What are the potential causes of elevated alanine aminotransferase (ALT) in a 16-year-old girl?

Causes of Elevated ALT in a 16-Year-Old Girl

In a 16-year-old girl with elevated ALT, nonalcoholic fatty liver disease (NAFLD) is the most common cause, followed by viral hepatitis (particularly hepatitis B and C), autoimmune hepatitis, medication-induced liver injury, and Wilson disease—all of which require systematic evaluation given the higher prevalence of autoimmune conditions and Wilson disease in adolescent females. 1, 2, 3

Understanding ALT Specificity in Adolescents

• ALT is the most liver-specific enzyme because it exists primarily in hepatocytes with minimal presence in cardiac muscle, skeletal muscle, or red blood cells, making its elevation highly indicative of hepatocellular damage. 1, 2, 3
• Normal ALT ranges for females are significantly lower than commercial laboratory cutoffs: 19-25 IU/L for adult women, with pediatric ranges being even lower at 35 IU/L after 18 months of age. 1, 4
• This means that even modest elevations in a 16-year-old girl are more clinically significant than the same absolute value in an adult male. 1, 4

Most Common Causes by Frequency

Nonalcoholic Fatty Liver Disease (NAFLD)

• NAFLD is the leading cause of elevated ALT in adolescents, affecting 20-30% of the general population and up to 70% in obese individuals. 2, 3, 5
• Characterized by an AST:ALT ratio <1, which distinguishes it from alcoholic liver disease. 2, 3
• Associated with metabolic syndrome components including obesity, insulin resistance, hypertension, and dyslipidemia. 6, 1, 7

Viral Hepatitis

• Hepatitis B and C are common causes in adolescents, particularly those with risk factors including maternal transmission, blood transfusions, or high-risk behaviors. 1, 5, 7
• Hepatitis B affects approximately 17% of patients with persistently elevated ALT in referral populations. 5
• Hepatitis C accounts for 4% of cases with persistently elevated ALT. 5

Autoimmune Hepatitis

• Autoimmune hepatitis is particularly important in adolescent females, accounting for 13% of cases with persistently elevated ALT. 5
• This condition disproportionately affects young women and can present with gradual ALT increases. 1, 5
• Typically shows higher elevations and elevated autoantibodies (ANA, anti-smooth muscle antibody). 1, 2

Medication-Induced Liver Injury

• Accounts for 8-11% of cases with elevated liver enzymes. 1, 7
• Requires comprehensive review of all prescription medications, over-the-counter drugs, herbal supplements, and dietary supplements. 1, 2

Wilson Disease

• Must be suspected in any patient <40 years with unexplained hepatocellular injury, accounting for 1% of cases. 2, 5
• Characterized by modest rises in aminotransferases and normal or markedly subnormal alkaline phosphatase. 2
• Requires urgent evaluation as it is a treatable condition that can lead to fulminant hepatic failure if missed. 2

Initial Diagnostic Algorithm

Immediate Laboratory Testing

• Complete liver panel: AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin, albumin, and prothrombin time/INR. 1, 2, 3
• Viral hepatitis serologies: HBsAg, anti-HBc IgM, and anti-HCV antibody. 1, 2, 3
• Metabolic parameters: Fasting glucose or HbA1c, fasting lipid panel, blood pressure, and waist circumference to assess for metabolic syndrome. 1, 7
• Autoimmune markers: ANA, anti-smooth muscle antibody (ASMA), and immunoglobulin G levels given the higher prevalence of autoimmune hepatitis in adolescent females. 1, 2
• Iron studies: Ferritin and transferrin saturation to screen for hereditary hemochromatosis. 1, 7
• Ceruloplasmin level to evaluate for Wilson disease, particularly important in this age group. 1, 2
• Thyroid function tests to rule out hypothyroidism as a cause of transaminase elevation. 1, 7, 8
• Creatine kinase to exclude muscle injury, especially if the patient engages in intensive exercise. 1, 2, 3

Initial Imaging

• Abdominal ultrasound is the first-line imaging test with 84.8% sensitivity and 93.6% specificity for detecting moderate to severe hepatic steatosis. 1, 2, 3
• Can identify structural causes including biliary obstruction, focal liver lesions, and portal hypertension features. 1, 2

Severity Classification and Management

Mild Elevation (<5× Upper Limit of Normal)

• Repeat liver enzymes in 2-4 weeks to establish trend and direction of change. 1, 3
• If values normalize or decrease, continue monitoring every 4-8 weeks until stabilized. 1
• If values remain elevated, proceed with comprehensive evaluation as outlined above. 1, 3

Moderate Elevation (5-10× Upper Limit of Normal)

• Requires prompt but not emergent evaluation with repeat testing within 2-5 days. 1, 3
• Intensify evaluation for underlying causes including viral hepatitis, autoimmune hepatitis, and medication-induced liver injury. 1, 3

Severe Elevation (>10× Upper Limit of Normal)

• Requires urgent hepatology referral within 2-3 days. 1, 3
• Immediate evaluation for acute ischemic hepatitis, acute drug-induced liver injury, acute viral hepatitis, or acute biliary obstruction. 1, 9

Risk Stratification for Advanced Fibrosis

• Calculate FIB-4 score using age, ALT, AST, and platelet count to determine need for hepatology referral. 1, 2, 3
• A score >2.67 indicates high risk for advanced fibrosis and warrants hepatology referral. 1, 2, 3
• A score <1.3 (<2.0 if age >65) indicates low risk with negative predictive value ≥90%. 1, 2

When to Refer to Hepatology

• ALT increases to >5× upper limit of normal (>125 IU/L for females). 1, 2, 3
• Bilirubin increases to >2× upper limit of normal. 1, 2, 3
• Evidence of synthetic dysfunction (low albumin, prolonged PT/INR). 1, 2, 3
• ALT remains elevated for ≥6 months without identified cause. 1, 2, 3
• Suspicion for autoimmune hepatitis or Wilson disease, both of which require specialized management. 1, 2

Critical Pitfalls to Avoid

• Do not assume NAFLD without excluding other causes, particularly autoimmune hepatitis and Wilson disease in this age group. 2, 5
• Do not overlook medication history including over-the-counter drugs, herbal supplements, and dietary supplements. 1, 2, 7
• Do not miss Wilson disease by failing to check ceruloplasmin in any patient <40 years with unexplained hepatocellular injury. 2, 5
• Do not attribute severe ALT elevation (≥5× ULN) to NAFLD alone, as this level is rare in NAFLD and usually indicates another cause. 1, 2
• Do not assume normal ALT excludes liver disease, as up to 10% of patients with advanced fibrosis may have normal ALT using conventional thresholds. 1, 2
• Recent intensive exercise can cause acute ALT elevation that may be mistaken for liver injury; checking creatine kinase differentiates muscle from liver origin. 1, 2, 3