What is the current status of adult living liver transplantation?

  1.Overview In order to solve the problem of shortage of donor organs, Yamaoka et al. performed the world’s first adult living right hemi-liver transplantation in 1994, which lit a new light of hope for many patients with end-stage liver disease. In 2001, our center successfully performed the first adult living right hemi-liver transplant in China, leading the country in terms of number of transplant cases and efficacy, and spared no effort to promote the successful experience and technology radiation in China, promoting the rise of adult living liver transplantation in China. Compared to cadaveric whole liver transplantation, living liver transplantation is more demanding in terms of surgical skills, and both the donor and recipient are exposed to surgical risks and the possibility of complications, and the safety of the donor is particularly important from an ethical point of view. Therefore, the evaluation and acquisition of the donor liver has been the focus of attention in the transplantation community as the most critical technology. Currently, there is no unified practice in the world’s major transplantation centers, and there are no definitive conclusions regarding the selection of donor volume, whether the right hemi-donor contains the middle hepatic vein, or whether to perform venous outflow tract reconstruction.  The choice of hemi-liver has evolved from the initial left outer lobe, left hemi-liver, to the right hemi-liver without the middle hepatic vein, and then to the right hemi-liver with the middle hepatic vein, with the greater the volume of liver obtained by the recipient, the higher the donor risk. In the early days of adult living liver transplantation, the left hemisphere was widely used, but many patients developed the so-called “small liver syndrome,” which was characterized by early graft malfunction, hepatocellular injury, early graft failure, and even recipient death. Kiuehi and Miyagawa retrospectively analyzed 276 adult living donor liver transplants and found that the survival rate of recipients was greatly reduced when the left half donor liver weight was less than 1% of the recipient’s body weight, which was mainly due to parenchymal damage of small volume grafts and the inability of the effective volume of the donor liver to meet the metabolic needs of the recipient. In general, patients with acute and subacute hepatic failure in a highly depleted and hypometabolic pathophysiological state clinically require a larger volume of a functioning graft to improve the recipient’s compensatory capacity after donor liver implantation. As a result, adult living right hemi-liver transplantation is accepted and widely used in most centers, and retrospective analyses of large samples have shown satisfactory recipient survival rates and donor safety. Currently, the right hemi-liver has become the dominant donor liver choice for living liver transplantation, but some scholars still insist on using the left hemi-liver for living liver transplantation. For example, Kawasaki of Juntendo University in Tokyo reported the successful experience of adult living left liver transplantation at the 1st Biennial Congress of the Asia-Pacific Hepatobiliary and Pancreatic Association (Fukuoka, 2007).  3. Evaluation of donor liver volume An important ethical prerequisite for living liver transplantation is that the donor’s health is not endangered. Therefore, the accuracy of donor liver volume assessment by preoperative imaging and the accuracy of residual liver volume prediction will directly affect the prognosis of the donor recipient in living liver transplantation. For most donors, the ratio of residual liver volume (RLV) to total donor liver volume (TLV) should be controlled at 30% or higher to ensure that the residual liver can recover early postoperative surrogate function and avoid complications as much as possible. The selection of the size of the transplanted liver is currently judged on the basis of the ratio of supply liver weight to recipient weight (GRWR), and it is recommended that the GRWR should be greater than 1%. Complications in the right hemispheric donor are largely attributed to excessive parenchymal resection and the small size of the residual left hemisphere that cannot compensate for the metabolic needs of the donor. Experience with resection of large hepatic tumors suggests that the residual 1/3 of liver tissue after hepatectomy is largely sufficient to meet the metabolic needs of the organism. Kubota suggests that healthy individuals can tolerate resection of more than 60% of normal liver tissue, and Fan Shangda in Hong Kong further suggests that 27% of RLV plant l1LV is the low limit to meet metabolic needs. A series of studies have found that for most normal individuals, functional recovery of the residual liver after right hemicolectomy tends to be worse than that of the left posterolateral lobe donor, and the duration of surgery and hospital stay is much longer than that of the left posterolateral lobe donor. Delayed recovery of liver function due to a small residual liver can cause a series of complications such as bile leak, infection, and bleeding, which can endanger the life of the donor. Recently, It0 et al. found no difference in prognosis between donors with RLV/TLV <30% and >30%; and Cho et al. also confirmed that RLV/SLV=35% is not a watershed for donor safety. Nevertheless, we should be cautious about expanding the volume of donor donor liver. In recent years, the concept of residual liver volume/body weight ratio (RLV/BWR) has been proposed. It is believed that RLV/BWR is more specific than RLV plant l1LV to distinguish normal parenchymal liver tissue from decompensated liver tissue with biliary obstruction and vascular embolism, thus allowing accurate preoperative assessment of the residual functional liver tissue after donor lobectomy.Truant retrospectively analyzed 31 right hemihepatic living liver transplants and suggested that donors with RLB/BWR ≥0.5% had a better prognosis. The evaluation of steatotic donor livers has been a new focus in recent years. cho reported a more satisfactory regeneration rate and functional recovery after implantation of right hemi-donor livers with steatosis <30%. The results of a study on the use of steatotic donor livers in our center showed that moderately steatotic donor livers have little effect on the postoperative recovery of liver and kidney function and survival of transplant recipients and can be safely used as part of the donor liver system.  4. Trade-offs for the middle hepatic vein There is currently controversy in the transplant community as to whether the middle hepatic vein should be included in the right hemi-liver graft. It is generally accepted that a right hemi-graft that includes the mid-hepatic vein increases the potential risk to the donor while providing more functional liver volume to the recipient. A right hemi-donor that does not contain the middle hepatic vein provides a good balance of liver volume to the recipient, but its main constraint is the potential for venous reflux and stasis in the anterior lobe of the right liver. Therefore, many scholars suggest that the right anterior hepatic outflow tract should be reconstructed when the middle hepatic vein is not included. The right hemiportal donor liver containing the middle hepatic vein was first used in adult liver transplantation at the Queen Mary Hospital in 1996, and the technique has since been replicated in several centers. In a retrospective analysis of 29 living right hemi-hepatic transplants containing the middle hepatic vein, they found that the regeneration of the donor's residual left liver after resection of the right hemi-hepatic vein together with the middle hepatic vein was inversely proportional to the ratio of the donor's left liver/total liver volume, i.e., "the more resection, the more regeneration". Postoperatively, none of the 29 donors experienced serious complications, and imaging monitoring such as CT and MRI revealed poorer regeneration if the IV segment of the middle hepatic vein of the donor was completely resected, whereas the residual liver regenerated more completely if the IVb segment of the venous outflow tract was preserved. Since the inclusion of the middle hepatic vein in the right half of the donor liver provides adequate venous drainage of the graft and provides sufficient volume of functional liver. This is important for those recipients with poor preoperative organism and high postoperative metabolic needs. In clinical practice, it has also been found that patients with fulminant liver failure or acute decompensation of chronic liver failure as the primary disease tend to achieve a higher survival rate after applying a right hemi-liver transplant containing the middle hepatic vein.Etben scholar Matsubara analyzed 42 living liver transplantation donor procedures and found that after excision of the right hemi-donor containing the middle hepatic vein, the majority of the residual liver was well preserved IVb segmental outflow tract. Therefore, both they and the Queen Mary Hospital of the University of Hong Kong recommend the routine inclusion of the middle hepatic vein in the right hemi-donor liver. In addition, a venoplasty has been proposed to replace the traditional end-to-end anastomosis of the right, middle hepatic vein of the donor-recipient liver. The application of this modified outflow tract plication technique in right hepatic living liver transplants containing the middle hepatic vein has resulted in graft survival rates of 100% and 96% at 1 and 2 years, respectively. No studies have reported an increase in postoperative donor complications as a direct result of right hemi-donor liver containing the middle hepatic vein; in contrast, two recent publications reported that right hemi-hepatectomy containing the middle hepatic vein neither increased donor postoperative mortality nor affected early postoperative liver function and regeneration of the residual liver. The University of Hong Kong study also found that regeneration of vessels and bile ducts in the liver parenchyma was not proportional to compensatory volume increase of the residual liver, and that postoperative liver regeneration occurred mainly in the first year, while residual liver volume reduction even in the second year with a decrease in platelet and white blood cell counts may be a compensatory change caused by postoperative elevated portal vein pressure. Therefore, even though the donor safety can be ensured in the short term after resection of the middle hepatic vein together with the right half of the liver, its long-term safety needs longer follow-up to be clarified. The technique of right hemi-hepatic acquisition including the middle hepatic vein is not routinely used in many transplantation centers in Europe, the United States, Japan, and Korea. Kim et al. in Korea advocated the inclusion of the median vein only in cases where the donor's right hemi-liver is small and may lead to postoperative microhepatic syndrome in the recipient. Centers such as those in mainland China and Taiwan currently advocate the trade-off of the middle hepatic vein based on the effective volume of the transplanted liver and the anatomical structure of the donor vein. It is generally accepted that preoperative CT assessment of the donor-recipient liver volume, when the residual donor liver is >35% and the right hemi-liver graft volume/recipient standard liver volume is >40% t1~, the application of right hemi-donor liver without intrahepatic vein is safe for both the donor and recipient.  5. Outflow tract reconstruction of right hemi-donor liver For right hemi-liver transplant recipients that do not contain the middle hepatic vein, the patency of the right anterior hepatic lobe venous return is an important factor affecting postoperative liver function recovery and liver tissue regeneration. Localized venous reflux in the liver after implantation is usually manifested by swelling and discoloration of segments V and VIII of the transplanted liver after portal vein reperfusion. In some patients, such as severe bruising and extreme swelling of the right anterior lobe of the liver, rupture of the transplanted liver may even occur after portal vein reperfusion. Poor venous return increases the risk of hepatic artery thrombosis and raises the sinusoidal pressure and damages the endothelial cells of the hepatic sinusoids, so this group of recipients can also present with small liver syndrome. In order to achieve a satisfactory transplant outcome, it is well established in major transplantation centers to reconstruct the outflow tract to ensure a smooth venous return to the right anterior lobe of the liver. It is important to accurately determine whether the donor liver requires outflow tract reconstruction and which areas need to be reconstructed. The size of the gray ischemic area on the surface of the graft (segments V and VIII), the hepatic artery/vein obstruction test, and the donor-recipient weight ratio can all be used as references for venous return reconstruction. In addition, the presence of venous stasis in the right anterior lobe of the liver can be determined by detecting changes in portal flow in the right anterior lobe with ultrasound after clamping the middle hepatic vein, or by clamping the right hepatic artery and middle hepatic vein during the donor acquisition procedure and observing the perfusion of the right anterior lobe of the liver. Currently, outflow tract reconstruction of the right hemi-donor liver that does not contain the middle hepatic vein is performed internationally by implanting autologous or allogeneic vein grafts between the severed ends of the V and VIII segments of the donor middle hepatic vein and the recipient hepatic vein or inferior vena cava. Venous grafts can be obtained from a variety of sources, including autologous saphenous veins, umbilical veins, and cryopreserved allogeneic iliac vessels, etc. In 2001, Lee et al. reported on five living liver transplants without venous return reconstruction of the right anterior lobe of the graft at their center, and two of them developed graft sludge, massive ascites, sepsis, or graft malfunction, and one of them died 20 d postoperatively. This led to the proposition of reconstructing the V and VIII outflow tracts with the external iliac vein or saphenous vein, which directly feeds into the inferior vena cava. This modified right hemihepatic living liver transplantation has gained a certain degree of popularity and achieved more satisfactory results. Outflow tract reconstruction of the right anterior lobe of the liver using the umbilical vein as a graft has also achieved similar results to that of a donor liver containing the middle hepatic vein. The Japanese experience is to selectively reconstruct the venous reflux of the right anterior lobe of the liver based on the anatomy of the donor liver instead of routinely including the middle hepatic vein. Most centers now advocate aggressive outflow tract reconstruction in principle for hepatic segmental reflux veins of 5 mm or greater. The experience of our center is to use the recipient’s own portal vein graft for venous bypass to reconstruct the outflow tract of the middle hepatic vein, a technical innovation that has gained the attention and recognition of the international transplantation community.  Liver transplantation for liver cancer As one of the indications for liver transplantation, the criteria for selecting the recipient for liver cancer are not uniform from center to center. In 1996, Mazzaferro proposed the Milan criteria, i.e., a single tumor diameter ≤ 5 cm, or a number of foci ≤ 3, each ≤ 3 cm in diameter. These criteria focus on tumor size and number, but do not take into account prognostic factors such as vascular invasion and histological differentiation. The Pittsburgh criteria improved the TNM staging by considering not only tumor size and distribution but also vascular invasion and lymph node metastasis when selecting liver transplants for hepatocellular carcinoma. After careful case selection, some liver transplantation research centers have found that many patients with liver cancer beyond the Milan criteria or UCSF criteria can still achieve similar treatment outcomes after liver transplantation as those who meet the criteria. Through a large-scale retrospective clinical study, our center has explored and developed the Hangzhou criteria for liver transplantation of liver cancer in accordance with China’s national conditions: patients without large blood vessel invasion, tumor diameter <8cm, AFP level <400ng/ml and histological grade of high/medium differentiation are given priority for liver transplantation; if the tumor diameter is >8cm, both AFP level <400ng/ml and histological grade of high/medium differentiation must be met. If the tumor diameter is >8cm, the AFP level must be <400ng/ml and the histological grade is high/medium differentiation, then liver transplantation can be considered. The selection criteria of liver transplantation for hepatocellular carcinoma in Hangzhou have been shared and well recognized in several international academic conferences. Further studies have found that living liver transplantation is no less effective than cadaveric liver transplantation for patients with liver cancer, provided that the indications are carefully controlled. All four patients with living liver transplantation for hepatocellular carcinoma performed in our center have had no recurrence in postoperative follow-up to date.  In the past decade, living liver transplantation has developed worldwide, especially in Asian countries where donor sources are relatively difficult, depending on strict donor selection, careful preoperative evaluation, delicate surgical techniques, and perfect postoperative care and proper management of complications. Improving the effective utilization of the donor liver and ensuring donor safety are a contradictory unity that guides surgeons to continuously explore and improve living liver transplantation techniques. In the past 5 years, living liver transplantation in China has flourished, with continuous improvement in transplantation surgical techniques and postoperative monitoring systems, and a steady increase in the number of transplantation cases and recipient survival rates, accumulating its own experience with Chinese characteristics and gradually integrating into the international transplantation community. Living liver transplantation not only makes liver transplantation an elective procedure, but also significantly reduces the waiting time for donor livers for critically ill patients with liver cancer and acute liver failure, and its superiority is becoming increasingly evident. Our center has successfully performed emergency live liver transplantation for advanced severe hepatitis and acute liver failure. Compared to the more mature cadaveric liver transplantation, living liver transplantation is still in its infancy, and China's living liver transplantation business is facing great challenges and opportunities. Not only are there still many sociological, ethical and legal issues related to organ donation, but the technical difficulties of living donor liver transplantation are also high, both in terms of ensuring that the remaining liver meets the donor's own needs (donor safety) and in ensuring that the donor liver functions adequately after transplantation (donor effectiveness). It is believed that with the joint efforts of the transplantation community, breakthroughs are expected to be made in solving these hot issues, and China's living liver transplantation will definitely usher in a more glorious tomorrow!