Disease gravity and urgency of need as guidelines for liver allocation

One thousand one hundred and twenty-eight candidates for liver transplantation were stratified into five urgency-of-need categories by the United Network for Organ Sharing (UNOS) criteria. Most patients of low-risk UNOS 1 status remained alive after 1 yr without transplantation; the mortality while waiting was 3% after a median of 229.5 days. In contrast, only 3% of those entered at the highest risk UNOS 5 category survived without transplantation; 28% died while waiting, the deaths occurring at a median of 5.5 days. The UNOS categories in between showed the expected gradations, in which at each higher level fewer patients remained as candidates throughout the 1-yr duration of study while progressively more died at earlier and earlier times while waiting for an organ. In a separate study of posttransplantation survival during the same time period, the best postoperative results were in the lowest-risk UNOS 1 and 2 patients (88% combined), and the worst results were those in UNOS 5 (71%). However, a relative risk cross-analysis showed that a negative benefit of transplantation may have been the result in terms of 1-yr survival for the low-risk elective patients, but that a gain in life extension was achieved in the potentially lethal UNOS categories 3, 4 and 5 (greatest for UNOS 3). These findings and conclusions are discussed in terms of total care of patients with liver disease, and in the context of organ allocation policies of the United States and Europe

Intestinal transplantation in children under FK 506 immunosuppression

Intestinal transplantation, solitary (n = 3) or in combination with the liver (n = 7), was performed in 10 pediatric patients with intestinal failure. The liver was only replaced if there was liver failure and portal hypertension. Immunosuppression was based on FK 506. Two patients died, one of graft-versus-host disease and one of lymphoproliferative disease. One patient was still in the intensive care unit 1 month posttransplantation due to perioperative complications. The function of the intestinal grafts in the remaining patients is normal. All nutrition and medications including immunosuppression are being administered enterally. This series indicates that small bowel transplantation, alone or in combination with the liver, is feasible in pediatric patients. © 1993

Lack of association between HLA antigen DR3 and α<inf>1</inf> deficiency in liver transplant recipients

The relationship between α1-antitrypsin deficiency (α-ATD) and the HLA antigen system was studied in 32 liver transplant recipients. Despite previous reports of an association of HLA antigen DR3 with homozygosity for α-AT ZZ, no such association was seen in this population of α-ATD homozygous ZZ patients with advanced hepatic disease. Thus, the reported association of HLA class II antigens and homozygosity for the Z allele for α-AT may be an artifact of either a small study population or geographic inbreeding and a coincidental association of certain HLA antigens with the presence of homozygosity for the Z allele of α-AT. © 1993 Plenum Publishing Corporation

Alpha-1-antitrypsin phenotypes in adult liver disease patients

Alpha-1-antitrypsin (AAT) is an important serine protease inhibitor in humans. Hereditary alpha-1-antitrypsin deficiency (AATD) affects lungs and liver. Liver disease caused by AATD in paediatric patients has been previously well documented. However, the association of liver disease with alpha-1-antitrypsin gene polymorphisms in adults is less clear. Therefore, we aimed to study AAT polymorphisms in adults with liver disease. We performed a case-control study. AAT polymorphisms were investigated by isoelectric focusing in 61 patients with liver cirrhosis and 9 patients with hepatocellular carcinoma. The control group consisted of 218 healthy blood donors. A significant deviation of observed and expected frequency of AAT phenotypes from Hardy-Weinberg equilibrium (chi-square = 34.77, df 11, P = 0.000) in the patient group was caused by a higher than expected frequency of Pi ZZ homozygotes (f = 0.0143 and f = 0.0005, respectively, P = 0.000). In addition, Pi M homozygotes were more frequent in patients than in controls (63% and 46%, respectively, P = 0.025). Our study results show that Pi ZZ homozygosity in adults could be associated with severe liver disease. Presence of Pi M homozygosity could be associated with liver disease via some mechanism different from Z allele-induced liver damage through accumulation of AAT polymers

Hepatic Transplantation

Liver transplantation has evolved to become a routine procedure. Donor shortage still limits access. Survival is now approaching 70% or more at 10°years for non-malignant disease. Few contraindications exist. Hepatitis B recurrence can be prevented with antiviral agents. Patients with alcohol-related cirrhosis undergo stringent evaluation, which includes monitoring of abstinence and psychosocial assessment. Hepatocellular carcinoma is an indication for transplantation, providing tumour burden is moderate; currently, a single lesion 5°cm or less diameter or three lesions each 3°cm or less diameter, without vascular invasion or extrahepatic spread based on pretransplant imaging. Allocation of donors and prioritization of recipients varies according to country. Medical urgency, based on likelihood of dying without transplantation, is the principal criterion in the USA and Eurotransplant area, which use the Model for End Stage Liver Disease (MELD score). Some countries take into account a utility criterion, that is expected survival after transplantation. Transplant benefit models are being developed, which estimate the greatest difference between pre- and post-transplantation survival, to determine priority for allocation. The number of whole grafts from brain stem dead, heart beating donors is falling. Reduced split and liver donor grafts, which are anatomical lobes or adjacent segments, allow greater rates of transplantation. Non-heart beating donors are increasingly used. The most frequent, early complication is infection; vascular complications have diminished. Biliary complications are frequent with reduced, split or live donor grafts. Ischaemic graft damage is more frequent with non-hearting beating donors. Late complications are related to cardiovascular morbidity due to an increased frequency of hypertension, diabetes and hyperlipidaemia. These modifiable diseases are due to immunosuppressive therapy. Other complications include malignancy, particularly skin cancer, but also lymphoproliferative disorders. Recurrent disease, particularly hepatitis C, but also hepatocellular carcinoma and primary sclerosing cholangitis, are major causes of late death. © 2011 Blackwell Publishing Ltd