What is the treatment plan for a patient with hyperferritinemia (elevated iron levels), elevated Gamma-Glutamyl Transferase (GGT) levels, and a history of heavy alcohol consumption?

Management of Hyperferritinemia with Elevated GGT in Heavy Alcohol Use

The cornerstone of treatment is immediate and complete alcohol abstinence, as this addresses both the elevated iron parameters and liver injury, with reassessment of ferritin after 2 weeks of documented abstinence to determine if true iron overload exists. 1, 2

Immediate Priority: Alcohol Cessation

• Patients with cirrhosis must completely abstain from alcohol - this is non-negotiable given clear data showing ongoing alcohol use worsens mortality and liver-related morbidity 1, 3
• For patients with iron overload and/or liver abnormalities, alcohol should be avoided or consumed minimally during the iron depletion phase 1
• Refer to alcohol services if AUDIT score >19, indicating alcohol dependency requiring specialized treatment 1
• The combination of excessive alcohol and elevated iron significantly increases risk of fibrosis progression, hepatocellular carcinoma, and oxidative stress 2

Diagnostic Algorithm for Iron Status

After 2 weeks of alcohol abstinence, recheck ferritin and transferrin saturation to distinguish alcohol-induced hyperferritinemia from true iron overload 2:

• If ferritin remains >1000 μg/L after abstinence with elevated liver enzymes: liver biopsy should be considered to assess for iron overload and fibrosis 2
• Check transferrin saturation - iron metabolism markers are frequently elevated in alcoholic liver disease but typically to a lesser extent than in homozygous hemochromatosis 1
• Consider MRI for non-invasive liver iron concentration assessment if ferritin remains elevated after cessation 2
• Screen for HFE mutations (C282Y and H63D) - heterozygosity for HFE mutations is more common in patients with alcohol use disorder but has no major influence on ALD progression 1

Risk Stratification for Liver Disease

All patients require assessment for advanced liver disease and fibrosis given the synergistic hepatotoxicity of alcohol and iron 1:

• Perform Fibroscan/ARFI elastography for non-invasive fibrosis assessment 1
• AST/ALT ratio >2 suggests alcoholic hepatitis (>3 is highly suggestive), though AST and ALT typically don't exceed 300 IU/L in ALD 1
• GGT is elevated in approximately 75% of habitual drinkers and is useful for monitoring abstinence, though it recovers slowly (over months) 1
• Patients with hereditary hemochromatosis who consume >60g alcohol/day have >60% risk of cirrhosis versus <7% in those drinking less 2

Treatment Based on Iron Status

For confirmed iron overload (ferritin persistently >1000 μg/L with elevated transferrin saturation after abstinence):

• Phlebotomy therapy is indicated - target serum ferritin 50-100 μg/L during maintenance phase 1
• Monitor hemoglobin at each phlebotomy session; discontinue if hemoglobin <11 g/dL 1
• Iron depletion is NOT indicated for patients with non-HFE mutations and mild hyperferritinemia from alcohol alone 1

For alcohol-induced hyperferritinemia without true iron overload:

• Ferritin should normalize with sustained abstinence alone 2
• Continue monitoring liver enzymes and ferritin every 3-6 months 1

Dietary Modifications During Treatment

• Avoid iron supplementation and iron-fortified foods 1
• Avoid supplemental vitamin C, especially before iron depletion, as it enhances iron absorption 1
• Limit red meat consumption 1
• Avoid raw or undercooked shellfish in regions with Vibrio vulnificus risk, as iron overload increases susceptibility to siderophilic pathogens 1

Screening for Complications

Patients with cirrhosis require:

• Screening for esophageal varices 1
• Hepatocellular carcinoma surveillance every 6 months, as risk remains elevated even with adequate iron depletion in cirrhotic patients 1
• Assessment for other alcohol-related organ damage: cardiomyopathy, pancreatitis, neuropathy 1

Common Pitfalls to Avoid

• Do not assume elevated ferritin equals hemochromatosis - ferritin is an acute phase reactant elevated by inflammation, liver damage, and malignancy in addition to iron overload 2, 4
• Do not initiate phlebotomy before confirming true iron overload after a period of abstinence, as alcohol-induced hyperferritinemia resolves without iron removal 2
• Do not overlook coexisting liver disease - screen for hepatitis B, hepatitis C, and NAFLD, as alcohol accelerates fibrosis in these conditions 1
• GGT elevation alone has low specificity and can be elevated by obesity, diabetes, smoking, or medications 1