Liver
Transplantation
Authored by Cosme
Manzarbeitia, MD, Chairman of Transplant Division,
Fellowship Director, Assistant Professor, Department of Surgery, Albert
Einstein Medical Center, Thomas Jefferson University
Cosme Manzarbeitia, MD, is a member of the
following medical societies: American
Association for the Study of Liver Diseases, American
College of Surgeons, American Medical
Association, American Society of Transplant
Surgeons, Association for Academic Surgery,
and Pan American Medical Association
Edited by Tushar Patel, MD,
Associate Professor, Department of Internal Medicine, Texas A&M College of
Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy
Editor, eMedicine; You Min Wu, MD, Chairman, Associate
Professor of Surgery, Transplant Division of Surgery, UIHC; Michael E
Zevitz, MD, Consulting Faculty, Clinical Assistant Professor,
Department of Medicine, Finch University of Health Science, Chicago Medical
School; and Julian Katz, MD, Professor, Department of Internal
Medicine, Division of Gastroenterology, MCP Hahnemann University
eMedicine Journal, June 12 2002, Volume 3, Number 6
|
|
INTRODUCTION |
Section
2 of 11 |
History of the Procedure: Liver transplantation (LT) started before the 1960s
with the pivotal baseline work of Thomas Starzl in Chicago and Boston, where
the initial LT techniques were researched in dogs. Starzl attempted the first
human LT in 1963 in Denver, but a successful LT was not achieved until 1967.
In 1970, with an immunosuppressive regimen
largely based on steroids and azathioprine, survival rates were
dismal—approximately 15% at 1-year follow-up. LT did not become a clinical
reality until the early 1980s, after the discovery of cyclosporine and
improvements in rejection rates.
In 1983, the National Institutes of Health
(NIH) established, by consensus, that LT was to be considered out of the
experimental realm and was to be clinically accepted as definitive therapy for
end-stage liver disease (ESLD). Additional improvements in immunosuppression
that were instrumental in advancing the science included the discovery of
monoclonal antibodies (ie, muromonab-CD3 [OKT3]) in 1986.
The combination of improvements in rejection
rates and in surgical technique led to an enormous expansion of the field
during the 1980s, with expansion from 3 centers in 1982 to more than 120
centers today. In 1999, 4500 procedures were performed, up from approximately
100 in 1982.
Of great importance in this expansion was
the development of the University of Wisconsin (UW) solution in 1988, which
increased preservation time and allowed for a smoother surgical procedure,
avoiding a rushed tour de force in the operating room. Finally, the coming of
age of newer immunosuppressants, such as tacrolimus and interleukin (IL)–2
receptor blockers, has paved the way for further growth in this field. All
these advances have produced excellent results, with current 1-year patient
survival rates of 85-90% and 5-year survival rates of 65%. Future advances may
include the development of xenotransplantation, which was pioneered by Starzl
in 1992, and the development of cloning techniques and their impact on organ
availability.
Problem:
End-stage liver disease magnitude and
organ shortage
The following list shows potential International
Classification of Diseases, Ninth Revision, Clinical Modification diagnoses that could indicate candidacy for LT. The
number of patients hospitalized with these primary and secondary diagnoses is
enormous. However, only a small percentage of these patients ultimately are candidates
for transplant because other criteria are also used to determine candidacy.
Diagnoses indicating potential candidacy for LT include the following:
The
major constraint to meeting the demand for transplants is the availability of
donated (cadaver) organs. Several steps have been taken, nationally and
locally, to alleviate the organ shortage. National required request laws
mandate that families of every medically suitable potential donor be offered
the option to donate organs and tissues. In addition, laws such as Act 102,
enacted in Pennsylvania, require all deaths to be reported to organ procurement
organizations. This is resulting in increased organ donations and soon will be
adopted nationwide. Rising public awareness about organ transplantation should
continue to reduce the organ shortage. Finally, aggressive usage of extended
donors and reduced-size, split, and living-related LT continue to expand the
organ donor pool, although these efforts still fail to meet the need.
In
terms of procurement and distribution, major improvements are being made
nationally to optimize distribution and to ensure good matches. Criteria for
inclusion on the waiting list are being standardized with the recent
development of listing criteria for all degrees of sickness. The United Network for Organ Sharing
(UNOS) maintains a computerized registry of all patients waiting for organ
transplants. All organs procured within a region are shared first within the
region; if an appropriate recipient cannot be found within the region, the
organ is directed by UNOS to the recipient with the greatest need in another
region. Organ recovery coordinators are on call 24 h/d and arrange for
serologic testing, removal, preservation, and distribution; additionally, they
educate the public regarding organ donation.
Frequency: According to
the latest US Centers for Disease Control and Prevention sources, cirrhosis
remains the 12th leading cause of death for adults in the United States, with
26,225 deaths reported in 1999 and a death rate of nearly 10 cases per 100,000
persons. This accounts for 1.1% of total deaths. Unfortunately, this number may
grossly underestimate the real impact of ESLD because it does not include acute
liver failure or other etiologies that may lead to the need for LT (see Problem).
Etiology: See Problem.
Clinical: Patients
present with signs and symptoms of ESLD, which is discussed in more detail in
the next section.
|
|
INDICATIONS |
Section
3 of 11 |
Currently,
any patient who has chronic or acute liver disease that leads to inability to
sustain a normal quality of life or that results in life-threatening
complications should be considered a candidate for LT.
The
common etiologies and indications for LT in adults can be seen in the red
portion of the pie chart shown in Image 2. The red part
represents the hepatocellular group of diseases, ie, those that primarily
affect hepatocyte function and thus lead to faster clinical deterioration and
life-threatening complications. The green part represents the group of
cholestatic diseases, in which the excretory function of the liver is primarily
compromised. In these latter cases, synthetic function is preserved for
prolonged periods. Additional indications, such as transplantation for
metabolic or inherited diseases (eg, familial hypercholesterolemia,
amyloidosis), are considered on a case-by-case basis.
Clinical
presentation
As
a general rule, the following complications of ESLD warrant LT:
Ascites
is associated with a poor prognosis in the mid- to short-term, especially when
it becomes unmanageable with diuretic therapy and requires repeated
paracentesis, transjugular intrahepatic portosystemic shunt (TIPS), or
insertion of a peritoneovenous shunt. Encephalopathy may develop rather
insidiously in most patients and may be difficult to elicit properly upon
examination.
Clinically,
encephalopathy is divided into 4 stages. Of these, the most obviously
life-threatening are stages 3 and 4 (somnolence and coma). Synthetic
dysfunction is perhaps the earliest manifestation of ESLD, often manifested by
decreased albumin levels alone or in combination with prolongation of the
prothrombin time and jaundice. In its most severe form, it can lead to severe
malnutrition. Portal hypertension can manifest either silently (ie, decreased
platelets and/or WBC count) or overtly, with variceal bleeding. Other
manifestations include the development of hepatocellular carcinoma (HCC), which
is common in patients with hepatitis B and C, or severe intractable pruritus.
Finally, a controversial indication for transplantation in the face of the
organ shortage is in those patients with severe disabling fatigue.
In
general terms, diseases that cause ESLD do so by affecting either the function
of the hepatocyte (eg, hepatocellular diseases) or the excretory function of
the biliary system (eg, cholestatic diseases). Their prognoses are different,
and their management must be individualized. As a general rule, hepatocellular
diseases cause a more profound derangement of hepatic synthetic function early
in the disease process. Conversely, cholestatic diseases preserve
hepatocellular function until more advanced stages of the disease process.
Indications
for LT can also be broadly categorized into severity of disease indications
(ie, the patient’s life is immediately threatened without transplant) and
quality of life indications (ie, the patient is permanently disabled, but his
or her life is not in immediate danger). While the former obviously mandates
urgent transplantation, great expertise is needed to address the latter.
|
|
RELEVANT ANATOMY AND CONTRAINDICATIONS |
Section
4 of 11 |
Contraindications: Currently
accepted absolute contraindications to LT by most programs include HIV
positivity, SBP or other active infection, severely advanced cardiopulmonary
disease, extrahepatic malignancy that does not meet cure criteria, active
alcohol or substance abuse, and inability to comply with immunosuppression
protocols because of psychosocial situations.
SBP,
sometimes protean in its manifestations (eg, malaise, abdominal discomfort),
can be devastating and can cause decompensation in an otherwise stable patient
with cirrhosis. The patient may present with encephalopathy, hypotension,
fever, leukocytosis, and an elevated WBC in the peritoneal fluid. The absolute
criteria for diagnosis of SBP are the presence of more than 200-250
polymorphonuclear leukocytes, the identification of bacteria in the fluid by
light microscopy, and/or subsequent positive bacterial culture results in the
appropriate clinical setting. The development of SBP in a patient with
cirrhosis is an indicator of a very poor prognosis.
If
pneumonia or other active infections are present, mortality rates after
transplantation are greatly increased. This emphasizes the need to have a high
index of suspicion for infection. If any doubt exists about the presence of
infection, abdominal paracentesis, chest radiograph, urine analysis, and/or pan
cultures may be indicated. In patients with a prior history of drug use,
examine arms and legs for evidence of new track marks. Patients with a history
of alcohol abuse should have an alcohol level test performed as part of the
preoperative workup through contract arrangements and upon admission for
transplant.
Secondary
liver malignancies are not indications for hepatic replacement because of
universal recurrence of the tumors under immunosuppression. Exceptions to this
rule include metastatic neuroendocrine malignancies such as carcinoid tumors.
An elicited history of previous malignancy in a transplant candidate should
prompt an extensive workup for metastatic disease, staging before and after
surgery or therapy, and consultation with an oncologist.
Relative
contraindications to LT are multiple, and each should be weighed when
considering the prospective recipient’s severity of illness. While no single
relative contraindication alone may prevent a given patient from receiving an
LT, these are red flags that, if multiple or if presenting in an otherwise
high-risk recipient, may proscribe LT. Most commonly, these red flags include
patients with chronic renal failure (in which combined liver-kidney transplant
may be required), advanced cachexia, large HCCs (>5 cm diameter),
lamivudine-resistant hepatitis B virus (HBV) cirrhosis, portal and mesenteric
vein thrombosis, history of prior cancer, active infections, and multisystem
organ failure states. Note that many of these contraindications are
program-specific and depend greatly on the volume and experience of each
individual program.
Age
is no longer considered an absolute contraindication. Physiological age, rather
than chronological age, dictates the individual’s suitability for candidacy.
However, careful judgment should be used in allocating donors to these
patients, given the organ shortage. With the development of refinements in
surgical techniques, selected patients with portal and/or mesenteric venous
thrombosis have undergone successful transplantation. The availability of
venous jump grafts to restore portal flow permits transplantation in these
generally advanced cases.
If
studied carefully, all patients with cirrhosis are found to have a certain
degree of intrapulmonary shunting. In certain patients, this can be disabling
and can lead to hypoxia at rest (hepatopulmonary syndrome). The successful
reversal of these shunts after LT makes this an indication rather than a
contraindication. However, selection of these candidates must be adequate and
precise, with sophisticated and directed pulmonary function testing.
The
presence of established anatomical portopulmonary hypertension is probably an
absolute contraindication for LT, but the situation varies for nonfixed
pulmonary hypertension. LT is contraindicated in patients with severe degrees
of pulmonary hypertension (mean peak airway pressure of >35),
especially if coupled with increased pulmonary vascular resistance. However,
for those patients with mild-to-moderate pulmonary hypertension and reasonable
right heart function, treatment with vasodilators and/or prostaglandin allows
safe LT.
The
existence of prior abdominal surgery and portosystemic shunts does not preclude
successful transplantation, although these factors make it a technical tour de
force and dramatically increase blood loss because of existing portal
hypertension. Recently, some groups have reported good results with selective
shunting or TIPS.
The
great likelihood of recurrent and aggressive disease precludes transplantation
in patients with actively replicating HBV infection. Recently, some groups have
tried xenotransplantation in this population, but better results must be
obtained prior to using this resource more widely. A subgroup of these patients
with a small viral load and/or no active replication but with ESLD may be
considered for candidacy. In these patients, the institution of lamivudine
therapy may render the viral replicative activity undetectable, hence allowing
safe transplantation. The emergence of lamivudine-resistant strains may limit
the long-term use of these therapies.
Very
weak and malnourished patients are poor candidates for LT because of an
extremely poor reserve. If their nutritional status can be improved by means of
total enteral nutrition or total parenteral nutrition, their odds improve. This
is difficult to accomplish in the face of a failing liver.
Frequently,
cirrhosis is associated with development of HCCs. In these patients,
transplantation must be performed under strict guidelines and protocols to
minimize and/or prevent recurrence. As a rule, HCCs smaller than 5 cm, ie,
incidental hepatomas, are associated with less chance of recurrence and
survival rates equal to those of patients undergoing transplant because of
nonmalignant conditions. Protocols using chemoembolization have shown promising
early results for larger tumors.
|
|
WORKUP |
Section
5 of 11 |
Lab Studies:
Table 1.
Child-Turcotte-Pugh Scoring System for Assessment of Severity of Disease (with
respect to listing)
|
Parameter |
1 |
2 |
3 |
|
Encephalopathy |
None |
Grade 1-2 |
Grade 3-4 |
|
Ascites |
None |
Medically controlled |
Uncontrolled |
|
Albumin |
>3.5 |
2.8-3.5 |
<2.8 |
|
Bilirubin |
<2 |
2-3 |
>3 |
|
International Normalized Ratio (INR) |
<1.7 |
1.7-2.3 |
>2.3 |
Imaging Studies:
Other Tests:
Diagnostic Procedures:
Histologic Findings: Discussion of all the histopathological findings of
the various diseases that lead to ESLD is beyond the scope of this article. In
general, they can be classified into 3 broad categories: cirrhosis and
fibroticlike states, acute hepatic necrosis, and malignancies.
|
|
TREATMENT |
Section
6 of 11 |
Medical therapy: Medical
management before transplantation is aimed at preventing and treating the
complications associated with ESLD. Thus, many patients take various
medications to control the consequences of liver failure and portal
hypertension. These complications include (but are not limited to) ascites,
SBP, HRS, encephalopathy, esophageal varices, and intense pruritus.
Ascites
presents a difficult treatment problem. As a first step, paracentesis should be
performed to confirm portal hypertension as the etiology. Initially, salt
restriction may be tried, although this is effective in fewer than 20% of
patients. Fluid restriction should be avoided unless patients have gross
anasarca and/or their serum sodium level is less than 120 mEq/L. Diuretics
remain the mainstay of medical management. The most commonly used are
spironolactone, furosemide, and hydrochlorothiazide. Diuretic therapy should be
adjusted or discontinued if serum sodium levels fall below 120 mEq/L or if the
creatinine level rises to more than 2 mg/dL. Other diuretics that may be used
include amiloride, triamterene, or ethacrynic acid.
If
the ascites become refractory because of an inability to diurese patients
and/or development of electrolyte abnormalities and renal failure, repeat
paracentesis may be performed every 2-3 weeks. TIPS may result in a significant
decrease in ascites; however, risk of ischemic hepatic failure and intractable
encephalopathy is higher, which limits its use in patients with cirrhosis
classified as Child class C because of an increased morbidity and mortality
rate. Other options include using peritoneovenous (LeVeen and Denver) shunts,
although these are prone to occlusion, disseminated intravascular coagulation,
and increased perioperative mortality.
SBP
presents in patients with cirrhosis who have ascites as an unexplained clinical
deterioration, with or without the classic signs of peritonitis, and is
associated with a high mortality rate. Paracentesis findings that are
diagnostic include an absolute neutrophil count in the ascitic fluid of greater
than 250/mm3 and/or positive results from peritoneal fluid cultures.
Antibiotic therapy, directed mostly toward gram-negative enteric organisms,
should be started early. Secondary peritonitis, such as that due to a
perforated viscus, should always be excluded prior to instituting therapy. Prophylactic
antibiotics are frequently employed in patients with cirrhosis who have severe
ascites, previous SBP episodes, or recent variceal bleeding.
HRS
is present in approximately 10% of hospitalized patients with cirrhosis. HRS is
defined as a deterioration of the renal function in a patient with advanced
cirrhosis, with a creatinine level of more than 1.5 mg/dL, a urine volume of
less than 500 mL/d, and a low urinary sodium level (<10 mEq/L). The
condition is common in patients with ascites.
Before
a diagnosis of HRS can be established, other specific causes of renal
dysfunction must be excluded. The diagnostic workup frequently includes
insertion of a Foley catheter, renal ultrasound, and fluid challenge.
Frequently unsuccessful, the medical treatment of HRS has been disappointing.
Preliminary data suggest that TIPS may be useful, but its precise role remains
to be defined for this indication.
As
many as 70% of decompensated patients with cirrhosis have some degree of
encephalopathy, ranging from subtle neurological dysfunction to frank coma.
Seek and correct potential precipitating causes such as GI bleeding,
constipation, infection, medications with CNS effects, or electrolyte
abnormalities. If ascites is present, exclude SBP via paracentesis. A search
for other reasons, such as PVT or occult HCC, should be made.
TIPS
can also lead to severe encephalopathy. In addition to this correction of
precipitating causes, treatment is by means of lactulose orally, via
nasogastric (NG) tube, or through enemas, with doses titrated to achieve both
2-4 soft bowel movements daily and improvement in mental status. Neomycin may
be added, although its potential for nephrotoxicity and ototoxicity can limit
its usefulness. The usefulness of flumazenil, a benzodiazepine antagonist,
remains to be defined.
Esophageal
variceal bleeding (EVB) is a major cause of morbidity and mortality in patients
with ESLD. The mortality rate during the initial EVB incident is as high as
50%, with an additional risk of recurrent bleeding of 70% within the first
year. Initial treatment includes aggressive fluid resuscitation, administration
of blood products to replace blood loss and/or to correct coagulopathy, and
emergent endoscopic evaluation with both diagnostic and therapeutic aims. Intubation
may become necessary because of encephalopathy and for airway protection.
Patients are usually placed on intravenous octreotide to reduce the portal
hypertension, H2 blockers to prevent stress ulceration, and antibiotics for SBP
prophylaxis.
EVB
may present overtly, with hematemesis and hemodynamic instability, or more
insidiously, with melena, hematochezia, or encephalopathy. After achieving
hemodynamic stability, perform an endoscopic evaluation of the upper GI tract
with the goals of diagnosis and endoscopic control via rubber band ligation,
sclerotherapy, or both. In approximately 5-10% of patients, these maneuvers
fail to control bleeding; therefore, consider TIPS, balloon tamponade, or
surgical shunts. Reserve the placement of emergency surgical shunts for
patients in Child class A to minimize morbidity and mortality.
Pruritus
is also common in liver disease, mostly in cholestatic liver diseases such as
primary biliary cirrhosis and sclerosing cholangitis, although it is also
common in hepatitis C virus (HCV) cirrhosis. In approximately 90% of patients,
the condition responds to sequential therapy with use of antihistamines,
ursodeoxycholic acid, and cholestyramine. The remaining 10% can be treated with
rifampicin, with a significant reduction of pruritus. Because of the potential
for bone marrow and hepatic toxicity, regular complete blood cell counts and
liver tests are necessary. Opiate antagonists (eg, naloxone, nalmefene,
naltrexone) have increasingly been used in the treatment of refractory pruritus.
Timing
of liver transplantation
The
1983 NIH consensus that finally put LT in the clinical arena stated that, in
order to be successful, LT had to be offered at an optimal time (see Image 3). Optimal timing of LT
is based on the natural history of the disease and the potential for
progression over time. Additionally, the patient must be in the system to have
the opportunity to undergo transplantation, ie, he or she must be listed with
UNOS. All too commonly, patients are referred to the transplant center late in
the stage of their disease, and only then is there an immediate sense of
urgency.
This
scenario results in accelerated and occasionally incomplete evaluations of very
ill patients. If these patients undergo transplantation, they are at a higher
UNOS status (2A or 1), with a resulting lower survival rate and a much greater
cost and length of stay in the hospital and intensive care unit (ICU). To avoid
this, UNOS revises their organ allocation schemes regularly (see Lab Studies). The issue of
transplantation timing is also full of challenges and controversies, as
outlined in Image 4.
To
whom these organs should go is another consideration in the timing of LT. An
ideal approach maximizes patient benefit and graft survival (see Image 5). This is an ongoing
discussion with many perspectives. The right approach is somewhere in the
middle, balancing patient outcome and utility. A move toward this has been made
with the establishment of minimal listing criteria for entry on to the waiting
list. The MELD system, apparently an even better solution for organ allocation,
still awaits full clinical validation.
Surgical therapy: The
different techniques used for liver replacement are discussed at length in the
following paragraphs.
Preoperative details: During
multiorgan procurements, the goal of management is to maintain physiologic
stability (ie, oxygenation, perfusion) so that the organs are in the best
possible condition at harvest. Donors are brain dead and thus do not require an
anesthetic, although they may still exhibit visceral, somatic, and autonomic
reflexes. Additionally, the anesthesiologist may be asked to administer certain
medications (eg, mannitol, furosemide, heparin) as part of the organ
procurement protocol. In general, the goal is to provide supportive care during
the procurement to avoid any insult to the organ(s) being harvested.
Anesthetic
management during the organ implantation procedure follows the same general
provisions as for other procedures, ie, hypnosis, amnesia, analgesia,
neuromuscular blockade, and hemodynamic stability. A rapid sequence induction
is used. Nasal intubation is avoided because of the potential for severe
epistaxis. Isoflurane in air plus a narcotic is the usual anesthetic technique,
and long-acting drugs, such as pancuronium, lorazepam, and methadone, may be
used. Nitrous oxide is avoided because of its effect on enteric distension.
Regional anesthesia for postoperative analgesia is contraindicated because of
actual or potential coagulopathies.
Besides
the standard intraoperative monitors, arterial and pulmonary artery catheters
are placed. In some centers, transesophageal echocardiography is added if
questions arise concerning cardiac function or to help detect significant
pulmonary emboli after reperfusion. An oral gastric tube is inserted, which
later may be changed to an NG tube.
Intraoperatively,
the Rapid Infusor System (RIS, Haemonetics Corporation, Braintree, Mass) is
routinely used. This device can warm and pump the contents of a reservoir at
rates up to 1.5 L/min through large-bore venous access. Blood products and
crystalloid solution are administered via the RIS.
Venovenous
bypass is used to divert inferior vena cava and portal blood flow around the
retrohepatic portion of the inferior vena cava when it is clamped. Cannulas are
usually placed in the femoral vein and the right internal jugular (IJ) or
axillary vein. A third cannula is inserted intraoperatively into the
recipient’s native portal vein. Blood from the femoral and portal cannulas is
then pumped via a centrifugal bypass pump toward the IJ or axillary vein
cannula. Placement of these cannulas can be accomplished percutaneously or via
direct cut down. The right IJ cannula also serves as the infusion site for the
RIS. These cannulae are not needed if bypass is not a requirement of the
surgical procedure.
After
reperfusion, inotropics, vasoconstrictors, calcium chloride, and nitroglycerin
should be immediately available. Epinephrine, norepinephrine, and phenylephrine
are the agents most commonly used at the author’s institution. Nitroglycerin
occasionally is needed after reperfusion if pulmonary artery pressures are
elevated. Transfusion of blood products is often required in LT. Packed red
blood cells and fresh frozen plasma (FFP) are administered via the RIS. Platelets
and cryoprecipitate generally are administered via a peripheral or central vein
after proper filtration.
Other
important intraoperative considerations include the use of antibiotics,
immunosuppression, cytoprotection, and adequate temperature homeostasis.
Prophylactic antibiotics are used frequently and dosed around the operative
procedure, which can be quite lengthy. After complete revascularization of the
allograft, methylprednisolone (1 g) is administered as immunoinduction.
In
addition, prostaglandin E1 is administered at a rate of 0.3-0.6
mg/kg/h in the postanhepatic portion of the surgery as a hepatic and renal
cytoprotective agent, adjusted to blood pressure levels. Finally, maintenance
of temperature is important because it plays a vital role in optimizing the
function of the coagulation system. Methods to achieve this include maintenance
of room temperature, warm air blankets, fluid warming via the RIS, low fresh
gas flow rates, and heat-moisture exchangers. If the venovenous bypass circuit
is used, a heating element may be placed in-line.
Intraoperative details: The
3 elements involved in a successful LT are donor procurement, recipient
implantation, and surgical coordination of these 2 procedures.
Donor
availability is made known to the transplant center with a suitable recipient,
usually with a certain margin of time. The allocation follows the rules of
UNOS. Surgical coordination of both the donor and the recipient operations is
made when declaration of death, proper consent, and adequacy of the donor liver
are evaluated and found to be adequate for the prospective recipient. The donor
team is then transported to the donor's hospital.
The
donor operation proceeds in cooperation with any other procurement teams present.
A long midline incision from suprasternal notch to the pubis is performed to
gain full exposure to the abdomen. The chest is opened via a median sternotomy.
This maneuver properly exposes the intrathoracic structures, allowing both
cardiac and pulmonary organ harvest; it also allows easier hepatic dissection
and extraction for the abdominal surgeon.
The
dissection starts with the mobilization of the liver by dividing its
ligamentous attachments. Sequentially, the left triangular and falciform
ligaments are divided with the aid of electrocautery and are joined in the
midline. Next, the gallbladder is emptied of its bile content by incising it at
the fundus and irrigating it with warm saline until the returns are clear.
Attention is then directed towards the hepatic hilum, which is carefully
examined and palpated by placing a finger in the Winslow foramen to assess for
the presence or absence of anatomic variations. The following are the most
frequently encountered variations:
The
importance of identifying these abnormalities is that any of these replaced or
substituted trunks may contribute a significant amount, if not all, of the
arterial blood supply to the respective lobe; therefore, preserve them whenever
possible. Also, the presence of an aberrant left branch means that the
dissection will be more tedious and delicate in order to preserve the left
gastric artery, the main origin of this aberrant branch, alongside the lesser
gastric curvature. Similarly, a right substituted or replaced branch requires
the delicate dissection of the SMA up to the point of its origin in the aorta.
At
this point in the operative procedure, a decision is made to either proceed in
the usual fashion or resort to the rapid flush technique. This depends on the
stability of the donor. For stable donors, the hepatic hilum is dissected
systematically, dividing and ligating successively the right gastric artery and
the gastroduodenal artery. The other branches of the celiac trunk are isolated
and tied, ie, the splenic artery on the superior edge of the pancreas and the
left gastric artery along the upper lesser curvature of the stomach; the ties are
cut long for posterior identification.
The
free edge of the common bile duct is exposed laterally and isolated, ligating
the distal portion and transecting it. This normally allows dissection of the
common hepatic artery upward and the pancreatic edge downward, thus bringing
into view the anterior surface of the portal vein. Mild blunt dissection is
used to separate the anterior portal surface from the pancreas, with care to
not injure minor tributaries. This allows visualization of the splenic, superior,
and inferior mesenteric veins and cannulation of the splenic vein with the
portal cannula for the portal flush afterward. To do this, the size of the
cannula is adjusted to the size of the vein (introduced after appropriate
venotomy) and is secured with ties.
After
the portal cannula is in place, attention is directed to the infrarenal aorta,
which is dissected free near its bifurcation; during this step, the inferior
mesenteric artery is divided near its origin to obtain a proper segment of
aorta for cannulation. Isolation of the supraceliac aorta follows by retracting
the esophagus to the left and the previously mobilized left hepatic lobe to the
right, thus exposing and dividing the diaphragmatic crura. This is used later
as the site for cross clamping.
The
scenario now is set for perfusion of the organs. The donor is heparinized with
20,000-30,000 IU of heparin, the aortic cannula is introduced in the infrarenal
aorta, the distal aorta is tied, and the suprarenal aorta is clamped. The
organs are then perfused with ice-cold UW solution, and the suprahepatic vena
cava is vented in the pericardial space. At this point, the cold, topical, iced
solution is poured in the abdomen for surface cooling. Some surgeons also vent
the vena cava via the infrarenal portion.
Removal
of the liver then proceeds. The suprahepatic vena cava is taken along with a
generous patch of diaphragm. The left gastric artery is dissected back, as is
the splenic artery. The duodenum is kocherized, and fingers are placed behind
the pancreas; the portal vein is dissected back, and its tributaries are
divided. The SMA is felt through the pancreatic parenchyma, is dissected free,
and is placed on traction with aid of a clamp. Sharp dissection proceeds to the
left of the SMA and is carried down to the aorta; then, dissection from left to
right is performed to identify potential right branches. The celiac trunk is
then removed along with a generous Carrel patch of aorta.
After
the hepatic hilar dissection is completed, the inferior vena cava is divided
above the renal veins and is taken along with the bisected right adrenal vein.
The remaining attachments of the liver and its hilar structures are carefully
divided, and the organ is removed and taken to the back table for an immediate
flush.
This
general procedure is modified in cases of aberrant vessels to include
dissection of the left gastric artery along the lesser curvature of the stomach
(for left branches), or the SMA is included in the Carrel patch and is
dissected very carefully from left to right to avoid injury to accessory right
branches. In unstable donors, the portal system is cannulated first, prior to
the hilar dissection, via the superior mesenteric vein in the inframesocolic
space; the aortic control and cannulation quickly follow, and, after
cross-clamping the supraceliac aorta, the cold flushing is performed.
Thereafter, hilar dissection and removal of the liver is performed in an
asanguinous field. Exquisite care must be exercised to avoid injury to the
vessels or biliary structures.
Once
removed from the body, the liver is again flushed with 1 L of UW on the back
table. After the organ has been properly flushed and packed, the internal iliac
arteries and veins of the donor are procured for potential use as grafts.
Transportation to the recipient's hospital immediately follows, in close
coordination with the recipient's preparation.
Back
table allograft preparation
Prior
to engraftment, the donor liver is removed from ice and prepared for implantation
in a back table procedure. In this procedure, the superfluous tissues that
accompany organs removed en bloc are trimmed, and, if any vascular
reconstruction is necessary, it is performed. The aim of the vascular
reconstruction procedures, usually arterial, is to provide a single common
inflow vessel of sufficient length so that only 1 anastomosis needs to be
performed in the recipient. All vessels are then tested for patency and
integrity by flushing with sterile preservation solution. The donor iliac
arteries and veins routinely procured at the termination of the donor operation
are also prepared for use, if necessary, as venous or arterial grafts in the
recipient.
Full
liver recipient procedure
The
goals of an orthotopic LT operation are to remove the diseased liver (total
hepatectomy) and then to replace it in exactly the same location with a healthy
liver. The recipient hepatectomy could result in massive bleeding; therefore,
paying careful attention to the meticulous gentle handling of tissues and
having a strict systematic approach to hemostasis at all times are crucial.
Proper usage of venovenous bypass and blood products can optimize this part of
the operation, thus decreasing morbidity rates.
A
bilateral subcostal incision with a midline extension to the xiphoid process is
routinely used (ie, "Mercedes-Benz" incision). After mobilizing and
dividing the round and falciform ligaments, a large self-retaining upper
abdominal retractor is placed (see Image 6). The ligamentous
attachments of the liver (ie, left triangular, right triangular, and
gastrohepatic ligaments) are then dissected to mobilize the liver in its
entirety.
Dissection
of the hilar structures then proceeds (see Image 7), with systematic
ligation of the hepatic artery, cystic duct, and common hepatic duct. The
portal vein is then cleaned of surrounding tissue from the level of the head of
the pancreas up to its bifurcation into right and left branches. The hepatic
artery is now formally dissected proximal to the gastroduodenal artery,
exposing the common hepatic artery to allow for subsequent anastomosis. The
gastroduodenal artery is left untied to avoid distal thrombosis or dissection,
which may happen if this is ligated.
Venovenous
bypass may now be initiated (see Image
8). Whether and when to start bypass depends on the degree of portal
hypertension, the extent of previous surgery with vascularized adhesions, and
the degree of bleeding within the operative field, notoriously from the
retroperitoneum. Thus, initiation of bypass may occur early or late during the
hepatectomy phase, as judged by the operating surgeon.
Once
bypass is initiated, the remaining attachments to the liver can be divided
rapidly and the liver can be removed, leaving both upper and lower caval cuffs
for later anastomosis. Depending on the degree of bleeding and the size of the
donor liver to be implanted, the bare area of the liver may be oversewn.
Following this, the vena caval cuffs are shaped for anastomosis.
Implantation
and caval techniques
To confirm adequacy
of the vascular reconstructions, flow is then measured with an ultrasonic or
electromagnetic flow meter. If flow is inadequate, the inflow, outflow, and
anastomoses are examined to determine the reason and to correct the problem(s).
After
achievement of adequate hemostasis, biliary reconstruction can begin. If the
recipient bile duct is of normal caliber and is free of intrinsic disease, a
donor-to-recipient duct-to-duct reconstruction can be performed over an
indwelling T-tube stent that is exteriorized through a separate stab wound
incision. If the 2 ends of the bile duct can be tailored to meet perfectly
without redundancy and are of similar caliber, this end-to-end reconstruction
can be performed without a T-tube. If the patient's native bile duct is
diseased or if the duct is too small, the bile duct of the donor is anastomosed
to a defunctionalized Roux-en-Y loop of jejunum over an internal stent (see Image 12).
Cholangiography
is performed to confirm a technically sound biliary reconstruction and may be
performed through the T-tube or via the cystic duct. With this completed,
closing the abdomen after leaving 3 closed suction drains above and below the
liver concludes the operation.
Recipient
procedure (special cases)
Partial
liver recipient procedures
While
the number of LTs has grown exponentially, the number of organ donors has not
kept pace with the growing number of candidates. This widening gap between
supply and demand has led to higher mortality rates among candidates on the
waiting list. In attempts to narrow this gap, transplant centers have broadened
their donor selection criteria and have begun to employ innovative surgical
techniques such as reduced-size LT, split LT, and living-donor LT.
Reduced-size
LT was introduced in the mid 1980s to provide size-matched grafts for pediatric
patients. In reduced-size LT, a cadaveric liver procured using standard
techniques is resected on the back table to create a smaller graft. The liver
allograft can be tailored based on the recipient’s body size. It is possible to
create a right lobe graft, left lobe graft, or left lateral segment graft. The
rest of the liver is discarded.
In
living-donor LT (see Image 13),
part of the liver from a living donor is resected and transplanted into a
recipient. The technique was first used for pediatric recipients and now has
been extended to the adult recipient population because of excellent results
and established donor safety. In pediatric recipients, either left lateral
segments or full left lobes usually suffice. For adults, right lobe grafts are
necessary to ensure enough liver volume.
This
new procedure provides many advantages to the recipient because of the elective
nature of the procedure (usually before severe hepatic decompensation) and the
assurance of a healthy donor organ with a short ischemia time, resulting in
better graft quality than with cadaveric liver allografts. Technical problems
in the recipient, such as hepatic artery thrombosis and biliary leaks, were
observed initially but have decreased dramatically with increasing experience
in technique and recipient selection. For the donors, the advantage is mainly
psychological.
Because
living-donor LT subjects a healthy individual to major surgery, donor safety is
essential and informed consent is crucial. The American Society of Transplant
Surgeons published guidelines for living-donor transplantation. The risks and
benefits of the living-donor operation must be explained to the donor, the
recipient, and their immediate families. In addition, donors should be thoroughly
evaluated by an unbiased physician. The workup should include a full medical,
psychosocial, and anatomical evaluation of prospective donors. Finally,
although the donor operation has been associated with low morbidity and
mortality rates, long-term follow-up is necessary to confirm the safety of this
procedure for donors, especially for donors of right lobe grafts.
In this case,
removal of the native liver by a piggyback technique is mandatory. The portal
vein anastomosis is performed between the allograft portal vein and the
recipient portal vein using 6-0 Prolene continuous suture. The hepatic artery
anastomosis is performed between the allograft hepatic artery (either right or
left) and the recipient right or left hepatic artery using 8-0 Prolene
interrupted sutures. Sometimes, an operating microscope may be needed,
especially for small arterial anastomoses. Extension grafts are rarely needed.
In most cases, the bile duct anastomosis is accomplished by Roux-Y
hepaticojejunostomy (although sometimes performing duct-to-duct anastomosis is
possible) using interrupted 6-0 polydioxanone sutures.
Not
all donors are suitable for split procedures. Donors should be older than 50
years and should be hospitalized for less than 3 days with perfect liver
function, minimal pressor support, and no steatosis. The final decision of
whether a liver is suitable for splitting should be made in the operating room.
Similarly, recipients should be selected carefully. Relatively stable patients
in Child class B or C tolerate split-related complications better.
Postoperative details:
Following
LT, the function of the new liver is monitored closely in an ICU setting.
Elevations of liver enzymes, notoriously transaminases (ie, aspartate
aminotransferase, alanine aminotransferase), early on are reflective of
preservation injury (cold preservation). On occasion, the enzymes rise sharply.
If they are higher than 2000, the overall viability function of the liver
should be monitored carefully to assess the need for retransplantation.
Usually, the liver enzyme levels normalize very quickly, typically within a
week of transplantation. The bilirubin level follows a similar pattern of early
rise and delayed clearing. However, if the preservation injury is severe, this
elevation can persist for 2-3 weeks and can be accompanied by a significant
rise in alkaline phosphatase levels.
Platelet
counts usually decrease in the first week after LT and recover during the
second week. This may be caused by platelet sequestration in the liver and
spleen due to preservation injury. Once the liver has recovered, as manifested
by the return of bilirubin to normal levels, the platelet count increases.
Recovery in a typical patient is rapid, as is discharge to the floor, usually
within 2-3 days. However, if the graft has suffered severe preservation injury,
return to normality may lag. Treatment is mostly supportive, with the goal of
maintaining stable hemodynamics while the liver recovers. In extreme cases,
termed primary graft nonfunction, the new liver never recovers and needs urgent
retransplantation.
After
the patient’s medical condition has stabilized and graft function is stable, he
or she is transferred from the ICU to the floor transplant unit. At this time,
tests are performed to assure adequacy of the new connections. A duplex Doppler
ultrasound helps check for patency of the vascular anastomoses and the presence
of abnormal fluid collections. If a tube is present, a T-tube cholangiogram is
performed to assure adequate biliary drainage and to exclude leaks.
During
the patient's stay on the floor unit, his or her laboratory studies, medications,
nutritional status, and exercise tolerance are monitored. As soon as patients
are able, discharge instructions begin to prepare them for going home. Most
patients with severe ESLD have a very low albumin level prior to
transplantation. After successful LT, the albumin level slowly rises to normal
levels. This explains the generalized edema that patients may experience
following transplantation, which begins to disappear once albumin levels start
to normalize.
Follow-up care: Upon
leaving the hospital, the patient receives a schedule of follow-up clinic
visits for laboratory tests and checkups. The idea is to track clinical
progress and to detect potential complications (eg, rejections, infections) as
early as possible. Patients are instructed to notify the transplant team if
they have any prolonged illness, fever, nausea, vomiting, or diarrhea or if
they experience any unusual symptoms or adverse effects potentially related to
the immunosuppressants.
Following transplantation, all patients are placed on immunosuppressive drugs to prevent rejection of the new liver. These medications are usually started in the operating room and are continued thereafter. The dose of the immuno