Positive (+) and Negative (–) Viral Hepatitis B and Viral Hepatitis C Profiles: Practical Interpretation with WHO & CDC 2024–25 Updates (Viral Hepatitis Profiles)
- Mayta
- Jun 14
- 3 min read
Below is a self-contained, exam-ready deep dive on reading positive (+) and negative (–) viral-hepatitis profiles. I keep the practical “what you do at the bedside” front-and-center while weaving in the newest WHO (2024 HBV, 2024 HCV), CDC (2025 HBV) and AASLD recommendations.
1 Why the marker is positive or negative matters
Marker class | “Positive” means … | “Negative” means … | Caveats you must always rule out |
Presence of virus (HBsAg, HCV RNA/Ag) | Detectable virions or viral proteins in blood | None detected at the assay’s limit | • Window periods (HBV “core-window”, very early acute HCV) • Low-level occult infection (HBsAg–/HBV-DNA+) |
Immune memory (anti-HBc, anti-HBs, anti-HCV) | B-cell response has occurred | No measurable antibodies | • Profound immunosuppression (chemo, anti-CD20) • Age < 18 mo (maternal antibody interference) |
Phase/infectivity (HBeAg, HBV-DNA titer) | Active transcription / high infectivity | “Pre-core mutant” or inactive carrier if negative | • Pre-core/ basal-core-promoter mutants generate high DNA but are HBeAg-negative |
2 Hepatitis B: interpretation grid
HBsAg | total anti-HBc | IgM anti-HBc | anti-HBs | Typical interpretation | Key follow-ups |
– | – | – | – | Susceptible | Vaccinate |
– | – | – | + | Immune – vaccine | None |
– | + | – | + | Immune – past infection | Check fibrosis only if past ALT peaks |
+ | + | + | – | Acute infection | HBV-DNA, ALT q4 wk; treat if fulminant |
+ | + | – | – | Chronic infection | Stage (ALT, elastography), treat per WHO 2024 simplified criteria who.int |
– | + | – | – | Isolated anti-HBc – four possibilities | Reflex HBV-DNA ± repeat anti-HBs in 6 wk |
2024 WHO shift: Treat earlier (HBV-DNA ≥ 2 000 IU/mL or ALT > 2×ULN) even when fibrosis is mild to cut lifelong HCC risk. who.int
Pitfalls of “negative” HBV markers
False-negative HBsAg in the core window (just after HBsAg disappears, before anti-HBs appears) – total anti-HBc plugs the gap.
Occult HBV (HBsAg– / HBV-DNA+) in HIV, dialysis, solid-organ transplant → screen with HBV-DNA when risk is high.
Vaccination failure: anti-HBs < 10 mIU/mL after full series warrants revaccination or high-dose schedules (CDC 2025) cdc.gov.
3 Hepatitis C: two-step reflex algorithm (WHO 2024)
Screen – anti-HCV EIA or rapid test.
If (+) – reflex HCV RNA (or core-Ag) on the same sample. Skipping the reflex step leaves up to 30 % of patients lost to follow-up. iris.who.int
Anti-HCV | HCV RNA | Interpretation | Action |
– | – | Never exposed (or < 3 wk incubation) | No further testing unless new exposure |
+ | – | Cleared (spontaneous or treated) or false-positive | If high suspicion, repeat RNA in 3 mo |
+ | + | Current infection (acute or chronic) | Stage liver (APRI/FIB-4); start pangenotypic DAA |
– | + | Early acute infection or severe immunosuppression | Repeat Ab in 4–6 wk; treat now if acute icteric |
Key nuance: Acute vs chronic HCV no longer changes the decision to start DAA—the earlier you treat, the higher the sustained virologic response.
When a “negative” test misleads
Anti-HCV-negative, RNA-positive – up to 30 % in bone-marrow transplant or rituximab recipients.
RNA false-negative on ultralow-viremia < 15 IU/mL – repeat in 4 wks if suspicion persists or use core-Ag assay (LOD ~ 500 IU/mL). who.int
4 Applying positives & negatives at the bedside
Patient with unexplained transaminase flare: order viral-hepatitis panel (HBsAg, anti-HBs, total anti-HBc, IgM anti-HBc, anti-HCV) + ALT/AST.
HBsAg+ → add HBeAg, HBV-DNA, platelets, and elastography.
Anti-HCV+ → reflex RNA; if (+) stage liver and treat.
Any chronic infection → test HIV, screen family/sexual partners, vaccinate against HAV/HBV as appropriate.
5 Cheat-sheet of “must-remember” positives and negatives
Scenario | Why it’s high-stakes | Don’t forget |
HBeAg+ & HBV-DNA > 2 000 IU/mL | Highly infectious – test household; consider early therapy in pregnancy to cut MTCT risk | Tenofovir 3rd-trimester prophylaxis per WHO 2024 |
Isolated anti-HBc before rituximab | 5–10 % risk of HBV reactivation | Pre-emptive antiviral (entecavir/ tenofovir) |
Anti-HCV+, RNA– | Up to one-third are already cured – avoid unnecessary DAA | Check for previous DAA, document SVR |
Anti-HCV–, ALT spike, risk factors | Could be very early acute HCV | Repeat anti-HCV + RNA in 3 wk |
HBsAg–, anti-HBs > 10 mIU/mL | Immune – can donate blood, no HBV prophylaxis needed | Re-check titer only in dialysis, immunocomp. |
Key take-home
Positive and negative are never absolute—they are snapshots in time limited by assay sensitivity, host immunity, and the natural history of the virus. Use the combination pattern, not single markers, chase every discordance, and lean on updated WHO/CDC algorithms to decide who needs vaccination, surveillance, or immediate antiviral therapy.
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