Hemochromatosis is the Most Likely Diagnosis
In this 36-year-old asymptomatic man with elevated liver enzymes, hepatomegaly, and clear laboratory evidence of iron overload (elevated serum iron, low TIBC, and markedly elevated ferritin at 423 μg/L), hemochromatosis is the most likely underlying cause of his liver disease. The constellation of findings—particularly the iron studies showing transferrin saturation approaching 100% (iron 35 ÷ TIBC 34) and ferritin >300 μg/L—strongly indicates hereditary hemochromatosis rather than alcoholic hepatitis, despite his weekend alcohol consumption 1.
Why Hemochromatosis is Most Likely
Iron Study Pattern is Diagnostic
The transferrin saturation is markedly elevated (>100% by calculation), which is the hallmark of hemochromatosis. Transferrin saturation ≥45% has 92% sensitivity and 93% specificity for hereditary hemochromatosis 1, 2.
Ferritin of 423 μg/L in a 36-year-old man exceeds the diagnostic threshold of >300 μg/L for men, strongly supporting iron overload 1, 3.
The combination of elevated transferrin saturation and elevated ferritin is highly specific for hereditary hemochromatosis rather than secondary causes of hyperferritinemia 2.
Age and Clinical Presentation Fit Hemochromatosis
Hereditary hemochromatosis is typically diagnosed in the 40s-50s, and this patient at age 36 fits the typical age range for early detection 1, 3.
Most patients with hemochromatosis are now identified while asymptomatic with abnormal liver enzymes and iron studies, exactly as in this case 1.
The AASLD guidelines specifically identify "unexplained elevation of liver enzymes" and "asymptomatic hepatomegaly" as target populations for hemochromatosis evaluation 1.
Why NOT Alcoholic Hepatitis
The AST:ALT ratio is approximately 2:1 (147:76), which could suggest alcoholic liver disease, but the iron overload pattern is not explained by alcohol alone 1.
Weekend drinking does not constitute the heavy alcohol consumption (>60-100 g/day) typically required to cause alcoholic hepatitis 4.
While alcohol can accelerate clinical expression of hemochromatosis, the primary diagnosis here is hemochromatosis with possible alcohol as a co-factor 4.
Ferritin elevation in alcoholic hepatitis is typically modest and reflects hepatocellular necrosis, not the marked elevation with high transferrin saturation seen here 5.
Why NOT Chronic Hepatitis B
- The hepatitis screen is negative, and specifically HBsAg is negative. The positive HBsAb (hepatitis B surface antibody) indicates prior vaccination or resolved infection, not chronic disease 1.
Why NOT Hepatocellular Carcinoma
- HCC does not cause this pattern of iron overload. HCC is a complication that can develop in hemochromatosis patients with cirrhosis, not a primary cause of iron overload 1, 6.
Critical Next Steps
Confirm the Diagnosis
HFE genetic testing for C282Y and H63D mutations should be performed to confirm hereditary hemochromatosis, as C282Y homozygosity accounts for 85-90% of clinically affected patients 2.
Liver biopsy may be warranted to assess hepatic iron concentration and calculate the hepatic iron index (>2.0 confirms hemochromatosis), and to exclude significant fibrosis or cirrhosis 1, 5.
Assess for Complications
Screen for diabetes, cardiac involvement, and arthropathy, as these are common manifestations of iron overload 1.
Echocardiography should be considered to detect early cardiac dysfunction, as cardiac involvement carries poor prognosis once heart failure develops 2.
Initiate Treatment Promptly
Therapeutic phlebotomy should be initiated promptly to prevent progression to cirrhosis and reduce risk of hepatocellular carcinoma, with target ferritin of 50-100 μg/L during maintenance 2, 3.
Survival is normal in hemochromatosis patients when treatment is initiated before development of cirrhosis or diabetes, emphasizing the importance of early diagnosis 1.
Screen Family Members
- All first-degree relatives should undergo screening with HFE genetic testing and phenotypic testing (transferrin saturation and ferritin) to prevent end-organ damage 2.
Common Pitfalls to Avoid
Do not dismiss iron overload as secondary to alcohol or hepatitis when transferrin saturation is markedly elevated. In chronic hepatitis, ferritin may be elevated due to hepatocellular necrosis, but the hepatic iron index is rarely in the hemochromatosis range 5.
Do not delay genetic testing and treatment while waiting for liver biopsy. The iron studies alone are sufficient to initiate evaluation and potentially start phlebotomy 1.
Do not assume the patient's alcohol use is the primary problem. While alcohol consumption >60 g/day increases cirrhosis risk ninefold in hemochromatosis patients, weekend drinking is unlikely to be the sole cause of this presentation 4.
Answer: A. Hemochromatosis