What's the next step in managing a 22-year-old female with mildly elevated Aspartate Aminotransferase (AST), significant hypertriglyceridemia, and evidence of fatty liver disease on ultrasound, who has shown a decrease in triglycerides from 330 to 180?

Risk Stratification for Fibrosis is the Next Step

The next step is to calculate a FIB-4 score or NAFLD Fibrosis Score to assess for clinically significant fibrosis, as this 22-year-old has confirmed NAFLD with multiple metabolic risk factors (low HDL <40 mg/dL and hypertriglyceridemia) that warrant fibrosis assessment. 1

Why Fibrosis Assessment is Critical Now

This patient has already completed the initial diagnostic workup with:

• Confirmed hepatic steatosis on ultrasound 1
• Mildly elevated AST (40 IU/L) consistent with hepatocellular injury pattern 1
• Multiple metabolic risk factors present 1

The 2021 Gastroenterology clinical care pathway specifically recommends screening patients with 2 or more metabolic conditions for NAFLD-related clinically significant hepatic fibrosis. 1 This patient has:

• Low HDL cholesterol (<40 mg/dL in women, where normal is >50 mg/dL) 1
• Hypertriglyceridemia (initially 330 mg/dL, now 180 mg/dL - still elevated above 150 mg/dL threshold) 1
• Incidental finding of hepatic steatosis with elevated aminotransferases 1

The Fibrosis Risk Stratification Algorithm

Calculate non-invasive fibrosis scores using readily available laboratory values: 1

FIB-4 Score Calculation

• Uses: age, AST, ALT, platelet count 1
• FIB-4 <1.3 = low risk for advanced fibrosis 1
• FIB-4 >2.67 = high risk for advanced fibrosis requiring hepatology referral 1, 2
• FIB-4 1.3-2.67 = indeterminate zone, consider additional testing 1

NAFLD Fibrosis Score

• Uses: age, BMI, impaired fasting glucose/diabetes, AST/ALT ratio, platelet count, albumin 1
• Score <-1.455 = low probability of advanced fibrosis 1
• Score >0.676 = high probability of advanced fibrosis 1

Why This Takes Priority Over Other Interventions

The 2012 AASLD/ACG/AGA guidelines emphasize that identifying patients at risk for steatohepatitis and advanced fibrosis determines who needs more aggressive monitoring and potential treatment. 1 Patients with NAFLD without steatohepatitis have excellent prognosis from a liver standpoint, so treatments aimed at improving liver disease should be limited to those with NASH. 1

Studies show that 11% of patients with incidentally discovered hepatic steatosis might be at high risk for advanced hepatic fibrosis, particularly those with elevated aminotransferases. 1 This patient's persistent AST elevation for one year makes fibrosis assessment essential before determining management intensity.

Concurrent Management Steps

While awaiting fibrosis score results, initiate these evidence-based interventions:

Lifestyle Modification (First-Line Treatment)

• Weight loss of 3-5% improves steatosis; 7-10% may be needed to improve necroinflammation 1
• Hypocaloric diet combined with increased physical activity 1
• Exercise alone can reduce hepatic steatosis even without weight loss 1

Address Metabolic Risk Factors

• The low HDL (36 mg/dL) and persistent hypertriglyceridemia (180 mg/dL) require aggressive management 1
• Screen for diabetes with fasting glucose or HbA1c, as insulin resistance is strongly associated with NAFLD even in lean patients with normal glucose tolerance 1, 3
• Assess for other metabolic syndrome components: hypertension, central obesity, impaired fasting glucose 1

Triglyceride Management

• While triglycerides improved from 330 to 180 mg/dL, they remain elevated above the 150 mg/dL threshold 1
• Continue lifestyle modifications as first-line therapy 1
• Fibrates are first-line pharmacotherapy for persistent hypertriglyceridemia if lifestyle modifications are insufficient 1, 4

Critical Pitfalls to Avoid

Do not assume this is simple steatosis without fibrosis assessment. 1 The 2021 guidelines specifically warn that patients with incidentally discovered hepatic steatosis and elevated aminotransferases have significantly higher risk of progression to cirrhosis or HCC. 1

Do not delay fibrosis assessment because the patient is young. 5 Wilson disease should be considered in any patient <40 years with unexplained hepatocellular injury, though the AST:ALT ratio and clinical context make NAFLD more likely here. 5

Do not ignore the persistently low HDL cholesterol. 1 This is an independent metabolic risk factor that increases cardiovascular risk and correlates with more severe NAFLD. 1, 6, 7

When to Refer to Hepatology

Immediate hepatology referral is indicated if: 5, 2

• FIB-4 score >2.67 1, 2
• NAFLD Fibrosis Score >0.676 1
• ALT increases to >5× upper limit of normal 5, 2
• Evidence of synthetic dysfunction develops 5, 2

Consider hepatology referral if: 1

• Indeterminate fibrosis scores (FIB-4 1.3-2.67) 1
• Competing etiologies cannot be excluded 1
• ALT remains elevated for ≥6 months despite lifestyle modifications 2