Viral hepatitis A to E

Overview

Five main viruses (A, B, C, D and E) attack the liver as their primary target. Acute illness looks similar for all of them: malaise, nausea, then jaundice. The important differences are how they spread, whether they become chronic, which markers diagnose them and how they are treated.

In Pakistan, hepatitis C (spread mostly by reused syringes and unsafe medical procedures) is the leading cause of cirrhosis and liver cancer. Hepatitis B is the other big chronic infection. Hepatitis A is common in children, and hepatitis E causes water-borne outbreaks.

The five viruses compared

Hepatitis A

• Picornavirus, faeco-oral spread through contaminated food or water; overcrowding and poor sanitation favour it.
• Virus is shed in stool before jaundice appears, so the patient is most infectious just before the jaundice.
• In children it is often anicteric and mild; adults are more symptomatic.
• Phases: prodrome (anorexia, nausea, distaste for cigarettes, fever) → jaundice with dark urine and pale stools, tender liver → recovery.
• Diagnosis: IgM anti-HAV. IgG anti-HAV means past infection or vaccination and lifelong immunity.
• No carrier state, no chronic hepatitis. Acute liver failure is rare.
• Management is supportive. Prevention: hygiene, safe water, hepatitis A vaccine (advised for people with chronic liver disease).

Hepatitis B

Virology and spread

• Partly double-stranded DNA virus that replicates through reverse transcription. A stable form called cccDNA stays in the liver cell nucleus, which is why the drugs suppress but rarely cure the infection.
• Spread: blood (unsafe injections, transfusion, needlestick), sexual, and vertical (mostly at birth).
• After a needlestick from an infected source, HBV carries the highest transmission risk of the blood-borne viruses.

Markers and what they mean

Common serology patterns

Acute hepatitis B

• Many adult infections are silent. Symptomatic disease is like hepatitis A but can be more severe.
• A serum-sickness-like prodrome (urticaria, fever, small-joint arthritis) occurs in some, caused by immune complexes of HBsAg and antibody.
• About 99% of adults clear the virus. Acute liver failure occurs in under 1%.
• Treatment is supportive. Oral antivirals are given in severe or prolonged cases.

Chronic hepatitis B

• Defined as HBsAg present for more than 6 months.
• Risk of chronicity depends on age at infection: about 90% of babies infected at birth become chronic, compared with about 1–10% of adults.
• Liver damage is caused by the host immune response (cytotoxic T cells) killing infected cells, not by the virus directly.
• Biopsy may show ground-glass hepatocytes (cytoplasm full of HBsAg).
• Extrahepatic features: polyarteritis nodosa, membranous nephropathy.
• HBV can cause hepatocellular carcinoma even without cirrhosis because viral DNA integrates into the host genome.

Who to treat: moderate to severe inflammation or fibrosis with HBV DNA above 2000 IU/mL and/or raised ALT; anyone with cirrhosis, whatever the ALT or viral load.

Drugs:

• Tenofovir or entecavir: first-line oral agents; potent, high barrier to resistance; usually long term.
• Pegylated interferon-alfa: weekly injection for a fixed course; side effects include flu-like illness, depression, low blood counts and thyroid disorders; avoid in cirrhosis.
• Lamivudine is now avoided because resistance (YMDD mutation) develops quickly.
• Tenofovir disoproxil can damage the proximal tubule (phosphate wasting, glycosuria) and bone.

Surveillance: chronic carriers have a raised lifetime risk of liver cancer and need 6-monthly ultrasound (with or without AFP) when at high risk.

Prevention

• Hepatitis B vaccine (recombinant HBsAg, given into the deltoid; buttock injections into fat respond poorly). In Pakistan it is part of the EPI pentavalent vaccine, with a birth dose. An anti-HBs level of 10 mIU/mL or more after vaccination shows protection.
• Babies of HBsAg-positive mothers: vaccine plus hepatitis B immunoglobulin (HBIG) at birth, ideally within 12 hours. Breastfeeding can continue.
• Pregnant women with very high HBV DNA: tenofovir in the third trimester reduces transmission.
• Needlestick in a non-immune worker: HBIG and vaccination.
• Before chemotherapy or rituximab, screen for HBsAg and anti-HBc because reactivation can be severe.

Hepatitis D (delta)

• A defective RNA virus that uses HBsAg as its coat; it can only infect people who also have HBV.
• Co-infection (HBV and HDV at the same time): usually acute and clears; looks like ordinary acute hepatitis B.
• Superinfection of a chronic HBsAg carrier: often severe, may cause acute liver failure, and leads to rapid progression to cirrhosis.
• Diagnosis: anti-HDV antibody (IgM in acute infection) and HDV RNA.
• HBV vaccination prevents HDV.

Hepatitis C

Spread and course

• RNA flavivirus spread mainly by blood: in Pakistan, reused syringes, unsafe injections, dental and surgical procedures, unscreened transfusion and barber shops. Sexual and vertical spread are uncommon.
• Its envelope proteins mutate rapidly, so the immune system cannot clear it well and there is no vaccine.
• Most acute infections are silent. The majority of infected adults become chronic.
• Chronic HCV progresses slowly over decades. Kumar notes about 16% have cirrhosis after 20 years; alcohol, HIV, obesity, diabetes and genotype 3 speed fibrosis.
• Once cirrhosis develops, liver cancer appears at about 1% per year. Unlike HBV, HCV rarely causes liver cancer without cirrhosis.
• Genotype 3 is the commonest genotype in the Indian subcontinent, including Pakistan.

Extrahepatic features: mixed cryoglobulinaemia (purpura, arthralgia, glomerulonephritis, low complement), porphyria cutanea tarda, lichen planus, diabetes, non-Hodgkin lymphoma.

Diagnosis

1. Anti-HCV antibody (ELISA): screening. It shows exposure, not necessarily current infection.
2. HCV RNA by PCR: confirms active infection and is used to check cure.
3. Genotype (if the regimen needs it), and assess fibrosis (elastography, APRI) and screen for HBV and HIV.

Treatment

• Direct-acting antivirals (DAAs) taken by mouth for 8–12 weeks cure (sustained virological response: no RNA 12 weeks after stopping) over 95%.
• Targets: NS5B polymerase (sofosbuvir), NS5A (velpatasvir, daclatasvir, ledipasvir), NS3/4A protease (glecaprevir, grazoprevir).
• Pan-genotypic combinations such as sofosbuvir with velpatasvir or sofosbuvir with daclatasvir are widely used in Pakistan.
• Ribavirin is sometimes added (for example in decompensated cirrhosis). It causes haemolytic anaemia and is teratogenic, so both partners need contraception during and for months after treatment.
• Interaction: sofosbuvir with amiodarone can cause severe bradycardia.
• After cure, people with cirrhosis still need HCC surveillance.

Pakistan has national hepatitis control programmes that offer screening and DAA treatment. Regimens and eligibility change, so check the current national guideline.

Hepatitis E

• RNA virus, faeco-oral (contaminated water); causes epidemics after floods and in areas with poor water supply. Some infection is zoonotic (pigs).
• Illness resembles hepatitis A. No carrier state in healthy people; chronic infection only in the immunosuppressed (e.g. transplant recipients).
• Diagnosis: IgM anti-HEV (or HEV RNA).
• Overall acute mortality is about 1–2%, but in pregnant women (especially the third trimester) it rises to about 20% due to acute liver failure.

Other viruses that inflame the liver

EBV (glandular fever), CMV and herpes simplex (immunosuppressed or pregnant; very high transaminases; treat with aciclovir) can all raise liver enzymes. Yellow fever and leptospirosis are other infective causes of jaundice.

Management of acute viral hepatitis (all types)

• Most cases are managed at home: rest, fluids, adequate diet, avoid alcohol and hepatotoxic drugs.
• Admit if there is persistent vomiting, confusion or drowsiness (encephalopathy), INR rising, hypoglycaemia, or pregnancy with severe illness. These suggest acute liver failure, which needs specialist care and assessment for transplant.
• Notify cases and trace contacts as local rules require.

Quick revision

• A and E: faeco-oral; not chronic (E chronic only if immunosuppressed).
• B, C, D: blood-borne; can become chronic, cirrhosis and HCC.
• HBsAg = infection; IgM anti-HBc = acute; HBeAg = infectious; anti-HBs only = vaccinated.
• Chronic HBV: HBsAg over 6 months; perinatal infection becomes chronic in about 90%.
• Treat chronic HBV with tenofovir or entecavir; avoid interferon in cirrhosis.
• Baby of HBsAg-positive mother: vaccine plus HBIG at birth.
• HDV needs HBsAg; superinfection of a carrier is severe.
• Anti-HCV positive → HCV RNA; DAAs for 8–12 weeks cure over 95%.
• HEV mortality about 20% in pregnancy.

Written by The House Job from standard references (Kumar and Clark's Clinical Medicine).

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