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hepatic veins. The lower cava is closed and never connected. Alternatively, a par­tially occluding clamp can be placed longitudinally along the recipient vena cava and a long longitudinal cavotomy is made (Fig.14.3).
The suprahepatic and lower vena cavae on the donor are closed and a matching cavotomy is made along the undersurface of the donor cava. The liver is positioned in the right abdomen, and the donor and recipient cavae are joined in side-to-side
Fig. 14.3 Technique for side-to-side cavocavostomy. (a) A Satinsky clamp is placed longitudinally along the recipient vena cava such that it only partially occludes ow. A longitudinal venotomy is made. A stay stitch can be used to open the venotomy. (b) The donor liver is placed in the right upper quadrant such that the donor and recipient cavae lie adjacent. The back wall of the cavocavostomy is completed from the inside and the front wall is completed from the outside. (c) Final conguration following side-to-side cavocavostomy
a
b
c
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fashion. Irrespective of technique, unobstructed outow is essential. Venous outow obstruction can cause venous congestion, hepatic dysfunction, ascites, and even thrombosis and allograft failure. In LDLT, the hepatic vein or veins are generally sewn to large cavotomies on the right-lateral side of the recipient cava so that the small hemi-liver can lie in the right abdomen, without twisting the recipient cava and obstructing hepatic venous outow (Fig.14.4).
Following the caval anastomosis, the donor and recipient portal veins are joined in end-to-end fashion taking care to shorten the donor vein as much as possible to avoid redundant bowing that can cause thrombosis. The arterial anastomosis can be completed before or after reperfusion of the allograft. A “parachuting” technique can facilitate rapid anastomosis when the arterial sewing angles are challenging. In DCD liver transplantation time to arterial reperfusion should be minimized to avoid ischemic cholangiopathy, and many centers infuse tissue plasminogen activator (TPA) via the hepatic artery prior to anastomosis to eliminate thrombi in the biliary microvasculature [68, 69].
Liver allograft reperfusion poses unique challenges [70]. Potassium and lactate loads, as well as cold preservation solution released from the donor liver, can cause substantial cardiac dysfunction as well as systemic vasoplegia. These are best avoided by thoroughly ushing and warming the liver. This can be achieved by opening the portal vein while the caval clamps remain in position. Blood lls the donor liver and can be drained through an open lower vena cava (in piggyback tech­nique) or through a venting hole in an untied caval anastomosis (in caval interposi­tion or LDLT). Once the liver is sufciently “blood ushed” the caval anastomosis can be tied or the lower vena cava can be rapidly closed with a vascular stapler. The
Fig. 14.4 Anatomic conguration of a living donor right lobe graft following venous, portal, and arterial anastomoses but prior to biliary reconstruction
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caval clamps are then removed and the donor liver is then in full continuity with the recipient circulation. This technique markedly reduces the incidence of post­reperfusion arrest.
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Biliary Reconstruction
Whenever possible, end-to-end anastomosis of the donor and recipient bile duct is preferred. Care is taken to make sure the anastomosis is well vascularized, tension­free, and non-redundant in length. Duct-to-duct anastomoses enable relatively easy post-transplant biliary interventions via endoscopic retrograde cholangio­pancreatography, which can be particularly useful in cases of biliary leak or stric­ture. Certain disease states (e.g. primary sclerosing cholangitis) or technical complications (e.g. dense scarring of the recipient duct in a re-operative scenario) prohibit use of the recipient duct. In these cases, biliary continuity is best restored with a Roux-en-Y hepaticojejunostomy. Choledochoduodenostomy has also been described and can be useful if the bowels are “frozen” from prior surgical proce­dures [71].
Hemostasis
Reoperation for post-operative bleeding occurs commonly in liver transplanta­tion. Causative factors include raw surface area within the abdominal cavity, delayed production of clotting factors by the freshly transplanted liver, acidosis, hypothermia, and sometimes massive-transfusion coagulopathy. Meticulous attention to hemostasis during the hepatectomy and after implantation is neces­sary. Aside from balanced resuscitation with red cells, fresh frozen plasma, platelets and cryoprecipitate, adjunctive agents including aminocaproic acid, tranexamic acid, and prothrombin complex concentrate are sometimes used [72]. Intraoperative use of thromboelastography is particularly useful to guide bal­anced resuscitation [73]. It is crucial to understand that clotting factor replace­ment is extremely dynamic in the operating room and early post-operative period. A perfectly resuscitated patient may again suffer from coagulopathy due to ongoing factor consumption and submaximal production by the recovering allograft.
Both lab values and drain output character and quantity should be used to guide post-operative resuscitation in the intensive care unit, and administered products should be given promptly and should be warmed if possible. Abdominal packing and use of a temporary abdominal closure can be considered in cases where surgical or medical hemostasis is particularly challenging.
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Complications
Current national one-year survival following adult liver transplantation in the US is estimated at 92% [3]. Causes of morbidity and mortality are varied but can be divided into intraoperative, perioperative, and remote events. Intraoperative catas­trophes including fatal hemorrhage, air embolism, intraoperative myocardial infarc­tion, post-reperfusion arrest, pulmonary embolism, and new right heart failure are all described. Fortunately, despite these possibilities, chances for on-table death during liver transplantation are exceedingly low in the modern era.
Primary Non-function (PNF)
This Primary non-function is a rare but ominous occurrence estimated to occur in ~2% of liver transplants [74]. Patients are urgently re-listed for liver transplantation. Occasionally the failing allograft acts similar to an abscess and patients can actually be stabilized by explanting the failed allograft, creating a portacaval shunt, and sup­porting the anhepatic patient in the intensive care unit prior to re-transplantation. More commonly, recipients experience early allograft dysfunction (EAD) [50] with elevated aminotranferases, bilirubin, or INR which reect delayed or submaximal functioning of the allograft. The exact relationship between EAD and long-term allograft survival is controversial, but EAD certainly leads to increased length of stay and vulnerability to other in-hospital complications.
Hepatic artery thrombosis (HAT) and bile leak are uncommon but serious peri­operative complications. HAT can, but does not always, manifest with deranged aminotransferases. Some centers perform routine post-transplant ultrasonography to surveil for HAT.If caught early, HAT can sometimes be salvaged with arterial thrombectomy, revision or the creation of a new arterial conduit. If undetected, HAT leads to progressive cholangiopathy, development of intrahepatic abscesses, and need for re-transplantation [75]. Bile leaks are estimated to occur following ~5–20% of liver transplants [76] and are typically detected via drain output, imaging, or a downturn in clinical trajectory. When a standard duct-to-duct biliary anastomosis was used, ERCP and stenting offer opportunity to control the leak. Reoperation for washout and wide drainage is sometimes necessary depending on the volume of bile spilled and the efcacy of the post-operative drains previously placed. Operative revision of the biliary anastomosis itself can be undertaken but is usually technically challenging in an inamed or infected eld with compromised tissue quality. Conversion to Roux-en-Y hepaticojejunostomy is often a preferred option when surgical revision is necessary. Percutaneous transhepatic cholangiocatheters are very useful for bile diversion in complex leaks.
Biliary stricture and ischemic cholangiopathy (IC) are often considered the Achilles’ heels of liver transplantation. Biliary strictures are estimated to occur in 15–30% of deceased donor liver transplant recipients and 30–60% of LDLT
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recipients [77, 78]. Stenting and balloon dilation are the mainstays of management. IC can occur following any type of liver transplant but is typically associated with DCD donors. Historically, 8–12% rates of IC have been reported in DCD liver transplantation; however, rates as low as 1–2% have been reported in modern series [51]. IC can be of varying severity and can be categorized by location within the biliary tree [48]. Some forms of IC are amenable to endoscopic intervention and others require re-transplantation.
Late Complications
In the months and years following liver transplantation, recipients are monitored for rejection, common complications of immunosuppression, and recurrent liver dis­ease. Rare but devastating conditions such as post-transplant lymphoproliferative disorder (PTLD) and graft-versus-host-disease (GVHD) do occur. Infections typi­cally associated with lifelong immunosuppressive use include cytomegalovirus (CMV), Epstein-Barr virus, and Pneumocystis carini pneumonia (PCP). Leading causes of late mortality in liver transplant recipients include de novo malignancies, cardiovascular complications, and infection (Table 14.5).
Table 14.5 Complications of liver transplantation
Intra-operative
Hemorrhage Air embolism Intraoperative myocardial infarction Post-reperfusion arrest Pulmonary embolism New right heart failure
Perioperative
Primary non-function (PNF) Early allograft dysfunction (EAD) Hepatic arterial thrombosis (HAT) Bile leak
Early and late post-operative
Biliary stricture Ischemic cholangiopathy (IC) Rejection Renal failure Recurrent liver disease Post-transplant lymphoproliferative disease (PTLD) Graft-versus host disease (GVHD) CMV, EBV, HSV, PCP infections de novo malignancy Cardiovascular complications
CMV Cytomegalovirus, EBV Epstein- Barr virus, HSV Herpes simplex virus, PCP Pneumocystis carini
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Post-Operative Care
The average hospital length of stay following liver transplantation is 10days. Many recipients require additional nursing care or physical therapy following hospital discharge which can involve a rehabilitation facility or at-home services. Most com­mon immunosuppression regimens include a calcineurin inhibitor, mycophenolate mofetil, and a corticosteroid taper [79]. Bloodwork is usually checked twice weekly initially and with reduced frequency as time passes. Particular attention must be paid to calcineurin inhibitor levels. High levels are nephrotoxic and cause a wide range of side effects, and low levels may precipitate rejection. Proactive long-term care of liver transplant recipients includes regular dermatology follow-up, timely cancer screening, attention to modiable cardiovascular risk factors, monitoring of bone density and renal function, and the provision of appropriate immunizations.
Measuring Success
One-year patient and graft survival, though valuable, fail to address the overall ef­cacy of the transplant center in serving a population of patients with ESLD and also fail to capture patient experience and satisfaction [80]. There is increasing interest in composite metrics, such as “textbook outcome,” that capture transplant center performance in multiple domains and offer more holistic denitions of quality and success [81]. Regulatory monitoring is evolving as well. Transplant centers are now accountable for risk-adjusted waitlist mortality and organ offer acceptance rates, in addition to patient and graft survival [82]. Lastly, numerous disparities in access to liver transplantation have been identied. Organ allocation policy has been substan­tially revised in an effort to promote equity [83].
Future Perspectives
Despite harrowing origins in which liver transplantation was described by some as unethical, liver transplantation is now widely recognized as safe standard-of-care therapy for patients with otherwise incurable liver disease. The future of liver trans­plantation is bright. Indications for liver transplantation, particularly within the emerging domain of transplant oncology, are expanding. Growing world-wide experience with LDLT has increased the safety prole of this operation. Broader donor utilization is now possible because of advances in organ preservation and maturation of the techniques required for safe utilization of DCD donors. Long­term patient and graft survival continue to improve. Better immunosuppressive drugs are in development and transplant immunobiologists are moving closer to the goal of immunologic tolerance. Moving forward, the eld is challenged to identify all potential beneciaries and ensure broad, rapid, and equal access to liver trans­plantation for all patients in need.
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