How would you approach the evaluation of a patient with decompensated cirrhosis, suspect to be due to alcohol, who is not a liver transplant candidate with iron studies showing elevated saturation and ferritin over 1000?

The finding of elevated iron saturation (I suspect means above 55%) and high ferritin raises the diagnosis of true iron overload. Certainly, a Ferritin level above 1000, when the patient is not actively drinking, is consistent with cirrhosis. So, I would start phlebotomies if the Hgb >11-12 g/dL allows. Chelation in anemic patients with cirrhosis is challenging, but we would discuss the best option with a hematologist. I would also consider the MRI of liver hemochromatosis protocol to evaluate the severity of iron overload without requiring a liver biopsy. I see no downside to checking for HFE mutations, in particular if the patient has offspring that could be carrying the same gene abnormalities as well.

Ferritin is an acute phase reactant and could be related to ongoing alcohol use. Ferritin also elevated in chronic alcohol use (secondary iron overload). Would still send genetic testing for HH. I would be unlikely to consider a liver biopsy or phlebotomy without a genetic diagnosis.