Department of Nephrology, Rabin Medical Center (Campus Golda) 1 Liver Transplantation Unit, Rabin Medical Center (Campus Beilinson), Petach Tikva, Israel
Sir,
Organ shortage has become the most vexing problem in liver transplantation, with 1025% of patients dying while awaiting transplantation [1]. Therefore, new strategies have been introduced in an attempt to narrow the gap between demand and supply of organs for such transplantations [2]. The liver is a `privileged' organ, with a dual blood supply, rarely involved by atherosclerosis, and with relatively preserved function at old age. Therefore, in adults, the idea of using `marginal' donors for liver transplantation has come into prominence over the last decade [36]. Usually, these are elderly patients with medical problems, thought originally to be unsuitable for organ harvesting, but who are now felt to be acceptable for liver transplantation. But what of chronically dialysed patients? Could the use of liver allografts from dialysed patients be safe? The case presented here may, in a small way, answer this question.
Case:
A 60-year-old woman was admitted to hospital with a massive intracerebral haemorrhage. Relevant past history included hypertension and end-stage renal failure, both diagnosed in September 1993. The patient did not have ADPKD or known AV malformations. Chronic haemodialysis was commenced in October 1993. During this period, a vague history of alcoholic abuse was obtained from the family. Mild elevations of serum liver enzymes were noted (bilirubin 0.7 mg/dl; SGOT 5060 U/l; SGPT 35-50 U/l; normal alkaline phosphate level). All acute viral hepatitis serology (HAV IgM, HbsAg, PCR HCV) was negative. By March 1994, all liver function tests were normal, and they remained so for the next 4 years.
From 1994 to 1995, symptomatic anaemia necessitated transfusions of 20 units of packed red blood cells. Recombinant human erythropoietin was started in 1996 and in January 1997 intravenous iron was added. Serum ferritin levels, which had peaked at 950 ng/ml in April 1996, dropped to 470 ng/ml by July 1997.
On admission the patient was intubated and treated supportively with fluids and dopamine (5 µg/kg/min). Repeated liver function tests were normal and viral hepatitis serology was negative. Brain death was pronounced 18 h after admission, and immediately thereafter family consent for liver harvesting was obtained. Because of the patient's past history, a liver biopsy was performed during hepatectomy. On frozen section, normal liver architecture, but with diffuse haemosiderosis in iron-stained Kuppfer cells and hepatocytes, was seen. This was felt to be secondary to previous blood transfusions and iron supplementation, and did not serve as a contraindication for transplantation.
The recipient was a 57-year-old man with end-stage liver failure, secondary to active hepatitis B. Cold ischaemic time was 6 h. N-acetylcysteine was started immediately after reperfusion and continued for 24 h. The graft showed immediate function, with adequate bile production and spontaneous correction of coagulopathy. Peak aminotransferase levels were below 1000 U/l. Mild cellular rejection was treated successfully at day 14. One month after transplantation the patient was discharged from hospital. Today, at 9 months post-transplantation, the patient maintains normal graft function.
Comment:
The few absolute contraindications for liver transplantation include severe macrosteatosis, liver necrosis or hepatitis in the donor liver [7]. In 1991, Belzer's group showed that if donor livers with biopsy findings of severe fatty liver infiltration, hydropic degeneration or centrilobular necrosis would not have been transplanted, then primary nonfunction of the transplant could have been reduced from 11% to 5% [7]. Other donor risk factors may also be associated with an increased risk for primary nonfunction: advanced age, obesity, acute infectious problems, hypotension or hypoxia. However, each of these factors, and even the presence of cardiovascular disease or chronic renal failure are not absolute reasons to discard these so-called `marginal' liver donors [5]. As early as 1987, Makowka et al. showed that such `marginal' donors, when compared to `acceptable' donors, had no increase in primary graft nonfunction and no overall difference in 2-year patient survival [3].
Up to 10% of dialysed patients die from acute cerebrovascular diseasemajor ischaemic strokes and intracranial haemorrhages [8]. These patients should be considered as potential liver donors, especially if they are free of known liver disease. A full viral hepatitis screen should be performed immediately. These patients should be treated aggressively in the first few hours after suffering a major cerebrovascular accident. Blood pressure should be maintained with blood products, colloids, and low-dose dopamine. High-dose dopamine is to be avoided as it decreases portal venous blood flow [4]. Hypervolaemia should also be avoided in order to prevent acute liver oedema [4]. If dialysis is indicated, for whatever reason, then it should be performed. Finally, in any dialysed patient, it would be wise to perform a liver biopsy at harvesting.
Pretransplant liver biopsies have become an accepted part of donor hepatectomies [7,9]. Acceptable cold ischaemic time for the liver has now reached 12 h. Therefore, when warranted, frozen section of any liver is feasable [7]. Indeed, discarding unacceptable livers, after biopsy, is a far safer option for the patient than transplantation of such a liver, as it may prevent the catastrophic possibility of primary nonfunction [7,9,10]. In 1990 Kakizoe et al. described their experience with 38 frozen section liver biopsies in donors. Twenty seven livers were subsequently not transplanted [9].
Liver biopsy in this patient revealed hepatic hemosiderosis. This histopathological finding is not a contraindication to liver harvesting. As early as 1980, Ali et al. demonstrated that nearly 50% of his studied dialysed patients had significant hepatic haemosiderosis, but with only a minor degree of liver fibrosis [11]. All five patients with serum ferritin levels of over 1000 ng/ml had massive liver iron deposits. In 1990, Fleming et al. showed that all dialysed patients who had received long-term parenteral iron dextran, had hepatic iron deposition [12]. Again, the risk of liver damage from the iron deposition was low [12].
In conclusion, this brief communication shows, for the first time, that using a heart-beating, liver allograft from a chronically dialysed patient is possible. With the ever-growing shortage of organs available for transplantation, there is ample reason for the clinical nephrologist to regard the dialysis patient, at the proper time, as a potential organ donor. Even if dialysis patients are to remain `marginal' donors, this in itself is not a reason to exclude them from entering the pool of possible organ donors. For the patient suffering from severe and irreversible liver failure, receiving a good liver transplantation is life-saving, `even' if it comes from a dialysis patient.
Acknowledgments
Our extremely sincere thanks to Ronit Reches RN, Transplantation Coordinator, for the Rabin Medical Center (Campus Golda). Without her devotion and her hard work this transplantation would not have been possible.
References