In an adult chronic alcoholic with low unsaturated iron‑binding capacity, markedly elevated serum iron, high transferrin saturation (~80%) and elevated ferritin (~700 ng/mL), what is the likely diagnosis and recommended management?

Alcoholic Liver Disease with Secondary Iron Overload

In a chronic alcoholic presenting with markedly elevated serum iron (290 µg/dL), very high transferrin saturation (~80%), elevated ferritin (697 ng/mL), and low UIBC (72 µg/dL), the diagnosis is alcoholic liver disease with secondary iron dysregulation—not hereditary hemochromatosis—and management centers on alcohol cessation, hepatic assessment, and avoidance of phlebotomy until iron parameters normalize after abstinence.

Understanding the Clinical Pattern

Chronic alcohol consumption disrupts normal iron metabolism through multiple mechanisms:

• Alcohol suppresses hepcidin transcription via oxidative stress, removing the physiologic brake on intestinal iron absorption and causing iron accumulation even without genetic predisposition 1
• Hepatocellular injury from alcohol releases stored ferritin and iron directly into circulation, producing acutely elevated serum iron and transferrin saturation that mimics primary iron overload 2, 3
• Upregulation of duodenal DMT-1 and ferroportin increases intestinal iron absorption in chronic alcohol users 1
• The combination of increased absorption and hepatocyte necrosis creates a pattern indistinguishable from hereditary hemochromatosis on initial laboratory testing 2, 4

This patient's iron parameters are characteristic of alcoholic hepatitis rather than genetic hemochromatosis:

• Transferrin saturation of 80% with serum iron of 290 µg/dL reflects acute hepatocellular release rather than chronic iron loading 2, 5
• Ferritin at 697 ng/mL is elevated but below the 1,000 µg/L threshold that predicts cirrhosis in true hemochromatosis 6, 7
• The highest frequency of this iron pattern occurs specifically in alcoholic liver disease, nonalcoholic fatty liver disease, and chronic hepatitis C 5

Critical Diagnostic Pitfall

The single most important error to avoid is diagnosing hereditary hemochromatosis and initiating phlebotomy based solely on elevated transferrin saturation in an active alcohol user 2, 4:

• Although transferrin saturation >45% has high sensitivity (84% in men, 73% in women) for detecting C282Y homozygosity, it has low specificity and positive predictive value in the setting of acute liver injury 6, 2
• Alcoholic hepatitis routinely produces transferrin saturation values exceeding 45%—and even exceeding 80%—through hepatocyte necrosis and iron release, not through genetic iron overload 2, 4
• Immediate phlebotomy in this setting is inappropriate and potentially harmful; the priority is treating the underlying liver disease 2

Immediate Diagnostic Workup

Order the following tests to assess liver injury severity and exclude alternative diagnoses:

Hepatic Function Panel

• AST, ALT, alkaline phosphatase, total and direct bilirubin to quantify hepatocellular and cholestatic injury 6, 7
• Albumin, prothrombin time/INR to assess synthetic liver function 6
• Platelet count <200,000/µL predicts cirrhosis in iron overload states and should be measured 6, 7

Inflammatory Markers

• CRP and ESR to identify systemic inflammation contributing to ferritin elevation 6, 7
• Ferritin is an acute-phase reactant that rises with inflammation independent of iron stores 6, 8

Imaging

• Abdominal ultrasound to detect fatty infiltration, hepatomegaly, cirrhotic morphology, or ascites 6
• Ultrasound identifies fatty liver in approximately 40% of patients with abnormal liver tests and is the first-line imaging modality 6

Viral Hepatitis Screening

• Hepatitis B surface antigen and hepatitis C antibody because approximately 50% of patients with chronic viral hepatitis exhibit abnormal iron parameters that can confound interpretation 6, 5

Management Algorithm

Phase 1: Immediate Interventions (First 2 Weeks)

Complete alcohol abstinence is the cornerstone of management 4:

• Iron parameters normalize rapidly after alcohol withdrawal: transferrin saturation falls from ~59% to ~36% and ferritin drops from ~900 to ~469 ng/mL within 14 days in cirrhotic patients 4
• In non-cirrhotic alcoholics, transferrin saturation decreases from ~46% to ~27% and ferritin from ~702 to ~340 ng/mL over the same period 4
• Do not order HFE genetic testing during active alcohol use; screening for hereditary hemochromatosis must be postponed until after complete abstinence and normalization of liver enzymes 4

Avoid iron supplementation and vitamin C:

• Iron supplements are contraindicated when ferritin is elevated 7
• Vitamin C accelerates iron mobilization and increases oxidative stress, worsening hepatotoxicity 7

Avoid raw shellfish:

• Iron-overloaded patients face increased risk of Vibrio vulnificus infection from raw oysters and other shellfish 7

Phase 2: Reassessment After Abstinence (2–4 Weeks)

Repeat transferrin saturation and ferritin after 14–28 days of documented abstinence 4:

• If transferrin saturation normalizes to <45% and ferritin declines substantially, the diagnosis is alcohol-induced iron dysregulation, not hereditary hemochromatosis 4
• If transferrin saturation remains ≥45% despite abstinence and normalization of liver enzymes, then proceed with HFE genetic testing for C282Y and H63D mutations 6, 7, 4

Phase 3: Risk Stratification and Liver Assessment

Assess for cirrhosis using non-invasive markers:

• FIB-4 score or NAFLD Fibrosis Score to stratify fibrosis risk 6
• Ferritin <1,000 µg/L has a 94% negative predictive value for advanced fibrosis, making liver biopsy unnecessary if liver enzymes normalize 6, 7
• Liver biopsy is indicated if ferritin remains >1,000 µg/L with elevated liver enzymes or platelet count <200,000/µL after abstinence, as this combination predicts cirrhosis in 80% of cases 6, 7

Consider liver MRI with T2 relaxometry:*

• If transferrin saturation remains ≥45% after abstinence, MRI quantifies hepatic iron concentration non-invasively 6, 7
• MRI shows 84–91% sensitivity and 80–100% specificity for hepatic iron overload 7

When to Refer to Hepatology

Immediate specialist referral is warranted if 6, 7:

• Ferritin >1,000 µg/L with elevated bilirubin
• Clinical evidence of cirrhosis (ascites, splenomegaly, platelet count <200,000/µL)
• Transferrin saturation remains ≥45% after 4 weeks of abstinence
• Bilirubin elevation suggesting decompensated liver disease

Addressing Metabolic Comorbidities

Evaluate for metabolic syndrome components that contribute to fatty liver and ferritin elevation 6, 8:

• Fasting glucose and lipid panel to assess for diabetes and dyslipidemia 6
• In nonalcoholic fatty liver disease (which may coexist with alcoholic liver disease), elevated ferritin reflects hepatocellular injury and insulin resistance rather than true iron overload 8
• Weight loss and lifestyle modification are first-line interventions when metabolic syndrome is present 8

Why Phlebotomy Is Contraindicated Now

Therapeutic phlebotomy should not be initiated in this patient 2, 4:

• The iron elevation is secondary to acute hepatocellular injury, not chronic iron loading requiring depletion 2
• Phlebotomy does not treat the underlying alcoholic liver disease and may worsen anemia if present 2
• Iron parameters will normalize spontaneously with abstinence, obviating the need for phlebotomy 4
• If hereditary hemochromatosis is ultimately confirmed (C282Y homozygosity with persistently elevated transferrin saturation after abstinence), phlebotomy can be initiated at that time with a target ferritin of 50–100 µg/L 7

Synergistic Hepatotoxicity in Hemochromatosis Carriers

If genetic testing eventually reveals C282Y heterozygosity or compound heterozygosity 3, 1:

• Alcohol and iron exert synergistic hepatotoxic effects through free radical-mediated injury 3
• Hemochromatosis patients who consume alcohol develop cirrhosis earlier than those with either condition alone 3, 1
• Lifelong alcohol abstinence is mandatory if any HFE mutation is detected, even if not homozygous C282Y 3

Expected Outcomes with Abstinence

With complete alcohol cessation 4:

• Transferrin saturation and ferritin decline significantly within 7–14 days
• Liver enzymes improve over weeks to months depending on baseline severity
• If cirrhosis is not yet present, continued abstinence prevents progression to end-stage liver disease 7
• If cirrhosis is established, abstinence halts progression but does not reverse fibrosis 7

Family Screening Considerations

Do not screen first-degree relatives until the patient's own iron status is clarified after abstinence 6, 7:

• If HFE genetic testing ultimately confirms C282Y homozygosity, all first-degree relatives require screening with transferrin saturation, ferritin, and HFE genotyping 7
• Penetrance of C282Y homozygosity is higher in family members than in the general population 7