Should a patient with hyperferritinemia and normal transferrin levels undergo an abdominal ultrasound to rule out liver disease?

Should You Order an Abdominal Ultrasound for High Ferritin with Normal Transferrin?

Yes, an abdominal ultrasound should be performed as part of the standard initial workup for hyperferritinemia, regardless of transferrin saturation levels, to evaluate for underlying liver disease including fatty liver, chronic liver disease, and hepatomegaly. 1

Why Ultrasound is Recommended

The 2018 Gut guidelines explicitly state that abdominal ultrasound should be included in the standard liver aetiology screen for adults with abnormal liver parameters 1. This recommendation applies to your scenario because:

• Elevated ferritin with normal transferrin saturation (<45%) strongly suggests secondary causes rather than iron overload 1, 2
• Over 90% of hyperferritinemia cases are caused by non-iron overload conditions: chronic alcohol consumption, inflammation, liver disease (including NAFLD), metabolic syndrome, and cell necrosis 3, 4, 2
• Ultrasound identifies the most common culprit: In the BALLETS study, nearly 40% of adults with abnormal liver tests had fatty liver on ultrasound, and obesity was more strongly associated with fatty liver than alcohol excess 1

The Diagnostic Algorithm

First: Confirm the Pattern

Your patient has hyperferritinemia with normal transferrin saturation, which means:

• Iron overload is unlikely 1, 3, 2
• Secondary causes predominate 3, 4, 5
• The ferritin elevation reflects inflammation, metabolic dysfunction, or hepatocellular injury—not iron accumulation 1, 3, 4

Second: Order the Standard Workup

According to EASL and British Society of Gastroenterology guidelines, the complete initial evaluation includes 1:

• Abdominal ultrasound (to detect fatty liver, cirrhosis, hepatomegaly, bile duct dilation)
• Hepatitis B surface antigen and hepatitis C antibody (to exclude viral hepatitis)
• Autoantibodies (anti-mitochondrial, anti-smooth muscle, antinuclear antibodies)
• Serum immunoglobulins
• Simultaneous ferritin and transferrin saturation (already done in your case)

Third: Interpret the Ultrasound Findings

If ultrasound shows fatty liver (echobright liver):

• Diagnose NAFLD if alcohol consumption is not excessive 1
• This explains the elevated ferritin: In NAFLD, ferritin elevation reflects hepatocellular injury and insulin resistance, not iron overload 1, 3, 4
• Assess for metabolic risk factors: obesity, glucose intolerance, dyslipidemia 1
• Use non-invasive fibrosis scores (FIB-4 or NAFLD Fibrosis Score) to stratify risk 1

If ultrasound shows other abnormalities:

• Hepatomegaly, cirrhotic features, or bile duct dilation require specialist referral 1
• Normal ultrasound with persistent hyperferritinemia warrants investigation for inflammatory conditions, malignancy, or metabolic syndrome 1, 4, 2

When Liver Biopsy is NOT Needed

You do NOT need liver biopsy or advanced imaging if 1:

• Ferritin <1,000 μg/L (94% negative predictive value for advanced fibrosis)
• Normal transaminases
• No hepatomegaly
• Normal platelet count

This combination has a 94% negative predictive value for advanced liver fibrosis in hemochromatosis patients, and the risk is even lower when transferrin saturation is normal 1.

Critical Pitfalls to Avoid

Do not assume iron overload when transferrin saturation is normal 3, 4, 5. The pattern of elevated ferritin with normal transferrin saturation indicates:

• Inflammation (ferritin is an acute phase reactant) 3, 4, 2
• Liver disease (alcoholic, viral, NAFLD) 1, 2
• Metabolic syndrome 1, 3, 4
• Cell necrosis or tissue damage 3, 4, 2

Do not skip the ultrasound 1. It is explicitly recommended in guidelines as part of the standard workup and frequently identifies the underlying cause (fatty liver in 40% of cases) 1.

Do not order HFE genetic testing when transferrin saturation is <45% 1, 3, 4. Genetic testing is only indicated when transferrin saturation ≥45%, as this is the key discriminator for true iron overload 1, 3, 4.

Bottom Line

Order the abdominal ultrasound. It is part of the guideline-recommended standard workup for hyperferritinemia, will likely identify fatty liver or other liver pathology explaining the elevated ferritin, and will guide appropriate management of the underlying condition rather than unnecessary iron-focused interventions 1, 3.