Live donors in liver transplantation

Living donor liver transplantation (LDLT) has been controversial since its inception. Begun in response to deceased donor organ shortage and waiting list mortality, LDLT was initiated in 1989 in children, grew rapidly after its first general application in adults in the United States in 1998, and has declined since 2001. There are significant risks to the living donor, including the risk of death and substantial morbidity, and 2 highly publicized donor deaths are thought to have contributed to decreased enthusiasm for LDLT. Significant improvements in outcomes have been seen over recent years, and data, including from the National Institutes of Health-funded Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL), have established a survival benefit from pursuing LDLT. Despite this, LDLT still composes less than 5% of adult liver transplants, significantly less than in kidney transplantation where living donors compose approximately 40% of all transplantations performed. The ethics, optimal utility, and application of LDLT remain to be defined. In addition, most studies to date have focused on posttransplantation outcomes and have not included the effect of the learning curve on outcome or the potential impact of LDLT on waiting list mortality. Further growth of LDLT will depend on defining the optimal recipient and donor characteristics for this procedure as well as broader acceptance and experience in the public and in transplant centers.     

First successful case of simultaneous liver and kidney transplantation for patients with chronic liver and renal failure in Japan

Establishment of a preferential liver allocation rule for simultaneous liver and kidney transplantation (SLK) and revisions of laws regarding organ transplants from deceased donors have paved the way for SLK in Japan. Very few cases of SLK have been attempted in Japan, and no such recipients have survived for longer than 40 days. The present report describes a case of a 50‐year‐old woman who had undergone living donor liver transplantation at the age of 38 years for management of post‐partum liver failure. After the first transplant surgery, she developed hepatic vein stenosis and severe hypersplenism requiring splenectomy. She was then initiated on hemodialysis (HD) due to the deterioration of renal function after insertion of a hepatic vein stent. She was listed as a candidate for SLK in 2011 because she required frequent plasma exchange for hepatic coma. When her Model for End‐stage Liver Disease score reached 46, the new liver was donated 46 days after registration. The reduced trisegment liver and the kidney grafts were simultaneously transplanted under veno‐venous bypass and intraoperative HD. The hepatic artery was reconstructed prior to portal reconstruction in order to shorten anhepatic time. Although she developed subcapsular bleeding caused by hepatic contusion on the next day, subsequent hemostasis was obtained by transcatheter embolization. Thereafter, her recovery was uneventful, except for mild rejection and renal tubular acidosis of the kidney graft. This case highlights the need to establish Japanese criteria for SLK.     

Technical advances in living-related liver transplantation

Since it was first reported in 1989, living-related liver transplantation (LRLT) has developed, and up to April, 1998, over 800 LRLTs had been performed worldwide. The past few years have seen considerable technical advances in LRLT, including selective vascular occlusion techniques for donor hepatectomy, arterial reconstruction using microscopy, and the introduction of intraoperative ultrasound and graft volume estimation, using the concept of standard liver volume, which have enabled LRLT to be extended to adult recipients. Successful results have led to LRLT becoming an indispensable modality to overcome the shortage of cadaveric liver grafts in Western countries. In places where transplantation of organs from brain-dead donors is rarely practiced, such as in most Asian countries, LRLT is the only means of saving patients with end-stage liver disease who otherwise would have no chance of survival. LRLT is now globally accepted as an effective liver transplantation modality.     

Present status and prospects of living-related liver transplantation

Living-related liver transplantation (LRLT) is a relatively new surgical modality that has developed, in part, to overcome the shortage of available cadaveric livers for transplantation and as a method to provide liver graft implants from living donors for patients end-stage with liver disease in areas where the use of cadaveric livers is not yet practiced or permitted. Since 1988 almost 500 LRLTs have been performed globally. The safety of donors who provide a portion of their liver for grafting is of utmost concern, and only one donor death from this procedure has been reported in the literature. Postoperative survival in recipients depends on their pretransplant physical status, but emergency patients in rapid need of a liver have a poorer survival than elective LRLT patients for whom survival is about 80%. Children and infants are the main recipients of LRLTs, but adult patients particularly in Japan, are increasing in number, and present indications for LRLT surgery include not only cholestatic end-stage liver diseases but also metabolic disorders affecting the liver and emergency LRLTs for fulminant hepatic failure. Many ethical problems relating to the concept of liver transplantation, donor liver source, recipient selection, and reimplantation have yet to be resolved. But we believe that LRLTs and cadaveric liver transplantations are saving lives and that the practice should be continued.     

Domino liver transplantation

Orthotopic liver transplantation is today an established treatment for end stage liver diseases. However, the ongoing shortage of suitable livers together with progressively longer waiting lists prevents many patients from being transplanted, and many patients die while being on the waiting list. Using livers from living donors is one way to increase the supply of liver grafts. Another group of potential living liver donors are some selected liver recipients, whose native explanted liver in turn can be considered for transplantation into another patient. This unorthodox procedure have been named domino liver transplantation (DLT). The domino approach can be considered in patients with some genetic or biochemical disorders that today are treated by liver transplantation. The underlying rationale is that such livers ultimately cause severe systemic disease but are otherwise normal. In this review we present the current world status of DLT as well as updated results from the Domino Liver World Transplant Register (DLTR) and our own experience at the Karolinska University Hospital Huddinge with the DLT procedure.     

Living-donor liver transplantation in adults: Tokyo University experience

The objective of this study was to analyze the experience of a single center with living-donor liver transplantation (LDLT) for adult patients. Ninety consecutive LDLT procedures were analyzed. Preoperative status, morbidity, hospital stay duration, and postoperative graft function and survival rates were examined. Donors showed only minimal morbidity and were discharged 15 ± 6 days after LDLT. Morbidity in the patients included acute rejection (32%), vascular complications (8%), and biliary complications (20%). The mortality rate was 6% and three additional patients experienced late death. The 2-year cumulative survival rate was 92%. The present results suggest that LDLT can be performed with an acceptable outcome in adult patients.     

Living donor liver transplantation: issues regarding left liver grafts

BackgroundThe necessity of widening the indications for living donor liver transplantation (LDLT) has been emphasised. Clarification of the advantages and limitations of using a left liver graft for LDLT in adults is essential for donor safety.MethodsBetween June 1990 and November 2002, 185 patients underwent LDLT at Shinshu University Hospital, Japan. In 97 of these, the graft comprised the left liver with or without the left portion of the caudate lobe. The peri-hepatectomy profiles of the donors, significance of left liver grafts, postoperative courses of the donors and recipients, and survival of the recipients were investigated.ResultsAll the donors recovered well and returned to a normal lifestyle. None required banked-blood transfusion or repeat surgery, and postoperative liver function tests had satisfactory results. The cold ischaemic time for the graft was 127±54 minutes. The graft volumes (GVs) ranged from 230 to 625 ml, and GV/standard liver volume (SV) ratios varied from 22% to 65%, at the time of transplantation. Although 85% of the liver grafts had GV/SV ratios <50%, no patient developed immediate postoperative liver failure. Patient survival rates were 89%, 84% and 84% at 1, 3 and 5 years, respectively.DiscussionAlthough LDLT using a left liver graft imposes potential postoperative complications (a small liver is more vulnerable to injury, and recipients of small grafts are at higher risk of complications during recovery), such grafts have yielded acceptable results in adult LDLT, with minimal burden to the donors.     

Subcapsular hematoma after right-lobe living-donor liver transplantation

Because right-lobe living-donor liver transplantation was introduced in adult-to-adult liver transplantation to mitigate the problems of small-for-size grafts, some technical controversies have been reported. This report describes a case of graft subcapsular hematoma due to parenchymal injury. A 53-year-old woman underwent a right-lobe living-donor liver transplantation for acute-on-chronic liver failure due to primary biliary cirrhosis. A huge subcapsular hematoma was discovered by routine Doppler echogram examination on the first posttransplantation day. Relaparotomy findings revealed that rotation of the graft for the hemostasis procedure during the transplant operation had induced a compression injury to the graft by the xiphoid process. It was speculated that a small laceration in the graft parenchyma led to the major subcapsular hematoma. This experience suggests that the graft liver must be handled with special care to prevent potential mechanical injury.     

Strategies for improving the outcomes of small-for-size grafts in adult-to-adult living-donor liver transplantation

Living-donor liver transplantation (LDLT) has been refined and accepted as a valuable treatment for patients with end-stage liver disease in order to overcome the shortage of organs and mortality on the waiting list. However, graft size problems, especially small-for-size (SFS) grafts, remain the greatest limiting factor for the expansion of LDLT, especially in adult-to-adult transplantation. Various attempts have been made to overcome the problems regarding SFS grafts, such as increasing the graft liver volume and/or controlling excessive portal inflow to a small graft, with considerable positive outcomes. Recent innovations in basic studies have also contributed to the treatment of SFS syndrome. Herein, we review the literature and assess our current knowledge of the pathogenesis and treatment strategies for the use of SFS grafts in adult-to-adult LDLT.     

Biliary complications in recipients of living-donor liver transplantation

The key points of the management of biliary complications in recipients of living-donor liver transplantation are described. The characteristics of these complications are somewhat different from those in deceased-donor liver transplantation, mainly due to the technical difficulties. Appropriate prevention, diagnosis, and treatment are essential for successful transplants, to avoid the development of secondary biliary cirrhosis when complication occurs.     

Hepatitis B vaccination after living donor liver transplantation.

BACKGROUND: The efficacy of hepatitis B vaccination after living donor liver transplantation (LDLT) in patients transplanted anti-HBc-positive grafts or in patients who underwent LDLT for fulminant hepatitis B remains unknown. METHOD: A total of 11 recipients who underwent LDLT between October 1996 and October 2002 prospectively received hepatitis B vaccination three times within 6 months, starting a few weeks after the cessation of hepatitis B immunoglobulin (HBIG) prophylaxis. Serial quantification of the hepatitis B surface antibody (HBsAb) was performed. RESULTS: At the last follow-up, six out of 11 patients (54.5%) had seroconversion and were free from HBIG thereafter. Four out of those six responders had a peak HBsAb level of more than 1000 IU/L, while the other two patients had peak HbsAb levels below 1000 IU/L. Five patients never responded to the treatment and were back to HBIG prophylaxis. The average age of the six responders was 25.5 years, which was significantly younger than that of non-responders (44.4 years, P<0.05). None had side effects or hepatitis B infection during the study period. CONCLUSIONS: In conclusion, the use of this treatment modality could be used to reduce the cost of HBIG.     

Adult-to-adult live-donor liver transplantation: the current status

Adult-to-adult live-donor liver transplantation (ALDLT) has emerged successfully to partially relieve the refractory shortage of deceased donor grafts caused by the increasing demands of patients with endstage liver diseases. Following the first successful live-donor liver transplantation (LDLT) for a child with biliary atresia in 1989, further extension of the technique, using left-lobe liver grafts for LDLT for large adolescents and adults, has resulted in satisfactory graft and patient survival outcomes. However, small-for-size syndrome may occur in some patients with large body size, and in those with acute-on-chronic liver failure or severe portal hypertension. To overcome the problem of graft-to-body-size mismatch, ALDLT, using a right-lobe liver graft was developed. Although routine inclusion of the middle hepatic vein (MHV) in the right-lobe liver graft is still controversial, the importance of providing good venous drainage for the right anterior sector to ensure better early graft function has gained wide recognition. Preservation of the MHV in the donor is intuitively considered important in reducing the donor risk. However, there are scarce data supporting the contention that postoperative complication is related to the absence of the MHV in the left-liver remnant. Duct-to-duct biliary reconstruction has potential advantages over hepaticojejunostomy, and has become the preferred technique in ALDLT. However, biliary complications, especially biliary strictures on long-term follow-up, occur in about 30% of the recipients. The potential beneficial effect of internal or external biliary drainage in reducing the biliary complication rate after duct-to-duct biliary reconstruction in ALDLT also remains controversial. Dual-liver grafts and right-posterior sector grafts have been used in ALDLT, and are reported to result in satisfactory survival outcomes at selected transplant centers. There is no strong evidence supporting the postulate that patients with hepatitis C infection have an inferior survival outcome after ALDLT when compared with recipients of a deceased-donor liver transplant. ALDLT has contributed to satisfactory survival outcomes in patients with hepatocellular carcinoma (HCC). It allows early surgery for the patients and eliminates the uncertainty of prolonged waiting for a deceased-donor liver graft, and the risks of dropout related to disease progression. The exact selection criteria of patients with HCC for ALDLT have yet to be defined.     

Simplifying living donor liver transplantation

BACKGROUND:Living donor liver transplantation is a complex surgical operation.Treatment policies and operative techniques evolved in the last two decades.DATA SOURCES:Our center's experience in living donor liver transplantation was reviewed in conjunction with relevant publications in the literature.RESULTS:The surgical techniques and perioperative surgical therapeutics could be modified towards simplicity.Examples include regular inclusion of the middle hepatic vein without compromising the venous outflow...     

Living donor liver transplantation: Eastern experiences

BACKGROUND: The techniques of living donor liver transplantation (LDLT) developed rapidly in the 1990s to compensate for a severe deficiency in the availability of liver grafts from cadaveric donors for the treatment of patients with end-stage liver disease. This tendency was particularly prominent in East Asia, as brain-death donors have remained largely unavailable for a variety of reasons. Thanks to refinements in surgical technique and postoperative management for LDLT, the cumulative total of LDLTs in East Asian countries has exceeded 2000 and, importantly, donor mortality has yet to be encountered. Moreover, indications for LDLT have been successfully expanded from paediatric to adult cases, following the introduction of right lobe graft. The significance of LDLT under conditions of limited opportunities for cadaveric liver transplantation, as experienced in these countries, differs significantly from that seen with the numerous opportunities for cadaveric donors in Europe and the USA. This review describes not only the experiences of East Asia, but also the specific differences from Western countries, such as indications, graft size issues and ABO blood type combinations, to shed light on the future of liver transplantation.     

The role of living-donor liver transplantation in surgical treatment for hepatocellular carcinoma

Background/Purpose

The role of living-donor liver transplantation (LDLT) in the surgical treatment of patients with hepatocellular carcinoma (HCC) has not been established as yet.

Methods

Preliminary experience gained from 24 patients who underwent LDLT for HCC between March 2002 and November 2004, and the results of the 131 patients who underwent hepatic resection (HR) for HCC between January 1990 and December 2003 were retrospectively analyzed. The exclusion criteria for LDLT for HCC included extrahepatic metastasis and major vascular invasion.

Results

(1) LDLT: the median age of the patients was 57 years and the Child-Pugh grades (A/B/C) of the patients were 6, 12, and 6, respectively. The tumor size was 3?cm or less in 15 patients, multinodular tumors were present in 23 patients, and 11 patients (45.8%) met the Milan Criteria. The overall 2-year survival rate was 72.3%, without a significant difference as to whether or not patients met the Milan criteria. (2) HR: on multivariate analysis, the Child-Pugh grade, the presence of cirrhosis, and the number of tumor nodules were considered as independent risk factors for unfavorable survival (P < 0.05). The 84 patients who met the Milan criteria and were Child-Pugh grade A had a 5-year survival rate of 71.3%; this was significantly better than those of the other patients (P < 0.005). Among the 57 patients with intrahepatic recurrence, 18 patients who were Child-Pugh grade A, met the Milan criteria, and were treated by re-resection or ablation therapy achieved a significantly better 5-year survival rate, of 73.1%, as compared to 19.7% in the other 39 patients (P < 0.0045).

Conclusions

HR could be a first-line treatment with a favorable prognosis for patients who have resectable HCC, preserved liver function, and who meet the Milan criteria. Salvage LDLT could be employed in patients with recurrent tumors that cannot be controlled by conventional treatment or in patients in whom liver function has deteriorated to Child-Pugh grade B or C.     

Liver transplantation for HCC: its role

Liver transplantation (LT) is the only treatment that offers a chance of cure for hepatocellular carcinoma (HCC) and the underlying liver cirrhosis simultaneously, but the availability of liver grafts and the aggressiveness of tumor recurrence are critical limiting factors of LT for patients with HCC. In most Asian countries, the serious shortage of deceased donors and the strong demand for LT has lead to the development of living-donor LT (LDLT) as a practical alternative replacing deceased-donor LT (DDLT). Grafts in Western countries are issued from DDLT and graft allocations are under the responsibilities of state agencies which apply strict rules based on the MELD (model for end-stage liver disease) score. Considering that HCC recurrence is the most common cause of post-transplant patient death, recipient candidates should be prudently selected through objectively established criteria. Points in addition to the MELD score can be allotted to patients with HCC providing that the HCC remains within the Milan criteria. The increasing number of LT candidates with HCC results in increasing waiting periods, which necessitate the consideration of pretransplant treatment of HCC, including partial liver resection. Both specific Western units and some Asian major LDLT centers have challenged the Milan criteria. The eligibility criteria of both DDLT and LDLT for HCC are likely to be expanded more than before, but this still requires further qualified risk–benefit analyses. The development of new effective treatment modalities before LT and for HCC recurrence might expand the selection criteria further without incurring an increased recurrence rate.