Fatty Liver Disease: Which Blood Tests Identify It?

Fatty liver disease — formally renamed Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) in 2023, previously called Non-Alcoholic Fatty Liver Disease (NAFLD) — is the accumulation of excess fat (steatosis) in liver cells. It's the most common chronic liver disease worldwide, affecting an estimated 25-30% of US adults and rising sharply with the obesity and metabolic syndrome epidemics. Most people who have it don't know.

MASLD exists on a spectrum:

• Simple steatosis (fatty liver alone) — fat accumulation without significant inflammation or damage. Generally considered relatively benign but a precursor to more advanced disease.
• MASH (formerly NASH — Non-Alcoholic Steatohepatitis) — fatty liver PLUS active inflammation and liver cell damage. Progresses to fibrosis and cirrhosis in a significant subset of patients.
• Advanced fibrosis (F3) and cirrhosis (F4) — scarring of the liver. End-stage liver disease, liver cancer (hepatocellular carcinoma), and need for liver transplantation are all possible outcomes.

The connection to metabolic health: MASLD is essentially the liver manifestation of insulin resistance and metabolic syndrome. Roughly 70-80% of people with type 2 diabetes have MASLD. The relationship is bidirectional — MASLD increases diabetes risk; diabetes accelerates MASLD progression. MASLD also independently increases cardiovascular disease risk by 1.5-2x.

Why most cases go undiagnosed: routine bloodwork often shows only mildly elevated liver enzymes (ALT, AST), which doctors frequently dismiss as "mild elevation, no action needed." The reality is that ALT above the modern thresholds (>33 IU/L for men, >25 IU/L for women — lower than older lab reference ranges) is a meaningful signal of liver injury, especially in someone with metabolic risk factors. Diagnostic confirmation typically requires imaging (FibroScan, MRI elastography) and sometimes biopsy in advanced cases — but blood markers catch the initial suspicion.

Who should consider fatty liver screening:

• Type 2 diabetes or pre-diabetes (70-80% have MASLD)
• Obesity (BMI ≥30) or abdominal obesity (waist >40 inches men, >35 women)
• Metabolic syndrome features: high triglycerides, low HDL, high blood pressure, abdominal obesity
• PCOS (polycystic ovary syndrome) — closely associated with MASLD
• Family history of fatty liver or liver disease
• Persistent ALT or AST elevation on routine bloodwork
• Unexplained fatigue + elevated metabolic markers

Liver enzymes (ALT, AST, GGT, alkaline phosphatase). The headline markers for fatty liver workup.

• ALT (Alanine Aminotransferase) — the most liver-specific enzyme. Modern healthy thresholds: <33 IU/L for men, <25 IU/L for women. Many labs still use older reference ranges (up to 40-55) that miss early disease. Elevation suggests liver cell damage; in MASLD, typically mild to moderate (1-3x upper limit of normal).
• AST (Aspartate Aminotransferase) — less liver-specific (also present in heart, muscle, RBCs). In MASLD, AST is typically equal to or lower than ALT (AST/ALT ratio <1). An AST/ALT ratio >2 suggests alcoholic liver disease rather than MASLD; AST/ALT ratio >1 in someone with MASLD suggests progression to fibrosis.
• GGT (Gamma-Glutamyl Transferase) — sensitive to alcohol use, medications, and biliary issues. In MASLD, GGT is often elevated alongside ALT. Markedly elevated GGT (without proportional ALT) suggests alcohol or biliary causes rather than MASLD.
• Alkaline phosphatase + bilirubin — typically normal in early MASLD. Elevation suggests biliary involvement or more advanced disease.

The Liver Health Panel ($X) covers all of these in one order.

Platelets. Included in CBC. Critical for the FIB-4 calculation (see below). Decreased platelet count can indicate advanced fibrosis or portal hypertension.

Albumin and bilirubin. Generally normal in early MASLD. Decreased albumin or elevated bilirubin can indicate more advanced disease.

FIB-4 calculation. A non-invasive score that estimates likelihood of significant fibrosis using age + ALT + AST + platelet count. Formula: (Age × AST) / (Platelets × √ALT). Interpretation:

• FIB-4 <1.3 — low risk of advanced fibrosis (excellent negative predictive value)
• FIB-4 1.3-2.67 — indeterminate; consider FibroScan or other non-invasive imaging
• FIB-4 >2.67 — high probability of advanced fibrosis; warrants hepatology referral

FIB-4 is used by hepatologists as a first-line non-invasive screen for fibrosis risk. You can calculate yours from a standard CBC + Liver Health Panel.

Metabolic workup (A1c + Fasting Glucose + Fasting Insulin + Lipid Panel). The Diabetes Screening Panel ($59.99) + Lipid Panel covers this. MASLD is essentially insulin resistance manifesting in the liver — characterizing the metabolic side is essential. Pattern that suggests MASLD: elevated fasting insulin, A1c trending toward pre-diabetic range (5.5+), high triglycerides (often above 150 mg/dL), low HDL (below 40 men / 50 women), often elevated ApoB.

hs-CRP. Systemic inflammation marker. Often elevated in active MASH (the inflammatory form of MASLD).

Ferritin. Can be elevated in MASLD (often called "hyperferritinemia of metabolic syndrome"). Important to distinguish from hereditary hemochromatosis (iron overload disease) — usually requires transferrin saturation to differentiate.

Before concluding "fatty liver" from elevated liver enzymes, several other causes need to be considered:

Alcohol-related liver disease. If you drink moderately or more, alcohol may be contributing. The threshold for alcohol-related fatty liver is generally considered >30g/day for men (about 2 standard drinks) or >20g/day for women (about 1.5 standard drinks). The diagnostic distinction matters because treatment differs. Honest discussion with your doctor is essential — many patients underreport alcohol use and end up labeled with MASLD when alcohol contribution is significant. Note: MASLD and alcohol-related liver disease can coexist (called MetALD — Metabolic and Alcohol-related Liver Disease).

Viral hepatitis. Hepatitis B and C cause chronic liver inflammation and can mimic or coexist with MASLD. The Hepatitis Panel covers screening for both. Recommended at least once for everyone (CDC guidelines as of 2020 recommend universal screening for hepatitis B and C in all adults).

Autoimmune hepatitis. Less common but important. ANA, anti-smooth muscle antibody, and anti-LKM-1 antibody are the screening markers. More common in women.

Hemochromatosis (iron overload). Genetic condition causing iron accumulation in organs including liver. Screen with ferritin (elevated) + transferrin saturation (typically >45%). Genetic testing for HFE mutations confirms.

Wilson disease (copper overload). Rare, typically presents in younger patients. Screen with ceruloplasmin (low in Wilson disease).

Alpha-1 antitrypsin deficiency. Rare genetic condition. Screen with alpha-1 antitrypsin level if other causes are excluded.

Medication-induced. Many medications can elevate liver enzymes — statins (usually mild and not requiring discontinuation), antibiotics, acetaminophen overuse, many others. Review medications with your prescriber.

This is why elevated liver enzymes always warrant a complete workup rather than jumping to "must be fatty liver." A liver-focused primary care doctor or hepatologist can work through the differential systematically.

The good news: MASLD is one of the most modifiable chronic diseases. Lifestyle intervention frequently reverses both fat accumulation and inflammation, especially in earlier stages.

The first-line treatment is weight loss + diet + exercise:

• Weight loss of 5-10% body weight can reduce liver fat by 30-40% and resolve simple steatosis in many cases. Weight loss of 10%+ can reverse some fibrosis.
• Dietary patterns that help: Mediterranean diet has the most evidence specifically for MASLD. Lower carbohydrate diets also help by reducing the insulin signaling that drives liver fat storage. Reducing fructose (especially from high-fructose corn syrup in sugary drinks) is particularly important — fructose is preferentially converted to liver fat.
• Exercise: both aerobic and resistance exercise independently reduce liver fat. Combined is best. Even 150 min/week of moderate exercise has measurable effects.
• Alcohol elimination or significant reduction.

Medications:

• Resmetirom (Rezdiffra) — FDA-approved in 2024 specifically for MASH with significant fibrosis. The first MASLD-specific medication.
• GLP-1 medications (semaglutide, tirzepatide) — increasingly used; significant evidence for reducing liver fat and improving MASH. Often appropriate for patients with both MASLD and obesity or diabetes.
• Vitamin E (800 IU/day) — has evidence in non-diabetic adults with MASH; less benefit in diabetics.
• Statins — safe to use in MASLD (do not avoid them due to mild liver enzyme elevation); may improve liver outcomes independent of cholesterol effects.
• Pioglitazone — diabetes medication with evidence for improving MASH; balanced against side effects (weight gain, fluid retention).

Monitoring:

• Annual liver enzymes + FIB-4 calculation. Track trend over time.
• Annual A1c, lipid panel, fasting insulin. Metabolic markers tend to move in parallel with liver markers.
• FibroScan or MRI elastography every 2-3 years if FIB-4 is indeterminate or if there's concern about progression. These imaging tests measure liver stiffness (a proxy for fibrosis) noninvasively.
• Liver biopsy only in selected advanced cases — increasingly avoided in favor of imaging.
• Hepatology referral if FIB-4 >2.67, if FibroScan shows significant fibrosis, or if liver enzymes are markedly elevated or worsening despite treatment.