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M. Zhang et al.
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
conguration following
side-to-side cavocavostomy
a
b
c
14 Safety andSuccess inModern Liver Transplantation
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235
fashion. Irrespective of technique, unobstructed outow is essential. Venous outow
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 outow (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 sufciently “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 conguration 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.
M. Zhang et al.
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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237
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 reect 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 efcacy of the post-operative drains previously placed. Operative
revision of the biliary anastomosis itself can be undertaken but is usually technically
challenging in an inamed 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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M. Zhang et al.
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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239
Post-Operative Care
The average hospital length of stay following liver transplantation is 10days. 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 modiable 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 efcacy 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 denitions 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 identied. 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 prole 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 beneciaries and ensure broad, rapid, and equal access to liver transplantation for all patients in need.
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M. Zhang et al.
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