Split-liver transplantation: a comparison of ex vivo and in situ techniques.

BACKGROUND/PURPOSE: The expanding applicability of liver transplantation as treatment for end-stage liver disease has fostered a disproportionate increase in liver transplant candidates in the face of an unchanging pool of donor organs. This has resulted in disparities in pretransplant waiting times and deaths. The splitting of a liver allograft allows for the transplantation of 2 recipients, usually an adult and a child, thus providing a means to expand the cadaveric donor pool. METHODS: The authors present their results on the performance of an ex vivo (back table) split and in situ (in a hemodynamically stable cadaveric donor) split to evaluate safety, applicability, and effectiveness. Between November 1989 through April 1998, 54 split-liver transplant recipient operations were performed (24 pediatric and 30 adult). Thirty donors were procured: the ex vivo splitting yielded 25 grafts from 13 donors (donor age, 24.6+/-11 years), and the in-situ technique yielded 29 grafts from 17 donors (mean donor age of 25.5+/-10.4 years). Five donors involved interinstitutional sharing for which the left side of the graft was kept at the host hospital and the right side grafts were utilized at our center. RESULTS: Overall 1-year patient survival was 85%, with a graft survival of 72%. Patient survival was similar with ex vivo (74%) as compared with the in situ splitting group (96%; P = .06), as was graft survival in ex vivo (61 %) versus in situ (81%) splitting (P = .15). The pediatric population benefited most from the in situ technique, with a 1-year patient survival rate of 100% with the in situ technique versus the ex vivo technique survival rate of 64% at 1 year (P = .02). The 1-year graft survival comparing these 2 techniques was 83% for the in situ group versus 45% for the ex vivo group. Analysis of the program evolution of split-liver transplantation suggested a time-dependent learning curve, which was applicable to surgical splitting technique, implantation, and recipient selection. CONCLUSIONS: The principle of splitting livers from cadaveric donors is fundamentally sound and technically feasible. The authors' outcomes analysis using 2 different procurement techniques suggests that the in situ technique is clinically efficacious, can be used alternatively with the ex vivo technique, and is comparable to whole-liver allograft transplantation.

The influence of hepatitis C virus genotypes on the outcome of liver transplantation.

BACKGROUND: The aim of this study was to report the influence of hepatitis C virus (HCV) genotypes and HLA matches on the outcome of liver transplantation, hepatitis recurrence, and progression to cirrhosis after transplantation. METHODS: HCV genotypes were determined from pretransplantation sera and/or liver explant tissues from 202 patients with HCV-related end-stage liver disease. One hundred fifty patients with known infecting genotype for whom posttransplantation biopsy specimens were available or who had normal results of liver injury tests constituted the group analyzed. Patients were followed up for up to 4.5 years. Hepatitis activity index scores at the time of disease recurrence were used to assess disease activity. Cirrhosis was diagnosed by using histological evidence. The number of HLA matches with respect to A, B, DR, and DQ loci was determined. RESULTS: The rates of hepatitis recurrence were 25% and 75% at 1 year and 4 years, respectively; Kaplan-Meier survival analysis did not reveal significant differences between the infecting genotypes with respect to overall rates of survival or recurrence of hepatitis. At hepatitis recurrence, hepatitis activity index scores did not differ between the genotype groups. The distribution of infecting genotypes among the 7 patients who developed cirrhosis is reflective of pretransplantation distribution. Neither HLA site-specific nor total matches affected the rates of survival or disease recurrence. CONCLUSIONS: The infecting HCV genotype had no influence on the incidence or severity of recurrent hepatitis, rate of survival, or development of cirrhosis. HLA matching does not influence transplantation outcome for HCV-related disease.

Treatment of fibrolamellar hepatoma with subtotal hepatectomy or transplantation.

Fibrolamellar hepatoma (FL-HCC) is an uncommon variant of hepatocellular carcinoma (HCC), distinguished by histopathological features suggesting greater differentiation than conventional HCC. However, the optimal treatment and the prognosis of FL-HCC have been controversial. Follow-up studies are available from 1 year to 27 years, after 41 patients with FL-HCC were treated with partial hepatectomy (PHx) (28 patients) or liver transplantation (13 patients). In this retrospective study, the effect on outcome was determined for the pTNM stage and other prognostic factors routinely recorded at the time of surgery. Cumulative survival at 1, 3, 5, and 10 years was 97.6%, 72.3%, 66.2%, and 47.4%. Tumor-free survival at these times was 80.3%, 49.4%, 33%, and 29.3%. The TNM stage was significantly associated with tumor-free survival. Patients with positive nodes had a shorter tumor-free survival than those with negative nodes (P < .015). Patient survival was most adversely affected by the presence of vascular invasion (P < .05). FL-HCC is an indolently growing tumor of the liver, which usually was diagnosed in our patients at a stage too advanced for effective surgical treatment of most conventional HCC. Nevertheless, long-term survival frequently was achieved with aggressive surgical treatment. When a subtotal hepatectomy could not be performed, total hepatectomy (THx) with liver transplantation was a valuable option.

The prediction of risk of recurrence and time to recurrence of hepatocellular carcinoma after orthotopic liver transplantation: a pilot study.

Orthotopic liver transplantation (OLTx) in the presence of hepatocellular carcinoma (HCC) has been complicated by high recurrence rates. The ability to determine the risk and timing of HCC recurrence on an individual basis would greatly aid in the candidate selection process resulting in a more efficient use of donated organs and allow the individualization and better evaluation of adjuvant chemotherapy. The 214 patients who underwent OLTx in the presence of HCC were analyzed. From the 178 patients who survived more than 150 days, 71 (40%) have suffered HCC recurrence. Based on five risk factors, that is, gender, tumor number, lobar tumor distribution, tumor size, grade of vascular invasion, artificial neural network models predicting the likelihood of HCC recurrence within 1, 2, and 3 consecutive years after transplantation were developed. Based on model predictions, those combinations of risk factors that should/should not lead to recurrence were generated, allowing stratification of patients into the following three groups: 1) patients who should not suffer HCC recurrence and who should not need adjuvant therapy, 2) patients who will suffer recurrence and for whom postoperative chemotherapy significantly prolonged survival (but did not prevent recurrence), and 3) patients who may or may not suffer HCC recurrence and whose recurrence may be prevented by adjuvant chemotherapy. The outcome of OLTx for patients with HCC can be prognosticated based on a number of clinical variables. If verified through multicenter trials, these models could be made available to transplantation programs performing OLTx in the presence of HCC.

Distribution of infecting hepatitis C virus genotypes in end-stage liver disease patients at a large American transplantation center.

The distribution of hepatitis C virus (HCV) genotypes was studied in 202 anti-HCV-positive liver transplant candidates with end-stage liver disease. HCV sequences were successfully amplified from 185 patients: In the first 100, the genotype was determined by direct sequencing in the NS5 region, and in the remaining 85, type-specific primers were used for genotyping. Eighty-five patients (46.0%) were infected with type 1a HCV strains, 52 (28.1%) with type 1b, 14 (7.6%) with type 2b, 13 (7.0%) with type 4, 5 (2.7%) with type 3a, 2 (1.1%) with type 2a, and 1 (0.5%) with type 2c. Thirteen HCV-positive patients (7.0%) could not be genotyped. The relatively low prevalence of genotype 1b in this population of end-stage liver disease patients speaks against postulated higher pathogenicity of this genotype.

Cadaveric liver donors; what are the limits?

The current crisis in organ availability will only be solved by aggressive and innovative solutions. One approach, outlined here, is to more carefully assess current donors and determine how to safely "push the limits" of acceptable cadaveric liver donors. Our experience, as well as that of others, indicates that donors with these higher risk factors may be used in certain carefully defined situations. The key elements to an appropriate use of these donors are careful donor and recipient assessment, and avoiding the presence of multiple risk-factors. These guidelines form a foundation for continuing assessment of methods to increase, in an incremental fashion, the number of cadaver livers successfully transplanted.

Experience with liver and kidney allografts from non-heart-beating donors.

Given the shortage of cadaveric organs, we began a study utilizing NHBD for OLTx and KTx. There were 24 NHBD between January 1989 and September 1993. These donors were divided into 2 groups: uncontrolled NHBD (G1) (n = 14) were patients whose organs were recovered following a period of CPR; and controlled NHBD (G2) (n = 10) were patients whose organs were procured after sustaining cardiopulmonary arrest (CA) following extubation in an operating room setting. Eight kidneys and 5 livers were discarded because of macroscopic or biopsy findings. In G1, 22/27 (81.5%) kidneys were transplanted; 14/22 (64%) developed ATN; 20/22 (95%) recipients were off dialysis at the time of discharge. With a mean follow-up of 32.7 +/- 21.1 months, sixteen (73%) kidneys are still functioning, with a mean serum creatinine of 1.7 +/- 0.6 mg/dl. The one-year actuarial patient and graft survivals are 95% and 86%. In G2, 17/20 (85%) kidneys were transplanted; 13/17 (76%) kidneys experienced ATN. All patients were off dialysis by the time of discharge. With a mean follow-up of 17.6 +/- 15.4 months, twelve (70%) kidneys are still functioning, with a mean serum creatinine of 2.5 +/- 2.1 mg/dl. The one-year actuarial patient and graft survivals are 94% and 82%, respectively. In G1, 6/10 (60%) livers were transplanted; 3/6 (50%) livers functioned, the other 3 patients required ReOLTx in the first week postoperatively because of PNF (n = 2) and inadequate portal flow (n = 1). Two functioning livers were lost due to HAT (n = 1) and CMV hepatitis (n = 1). In G2, 6/7 (85.7%) livers were transplanted. All the livers (100%) functioned. 2 patients required ReOLTx for HAT at 0.9 and 1.0 months. Both patients eventually died. One patient with a functioning liver died 2 months post OLTx. The remaining 3 patients are alive and well at 27 months of follow-up. This study shows that the procurement of kidneys from both uncontrolled and controlled NHBD leads to acceptable graft function despite a high incidence of ATN. The function of liver allografts is adequate in the controlled NHBD but suboptimal in the uncontrolled NHBD, with a high rate of PNF.

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.

Small intestinal transplantation in humans with or without the colon.

Under FK506-based immunosuppression, 16 cadaveric small bowel transplantations were performed in 15 recipients with (n = 5) or without (n = 11) the large bowel. Twelve (80%) patients are alive after 1.5 to 19 months, 11 bearing their grafts, of which 4 include colon. The actuarial one-year patient and graft survivals are 87.5% and 65.9%, respectively. Five grafts were lost to acute (n = 4) or chronic (n = 1) rejection, and 3 of these patients subsequently died after 376, 440, and 776 days total survival. Six recipients developed severe CMV infection that was strongly associated with seronegative status preoperatively and receipt of grafts from CMV positive donors; 3 died, and the other 3 required prolonged hospitalization. Currently, 9 patients are free from TPN 1-18 months postoperatively, 2 require partial TPN, and one has returned to TPN after graft removal. The results show the feasibility of small bowel transplantation but emphasize the difficulty of managing these recipients not only early but long after their operation.