Case Presentation: A 65 year old male with no significant medical history presented to an outside facility complaining of fatigue, weakness, nausea and vomiting. He had moderate alcohol history and significant weight loss over the past 6 months. Initial lab workup was notable for elevated liver transaminases with a hepatocellular pattern, Maddrey score of 53.6 and MELD score of 35 on presentation. Right upper quadrant (RUQ) ultrasound notable for increased liver echogenicity throughout with concomitant ascites. N-acetylcysteine and steroids were initiated early on as well as thiamine. His hospital course was complicated with hepatic encephalopathy and was started on lactulose and rifaximin as well as an eventually hepatic vein thrombosis. Autoimmune and infectious work up work including ANA, AFP, Antimitochondrial, Antismooth, CMV, EBV, HSV, hepatitis panel were all negative. Ferritin levels were above 14,000 and transferrin saturation (TSAT) was 73%. Patient subsequently underwent liver biopsy as he failed to improve on steroids and continued to remain encephalopathic with increasing bilirubin, past 48g/dl total. Genetic testing was positive for the HFE mutation; he was a heterozygote for C282Y and H63D. Given his worsening encephalopathy and synthetic liver function, decision was made to transfer him to a liver transplant center for further workup due to the possibility of underlying hemochromatosis. However he was ultimately determined to be a poor candidate for liver transplantation given grave prognosis and alcohol history. His family ultimately elected for palliative care talks after final evaluation by a liver transplant team.
Discussion: HFE hemochromatosis is an autosomal recessive disorder associated with an increased lifetime risk of end stage liver disease due to excess iron deposition. We present an interesting and challenging case of cirrhosis and liver failure that presented to our hospital. While the history and presentation of the patient was partially consistent with alcoholic cirrhosis; the lab values, liver biopsy, and genetic testing all combined to make a clouded picture as to pinpoint the exact etiology of his acute liver failure. This case is complex both clinically and pathologically as it is unknown how much of the alcohol abuse and genetic predisposition contributed to his cirrhosis.
Conclusions: This case highlights the importance of early transfer to transplant centers and expert referral but also understanding the role that genetic predisposition plays in disease. Many hypotheses surmise that disease results from susceptibility and insult; in this case our patient had an underlying late onset of hemochromatosis with elevated ferritin and TSAT that clinically went undetectable until his alcohol use accelerated liver damage to render treatment and supportive care null. It is unknown whether how much alcohol use versus genetic predisposition contributed to the disease process. This case brings up an important question on whether these patients should be referred early to a transplant center despite alcohol use. Initial triage to these centers so evaluation by transplant teams can guide therapy more suitably than centers lacking these resources. It also emphasizes the importance of investigating these patients as thoroughly as possible, especially when clinical history and laboratory abnormalities do not appear consistent.