CPC November 3, 2009

Charles Steenbergen

csteenb1@jhmi.edu

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.

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)

Patchy interstitial fibrosis of the left ventricular myocardium

Brown granular deposits in the middle of cardiac myocytes

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

No evidence of extrahepatic biliary obstruction or periportal damage

Centrilobular congestion and necrosis

Centrilobular fibrosis and canalicular cholestasis

Iron deposition in reticuloendothelial cells (Prussian blue stain for iron) and

canalicular bile plugs

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

Fibrosis and calcification of the pancreas

Microcalcifications within tubules of kidneys

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.

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).

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.