A 48-year-old woman from Delhi is screened during a health check-up and found to have HBsAg positive. She is asymptomatic with normal liver function tests (ALT 35 IU/L, AST 32 IU/L, bilirubin 0.9 mg/dL). Further serological testing shows: anti-HBc total positive, anti-HBc IgM negative, HBeAg negative, anti-HBe positive, anti-HBs negative, and HBV DNA 8,200 copies/mL (detectable but low). What is the most likely diagnosis?

Explanation

## Diagnosis: Chronic Hepatitis B — HBeAg-Negative Phase ### Serological Profile Interpretation | Marker | Result | Significance | |--------|--------|-------------| | **HBsAg** | Positive | Indicates chronic infection (persists >6 months) | | **Anti-HBc IgM** | **Negative** | Rules out acute infection | | **Anti-HBc total** | Positive | Confirms past/current HBV exposure | | **HBeAg** | Negative | Patient has seroconverted; low infectivity phase | | **Anti-HBe** | Positive | Confirms HBeAg seroconversion | | **Anti-HBs** | Negative | No protective immunity developed | | **HBV DNA** | Detectable (8,200 c/mL) | Confirms ongoing viral replication despite HBeAg negativity | ### Key Point: **HBeAg-negative chronic hepatitis B** represents a later phase of chronic infection characterized by: - Persistent HBsAg (>6 months) - Absence of anti-HBc IgM (not acute) - HBeAg-negative, anti-HBe-positive (seroconversion) - Detectable HBV DNA (often lower than HBeAg-positive phase, but still replicating) - Variable ALT levels (can be normal or elevated) ### High-Yield: The **HBeAg-negative phase** accounts for ~30–50% of chronic HBV cases globally and is increasingly common in Asia. Despite lower HBV DNA levels compared to HBeAg-positive disease, these patients remain infectious and can progress to cirrhosis and HCC. ### Clinical Pearl: Asymptomatic HBsAg-positive individuals with normal ALT and low HBV DNA (like this patient) are often labeled "inactive carriers," but 15–30% will experience HBeAg-negative chronic hepatitis with ALT flares and progressive fibrosis. Regular monitoring (ALT, HBV DNA, ultrasound, FibroScan) is essential. ### Mnemonic: **"HBeAg-negative = Later phase, lower DNA, but still dangerous"** — Do not mistake HBeAg negativity for cure or inactivity.