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?

Question

Accepted Answer

D. Anti-HEV IgM antibody. ## 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]

Answer

A. Anti-HEV IgG antibody

Answer

B. Liver biopsy with immunohistochemistry

Answer

C. HEV RNA by RT-PCR

Explanation

Diagnosis of Acute Hepatitis E

Clinical Context

Why Anti-HEV IgM is the Investigation of Choice

Diagnostic Timeline of HEV Serology

Why Other Tests Are Not First-Line

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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