Clinical reasoning notes. Treatment thresholds change with new guidance: check your current national guidelines before treating.
The reasoning chain: what is the pattern of liver injury → what is the cause (virus, drug, autoimmune, alcohol) → which virus and which phase → does this patient need treatment → what could go wrong later (cirrhosis, liver cancer).
1. Presentation
Jaundice, fatigue, right upper quadrant pain, nausea and vomiting, fever, dark urine and pale stools. Many patients, especially with chronic hepatitis B, have no symptoms until the liver is badly scarred.
2. Start with the pattern: liver function tests
| Pattern | What is raised | Think of |
|---|---|---|
| Hepatocellular | ALT and AST high | Viral hepatitis, drugs, alcohol, autoimmune hepatitis |
| Cholestatic | ALP and GGT high | Gallstones in the bile duct, tumour, primary biliary cholangitis |
| Synthetic function | Low albumin, prolonged INR | How badly the liver is failing (more serious than ALT) |
3. Find the cause
Viral: hepatitis A, B, C and E.
Drugs and toxins: anti-TB drugs (isoniazid, rifampicin, pyrazinamide), co-amoxiclav, paracetamol overdose, herbal remedies and alcohol. Always take a drug history, including traditional medicines.
Autoimmune: ANA, anti-smooth muscle antibody and anti-LKM1 for autoimmune hepatitis; antimitochondrial antibody for primary biliary cholangitis.
Always do: a toxicology and drug review, and viral screening.
4. Hepatitis B serology: read it like a story
| Marker | What it tells you |
|---|---|
| HBsAg | The patient has the virus now (acute or chronic). Positive for more than 6 months means chronic infection |
| Anti-HBc IgM | Acute (recent) infection |
| Anti-HBc IgG | Past or chronic infection |
| Anti-HBs | Immunity: from vaccination (anti-HBs alone) or after recovery (with anti-HBc IgG) |
| HBeAg | The virus is actively replicating: high infectivity |
| HBV DNA (viral load) | How much virus there is: the key number for the decision to treat |
5. Chronic hepatitis B: who needs treatment?
Classic thresholds (a plain-language rule to remember):
- HBeAg positive with HBV DNA above 20,000 IU/mL and a raised ALT or significant fibrosis
- HBeAg negative with HBV DNA above 2,000 IU/mL and a raised ALT or significant fibrosis
- Cirrhosis: treat if the DNA is detectable at all
Newer WHO guidance has widened who is eligible for treatment, so check what is current in your country.
6. Drugs: why this one and not that one
| Drug | Role | The point to remember |
|---|---|---|
| Tenofovir | First line | Very high barrier to resistance; check kidney function and bone health |
| Entecavir | First line | High barrier to resistance |
| Lamivudine | Cheap but no longer first line | Resistance develops through the YMDD mutation in the viral reverse transcriptase |
| Pegylated interferon-α | A finite course in selected patients | Many side effects; not for cirrhosis with decompensation |
| Ribavirin | Hepatitis C, not hepatitis B | A classic exam trap: do not confuse the two viruses' drugs |
7. Supportive care, and why
- Vomiting: antiemetics (such as metoclopramide or ondansetron) and fluids.
- Fever or pain: paracetamol is acceptable at a reduced dose; the liver clears it more slowly.
- Avoid NSAIDs such as diclofenac: low clotting factors raise the risk of bleeding, they can bleed the stomach, and they injure the kidneys.
- Avoid aspirin: bleeding, and Reye's syndrome in children.
- Stop alcohol and any suspected hepatotoxic drug.
8. Complications and surveillance
Cirrhosis, liver failure and hepatocellular carcinoma (HCC). In chronic hepatitis B and in cirrhosis, screen for HCC with ultrasound, with or without AFP, every 6 months. A suspicious lesion is characterised with triple-phase CT of the abdomen (arterial enhancement then washout is typical).
9. Prevention
Vaccinate all infants and health workers, give hepatitis B immunoglobulin plus vaccine to babies of infected mothers, screen blood and contacts, and counsel on safe sex and needles.
Examiner questions
- A patient is HBsAg positive and anti-HBc IgM negative with positive anti-HBc IgG. What does that mean?
- Why is lamivudine no longer first line?
- Why not diclofenac for fever in a patient with hepatitis?
Practice questions
1. HBsAg negative, anti-HBs positive, anti-HBc negative. The patient is: A. Acutely infected · B. Chronically infected · C. Immune through vaccination · D. A carrier · E. Immune after natural infection Answer: C. Anti-HBs alone means vaccine immunity.
2. The mutation that makes hepatitis B resistant to lamivudine is: A. T790M · B. YMDD · C. V600E · D. BRCA1 · E. K103N Answer: B.
3. Which drug is used for hepatitis C but not hepatitis B? A. Tenofovir · B. Entecavir · C. Ribavirin · D. Lamivudine · E. Pegylated interferon-α is used for neither Answer: C.
4. The best way to screen a patient with cirrhosis for hepatocellular carcinoma is: A. A liver biopsy every year · B. Ultrasound with or without AFP every 6 months · C. Chest X-ray · D. ALT every month · E. No screening is needed Answer: B.