Elevated GGT, ALT, AST with Normal Bilirubin and ALP in a 20-Year-Old with Leukocytosis
In a 20-year-old with elevated transaminases (ALT, AST), elevated GGT, leukocytosis, but normal bilirubin and ALP, you should immediately perform a comprehensive liver etiology screen including hepatitis B surface antigen, hepatitis C antibody, anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody, serum immunoglobulins, ferritin, transferrin saturation, and abdominal ultrasound, while simultaneously evaluating for drug-induced liver injury, alcohol use, and metabolic syndrome. 1
Immediate Repeat Testing and Monitoring
Repeat liver biochemical tests within 1-2 weeks to confirm the abnormality and establish the trend, as transient elevations can occur with systemic inflammation or medications. 1
The repeat panel should include ALT, AST, ALP, GGT, total bilirubin, direct bilirubin, albumin, PT/INR, and complete blood count with platelets. 1, 2
If ALT/AST remain >3x upper limit of normal (ULN) on repeat testing, initiate close monitoring every 2-5 days until the pattern stabilizes or resolves. 1
Pattern Recognition: Hepatocellular Injury
The combination of elevated transaminases (ALT, AST) with normal ALP indicates a hepatocellular pattern of injury rather than cholestatic injury. 1, 3
GGT elevation in this context suggests oxidative stress rather than cholestasis, since ALP is normal. 4
The R ratio (ALT/ALP in multiples of ULN) would be >5, confirming hepatocellular injury pattern. 5
Comprehensive Liver Etiology Screen
Standard workup for adults should include: 1
- Viral hepatitis: Hepatitis B surface antigen, hepatitis C antibody (with reflex PCR if positive)
- Autoimmune markers: Anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody, serum immunoglobulins
- Metabolic screening: Simultaneous serum ferritin and transferrin saturation (for hemochromatosis)
- Imaging: Abdominal ultrasound with Doppler to evaluate for hepatic steatosis, focal lesions, vascular abnormalities, and biliary anatomy 2
For patients under 25 years, additional testing should include: 1
- Alpha-1-antitrypsin level
- Ceruloplasmin (for Wilson disease, especially critical in young adults with hepatocellular injury)
- Anti-liver kidney microsomal antibody (for autoimmune hepatitis type 2)
- Celiac antibodies
Critical Differential Diagnoses in Young Adults
Drug-Induced Liver Injury (DILI)
Conduct a meticulous medication review including prescription drugs, over-the-counter medications, herbal supplements, and recent antibiotic courses. 1, 3
DILI is a common cause of hepatocellular injury and can present with leukocytosis as part of a hypersensitivity reaction. 1
If DILI is suspected and ALT/AST >5x ULN, withhold the suspected agent immediately and monitor closely. 1
Alcohol-Related Liver Disease
Assess alcohol consumption using AUDIT score; harmful drinking is a leading cause of elevated transaminases in young adults. 1, 3
AST/ALT ratio >2 suggests alcoholic liver disease, though this is less reliable in younger patients. 3
Non-Alcoholic Fatty Liver Disease (NAFLD)
Evaluate for metabolic syndrome components: waist circumference, blood pressure, fasting lipid panel, fasting glucose or HbA1c. 1, 3
NAFLD is the most common cause of asymptomatic transaminase elevation, affecting approximately 10% of the population. 3
If metabolic risk factors are present, calculate FIB-4 or NAFLD Fibrosis Score to stratify fibrosis risk. 1
Wilson Disease
Critical not to miss in a 20-year-old with hepatocellular injury; check ceruloplasmin and consider slit-lamp examination for Kayser-Fleischer rings. 1, 6
Wilson disease presenting as acute liver failure has high mortality without transplantation. 6
Autoimmune Hepatitis
- More common in young women but can occur in men; check autoimmune markers as part of standard screen. 1, 3
Leukocytosis Considerations
Leukocytosis may indicate:
- Drug hypersensitivity reaction (DILI with eosinophilia)
- Acute viral hepatitis
- Systemic inflammatory response
- Underlying infection triggering transient transaminase elevation
Review the white blood cell differential to distinguish between these possibilities. 1
Management Algorithm Based on Severity
If ALT/AST >5-10x ULN with Normal Bilirubin (Grade 3):
- Withhold any potentially hepatotoxic medications immediately. 1
- Repeat blood tests within 2-3 days including ALT, AST, ALP, GGT, total and direct bilirubin, INR. 1
- Monitor 2-3 times weekly until improvement to Grade 1 (<3x ULN). 1
If ALT/AST 3-5x ULN with Normal Bilirubin (Grade 2):
- Withhold suspected causative agents. 1
- Repeat testing within 2-5 days. 1
- Initiate close monitoring and complete etiology workup. 1
If ALT/AST >ULN to 3x ULN (Grade 1):
- Continue current management but repeat testing within 1-2 weeks. 1
- Complete standard liver etiology screen. 1
Critical Pitfalls to Avoid
Do not assume normal bilirubin means benign disease—severe hepatocellular injury can occur before jaundice develops. 1
Do not delay ceruloplasmin testing in young adults—Wilson disease requires urgent diagnosis and can present with isolated transaminase elevation before fulminant failure. 1, 6
Do not attribute elevated GGT solely to alcohol without investigation—GGT has low specificity and can be elevated in NAFLD, DILI, and oxidative stress states. 7, 4
Do not ignore the leukocytosis—it may indicate drug hypersensitivity (check eosinophils) or acute viral/autoimmune hepatitis requiring specific management. 1
If Initial Workup is Negative
If the extended liver etiology screen is negative and metabolic risk factors are absent, refer to gastroenterology/hepatology for further evaluation including consideration of less common causes (celiac disease, thyroid disorders, muscle disorders, hereditary conditions). 1, 3
Consider trial of lifestyle modification if NAFLD is suspected despite negative metabolic markers, with repeat testing in 3-6 months. 1, 3
Persistent unexplained elevation warrants hepatology referral even with negative initial workup. 1