis	Four phases — incubation, pre-icteric (prodromal: malaise, anorexia, nausea, distaste for cigarettes, fever), icteric (jaundice, dark urine, pale stools, tender hepatomegaly), and convalescent
Fulminant hepatitis	Massive hepatic necrosis with encephalopathy within 8 weeks; commonest with HBV+HDV and with HEV in pregnancy; mortality above 50%
Chronic hepatitis	Biochemical or histological evidence persisting beyond 6 months
Carrier state	Harbours and transmits the virus with little or no liver damage

Morphology

Acute hepatitis

Ballooning degeneration of hepatocytes — swollen, empty-looking cytoplasm
Councilman (acidophil) bodies — shrunken, deeply eosinophilic apoptotic hepatocytes
Lobular disarray — loss of the normal cord architecture
Mononuclear portal and lobular inflammation; Kupffer cell hyperplasia
Cholestasis with bile plugs in canaliculi
Bridging necrosis linking portal tracts and central veins indicates severe disease and a risk of progression

Chronic hepatitis

Portal tract lymphocytic infiltrate
Interface hepatitis (piecemeal necrosis) — inflammation spilling across the limiting plate and destroying periportal hepatocytes; the key feature of progressive disease
Fibrosis — portal, then periportal, then bridging, then cirrhosis
Ground-glass hepatocytes — finely granular eosinophilic cytoplasm from accumulated HBsAg in the endoplasmic reticulum; characteristic of chronic HBV
Chronic HCV — portal lymphoid aggregates or follicles, bile duct damage, and macrovesicular steatosis
Grading assesses inflammatory activity; staging assesses fibrosis — two different questions answered by the same biopsy

Hepatitis B Serology

Marker	Meaning
HBsAg	Surface antigen — the first marker to appear; indicates current infection. Persistence beyond 6 months means chronic infection
Anti-HBs	Immunity — from recovery or vaccination; the only marker present after vaccination
HBeAg	Active viral replication and high infectivity
Anti-HBe	Seroconversion; falling replication and infectivity
Anti-HBc IgM	Acute or recent infection; the only marker positive during the "window period" when HBsAg has gone and anti-HBs has not yet appeared
Anti-HBc IgG	Past or ongoing infection; never produced by vaccination
HBV DNA	The most accurate measure of viral load; guides treatment

CLINICAL PEARL

Anti-HBc is what distinguishes vaccination from past infection. A vaccinated person has anti-HBs alone, because the vaccine contains only surface antigen. Someone who has recovered from infection has anti-HBs and anti-HBc. And in the window period, anti-HBc IgM is the only positive marker — so a patient with acute hepatitis and negative HBsAg is not so excluded.

Complications of Chronic Viral Hepatitis

Complication	Notes
Cirrhosis	In 20–30% of chronic hepatitis C over 20–30 years; less often with hepatitis B
Hepatocellular carcinoma	Hepatitis B can cause it without cirrhosis by integrating into the host genome; hepatitis C almost always acts through cirrhosis
Extrahepatic — hepatitis B	Polyarteritis nodosa (about 30% of cases), membranous glomerulonephritis
Extrahepatic — hepatitis C	Mixed cryoglobulinaemia with vasculitis, membranoproliferative glomerulonephritis, porphyria cutanea tarda, lymphoma
Fulminant failure	Hepatitis B with D superinfection; hepatitis E in pregnancy

Applied Aspects

Hepatitis A and E are prevented by clean water, sanitation and food hygiene; both cause large waterborne outbreaks in India
HBV vaccination is part of the universal immunisation programme in India, and the birth dose within 24 hours is critical, since neonatal infection becomes chronic in 90%
HBV and HCV are major causes of cirrhosis and hepatocellular carcinoma; HBV can cause carcinoma even without cirrhosis, by integrating into the host genome
Hepatitis C is now curable in over 95% with direct-acting antivirals, a genuinely transformative development; there is still no vaccine
Screening of blood donors for HBsAg, anti-HCV and HIV, with nucleic acid testing where available, has greatly reduced transfusion-transmitted hepatitis
Post-exposure prophylaxis after a needlestick — hepatitis B immunoglobulin and vaccination; there is none for hepatitis C, so early detection and treatment is the approach
Universal precautions protect health workers, and HBV vaccination should be mandatory for all of them

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