Is it common for patients with hemochromatosis to have elevated Liver Function Tests (LFTs)?

Elevated LFTs are Common in Hemochromatosis Patients

Yes, it is common for patients with hemochromatosis to have elevated liver function tests (LFTs). According to the American Association for the Study of Liver Diseases (AASLD) guidelines, liver involvement is a hallmark feature of hemochromatosis, with abnormal liver function tests often being one of the first clinical manifestations of the disease 1.

Prevalence and Significance of Elevated LFTs in Hemochromatosis

The relationship between hemochromatosis and elevated LFTs is well-established:

• The AASLD guidelines specifically recommend that "all patients with abnormal liver function have iron studies done at some point in their evaluation" 1, highlighting the common association between abnormal LFTs and hemochromatosis.

• Historical data from multiple studies cited in the guidelines show that hepatomegaly was present in 54-83% of hemochromatosis patients, with cirrhosis found in 3-94% depending on when in the disease course patients were diagnosed 1.

• Liver involvement in hemochromatosis progresses through several stages:

  • Initial iron accumulation in hepatocytes
  • Development of hepatic inflammation
  • Progression to fibrosis and eventually cirrhosis if untreated

Diagnostic Implications

The presence of elevated LFTs in a patient should trigger consideration of hemochromatosis:

• The European Association for the Study of the Liver (EASL) guidelines state that "patients from liver clinics should be screened for fasting transferrin saturation and serum ferritin" 1.

• When evaluating abnormal LFTs, iron studies (transferrin saturation and ferritin) should be included in the workup 1.

• A serum ferritin level >1000 μg/L with elevated aminotransferases (ALT or AST) and a platelet count <200 is highly predictive of cirrhosis in C282Y homozygotes 1.

Clinical Presentation and LFT Patterns

The pattern of LFT abnormalities in hemochromatosis typically includes:

• Mild to moderate elevations in aminotransferases (AST and ALT)
• Possible elevation in alkaline phosphatase in more advanced disease
• Progressive worsening of LFTs as iron accumulation increases

Case reports demonstrate that even patients with less common mutations like H63D homozygosity can present with elevated LFTs as their primary clinical finding 2.

Diagnostic Algorithm for Patients with Elevated LFTs

When encountering a patient with elevated LFTs:

1. Include iron studies (transferrin saturation and ferritin) in the initial workup
2. If transferrin saturation is ≥45% and/or ferritin is elevated:
   • Proceed with HFE genetic testing for C282Y and H63D mutations
3. If genetic testing confirms hemochromatosis (C282Y homozygosity or C282Y/H63D compound heterozygosity):
   • Assess for liver damage based on degree of ferritin elevation
   • Consider liver biopsy if ferritin >1000 μg/L, elevated aminotransferases, hepatomegaly, or age >40 years

Important Caveats and Pitfalls

• Not all patients with hemochromatosis will have elevated LFTs, especially in early disease

• Elevated ferritin alone is not diagnostic of hemochromatosis, as it can be elevated in:

  • Alcoholic liver disease
  • Chronic viral hepatitis
  • Non-alcoholic fatty liver disease (NAFLD)
  • Inflammatory conditions
  • Malignancies

• Approximately 50% of patients referred for hemochromatosis genetic testing do not have biochemical evidence of iron overload 3, highlighting the importance of following proper diagnostic algorithms.

• Diagnosis of hemochromatosis requires both genetic and phenotypic evidence of iron overload, not just abnormal LFTs 4.

By understanding the common association between hemochromatosis and elevated LFTs, clinicians can ensure appropriate diagnostic testing and early intervention to prevent progression to irreversible liver damage.