Kidney transplant from donors with hepatitis C virus (HCV) antibody has been limited to HCV viremic recipients only, due to concern of the HCV transmission. However, the new antiviral medications provide an opportunity to expand the utilization of these donors. To study the risk of HCV transmission in kidney transplantation, we used discarded donor kidneys and determined HCV RNA levels by quantitative real-time PCR in bilateral (right and left) kidney biopsies and plasma from 14 HCV antibody-positive donors (sensitivity: 15 international unit (IU)/mL plasma; 1.8 IU/50 nL kidney). In three NAT-negative donors, HCV RNA was negative in plasma and kidney. In all 11 NAT-positive donors, HCV RNA was positive in plasma (range: 5807-19 134 177 IU/mL) but negative in six kidneys from four donors with plasma HCV RNA <1.5 million IU/mu L HCV RNA correlated between right and left kidneys (P = 0.75) and between kidney and plasma (r = 0.86). When normalized by volume, HCV RNA median (range) was 49 (0-957) IU/50 nL plasma and 1.0 (0-103) IU/50 nL kidney, significantly lower in kidney (P = 0.005) than in plasma (14-fold). Plasma HCV RNA can be used to predict the kidney HCV load. Future studies are needed if plasma/kidney HCV levels can be used to stratify donors for transmission risk and recipients for post-transplant management in extended utilization of HCV antibody-positive donors.
Purpose. We present a retrospective study describing the perioperative use of continuous renal replacement therapy (CRRT) for orthotopic liver transplantation (OLT).Materials and Methods. We retrospectively reviewed the clinical course of patients who underwent OLT with the perioperative use of CRRT. The following variables were recorded: Gender, age, indication for transplantation, time when CRRT was initiated, postoperative need for CRRT, and the patient and organ (liver, kidneys) outcome up to 1 year after transplantation.Results. Among 105 patients who underwent OLT from 2006 to 2010; we used CRRT in 12 cases (11.4%) perioperatively, including 9 (8.3%) patients intraoperatively. Perioperative CRRT was employed for volume, electrolyte, and/or pH management. All patients who underwent CRRT perioperatively were alive at 1 month, 10 (83.3%), at 3 and 6 months and 9 (75%) at 1 year after OLT. Only 1 surviving patient (8.3%) required renal replacement therapy at 1 month after surgery. Renal replacement therapy was not required in any surviving patient up to 12 months posttransplantation.Conclusion. Perioperative and especially intraoperative use of CRRT therapy can potentially improve the outcomes of patients undergoing OLT.
Donation after cardiac death (DCD) liver transplantation is increasing largely because of a shortage of organs. However, there are almost no data that have specifically assessed the impact of using DCD livers for HCV patients. We retrospectively studied adult primary DCD liver transplantation (630 HCV, 1164 non-HCV) and 54 129 donation after brain death (DBD) liver transplantation between 2002 and 2009 using the UNOS/OPTN database. With donation after brain death (DBD) livers, HCV recipients had significantly inferior graft survival compared to non-HCV recipients (p < 0.0001). Contrary to DBD donors, DCD livers used in HCV patients showed no difference in graft survival compared to non-HCV patients (p = 0.5170). Cox models showed DCD livers and HCV disease had poorer graft survival (HR = 1.80 and 1.28, p < 0.0001, respectively). However, the hazard ratio of DCD and HCV interaction was 0.80 (p = 0.02) and these results suggest that DCD livers on HCV disease do not fare worse than DCD livers on non-HCV disease. The graft survival of recent years (2006-2009) was significantly better than that in former years (2002-2005) (p = 0.0482). In conclusion, DCD liver transplantation for HCV disease showed satisfactory outcomes. DCD liver transplantation can be valuable option for HCV related end-stage liver disease.
Background: Perihilar cholangiocarcinoma (PHC) is a deadly disease within a few months. Only complete resection offers a chance of cure with reported 25-45% survival at 5 years. However, the tumor mass spreading along the biliary tree and vascular invasion often prevent surgical resection. The Mayo Clinic group introduced a new approach using liver transplantation (LT) after neoadjuvant chemoradiation in highly selected patients presenting with unresectable PHC ≤ 3cm and in absence of lymph nodes (LN) invasion. Among few centers, we developed a similar protocol in 2001 including patients beyond the Mayo criteria. Here, we report our indications and results within and beyond Mayo criteria. Methods: Patients with unresectable PHC, who were included in our neoadjuvant chemo-radiotherapy protocol followed by either living donor liver transplantation (LDLT) or orthotopic liver transplantation (OLT) were evaluated regarding indication and results from 2001 - 2012. While our protocol is based on Mayo criteria, we omitted brachytherapy and used extended criteria in a few cases. Our protocol was approved by our local IRB. Results: Among 351 LT performed during the same period, 11 were performed for unresectable PHC under our neodjuvant protocol. The majority were male (n=8; 73%) and the population median age was 48 years (R: 36-65). Five patients underwent LT outside the Mayo criteria (4 LDLT and 1 OLT); two patients had micro-metastasis in one LN, one had previous major liver resection with questionable R1 margin, another had positive margin in the vena cava confirmed after LT, and one underwent extensive surgery including surgical placement of a stent in the biliary system at another institution. Three patients outside of Mayo died from tumor recurrence between 8 and 20 months after LT, while 2 are alive, one at 1 year, but with recurrent disease, and one (previous surgery and stent, but N0) is alive without recurrence after 5-years. Among the remaining 6 patients within the selection criteria, 3 underwent LDLT and the other 3 OLT. Among those patients, five are alive without evidence of recurrent disease, while one died from sepsis 47 days after LDLT. Overall survival rate at 3 years was 80% within Mayo criteria vs. 30% outside. Conclusion: LT after neodjuvant chemoradiation may enable cure in patients with unresectable PHC with results possibly superior to resection. Previous resection with R1 margin and positive LN, even with micro-metastasis, are absolute contraindication for LT, which support the Mayo protocol. LDLT may be an important approach to minimize the impact on the waiting list and secure an optimal timing for the LT.
We present a case of severe hyperammonemia with subsequent brain herniation in an adult man after renal transplantation. After successful surgery and an initially uneventful postoperative course, the patient developed significant mental status changes associated with seizure activity. His condition rapidly deteriorated, requiring mechanical ventilation and cardiovascular support. Laboratory studies at that time demonstrated an increased serum ammonia level without evidence of liver or kidney dysfunction. Further investigation revealed an increased orotic acid level in the urine, suggesting a urea cycle disorder (UCD). Despite aggressive therapy, the patient's condition continued to deteriorate. Magnetic resonance imaging demonstrated severe brain edema with no cerebral perfusion; after consultation with the family, care was withdrawn. The combination of hyperammonemia and elevated urine orotic acid with normal liver and kidney function suggested a UCD. It is important to note that patients with a UCD may be free of symptoms for many years. Several factors are able to trigger the disease in adulthood, leading to encephalopathy and death. In this case, the patient's seizures were initially assumed to be a side effect of immunosuppressive therapy. Further diagnostic measures were only performed late in the course of the disease, which delayed the diagnosis of UCD.
Long-term benzimidazole therapy benefits patients with non-resectable alveolar echinococcosis (AE). Methods to assess early therapeutic efficacy are lacking. Recently, AE liver lesions were reported to exhibit increased F-18-fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET). To assess the value of FDG-PET for diagnosis and follow-up of AE patients.
BACKGROUND:Although selective intrahepatic arterial chemotherapy successfully downstaged irresectable colorectal liver metastases in a previous study, curative resection was rarely possible, as the remnant healthy liver volume was inadequate. This pilot study evaluated the efficacy of concomitant unilateral portal vein ligation and selective intrahepatic arterial chemotherapy in downstaging such tumours.METHODS:The study included 11 patients with irresectable colorectal liver metastases. Selective intrahepatic arterial chemotherapy was delivered using a subcutaneous pump, and each patient underwent concomitant unilateral portal vein ligation of the hemiliver judged to have the higher tumour load. Chemotherapy involved serial administration of floxuridine for 2 weeks every 4 weeks.RESULTS:All patients developed significant atrophy of the hemiliver subjected to portal vein ligation and contralateral hypertrophy. There was no increase in tumour load within 6 months of therapy, and the load decreased by 60 per cent in the hemiliver ipsilateral to the ligated vein. At 3 months, six of 11 patients showed a significant response to chemotherapy. In four patients, downstaging allowed curative resection after only three cycles of chemotherapy. These patients survived at least 20 months afterwards.CONCLUSION:Combined unilateral portal vein ligation and selective intrahepatic arterial chemotherapy produced substantial atrophy of the ipsilateral hemiliver along with contralateral hypertrophy, without increased tumour growth in the regenerating hemiliver.
BACKGROUND:Alveolar echinococcosis is a rare disorder, which makes a comparison of different treatment modalities within a clinical trial difficult to perform. Data prospectively recorded over a period of 25 years were used to evaluate three therapeutic strategies: benzimidazole therapy alone, complete 'curative' resection followed by 2 years of adjuvant benzimidazole treatment, and partial debulking resection followed by continuous administration of a benzimidazole.METHODS:Details of 113 patients with hepatic alveolar echinococcosis treated between 1976 and 2003 were analysed. Kaplan-Meier survival curves were constructed and, using a Cox regression model, patient age, year of initial treatment and PNM stage were entered as co-variates in the analysis.RESULTS:Kaplan-Meier overall survival curves stratified for treatment strategy indicated an improved long-term survival in patients undergoing the debulking procedure (P = 0.061) or curative resection (P = 0.002) compared with benzimidazole therapy alone. However, when PNM stage, patient age and year of initial treatment were introduced into the analysis, there was a trend for survival advantage only with curative resection (P = 0.07 versus benzimidazole alone). Debulking resulted in a higher rate of progression of hepatic echinococcosis than curative surgery (P = 0.008). The incidence of parasite-related complications was similar for debulking resection and benzimidazole therapy alone (P = 0.706).CONCLUSION:Debulking hepatic resections do not appear to offer any advantage in the treatment of patients with alveolar echinococcosis.
The critical shortage in donor organs is generally proffered as the main impetus behind the development of living donor liver transplantation (LDLT), and although the procedure has significantly impacted since its initial development approximately 17 years ago on the pediatric waiting list mortality and morbidity, the same cannot be stated with reference to the adult population of potential liver transplant recipients [1Raia S.N.J. Mies S. Liver transplantation from live donors.Lancet. 1989; 2: 497Abstract PubMed Scopus (607) Google Scholar, 2Strong R.W. Lynch S.V. Ong T.H. Matsunami H. Koido Y. Balderson G.A. Successful liver transplantation from a living donor to her son.N Engl J Med. 1990; 322: 1505-1507Crossref PubMed Scopus (697) Google Scholar]. The picture which emerges is complex and is affected by a variety of factors such as geographic variability in the availability of deceased donor (DD) organs, differences in institutional commitments, surgical expertise, the availability of ancillary support services, emerging data on donor and recipient outcomes and complications, anatomic as well as psychosocial limiting factors in both potential donors and recipients, and ethical considerations as well as conflicting viewpoints within the transplant community. In addressing the question ‘Should LDLT be part of every liver transplant program?’ all of the issues listed need to be discussed. Although the transplant community has been developing a number of guidelines as to who should or should not perform LDLT, the question of level of need for LDLT and donor/recipient risk are constantly being weighed against the required threshold of surgical and institutional expertise. In addition, to further add complexity to this situation, we are concomitantly re-evaluating and extending our accepted indications for liver transplantation within the context of LDLT, with changes in our perceptions of minimal outcome limits in specific oncologic diseases. Ultimately, the question as to who should be performing LDLT should also enter into the realm of ‘Who oversees innovative practice?’ and ‘Do we have a structure to monitor the development and evolution of innovative techniques such as LDLT?’ The dichotomy which has developed with LDLT between our rule as physicians to ‘primum non nocere’: first do no harm, and our desire to help an ever-increasing population of patients with end stage liver disease places us in urgent need of structure and guidelines. Looking at cadaveric organ donation rates in various countries, there is a recognized diversity in the percentage of organ donors per million population. Geographic variability in the availability of DD and social acceptance of cadaveric organ donation, in conjunction with the stimulus of the growing mortality of patients with end stage liver disease (ESLD) in need of liver transplantation, appear to play a crucial role in the development of LDLT [3Tanaka K. Yamada T. Living donor liver transplantation in Japan and Kyoto University: what can we learn?.J Hepatol. 2005; 42: 25-28Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 4Trotter J.F. Living donor liver transplantation: is the hype over?.J Hepatol. 2005; 42: 20-25Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 5Hepp J. Innocenti F.A. Liver transplantation in Latin America: current status.Transplant Proc. 2004; 36: 1667-1668Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar]. In spite of the 1997 approval in Japan of the law for organ retrieval from brain dead donors, the low popular acceptance of cadaveric donation that has ultimately resulted in an extreme paucity of DD organs, has caused LDLT to remain as the main technique of liver transplantation performed in that country [[3]Tanaka K. Yamada T. Living donor liver transplantation in Japan and Kyoto University: what can we learn?.J Hepatol. 2005; 42: 25-28Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar]. Trotter et al. found that LDLT centres in the United States had significantly fewer (46% less) DD liver grafts available per listed patient compared to non-LDLT centres [[4]Trotter J.F. Living donor liver transplantation: is the hype over?.J Hepatol. 2005; 42: 20-25Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar]. In Latin America, where cadaveric donation rates vary between countries in the range of 4.5 to 11.8 per million population per year, LDLT is performed in most countries for pediatric recipients and in 3 Latin American countries for adult patients [[5]Hepp J. Innocenti F.A. Liver transplantation in Latin America: current status.Transplant Proc. 2004; 36: 1667-1668Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar]. In Switzerland, faced with a non patient based liver allocation system where donor hepatic allografts originating from non transplant centres are distributed into a national pool rotated between liver transplant centres, the University of Zurich initiated their LDLT program in the year 2000 to address their low local donor rates, high waiting list numbers and significant mortality and drop out of patients due to progressive advancement of liver disease [[6]Kadry Z. Renner E.L. Clavien P.A. Transplant legislation: ethical and practical issues in liver allocation—the case of Switzerland.Liver Transpl. 2001; 7: 658-660Crossref PubMed Scopus (5) Google Scholar]. The donation rates from deceased donors are lowest in the German part of Switzerland despite numerous efforts from the Swiss transplant community to change this cultural barrier [[7]Swisstransplant, Donation and Transplantation Activities in Switzerland 2000–2004. Accessed 22 February 2005. p. at http://www.swisstransplant.org.Google Scholar]. In Europe, data relating to LDLT activity can be obtained from the European Liver Transplant Registry (ELTR). Although the number of adult LDLT procedures began to exponentially increase as of 1999 until the present time, LDLT is only performed by 48% of European liver transplant centres (n=61/126) and forms only 2.9% of all liver transplantations recorded in the ELTR database (n=1468/50577) [[8]ELTR. Accessed 23 November 2004. p. www.eltr.org.Google Scholar] (Fig. 1, Fig. 2). This same trend can be seen in the USA where LDLT only makes up approximately 5–9% of all liver transplantations performed, even at the time of its peak in 2001 when 506 LDLT were recorded by UNOS [[9]UNOS, National Data. Accessed 22 Feb 2005. p. http://www.unos.org.Google Scholar]. The initial enthusiasm as well as the projected major increase in LDLT procedures has not occurred in countries where cadaveric organ donation is present despite the availability of LDLT for a number of years [[4]Trotter J.F. Living donor liver transplantation: is the hype over?.J Hepatol. 2005; 42: 20-25Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar]. Reasons for this are multiple and complex. From the perspective of donor suitability, approximately >50% of potential liver transplant recipients do not have at the outset an identifiable potential donor based on either a lack of family members or other significant person willing to donate, or based on general donor medical contra-indications such as cumulative co-morbidities, age, obesity and psychosocial reasons [10Renz JF, Mudge CL, Heyman MB, Tomlanovich S, Kingsford RB, Moore BJ, et al. Donor selection limits use of living-related liver transplantation. Hepatology 1995;22: 1122–1126.Google Scholar, 11Sterneck M. Fischer L. Nischwitz U. Burdelski M. Kjer S. Latta A. et al.Selection of the living liver donor.Transplantation. 1995; 60: 667-671Crossref PubMed Scopus (108) Google Scholar, 12Trotter J.W.M. Everson G. Kam I. Adult-to-Adult transplantation of the right hepatic lobe from a living donor.N Engl J Med. 2002; 346: 1074-1082Crossref PubMed Scopus (416) Google Scholar]. After further detailed evaluation of those living donors who appear to be initially suitable, stringent exclusion criteria based on liver anatomy, degree of hepatic steatosis and graft volume size, only 11–45% eventually proceed with liver donation [4Trotter J.F. Living donor liver transplantation: is the hype over?.J Hepatol. 2005; 42: 20-25Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 10Renz JF, Mudge CL, Heyman MB, Tomlanovich S, Kingsford RB, Moore BJ, et al. Donor selection limits use of living-related liver transplantation. Hepatology 1995;22: 1122–1126.Google Scholar, 11Sterneck M. Fischer L. Nischwitz U. Burdelski M. Kjer S. Latta A. et al.Selection of the living liver donor.Transplantation. 1995; 60: 667-671Crossref PubMed Scopus (108) Google Scholar, 12Trotter J.W.M. Everson G. Kam I. Adult-to-Adult transplantation of the right hepatic lobe from a living donor.N Engl J Med. 2002; 346: 1074-1082Crossref PubMed Scopus (416) Google Scholar, 13Russo M.W. Brown R.S. Adult living donor liver transplantation.Am J Transpl. 2004; 4: 458-465Crossref PubMed Scopus (61) Google Scholar] (see previous article by HP Tan, K Patel-Tom, and A Marcos in this forum). In other examples of how social acceptance of LDLT and availability of DD organs can impact to some extent on the degree to which donor restrictions apply, Morimoto et al. evaluated 135 patients for living donation and only 11% of cases were rejected, whereas Renz et al. describe an acceptance rate of 13% of the 75 potential donors who underwent evaluation in their institution. Other liver transplant centers have published acceptance rates ranging between these two extremes, generally ∼30% [4Trotter J.F. Living donor liver transplantation: is the hype over?.J Hepatol. 2005; 42: 20-25Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 10Renz JF, Mudge CL, Heyman MB, Tomlanovich S, Kingsford RB, Moore BJ, et al. Donor selection limits use of living-related liver transplantation. Hepatology 1995;22: 1122–1126.Google Scholar, 11Sterneck M. Fischer L. Nischwitz U. Burdelski M. Kjer S. Latta A. et al.Selection of the living liver donor.Transplantation. 1995; 60: 667-671Crossref PubMed Scopus (108) Google Scholar, 12Trotter J.W.M. Everson G. Kam I. Adult-to-Adult transplantation of the right hepatic lobe from a living donor.N Engl J Med. 2002; 346: 1074-1082Crossref PubMed Scopus (416) Google Scholar, 13Russo M.W. Brown R.S. Adult living donor liver transplantation.Am J Transpl. 2004; 4: 458-465Crossref PubMed Scopus (61) Google Scholar, 14Morimoto T, Ichimiya M., Tanaka A, Ikai I, Yamamoto Y, Nakamura Y, et al. Guidelines for donor selection and an overview of the donor operation in living related liver transplantation. Transpl Int 1996;9: 208–213.Google Scholar].Fig. 2Average number of LDLT per center in Europe, 1997–2003 (European Liver Transplant Registry). No data available in the UNOS registry website (USA).View Large Image Figure ViewerDownload (PPT) Donor safety, emphasized after the highly publicized death of a living liver donor in New York in 2001 as well as other data either published or communicated at international transplant meetings relating to instances of donor morbidity and mortality, has played a major role in the reticence of the transplant community to adopt the widespread use of LDLT [8ELTR. Accessed 23 November 2004. p. www.eltr.org.Google Scholar, 15Akabayashi A.S.B. Fujita M. The first donor death after living-related liver transplantation.Transplantation. 2004; 77: 634-639Crossref PubMed Scopus (131) Google Scholar, 16Miller C. Florman S. Kim-Schluger L. Lento P. De La Garza J. Wu J. et al.Fulminant and fatal gas gangrene of the stomach in a healthy live liver donor.Liver Transpl. 2004; 10: 1315Crossref PubMed Scopus (134) Google Scholar, 17Beavers K.L. Sandler R.S. Shrestha R. Donor morbidity associated with right lobectomy for living donor liver transplantation to adult recipients: a systematic review.Liver Transpl. 2002; 8: 110-117Crossref PubMed Scopus (196) Google Scholar]. To date, there have been three reported donor deaths in the USA, four in Europe, and one in Japan, India, Egypt and South America, respectively. Three other donors have required liver transplantation and one donor is in a persistent vegetative state due to complications from right hemi liver donation [15Akabayashi A.S.B. Fujita M. The first donor death after living-related liver transplantation.Transplantation. 2004; 77: 634-639Crossref PubMed Scopus (131) Google Scholar, 16Miller C. Florman S. Kim-Schluger L. Lento P. De La Garza J. Wu J. et al.Fulminant and fatal gas gangrene of the stomach in a healthy live liver donor.Liver Transpl. 2004; 10: 1315Crossref PubMed Scopus (134) Google Scholar, 18Surman O.S. The ethics of partial-liver donation.N Engl J Med. 2002; 346: 1038Crossref PubMed Scopus (169) Google Scholar, 19Pomfret, E., The Donor: Assessment, Selection, Morbidity and Mortality. In AASLD/AHPBA Surgical Forum: Update on benign liver lesions, surgical considerations in steatosis and cirrhosis and the latest in living donor liver transplantation (LDLT). 2004. Boston, Massachusetts.Google Scholar]. This data is difficult to translate into an accurate overall operative mortality since the exact number of living liver donor operations performed worldwide have not been recorded in all countries. Estimated living donor mortality risk has been quoted to range from 0.04% in Japan to 0.11% in the USA and 0.27% in Europe [8ELTR. Accessed 23 November 2004. p. www.eltr.org.Google Scholar, 9UNOS, National Data. Accessed 22 Feb 2005. p. http://www.unos.org.Google Scholar, 15Akabayashi A.S.B. Fujita M. The first donor death after living-related liver transplantation.Transplantation. 2004; 77: 634-639Crossref PubMed Scopus (131) Google Scholar]. Although the recipient indications for LDLT have been described as being the same as for cadaveric liver transplantation, the reality of the situation is that only a limited fraction of patients suffering from ESLD can undergo LDLT. Certain urgent situations such as fulminant liver failure have brought into question the clarity and freedom with which the potential donor can base his or her decision to donate. In the USA, both the New York State Health Department and the UNOS Ad Hoc Committee on Live Donation have recommended against live donation in this acute situation [4Trotter J.F. Living donor liver transplantation: is the hype over?.J Hepatol. 2005; 42: 20-25Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 20New York State Department of Health, New York State Committee on Quality Improvement in Living Liver Donation. 2002. available at www.health.state.ny.us.Google Scholar, 21Ad Hoc UNOS Committee on Living Donor Liver Transplantation, recommendations available at http://www.unos.org/living_donation.asp.Google Scholar]. Also critically ill patients with acute severe decompensation of an underlying cirrhosis have been shown to have an associated high postoperative mortality with LDLT which some consider to be excessive for a healthy living donor to be placed at risk [12Trotter J.W.M. Everson G. Kam I. Adult-to-Adult transplantation of the right hepatic lobe from a living donor.N Engl J Med. 2002; 346: 1074-1082Crossref PubMed Scopus (416) Google Scholar, 22Brown Jr, R.S. Russo M.W. Lai M. Schiffman M.L. Richardson M.C. Everhart J.E. et al.A survey of liver transplantation from living adult donors in the United States.N Engl J Med. 2003; 348: 818-825Crossref PubMed Scopus (462) Google Scholar, 23Todo S, Furukawa H., Jin MB, Shimamura T, Living donor liver transplantation in adults: outcome in Japan. Liver Transpl 2000;6 (Suppl 2): S66–72.Google Scholar]. This trend can be seen when examining the data pertaining to LDLT and DD liver transplantation in the USA: 79% of LDLT recipients were reported to have been not hospitalized at the time of transplantation compared to 69% of DD recipients [[24]Brown R.S. Rush R.S. Rosen H.R. Langnas A.N. Klintmalm G.B. Hanto D.W. Punch J.D. Liver and intestine transplantation.Am J Transpl. 2004; 4: 81-92Crossref PubMed Scopus (43) Google Scholar]. Additionally 8% were ICU bound compared to 15% of DD liver recipients, and MELD scores (Model for End Stage Liver Disease) were more frequently in the 11–20 range (41%) than in the higher 21 to 30 score (3.9%) [[24]Brown R.S. Rush R.S. Rosen H.R. Langnas A.N. Klintmalm G.B. Hanto D.W. Punch J.D. Liver and intestine transplantation.Am J Transpl. 2004; 4: 81-92Crossref PubMed Scopus (43) Google Scholar]. Technical issues do seem to play a role in these trends, since severity of recipient disease and degree of portal hypertension have been reported to impact on graft outcome particularly if the graft to body weight ratio is in the lower range [25Ben-Haim M, Emre S., Fishbein TM, Sheiner PA, Bodian CA, Kim-Schluger L, et al. Critical graft size in adult-to-adult living donor liver transplantation: impact of the recipient's disease. Liver Transpl 2001;7: 948–53.Google Scholar, 26Sugawara Y. Makuuchi M. Kaneko J. Kokudo N. MELD score for selection of patients to receive a left liver graft.Transplantation. 2003; 75: 573-574Crossref PubMed Scopus (25) Google Scholar, 27Shimamura T. Taniguchi M. Lin M.B. Suzuki T. Matsushita M. Furukawa H. et al.Excessive portal venous inflow as a cause of allograft dysfunction in small-for-size living donor liver transplantation.Transpl Proc. 2001; 33: 1331Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar]. Data from the ELTR shows an overall lower LDLT graft survival in adults, especially when a lower graft volume such as a left hemiliver is used [[8]ELTR. Accessed 23 November 2004. p. www.eltr.org.Google Scholar]. Right hemiliver LDLT is also associated with anatomic variations in the biliary anatomy in up to 53% of cases, which has been shown to result in a higher incidence of postoperative biliary complications and a higher risk of graft loss [4Trotter J.F. Living donor liver transplantation: is the hype over?.J Hepatol. 2005; 42: 20-25Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 12Trotter J.W.M. Everson G. Kam I. Adult-to-Adult transplantation of the right hepatic lobe from a living donor.N Engl J Med. 2002; 346: 1074-1082Crossref PubMed Scopus (416) Google Scholar, 28Kadry Z. et al.The pitfall of the cystic duct biliary anastomosis in right lobe living donor liver transplantation.Liver Transpl. 2004; 10: 1549-1550Crossref PubMed Scopus (12) Google Scholar] (see previous article by S Todo, H Furukawa and T Kamiyama in this forum). In essence all of this translates into important technical and physiologic issues in LDLT which impact on the overall successful outcome of this procedure. It also questions the concept of relief in the size of the waiting list since patients in acute decompensation of their liver disease probably cannot benefit from LDLT and, in situations of LDLT graft failure this may actually worsen the competition within the allocation system. Suggested implementation of extended criteria specific to LDLT such as advanced stage hepatocellular cancer or other primary liver malignancies such as hemangioendothelioma or cholangiocarcinoma [29Todo S. Furukawa H. Living donor liver transplantation for adult patients with hepatocellular carcinoma: experience in Japan.Ann Surg. 2004; 240: 451-459Crossref PubMed Scopus (360) Google Scholar, 30Kadry Z. Cintorino D. Foglieni C.S. Fung J. Living donor liver transplantation and tolerance: a potential strategy in cholangiocarcinoma.Transplantation. 2003; 76: 1003-1006Crossref PubMed Scopus (41) Google Scholar, 31Malago M. Testa G. Marcos A. Fung J.J. Siegler M. Cronin D.C. et al.Ethical considerations and rationale of adult-to-adult living donor liver transplantation.Liver Transpl. 2001; 7: 921-927Crossref PubMed Scopus (93) Google Scholar, 32Hassoun Z. Gores G.J. Rosen C.B. Preliminary experience with liver transplantation in selected patients with unresectable hilar cholangiocarcinoma.Surg Oncol Clin N Am. 2002; 11: 909-921Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar] may also create new groups of candidates for liver transplantation [[33]Shaw Jr, B.W. Where monsters hide.Liver Transpl. 2001; 7: 928-932Crossref PubMed Scopus (21) Google Scholar]. These are strong arguments to limit LDLT to academic centers with a wide experience in this procedure, and in cases where extended indications to liver transplantation apply, to direct patients to specific study protocols, rather than have a widespread implementation of LDLT. The question as to whether LDLT should be part of every liver transplant program was partly addressed in an interesting survey of 100 liver transplant surgeons published in 2003 [[34]Cotler S.J. Cotler S. Gambera M. Benedetti E. Jensen D.M. Testa G. Adult living donor liver transplantation: perspectives from 100 liver transplant surgeons.Liver Transpl. 2003; 9: 637-644Crossref PubMed Scopus (28) Google Scholar]. In this survey 72% of responders considered that transplant programs have a duty to their patients to offer adult LDLT [[34]Cotler S.J. Cotler S. Gambera M. Benedetti E. Jensen D.M. Testa G. Adult living donor liver transplantation: perspectives from 100 liver transplant surgeons.Liver Transpl. 2003; 9: 637-644Crossref PubMed Scopus (28) Google Scholar]. There is general agreement however that requirements need to go further with LDLT. This is a procedure, which should be performed in institutions with surgical teams having an established experience in liver transplantation, where there is appropriate ongoing oversight. LDLT centers should have a solid basis in academic surgery and clinical and scientific research: efforts to reduce donor risk will involve research and development of safe use of smaller volume grafts and in depth examination of the process of liver regeneration. The necessary multidisciplinary approach with medical, radiological and surgical alternatives to transplantation and a wide range of ancillary services are a central adjunct, which can be best provided by an academic liver transplant center. True institutional support will require a willingness to invest in LDLT, as well as the provision of a ‘safe’ environment through the establishment of dedicated staff for the LDLT process and donor/recipient care, the presence of an adequate operating room space, instrumentation and staff, the inclusion of a donor advocate or a donor evaluation team that is separate to the physicians involved in the LDLT recipient's care as well as a functioning ethical committee. Centers preparing to perform LDLT should undergo careful institutional planning and have an internal peer review mechanism. A prepared ‘disaster plan’ already in place in case of donor death has also been suggested and an additional outside institutional review mechanism or outside expert available for particular controversial cases has been recommended [35Miller, C.M., Who should and who should not do LDLT? in AASLD/AHPBA Surgical Forum; Boston, Massachusetts; 2004.Google Scholar, 36Miller C.M. Regulation and oversight of adult living donor liver transplantation.Liver Transpl. 2003; 9: S69-S72Crossref PubMed Scopus (19) Google Scholar]. In the USA, guidelines have been published regarding the regulation and oversight of adult LDLT by both the US Department of Health and Human Services Advisory Committee on Organ Transplantation (ACOT) and the New York State Committee on Quality Improvement in Living Liver Donation [[36]Miller C.M. Regulation and oversight of adult living donor liver transplantation.Liver Transpl. 2003; 9: S69-S72Crossref PubMed Scopus (19) Google Scholar]. Furthermore, the UNOS ad Hoc Living Donor Committee has developed requirements which institutions and their transplant teams must fulfill in order to be eligible for submission of verification and to ultimately qualify as a UNOS-certified LDLT center [[37]UNOS, Transplant Programs Appendix B, Attachment 1 (XII). Accessed 22 February 2005. at http://www.unos.org/policiesandbylaws/bylaws.asp.Google Scholar]. In terms of surgical experience, there is general agreement that experience in both hepatobiliary surgery and cadaveric liver transplantation is essential in the creation of a LDLT center, even though the living donor hepatectomy technically somewhat differs from an ‘oncologic’ hepatic resection. Optimal suggested minimum prerequisites for LDLT teams have included a yearly volume of 50 orthotopic liver transplants, 20 to 50 hepatectomies, 20 pancreatico-duodenectomies and 10 complicated biliary reconstructions [31Malago M. Testa G. Marcos A. Fung J.J. Siegler M. Cronin D.C. et al.Ethical considerations and rationale of adult-to-adult living donor liver transplantation.Liver Transpl. 2001; 7: 921-927Crossref PubMed Scopus (93) Google Scholar, 35Miller, C.M., Who should and who should not do LDLT? in AASLD/AHPBA Surgical Forum; Boston, Massachusetts; 2004.Google Scholar, 36Miller C.M. Regulation and oversight of adult living donor liver transplantation.Liver Transpl. 2003; 9: S69-S72Crossref PubMed Scopus (19) Google Scholar, 37UNOS, Transplant Programs Appendix B, Attachment 1 (XII). Accessed 22 February 2005. at http://www.unos.org/policiesandbylaws/bylaws.asp.Google Scholar]. In setting guidelines however, one must not lose sight of the fact that the greatest need for LDLT has been seen by institutions lacking in deceased donor organs, that probably are unable to reach the suggested annual rate of 50 cadaveric liver transplants. Mortality on the waiting list is an important prerequisite to justify establishment of LDLT programs in countries and transplant centers where DD are scarce. It varies widely however between centers and may be underestimated if patients are removed from the transplant waiting list based upon clinical deterioration. In an intention to treat analysis, patients removed from the waiting list due to deterioration should be included in a waiting list mortality analysis. Centers having a waiting list mortality >10% despite all efforts to increase the decreased donor pool, including the use of marginal donors, could consider initiating a LDLT program. Not all transplant physicians have embraced LDLT as manifested by the fact that by 2003 only 41% of US and 48% of European liver transplant centers were offering this procedure to their patients [8ELTR. Accessed 23 November 2004. p. www.eltr.org.Google Scholar, 9UNOS, National Data. Accessed 22 Feb 2005. p. http://www.unos.org.Google Scholar]. This could be due to personal physician choice, lack of institutional resources, insufficient technical expertise, few potential LDLT recipients and donors as well as perceived adequate numbers of DD. The issue of donor safety is probably an excellent dissuasive factor for the initiation of a LDLT program. However, both institutional and peer reviewed oversights and self-regulation within the liver transplant community are necessary to maintain high standards, patient/donor safety as well as public trust. With the cumulating data on donor morbidity and mortality and recipient outcomes in LDLT, the presence of an appropriate consent process is essential. There have been guidelines published relating to this question in a consensus meeting organized by the American Society of Transplant Surgeons in 2000 and ACOT has recommended in the USA that the document be accessible to all educational levels and be aimed at 8th or 9th grade level of education to facilitate understanding [36Miller C.M. Regulation and oversight of adult living donor liver transplantation.Liver Transpl. 2003; 9: S69-S72Crossref PubMed Scopus (19) Google Scholar, 38American Society of Transplant Surgeons' position paper on adult-to-adult living donor liver transplantation. Liver Transpl; 2000 6: 815–7.Google Scholar]. The ability to speak the language and to communicate appropriately with both potential donor and recipient is of utmost importance if informed consent is to be obtained. In addition to international published data relating to morbidity and mortality rates, each center should give information on the local experience by providing the number of cases performed by the surgical team and by comparing outcomes to published data on the procedure. Information should include details pertaining to the operative technique, hospital stay, complications experienced, and documented mortality risk within the local transplant center. Short and long term results of LDLT should undergo continuous and prospective reporting to intra and extra institutional committees, authorities or societies. In fact, some regulation by government agencies has been suggested [12Trotter J.W.M. Everson G. Kam I. Adult-to-Adult transplantation of the right hepatic lobe from a living donor.N Engl J Med. 2002; 346: 1074-1082Crossref PubMed Scopus (416) Google Scholar, 18Surman O.S. The ethics of partial-liver donation.N Engl J Med. 2002; 346: 1038Crossref PubMed Scopus (169) Google Scholar, 22Brown Jr, R.S. Russo M.W. Lai M. Schiffman M.L. Richardson M.C. Everhart J.E. et al.A survey of liver transplantation from living adult donors in the United States.N Engl J Med. 2003; 348: 818-825Crossref PubMed Scopus (462) Google Scholar]. In Europe, the ELTR maintains a database on both cadaveric and living donor liver transplant activity and outcomes from information supplied by participating centers [[8]ELTR. Accessed 23 November 2004. p. www.eltr.org.Google Scholar]. In the USA, the National Institute of Health (NIH) is setting up a database panel of peer experts to assess and provide quality control in all the LDLT centers [12Trotter J.W.M. Everson G. Kam I. Adult-to-Adult transplantation of the right hepatic lobe from a living donor.N Engl J Med. 2002; 346: 1074-1082Crossref PubMed Scopus (416) Google Scholar, 13Russo M.W. Brown R.S. Adult living donor liver transplantation.Am J Transpl. 2004; 4: 458-465Crossref PubMed Scopus (61) Google Scholar, 39Neuberger J.M. Lucey M.R. Living-related liver donation: the inevitable donor deaths highlighted the need for greater transparency.Transplantation. 2004; 77: 489-490Crossref PubMed Scopus (10) Google Scholar, 40Shiffman ML, Brown RS, Jr., Olthoff KM, Everson G, Miller C, Siegler M, et al. Living donor liver transplantation: summary of a conference at The National Institutes of Health. Liver Transpl 2002; 8: 174–188.Google Scholar]. In conclusion: Should LDLT be part of every liver transplant program? The answer is definitely no. Although it is likely that families of patients on the waiting list will continue to want to donate due to the restricted cadaveric donor pool, LDLT programs can only be justified when all the necessary institutional resources and surgical expertise are in place, and when every effort continues to be made to enhance cadaveric organ donation rates (Table 1).Table 1Recommended requirements for a living donor liver transplant programMedical requirementsInstitutional requirements(1) Established need for LDLT(1) Adequate resources >10% annual waiting list mortality and/or drop out in spite of efforts(2) Donor advocate team (a) To increase local cadaveric donation rate(3) Ongoing internal and external oversight (b) To expand donor pool (marginal donors, domino and split)(4) Local and national LDLT date registry(2) Active liver transplant program(5) Presence of a disaster plan in case of LDLT donor death (a) 20–50 cadaveric liver transplantation/year (b) Commitment to research(3) Wide experience in hepatobiliary surgery (a) 20–50 liver resections per year (b) 20 pancreato-duodenectomies per year (c) 10–20 complex biliary reconstructions per year Open table in a new tab The reality of donor deaths and published donor morbidity highlight the importance of a continuous and obligatory oversight of LDLT programs worldwide. There is an urgent need for national and international registries with mandatory reporting requirements to collect the real donor and recipient outcomes after living donation. The combined extensive surgical experience in hepatobiliary surgery and liver transplantation should be today a limiting factor to the performance of LDLT in some centers regardless of the mortality in the waiting list. On the other hand, the sentiment that ‘just because you can do something does not mean that you have to do it’ should be part of the thought process of every surgical team examining the possibility of offering LDLT to their patients. The establishment of an adequate network of referral centers will allow transplant teams, who do not fulfill the criteria required for a LDLT program, to refer potential donors and patients who would like to proceed with living donation to recognized LDLT centers. Continued quality control by the transplant community through a self-regulation process with the development of necessary guidelines for the implementation of LDLT can only serve to reduce donor risk and improve LDLT outcomes.
Orthotopic liver transplantation (LTX) has become an accepted means for the treatment of end-stage liver disease. Although the technique of LTX has been refined to a relatively standardized approach, the operation remains a formidable surgical challenge. As such, LTX can have numerous technical complications, in which the recipient’s pretransplant condition, donor and immunologic factors, may all contribute. These risks can be minimized by appropriate ABO matching, size matching, adequate maintenance of donor physiology and graft quality and procurement. The purpose of this review is to discuss the operative procedure and to highlight some of the more important intraoperative and early and late post-operative complications.