Case Presentation: The patient is a 32-year-old male with a history of alcohol abuse who presented with two days of right upper quadrant pain and non-bloody emesis. He denied any prior diagnosis of liver disease (although alluded to a family history of cirrhosis), renal disease, confusion, or jaundice. He reported drinking a fifth of liquor daily as well as taking acetaminophen tablets to medicate a toothache. On presentation, he was hemodynamically stable, but had significantly elevated liver enzymes (AST: 27,756 IU/dL, ALT: 6,851 IU/L, total bilirubin: 1.4 mg/dL, alkaline phosphatase: 72 IU/L) and a serum creatinine of 5.90 mg/dL. INR was elevated at 1.5 and urine toxicology was positive for ethanol. Acute hepatitis panel, HIV, ceruloplasmin, alpha-1-antitrypsin, salicylate level, acetaminophen level, ANA, anti-smooth muscle antibody (Ab), anti-liver-kidney Ab, and anti-mitochondrial Ab were all negative. He was, however, found to have a significantly elevated ferritin of 29,734 ng/mL and a transferrin saturation that was too high to calculate. Magnetic resonance imaging showed normal liver morphology without cirrhosis. Given the patient’s elevated ferritin and transferrin saturation, combined with family history of cirrhosis, he underwent HFE genotype testing to evaluate for possible hereditary hemochromatosis (HH). This identified the H63D mutation in heterozygous form, but the C282Y mutation was not detected. His ferritin level, as well as liver and renal function improved with conservative management and his presentation was ultimately attributed to severe alcoholic hepatitis.
Discussion: Iron overload syndromes can be classified into hereditary, secondary, or miscellaneous categories. HH is the most common cause of hereditary iron overload, and is initially suspected based on markers of increased iron stores, i.e. serum ferritin and transferrin saturation. The majority of patients with HH possess homozygous C282Y mutations in the HFE gene, while a minority have heterozygous, C282Y/H63D or C282Y/S65C mutations. However, patients with a single H63D or S65C mutation are generally not at risk for significant iron overload. Substantial alcohol consumption, on the other hand, may disrupt the process of iron metabolism via hepcidin deregulation and lead to excess deposition of iron in the liver. Serum iron and ferritin levels can also increase proportionally with the severity of alcoholic liver disease (ALD). While phlebotomy has demonstrated utility in some patients with secondary iron overload, there is not strong evidence to support its use in ALD.
Conclusions: This case represents a unique presentation of secondary iron overload and a significantly elevated ferritin level in the setting of severe alcoholic hepatitis. It highlights the importance of considering ALD in the differential of iron overload and demonstrates that HH is not the sole cause of an elevated ferritin level in the setting of liver dysfunction or an acute inflammatory state.