A 32-year-old man from rural India presents with jaundice, dark urine, and abdominal pain for 10 days. Serum ALT is 2400 U/L, AST is 2100 U/L, and total bilirubin is 8.2 mg/dL. Prothrombin time is normal. Anti-HAV IgM is negative. Which investigation is most appropriate to confirm the diagnosis of acute hepatitis E?

Explanation

## Diagnosis of Acute Hepatitis E ### Clinical Context The patient presents with acute hepatitis (markedly elevated transaminases, jaundice, normal PT) in a rural Indian setting with negative anti-HAV IgM. Hepatitis E is endemic in India and is a leading cause of acute viral hepatitis in this region. ### Why Anti-HEV IgM is the Investigation of Choice **Key Point:** Anti-HEV IgM is the gold standard for diagnosis of acute hepatitis E infection and appears early in the course of disease (within the first 1–2 weeks of symptom onset). **High-Yield:** Anti-HEV IgM is: - Highly specific (>95%) for acute HEV infection - Detectable in serum during the acute phase and early convalescence - More practical and cost-effective than RT-PCR in resource-limited settings - Recommended as the first-line diagnostic test by WHO and Indian guidelines ### Diagnostic Timeline of HEV Serology | Marker | Appearance | Peak | Duration | Clinical Use | |--------|-----------|------|----------|---------------| | **Anti-HEV IgM** | Day 1–7 of illness | Week 2–3 | 4–6 months | **Acute infection** | | **Anti-HEV IgG** | Week 2–3 | Month 3–4 | Years to lifetime | Past/convalescent infection | | **HEV RNA** | Day 1–7 | Week 1–2 | 4–6 weeks | Early acute, viraemia | **Clinical Pearl:** In acute hepatitis E, anti-HEV IgM becomes positive before anti-HEV IgG and persists for several months, making it the ideal marker for acute-phase diagnosis. ### Why Other Tests Are Not First-Line **HEV RNA by RT-PCR:** Although highly specific, it is: - More expensive and technically demanding - Reserved for confirmatory testing, immunocompromised patients, or research - Not routinely available in primary care settings in India **Anti-HEV IgG:** Appears later (week 2–3) and indicates past or convalescent infection, not acute disease. It is useful for epidemiological surveys and assessing immunity, not for acute diagnosis. **Liver biopsy:** Invasive, non-specific, and unnecessary when serology is diagnostic. Reserved for cases with atypical presentation or to assess fibrosis in chronic HEV (rare in immunocompetent hosts). [cite:Harrison 21e Ch 297]