Differentiating Typhoid Hepatitis from Viral Hepatitis
The ALT/LDH ratio (expressed as multiples of upper limit of normal) is the single best discriminator: a ratio <4-9 indicates typhoid hepatitis, while a ratio >5-9 indicates viral hepatitis. 1, 2
Key Diagnostic Algorithm
Primary Discriminator: ALT/LDH Ratio
- Calculate the ratio by expressing both ALT and LDH as multiples of their upper limit of normal values 2
- Typhoid hepatitis: ALT/LDH ratio <4 (some studies use <9 as cutoff) 1, 2
- Viral hepatitis: ALT/LDH ratio >5 (some studies use >9 as cutoff) 1, 2
- This ratio at admission showed 100% discrimination in a study of 54 patients, with no overlap between groups 2
Clinical Features Favoring Typhoid Hepatitis
- High fever >104°F (>40°C) occurs in 44% of typhoid hepatitis vs. 4% of viral hepatitis 2
- Relative bradycardia (pulse-temperature dissociation) present in 42% of typhoid vs. 4% of viral hepatitis 2
- Recent travel history within 1 month (40% of typhoid cases) 2
- Abdominal pain and vomiting are more prominent 3
Laboratory Pattern Differences
Transaminase Levels:
- Typhoid hepatitis: Lower peak ALT (mean 296 U/L vs. 3,234 U/L in viral hepatitis) 2
- Typhoid hepatitis: Lower peak AST (mean 535 U/L vs. 2,844 U/L in viral hepatitis) 2
- Typhoid typically shows ALT 100-620 IU/L range 4
Alkaline Phosphatase:
- Typhoid hepatitis: Higher alkaline phosphatase (mean 500 U/dL vs. 228 U/dL in viral hepatitis) 2
- This reflects the cholestatic component more common in typhoid 3
White Blood Cell Pattern:
- Left shift of WBCs occurs in 83% of typhoid hepatitis vs. 37% of viral hepatitis 2
- Eosinopenia is characteristic of typhoid fever but not specifically validated as a discriminator in hepatitis presentations 2
Bilirubin Patterns
- Typhoid hepatitis typically shows moderate elevation (2.5-5.8 mg/dL range) 4
- Both conditions can present with jaundice, making this less discriminatory 4, 3
Diagnostic Workup When Suspecting Typhoid Hepatitis
Microbiological Confirmation:
- Blood cultures are essential and positive in typhoid fever 5, 2, 3
- Urine, stool, and bone marrow cultures should be obtained in patients with fever >38.5°C and liver abnormalities 5
- Repeat cultures if initial cultures negative but clinical suspicion high 3
Imaging Findings:
- CT abdomen may show mesenteric and porta-hepatis lymphadenopathy 3
- Terminal ileum thickening can be present 3
- Ultrasound typically shows normal biliary system 3
Liver Biopsy:
- Shows focal hepatocellular necrosis and nonspecific inflammation in typhoid 5
- May help differentiate when diagnosis unclear, but not routinely needed 5
Critical Clinical Pitfalls
Do not assume normal or mildly elevated transaminases exclude significant disease - approximately 50% of viral hepatitis patients can have normal transaminases despite active disease 6, and typhoid hepatitis characteristically has lower transaminase elevations than viral hepatitis 2
Do not delay antibiotics while awaiting culture results - typhoid hepatitis can progress to acute liver failure rapidly, and multidrug-resistant strains are emerging 3
Do not rely solely on fever pattern - while high fever and relative bradycardia favor typhoid, these are not universally present 2
Calculate the ALT/LDH ratio correctly - both values must be expressed as multiples of the upper limit of normal for your laboratory, not as absolute values 2
Prognosis and Response Patterns
- Typhoid hepatitis requires longer hospitalization (mean 14.8 days vs. 6.5 days for viral hepatitis) 2
- Response to antibiotics is often delayed despite appropriate therapy 5
- Complete clinical and biochemical recovery occurs with proper antibiotic treatment 4
- Mortality is rare with appropriate management in both conditions 2