Navigation

Pathophysiology Of Liver Cancer

Hemochromatosis is a disorder of excess iron deposition in tissues that may cause multiorgan dysfunction. Because the early symptoms of hemochromatosis are nonspecific, the diagnosis is frequently overlooked until significant organ failure has developed. The primary cause of death in these patients is usually liver cancer related to cirrhosis. Patients who are candidates for liver transplantation should be referred for evaluation. For patients with severe cardiomyopathy, in addition to end-stage liver disease, combined transplantation may be performed. Although there is a limited number of combined heart-liver transplantations that have been performed, successful outcomes can be achieved with close monitoring and a multidisciplinary team approach. In this case report, we will discuss the prevalence, pathophysiology, and treatment of hemochromatosis and potential complications of combined heart-liver transplantation. (Progress in Transplantation. 2004; 14:39-40)

Hemochromatosis is a disorder of excess iron deposition in tissues that may cause multiorgan dysfunction; it is classified as hereditary or secondary according to the underlying etiology. Hereditary hemochromatosis is an autosomal recessive genetic disorder. secondary disease is caused by excessive oral intake of iron or parenteral iron overload in patients requiring frequent blood transfusions. When the body absorbs more iron than is needed for daily requirements, it is not recycled and excreted. Persons with hereditary hemochromatosis absorb excess iron from the gastrointestinal tract resulting in iron deposition of the vital organs.1 The liver, where 90% of the excess iron is stored, is usually affected first, as well as the heart, pancreas, endocrine system, skin, and joints.2,3

About 1 in 200 persons in certain populations of northern-European descent has hereditary hemochromatosis.3 Symptoms present in men more than women, at an 8:1 ratio, and are seen earlier in men because women lose blood during their menstruation years.4 Clinical manifestations include hepatic cirrhosis, cardiomyopathy, diabetes, skin hyperpigmentation, arthralgia, and hypogonadism. The best screening tools are serum transferrin saturation, ferritin, and iron levels. Ferritin levels above 300 ng/mL for men and 200 ng/mL for premenopausal women are of concern.3 Periodic phlebotomy is the most effective method of depleting iron stores and is the treatment of choice for hereditary hemochromatosis. Treatment for those with secondary hemochromatosis does not include phlebotomy because of the underlying anemia. Administration of a chelating agent is the standard therapy.4

Because the early symptoms of hemochromatosis are often nonspecific, the diagnosis is frequently overlooked until significant organ failure has developed.4 The primary cause of death in these patients is usually liver cancer related to cirrhosis.5 Patients who are candidates for liver transplantation should be referred for evaluation. For patients with severe cardiomyopathy, in addition to end-stage liver disease, combined transplantation may be performed. We report a successful case for a patient with hereditary hemochromatosis who received a combined heart-liver transplantation. Informed written consent by the patient was obtained before submission of this case report.

Case Report

A middle-aged man was transferred to our facility with poor hemodynamics consistent with cardiogenic shock for further treatment of heart failure and heart transplant evaluation. His medical history was unremarkable except for remote alcohol use and smoking for 10 to 15 years before his diagnosis of cardiomyopathy. He had numerous emergency department visits and hospitalizations for atrial and ventricular arrhythmias, leading to the placement of an implantable cardioverter defibrillator. Upon transfer, echocardiogram showed a left ventricular ejection fraction of less than 0.20. Dobutamine and nitroprusside intravenous infusions were initiated, and the patient remained dependent on inotropes.

Transplant evaluation included the laboratory values: serum ferritin 4880 ng/mL (normal 30-400 ng/mL) and transferrin saturation of 98% (normal 13%-45%). Mild thrombocytopenia was noted, which was felt to be medication related and not a concern for transplantation. His endomyocardial biopsy revealed iron deposition and liver biopsy showed cirrhosis, chronic hepatitis, and extensive iron accumulation. The initial diagnosis of hemochromatosis was made.

After lengthy discussion between the cardiology and hepatology services, it was decided that the patient would benefit from a combined heart-liver transplantation. He was listed and underwent a combined heart-liver transplantation 18 days later, with the understanding that he would need lifelong phlebotomy to prevent posttransplant deposition of iron within the organs. Multiple complications occurred after the patient's surgery, including pneumonia, pneumothorax, persistent bilateral pleural effusions with subsequent placement of chest tubes, significant ascites requiring paracentesis, bile leak, abdominal abscess, hyperglycemia, severe debilitation, and liver rejection treated with intravenous methylprednisolone (Solu-Medrol).

The patient and his wife became tearful, helpless, and frustrated at times because of his prolonged recovery. A psychiatric liaison nurse was consulted to offer emotional support. He was discharged home 6 weeks after surgery with a supplemental percutaneous endoscopie gastrostomy tube feeding, home oxygen, and physical therapy. His diet instruction included avoiding alcohol and iron-fortified foods and supplements, as well as limiting red meats and vitamin C.'·6 His siblings were encouraged to be screened for hemochromatosis. One brother was diagnosed with hereditary hemochromatosis and therapeutic phlebotomy was initiated. The other brother was found to be a carrier.

Discussion

According to the United Network for Organ Sharing, 26 combined heart-liver transplantations have been performed in the United States as of March 2003, with survival rate of 81 % at 1 year and 72% at 4 years.7 Only a few cases have been performed for the indication of hemochromatosis.8 Because there is no process for listing combined organs at this time, patients requiring a heart and liver transplant are listed separately for each organ. Patients considered for this procedure should meet the criteria for transplantation for each organ.9

After the patient's discharge, therapeutic phlebotomy was initiated. His ferritin level is maintained between 50 and 100 ng/mL, and his hematocrit level between 0.35 and 0.39. These laboratory values must be monitored to ensure phlebotomy treatments are performed when indicated (a 500-mL phlebotomy removes 250 mg of iron4). Phlebotomy improves many of the problems associated with hemochromatosis (eg, fatigue, hepatomegaly, abdominal pain, skin hyperpigmentation, diabetes, and cardiomegaly), but not cirrhosis, arthropathy, thyroid dysfunction, or hypogonadism.3

Immunosuppression management is slightly different in our heart and liver transplant programs. Prednisone is tapered more rapidly in liver transplant recipients to promote anastomosis healing and lessen steroid-related complications after surgery. It is tapered slower in heart transplant recipients because of concerns for rejection. Although the patient experienced a liver rejection episode early on, research has shown the liver, when transplanted with other solid organs, provides an immunoprotective effect resulting in a lower than expected incidence in cellular rejection.9

Communication between physician and transplant coordinators is necessary for managing these patients. The heart transplant team took on the primary role of managing the patient's posttransplant immunosuppression, hypertension, hyperglycemia, and other medical issues. Two and a half years after transplantation, the patient has had no further rejection and has normal heart and liver function. His coronary arteries have remained normal on yearly angiograms. He is currently working full-time and volunteers within the transplant community.

We, as transplant coordinators and nurses, may encounter patients presenting for transplant evaluation with hemochromatosis and multiple end-organ damage. Beginning education on hemochromatosis and phlebotomy at this time is important to ensure that patients will understand their condition and what will be involved after transplantation. Although a limited number of combined heart-liver transplantations have been performed, successful outcomes can be achieved with close monitoring and a multidisciplinary team approach. Collaboration between specialties is essential for determining the best plan of patient treatment and nursing care.

References

1. Olynyk JK, Cullen DJ, Aqila S, et al. A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med. 1999;341:718-724.

2. Hash RB. Hereditary hemochromatosis. J Am Board Fam Pract. 2001;4:266-273.

3. Pearlman BL. Hereditary hemochromatosis: early detection of a common yet elusive disease. Consultant. February 2002;42:237-250.

4. Keller JF, Blausey LA. Diagnosis, treatment, and nursing management of the patient with hemochromatosis. Oncol Nurs Forum. 1992;19:1359-1365.

5. Schofield RS, Aranda JM, Hill JA, Streiff R. Cardiac transplantation in a patient with hereditary hemochromatosis: role of adjunctive phlebotomy and erythropoietin. J Heart Lung Transplant. 2001;20:696-698.

6. Cotoia JB. Diagnosing hemochromatosis. J Am Acad Nurs Pract. 1998;10:323-327.

7. United Network for Organ Sharing Web site. Available at: http://www.optn.org. Accessed October 2003.

8. Befeler AS, Schiano TD, Lissoos TW, et al. Successful combined liver-heart transplantation in adults: report of three patients and review of the literature. Transplantation. 1999;68:1423-I426.

9. Tazbir JS, Cronir DC. Indications, evaluations, and postoperative care of the combined liver-heart transplant recipient. AACN Clin Issues. 1999;10:240-252.

Hwajoo Haynes, RN, MSN, CCTC, Jennifer Farroni, RN, MSN, ANP, CCTC

The Medical University of South Carolina, Charleston, SC (HH), The Ohio State University Medical Center, Columbus, Ohio (JF)

To purchase reprints, contact:

The InnoVision Group

101 Columbia, Aliso Viejo, CA 92656

Phone (800) 809-2273 (ext 532) or

(949) 448-7370 (ext 532)

Fax (949) 362-2049

E-mail reprints@aacn.org

Copyright North American Transplant Coordinators Organization Mar 2004
Provided by ProQuest Information and Learning Company. All rights Reserved