Viral hepatitis — chronicity, serology and the HBV/HCV treatment divide viva

Interpretation

The examiner opens: "A 35-year-old healthcare worker is found to be HBsAg positive on routine screening. Her ALT is normal and HBV DNA is 80,000 IU/mL, HBeAg positive. She is anxious about chronic infection and asks whether hepatitis B can be cured like hepatitis C. Talk me through the five hepatotropic viruses, the chronicity of hepatitis B by age of acquisition, why we can cure HCV but not HBV, the meaning of her serology, and the principles of her management."^[1]

• The candidate must demonstrate command of the virology, the chronicity rates, the mechanism (cccDNA versus no DNA stage), the serology interpretation, and the therapeutic divide.

Key points

The examiner will probe each of these; be ready to defend them at viva depth:

1. The five hepatotropic viruses by transmission and chronicity^[1][4] — Memory aid: the vowels (A and E) are Enteric (faecal-oral) and never chronic; the consonants (B, C, D) are Blood-borne (parenteral). HAV (RNA, 2-6 weeks incubation, never chronic, vaccine-preventable); HBV (DNA, 30-180 days, chronic in 90% neonates and under 5% adults, vaccine-preventable); HCV (RNA, 75% chronic, no vaccine, curable with DAAs); HDV (defective RNA requiring HBsAg, superinfection 80-90% chronic); HEV (RNA, faecal-oral, never chronic in immunocompetent, 20-25% fulminant mortality in pregnancy).
2. Why HBV cannot currently be cured but HCV can — the HBV genome forms a covalently closed circular DNA (cccDNA) minichromosome in the hepatocyte nucleus that persists indefinitely and is NOT eliminated by nucleos(t)ide analogues (which only block new reverse transcription). Functional cure (HBsAg loss) occurs in only 1-3% per year on treatment. HCV has no DNA intermediate and no integration — DAAs targeting NS3/4A protease, NS5A, and NS5B polymerase eliminate the virus entirely in 8-12 weeks; SVR12 (HCV RNA undetectable 12 weeks after therapy) is virologically equivalent to cure.^[2][3]
3. Interpretation of her serology — HBsAg positive confirms infection; HBeAg positive and HBV DNA 80,000 IU/mL indicate active replication and high infectivity; ALT NORMAL places her in the HBeAg-positive immune-TOLERANT phase (common in perinatally acquired infection; high DNA, normal ALT, minimal fibrosis, no treatment now but monitor for transition to the immune-active phase). The next step is FibroScan to confirm no significant fibrosis and 3-6-monthly ALT/DNA monitoring.
4. When to treat chronic HBV^[1] — HBeAg-positive with ALT over 2x ULN and DNA over 20,000 IU/mL; HBeAg-negative with DNA over 2000 IU/mL and ALT over 2x ULN; any cirrhosis with detectable DNA; immunosuppression (prophylaxis); pregnancy with DNA over 200,000 IU/mL to prevent vertical transmission; HDV co-infection. First-line: tenofovir disoproxil fumarate 300 mg daily, tenofovir alafenamide 25 mg daily, or entecavir 0.5 mg daily — all with high genetic barrier to resistance (under 1% at 5 years), indefinite duration.
5. HBV serology patterns (the most-tested table) — acute (HBsAg pos, IgM anti-HBc pos, anti-HBs neg), window period (HBsAg neg, IgM anti-HBc pos — most sensitive), recovered (HBsAg neg, anti-HBs pos, total anti-HBc pos), chronic (HBsAg pos, total anti-HBc pos), vaccinated (HBsAg neg, anti-HBs pos, anti-HBc neg — the vaccine contains only surface antigen), occult (HBsAg neg, total anti-HBc pos, low-level DNA). The key teaching point: in any acute hepatitis with negative HBsAg, check IgM anti-HBc — it is the most sensitive marker of acute HBV.^[1][4]
6. The prevention strategy — universal birth-dose HBV vaccine plus HBIG within 12 hours for newborns of HBsAg-positive mothers; maternal tenofovir 300 mg daily from 28-32 weeks if HBV DNA over 200,000 IU/mL; harm reduction for people who inject drugs; blood-product screening; pre-immunosuppression HBV screening with prophylactic tenofovir or entecavir for high-risk regimens (rituximab, anti-CD20, high-dose steroids).
7. HBV is directly oncogenic; HCV is not — HBV causes hepatocellular carcinoma EVEN WITHOUT CIRRHOSIS (HBx protein, cccDNA integration, chronic inflammation); HCV causes HCC almost exclusively through cirrhosis. This is why HCC surveillance extends to high-risk chronic HBV patients (Asian men over 40, African men over 20, family history, HDV) even without cirrhosis, and to all HCV cirrhotics.^[1]

References

1. Terrault NA, Lok ASF, McMahon BJ, et al. AASLD 2018 hepatitis B guidance. Hepatology 2018.^[1]
2. AASLD-IDSA HCV Guidance Panel. Hepatitis C Guidance 2018 Update. Clinical Infectious Diseases 2018.^[2]
3. Ghany MG, et al. Hepatitis C Guidance 2023 Update. Clinical Infectious Diseases 2023.^[3]
4. Lok ASF, McMahon BJ. Chronic hepatitis B: AASLD Practice Guidelines. Hepatology 2007.^[4]

References4ShowHide

1. [1]Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology, 2018.PMID 29405329
2. [2]AASLD-IDSA HCV Guidance Panel. Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clinical Infectious Diseases, 2018.PMID 30215672
3. [3]Bhattacharya D, Aronsohn A, Price J, et al. Hepatitis C Guidance 2023 Update: AASLD-IDSA Recommendations. Clinical Infectious Diseases, 2023.PMID 37229695
4. [4]Lok ASF, McMahon BJ. Chronic hepatitis B: AASLD Practice Guidelines. Hepatology, 2007.PMID 17256718