1. CPC November 3, 2009 Charles Steenbergen csteenb1@jhmi.edu

2. 47 year old woman with history of alcoholic cirrhosis, diabetes, chronic pancreatitis, and hepatocellular carcinoma, who had liver transplant in 2/2008. Developed heart failure, renal failure, and dyspnea, and died 6/2008.

3. At autopsy, we found Massive ascites (4.9 liters, serosanguinous) Left pleural effusion (485 ml, serosanguinous) Transplanted liver with diffuse congestion Heart, 400 grams, with patchy LV fibrosis, mild aortic atherosclerosis, and moderate coronary atherosclerosis (< 50% stenosis)

4. Patchy interstitial fibrosis of the left ventricular myocardium

5. Brown granular deposits in the middle of cardiac myocytes

6. Massive iron deposition in cardiac myocytes (Prussian blue stain for iron)

7. No evidence of extrahepatic biliary obstruction or periportal damage

8. Centrilobular congestion and necrosis

9. Centrilobular fibrosis and canalicular cholestasis

10. Iron deposition in reticuloendothelial cells (Prussian blue stain for iron) and canalicular bile plugs

11. Hyaline membranes in left lung, indicative of diffuse alveolar damage (ARDS)

12. Fibrosis and calcification of the pancreas

13. Microcalcifications within tubules of kidneys

14. Myocardial iron deposition can be associated with myocyte damage and replacement fibrosis, which is thought to be mediated by oxygen free radical production catalyzed by iron. This can explain the rapid development of heart failure that occurred in this patient.

15. At transplant, the explanted liver was found to have marked iron deposition. Hepatic iron deposition can be genetic (hereditary hemochromatosis), but iron accumulation can also occur in patients with cirrhosis in the absence of HFE mutations. Iron deposition in liver explants is a risk factor for myocardial iron accumulation and heart failure. (Transplantation 2009;87:1256 ).

16. A similar conclusion was reached in an earlier study (Liver International 2005;25:513). Retrospective analysis of three autopsy cases of end-stage cirrhosis with marked hepatic iron overload also showed iron deposition in the heart and pancreas, as in the current case. In the 2005 study, two patients were heterozygous for HFE mutations and one was wild-type.