Irony of Iron Overload: Hereditary Hemochromatosis Complicated by Alcoholic Hepatitis, Gastrointestinal Bleeding, and Intramuscular Hematoma

Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive iron absorption and accumulation. The HFE gene C282Y mutation is most commonly implicated, while the H63D variant is less penetrant and rarely causes significant iron overload. However, alcohol use accelerates hepatic iron accumulation and worsens liver injury, creating a complex interplay between genetic and environmental factors. A 47-year-old woman with chronic heavy alcohol use presented with progressive jaundice and generalized weakness. Laboratory evaluation revealed markedly elevated aspartate aminotransferase (AST) of 542 U/L, alanine aminotransferase (ALT) of 185 U/L, total bilirubin of 22.2 mg/dL, and ferritin of 17,741 ng/mL. Imaging demonstrated hepatomegaly with coarse echotexture suggestive of cirrhosis. Genetic testing identified heterozygosity for the H63D variant of the HFE gene. She was initially treated for severe alcoholic hepatitis with oral prednisolone based on an elevated Maddrey’s Discriminant Function (MDF) score of 73.4; however, therapy was discontinued after the Lille score exceeded 0.45 at day 7, indicating poor response to corticosteroids. Her hospital course was complicated by recurrent gastrointestinal (GI) bleeding due to esophageal ulceration, esophageal varices, portal hypertensive gastropathy, and a Dieulafoy lesion requiring endoscopic clipping and band ligation. She also developed a large intramuscular hematoma in the left vastus lateralis muscle, requiring interventional drainage and multiple blood transfusions. She was ultimately discharged to a subacute rehabilitation facility for alcohol detoxification with plans for close outpatient follow-up with gastroenterology and hepatology. This case highlights the paradoxical coexistence of extreme hyperferritinemia with severe anemia in advanced liver disease complicated by recurrent hemorrhage. The markedly elevated ferritin likely reflected a combination of hepatic inflammation, alcohol-related injury, and dysregulated iron metabolism rather than primary genetic hemochromatosis. Although the H63D variant alone rarely leads to significant clinical disease, chronic alcohol use may contribute to worsening hepatic dysfunction and iron imbalance. Additionally, the presence of multiple GI bleeding sources and a spontaneous intramuscular hematoma illustrates the complex hemostatic disturbances associated with advanced cirrhosis. Early recognition of atypical bleeding manifestations in patients with decompensated liver disease is essential to guide timely intervention and improve clinical outcomes.