Viral hepatitis

The five viruses

• Pakistan carries one of the world's largest hepatitis C burdens, mainly from unsafe injections; the commonest genotype is genotype 3, which itself causes fatty liver.
• Acute hepatitis A is confirmed by IgM anti-HAV; IgG anti-HAV shows past infection or vaccination.

Why the viruses behave differently

• HBV DNA integrates into the host genome and its HBx protein disrupts cell-cycle control, so HCC can arise without cirrhosis.
• HBV persists in hepatocyte nuclei as covalently closed circular DNA (cccDNA). Nucleos(t)ide analogues block reverse transcription and make blood HBV DNA undetectable, but do not remove cccDNA, so the virus usually returns when the drug is stopped. Undetectable DNA is suppression, not cure.
• HBV itself barely damages cells: liver injury comes from CD8 cytotoxic T cells killing infected hepatocytes. That is why people infected at birth can have very high HBV DNA with normal ALT for years (immune tolerance), and why hepatitis flares when immunity returns.
• HCV mutates rapidly; its hypervariable envelope proteins escape neutralising antibodies, so most infections become chronic, anti-HCV does not mean immunity, and no vaccine exists.
• HDV has no envelope gene and must borrow HBsAg, so it infects only people with HBV. Co-infection (acquired together) usually clears; superinfection of a carrier causes a severe flare and rapid cirrhosis. Test for HDV in any HBsAg-positive patient with severe or progressive disease.
• Reactivation: a person with HBsAg negative but anti-HBc positive still has cccDNA in the liver. Rituximab or chemotherapy can cause HBsAg to reappear with very high HBV DNA and severe hepatitis; give antiviral prophylaxis.

Hepatitis B serology

• Reading the markers together gives the common patterns:

• Prodrome: one to two weeks before jaundice, fever, urticaria and arthralgia arise from HBsAg–antibody immune complexes (serum sickness-like). Immune complexes also explain polyarteritis nodosa and membranous nephropathy.
• After a vaccine course, anti-HBs of 10 mIU/mL or more shows adequate protection; health workers are checked after vaccination.

Exam trap Anti-HBs alone means vaccination; anti-HBs with anti-HBc means natural recovery.

Pathology and severity

• Acute hepatitis: ballooning degeneration, lobular inflammation, cholestasis and Councilman bodies: round, deeply eosinophilic hepatocytes with dense nuclear fragments, representing apoptosis, not necrosis. ALT is very high, often in the thousands, and above AST.
• Chronic hepatitis: portal inflammation spilling into the lobule (interface hepatitis), fibrosis, cirrhosis. HBV shows ground-glass hepatocytes (HBsAg in the cytoplasm); HCV shows lymphoid aggregates and fatty change.
• Severity: the prothrombin time / INR is the best single marker of liver synthetic failure and prognosis in acute hepatitis, because clotting factors have short half-lives; drowsiness or confusion means encephalopathy and acute liver failure.
• Autoimmune hepatitis is the main mimic when viral serology is negative: young woman, high IgG, anti-smooth muscle and antinuclear antibodies, interface hepatitis with plasma cells; it responds to steroids (with azathioprine).
• HCV extrahepatic disease: mixed cryoglobulinaemia, membranoproliferative glomerulonephritis, porphyria cutanea tarda, lichen planus.

Treatment

• Sofosbuvir with amiodarone can cause severe bradycardia and syncope, even if amiodarone was stopped recently (long half-life).
• Check HBV status before HCV treatment: HBV can flare when HCV is cleared. Stopping tenofovir in HBV/HIV co-infection can cause a hepatitis flare.

Mother and baby

• Baby of an HBsAg-positive mother: vaccine plus hepatitis B immunoglobulin within 12 hours of birth; tenofovir in the third trimester if maternal viral load is high.
• After this prophylaxis the mother should breastfeed normally; HBsAg alone is no reason to stop.

Blood exposure and needlestick injury

• Standard (universal) precautions: treat all blood and body fluids as potentially infectious, whatever the patient's test results.
• Prevent injuries: never recap needles (if unavoidable, one-handed scoop); drop sharps straight into a sharps bin; use a neutral zone to pass sharps; double gloving reduces the blood volume reaching the skin when the outer glove is punctured, since a solid needle wipes off blood as it passes through.
• Risk is highest with a deep injury from a hollow-bore needle just removed from a vein or artery, visible blood and a source with high viral load.

• First aid: let the wound bleed freely and wash with soap and water (do not scrub or suck); irrigate eyes and mouth with plenty of water or saline; then report and assess the source.
• Intact skin contaminated with blood: wash with soap and water; no PEP is needed. Broken skin (cuts, eczema) counts as significant exposure.
• HIV PEP: start as soon as possible, ideally within hours and no later than 72 hours, for 28 days; preferred adult regimen tenofovir, lamivudine and dolutegravir. Do not wait for source results after a high-risk injury.
• HBV: if the worker is non-immune, give HBIG and start or boost vaccination.
• HCV: no PEP; serial testing (HCV RNA early, antibodies later) and treat if infection develops.
• An HBeAg-positive surgeon with high HBV DNA is restricted from exposure-prone procedures because they could infect patients through their own injuries; antiviral treatment can lower the viral load to permit return. The worker's confidentiality is protected.

Remember Bleed, wash, report, and start HIV PEP within hours, not days.

How FCPS asks about this

• HBsAg +, IgM anti-HBc +, HBeAg +, anti-HBs −: acute hepatitis B, highly infectious; IgM anti-HBc alone is the window period.
• Why HBV causes HCC without cirrhosis: DNA integration and HBx protein.
• Why hepatitis B returns after stopping entecavir: cccDNA persists in hepatocytes.
• Why HDV infects only some patients: it needs HBsAg for its envelope.
• Best marker of severity in acute hepatitis: prothrombin time / INR.
• Commonest HCV genotype in Pakistan and sofosbuvir's target: genotype 3; NS5B polymerase.
• Needlestick from an HIV-positive patient: bleed and wash, then tenofovir, lamivudine and dolutegravir within 72 hours for 28 days.