A 32-year-old man from rural India presents with jaundice, malaise, and dark urine for 10 days. Liver function tests show ALT 2800 IU/L, AST 2200 IU/L, bilirubin 8.2 mg/dL, and INR 1.2. He denies alcohol use and has no risk factors for blood-borne viruses. Which investigation is most appropriate to establish the diagnosis of acute viral hepatitis and identify the causative agent?

Explanation

## Diagnostic Approach to Acute Viral Hepatitis ### Serological Markers for Viral Hepatitis **Key Point:** Serological testing is the gold standard for identifying the causative agent of acute viral hepatitis. The panel must include markers for HAV, HBV, and HCV — the three most common causes of acute hepatitis in India. ### Interpretation of Serological Markers in Acute Hepatitis | Virus | Acute Infection Marker | Interpretation | |-------|------------------------|----------------| | HAV | Anti-HAV IgM | Positive in acute hepatitis A; indicates recent infection | | HBV | HBsAg + Anti-HBc IgM | HBsAg positive; IgM anti-HBc confirms acute infection | | HCV | Anti-HCV (ELISA) | May be negative in first 1–2 weeks; HCV RNA (RT-PCR) is more sensitive in acute phase | **High-Yield:** In acute viral hepatitis, the combination of **HBsAg, anti-HCV, and anti-HAV IgM** is the first-line serological panel. Anti-HAV IgM is the most specific marker for acute hepatitis A, which is the most common cause of acute hepatitis in India due to poor sanitation. ### Why This Patient Needs Serological Testing 1. **Clinical presentation** (jaundice, dark urine, elevated transaminases) is non-specific and cannot differentiate between HAV, HBV, and HCV. 2. **Epidemiological clue:** Rural India has high prevalence of hepatitis A (fecal-oral route) and hepatitis B (horizontal transmission). 3. **Prognosis differs:** HAV is self-limited; HBV may progress to chronicity; HCV requires antiviral therapy. 4. **Public health implications:** Identifying the agent guides contact tracing and prevention measures. **Clinical Pearl:** In acute hepatitis with markedly elevated transaminases (ALT > 2000 IU/L) and normal/near-normal INR (1.2), viral hepatitis is the most likely diagnosis. The preserved synthetic function (INR 1.2) rules out fulminant hepatic failure. **Mnemonic — HAV, HBV, HCV Serology in Acute Infection:** - **HAV:** Anti-HAV IgM (most specific for acute) - **HBV:** HBsAg + Anti-HBc IgM (HBsAg appears first; IgM anti-HBc confirms acute) - **HCV:** Anti-HCV or HCV RNA-PCR (RNA-PCR is more sensitive in first 2 weeks) [cite:Harrison 21e Ch 297]