2 How is it possible to properly select patients and properly time transplantation so that the benefit of transplantation is assured? In 2002, the Organ Procurement and Transplantation Network began using the Model of End-stage Liver Disease (MELD)¹⁰ score as a method of prioritizing liver transplant recipients. The MELD score is an integer value based on three objective laboratory studies: creatinine, bilirubin, and the international normalized ratio (INR) (Table 37-1). This has been adapted to pediatric patients as the Pediatric End-Stage Liver Disease (PELD) utilizing the variables in MELD along with albumen instead of creatinine and including age as well as the presence of growth failure (Table 37-1). Analysis done by the Scientific Registry of Transplant Recipients (SRTR) has shown that patients with MELD scores of less than 15 have a mortality rate on the waiting list that is less than the mortality rate of the transplant procedure in the same population.¹¹ This suggests that patients with a MELD score of less than 15 do not receive an absolute survival benefit from transplantation whereas patients with higher MELD scores have the potential to receive a survival benefit with liver transplantation. In other words, there is no evidence that patients who are very ill from liver disease do not benefit from liver transplantation, but patients who have stable, mild liver disease should not receive a transplant until their disease has progressed to a more severe state.

Surprisingly, MELD more accurately predicts mortality than clinical factors that were previously thought to be ominous signs of reduced (6 months or less) survival. Such factors, including the presence of ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, or variceal hemorrhage, do not add to the predictive value of MELD.¹⁰ This finding may be related to the difficult nature of accurately quantifying clinical variables in registry databases or to the fact that MELD is such an accurate way of measuring functional hepatic capacity that no additional clinical variables are more relevant.

As will be discussed later, the transplant community has agreed upon certain exceptions to the MELD score for patients with chronic liver disease. It is generally supported that patients with diseases such as HCC, hepatopulmonary syndrome (HPS), primary oxaluria, and familial amyloidosis benefit from additional MELD points by regional review boards. Other diseases or complications such as portal vein thrombosis or portopulmonary hypertension (PPHTN) remain less clear and are handled on a case-by-case basis.¹²

The improved ability to predict mortality for patients with liver failure allowed the development of national allocation policies that direct livers to those patients that will benefit. Importantly, the implementation of the MELD system of liver allocation from deceased donors has been associated with a decrease in the death rate on the waiting list.¹³ Further refinements of our understanding will undoubtedly occur as improved long-term follow-up data on waiting list mortality become available and as quality of life considerations are added to the analysis.

These considerations apply to the chronic forms of liver failure, but not to the important emergency decisions about transplantation that must be made when a patient presents with fulminant hepatic failure (FHF), which is defined as the progression from good health to liver failure with hepatic encephalopathy within 8 weeks. Without transplantation, the mortality rate for FHF is approximately 75%.¹⁴ Death often occurs rapidly once patients progress to stage II (confusion), stage III, (stuporous), or stage IV (unresponsive) hepatic encephalopathy. In these cases, the decision to perform transplantation is based on clinical grounds. Current liver transplant allocation policy allows for the rapid transplantation of patients with fulminant hepatic failure. These patients can be listed as “status 1A,” (Table 37-2) which gives them higher priority for available livers than patients with chronic liver disease who are prioritized based on MELD score.

CONTRAINDICATIONS TO LIVER TRANSPLANTATION

The number of absolute contraindications to hepatic transplantation has steadily decreased during the past several years as experience with the procedure has increased. Many clinical situations once considered to be absolute contraindications for transplantation are now either no longer considered to be contraindications or to be only relative contraindications. A thrombosed portal vein is no longer a contraindication to transplantation because techniques have been devised to effectively deal with this condition (see Liver Transplantation: Surgical Procedure).¹⁵ The presence of juvenile-onset diabetes mellitus formerly precluded transplantation. In current practice, this is not usually the case, depending on the patient’s physiologic status at the time of evaluation. Similarly, advanced age causes concern, but in most centers the physiologic state of the patient is a more important consideration than the chronologic age.

The inability to withstand the operative procedure, usually for cardiovascular or pulmonary reasons, is still generally considered to be a contraindication to liver transplantation. Specific examples include patients with depressed ejection fraction secondary to ischemic cardiomyopathy, significant pulmonary hypertension, and significant chronic obstructive pulmonary disease. Cardiac disease that is not amenable to percutaneous therapy poses a particular problem because these patients are frequently unable to withstand a corrective cardiac procedure because of their severe liver disease. In highly selected patients it may be possible to perform combined heart and liver transplantation or combined lung and liver transplantation.

Recent intracranial hemorrhage is almost always a contraindication because during the liver transplant procedure, coagulopathy is often present along with significant alterations in arterial blood pressure. The risk of a catastrophic exacerbation of intracranial bleeding during a transplant is therefore high in this setting. However, the meaning of “recent” is not defined in either the transplant or the neurosurgical literature. Profound, irreversible neurologic impairment is also considered to be a contraindication. Active substance abuse remains a contraindication, as is the lack of the necessary social support network.

HIV infection, long considered a contraindication, is no longer an absolute exclusion due to the development of highly effective antiretroviral therapies.^16,17 Active sepsis or untreated infection and active extrahepatic malignancy continue to be contraindications.

Although renal insufficiency increases the risk of liver transplantation, it is not a contraindication. Patients who have hepatorenal syndrome (HRS) frequently experience recovery of renal function following liver transplantation. However, patients who have longstanding hepatorenal failure and patients with known renal parenchymal disease requiring renal replacement therapy are often best served by combined liver/kidney transplantation.

DISEASE-SPECIFIC INDICATIONS AND OUTCOMES

While the MELD score assessment plays a critical role in evaluating and listing patients that might benefit from liver transplantation, patients that develop liver disease–specific complications, regardless of MELD, are also appropriate to consider liver transplantation. Some of these complications along with other liver-specific metabolic diseases are listed in Table 37-3. Hepatitis C is currently the most common disease for which liver transplantation is currently performed in the United States (33%) (Fig. 37-1). Alcoholic liver disease, NASH, and cholestatic liver diseases are the next most common ranging from 10% to 14% of cases. However, this trend is believed to be changing with a greater proportion of liver transplants being performed for NASH (Fig. 37-2).⁵ Outcomes following liver transplantation are best for pediatric patients with biliary atresia, while patients with cholestatic liver diseases experience the best survival among adults (Fig. 37-3). Patients with hepatitis C or HCC experience worse survival secondary to disease recurrence although recent advances in hepatitis C antiviral therapy may change this trend.¹⁸ Disease-specific indications, outcomes, and considerations will be discussed in the following sections.

Alcoholic Liver Disease

Excessive alcohol consumption can lead to several hepatic abnormalities, ranging from alcoholic hepatitis to steatosis, hepatic fibrosis, and cirrhosis. Alcoholic liver disease was once thought to occur only in individuals who consumed large quantities of alcohol over long periods of time. It has recently become recognized that even moderate amounts of alcohol consumption can induce liver injury, suggesting that hereditary and or environmental factors are probably important. Hepatitis C viral infection, found in 15% to 25% of patients with alcoholic liver disease, appears to exacerbate alcohol-induced liver injury and vice versa.

When liver transplantation emerged as a standard therapy for end-stage liver disease in the 1980s, intense debates occurred surrounding the issue of offering liver transplantation. There were two broad areas of concern. First, many were skeptical that patients with a history of longstanding alcoholism would be able to successfully comply with the rigorous long-term medical treatment required of patients who receive lifelong immunosuppression. On a broader level, concern was expressed that scarce societal resources should not be used to treat patients with “self-induced” diseases. With more experience in this area, it has been recognized that the incidence of recidivism after transplantation is low, and both short- and long-term results in this category are as good as for nonalcohol-related categories. It has also become understood that determining worthiness for receiving a lifesaving organ by making a judgment about past behavior is neither ethical nor possible.

Today, the same methods of determining suitability for transplantation are used for patients with alcoholic liver disease as with other diagnoses with one proviso. Alcohol-induced liver injury frequently regresses following cessation of alcohol consumption as long as cirrhosis is not yet present. Patients with a history of recent alcohol abuse should therefore be observed for a minimum of 6 months to ensure that their hepatic dysfunction is not reversible. In addition, all patients with a history of substance abuse must be evaluated by individuals with expertise in addiction and found to have good insight into their past self-destructive behavior and a stable social support network for the posttransplant phase.

Viral Hepatitis

Most patients who become infected with hepatitis B develop an immunologic response to the virus that results in complete viral clearance. Patients who do not clear the hepatitis viral antigen may persist as carriers or may develop chronic hepatitis, which progresses to fibrosis and cirrhosis. In the 1980s, transplantation for hepatitis B was associated with universal recurrence of viral infection posttransplant and survival rates were poor. Fortunately, transplantation for this indication was revolutionized by the development of effective posttransplant prophylaxis using long-term, high-dose, hepatitis B immune globulin and the nucleoside inhibitors lamivudine or entecavir.^19,20 Today, outcomes for transplantation for hepatitis B–induced liver failure, while varying based on genotype, are equivalent to or better than those for other conditions.²¹

Hepatitis C has become the most common etiology among patients receiving liver transplants.⁵ Antiviral therapy using pegylated interferon and ribavirin for early hepatitis C infection has been demonstrated to have clinically important responses seen in over half of patients treated. However, complete clearance of HCV from the serum can only be achieved in a minority of patients which is largely related to viral genotype and whether significant toxicities to therapy develop.^22,23 Fortunately, multiple new anti-HCV medications have now been FDA approved and show much improved complete response rates and improved tolerability. These recent developments will serve to change the landscape for patients with chronic HCV, eliminating the need for transplantation in many cases, and offer new options to treat HCV recurrence following transplantation.¹⁸

Following liver transplantation, recurrence of HCV hepatitis in the transplanted liver occurs universally unless the virus was eradicated pretransplant with therapy.²⁴ Although some patients experience an indolent course, most patients experience a more rapid progression to liver failure once cirrhosis has developed posttransplant. These patients can progress to end-stage liver failure within 6 months. Short-term results of transplantation for this disease are comparable to those for the other noninfectious conditions. However, approximately 25% of patients develop recurrent cirrhosis within 5 years posttransplant, and long-term survival is less likely compared with patients who do not have hepatitis C infection. Use of livers from donors of increased age are thought to contribute to poorer results in hepatitis C patients.²⁵ Treatment of recurrent hepatitis C posttransplant is presently being attempted with some of the new antiviral therapies available and clinical trials underway.^18,26 Despite recurrence, transplantation appears to provide a substantial and worthwhile survival benefit to most patients with hepatitis C.

Hepatocellular Carcinoma and Other Hepatic Malignancy

Cirrhosis is a major risk factor for the development of HCC, and the majority of HCCs develop in patients who have cirrhosis. Curative resection is unsafe in the setting of advanced cirrhosis, and it does not eliminate the high likelihood of recurrent malignancy. Because most patients with HCC die of liver failure, rather than metastatic disease, it was reasoned that transplantation would be potentially curative. This approach yielded poor survival rates, and during the early 1990s primary hepatic malignancy was considered a contraindication to liver transplantation by many centers. This circumstance changed when Mazzaferro et al.²⁷ reported an 85% 4-year survival rate for patients who had cirrhosis and either stage I or stage II HCC (Table 37-4). Transplantation is now considered standard therapy for HCC and cirrhosis if there is no evidence of extrahepatic disease, vascular invasion, and if the tumor burden does not exceed stage II (single tumor ≤5 cm in diameter, or 2 to 3 tumors, none >3 cm in diameter). While some advocate transplantation of patients with larger tumors,^28,29 this practice is still controversial due to concerns of overall lower disease-free survival. Many centers now adopt a downstaging strategy with local regional therapies such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE) to bring patients down to stage II in order to list for liver transplantation.³⁰ Transplantation is clearly not beneficial in the presence of known positive nodal or distant metastases (stage IV disease). To create relative equality for a scarce resource, MELD allocation points are standardly allocated to HCC patients meeting the Milan criteria so as to minimize waitlist dropouts due to disease progression and at the same time not over utilize donor livers from the remainder of the recipient candidate pool. However, in recent reviews of outcomes of liver transplantation as reported by the SRTR,⁴ the adjusted 3-year survival rate for HCC patients was 74% and was statistically lower than non-HCC recipients (81%) during the MELD era while at the same time one of the lowest waitlist drop-off rates and higher transplant rate among other disease indications for transplantation,^4,31 suggesting that the allocation policy may need further refinements.

Other primary tumors of the liver include hepatoblastoma, cholangiocarcinoma, and primary sarcoma. Hepatoblastoma occurs primarily in children with resection or transplantation being used as potential curative options.³² Transplantation is utilized for patients who are unresectable because of bilobar disease or hilar location. Hepatoblastoma can respond partially to chemotherapy, but complete and sustained tumor regression is uncommon. Patients are often treated with chemotherapy until the time of transplantation to prevent extrahepatic growth prior to the definitive treatment. Hepatoblastoma is relatively unique among liver tumors in that long-term survival has been reported even in children who have had distant metastatic spread.

Cholangiocarcinoma has historically been considered a contraindication to transplantation because 5-year survival rates have been reported at less than 20%. Recently, success similar to other recipients has been reported for patients who have limited disease (<2.5 cm, no lymph node disease) and have received neoadjuvant chemotherapy and radiation along with aggressive staging prior to transplantation.^33,34

Although there are anecdotal reports of long-term survival following transplantation for primary sarcoma of the liver, the majority of experiences indicate that transplantation is not a curative therapy for this condition. Liver transplantation is generally not appropriate for patients who have secondary (metastatic) hepatic malignancy, because long-term survival rates are very poor due in part to the observation that immunosuppression promotes tumor growth. The possible exception to this rule is patients who have metastatic carcinoid or neuroendocrine tumor that is limited to the liver. These tumors can progress very slowly and local cure of the primary tumor is frequently possible. While it is still controversial when compared to other standard therapies, long-term disease-free survival following liver transplantation is possible in selected circumstances.³⁵

Nonalcoholic Fatty Liver Disease (NAFLD)

NAFLD may be the most common liver disease in the United States. It has a high incidence in obese patients and those with adult-onset diabetes mellitus. The disease resembles alcoholic liver disease, but patients do not report a significant history of alcohol use. The degree of hepatic injury varies from benign elevations of serum hepatic transaminases in association with hepatic steatosis or steatohepatitis to fibrosis and cirrhosis. A majority of patients previously classified as having cryptogenic cirrhosis probably have longstanding steatohepatitis. It is estimated that at least two-thirds of the obese population in the United States has hepatic steatosis and close to one-fifth have steatohepatitis.³⁶ Patients who develop cirrhosis and progress to end-stage liver disease are appropriate candidates for liver transplantation. Recurrence of steatohepatitis leading to graft dysfunction is possible. Recipient diabetes or obesity appears to be independent negative prognostic indicators for survival after liver transplantation.³⁶

Fulminant Hepatic Failure

Acute hepatic failure, defined as the development of altered mental status, coagulopathy and hepatic dysfunction within 8 weeks of the onset of an acute hepatic disease, is a rare, but lethal disease.^14,37 There are over 2,000 cases of acute hepatic failure per year in the United States. The mortality rate approaches 80% in patients who do not receive liver transplants. The causes of acute hepatic failure include viral hepatitis, toxins such as aflatoxins from the poisonous mushroom family Amanita phalloides, acute fatty liver of pregnancy, acute Budd–Chiari syndrome, and drug toxicities. Drug toxicities include both idiosyncratic reactions and drugs with predictable toxicity when taken in excess. Drugs that have been reported to induce idiosyncratic liver failure include isoniazid, halothane, valproate, disulfram, and phenytoin, among many others. The over-the-counter analgesic, acetaminophen, causes dose-dependent hepatic failure and is now the single most common cause of acute hepatic failure in the United States.

The most generally accepted criteria for transplantation of patients with FHF were described by the group at the King’s College hospital in London, England (Table 37-5).³⁸ While the King’s College criteria has been separately validated in other studies, more recent studies have begun to evaluate whether other scoring systems may have improved abilities to measure severity of illness. MELD has come under recent investigation in this regard and has been found to be additive to the King’s College criteria in predicting outcome following FHF.^39,40 The current United National Organ Sharing (UNOS) listing criteria for patients with FHF is in Table 37-2. The outcomes following transplantation have shown overall higher perioperative mortality, compared to other diseases, with overall similar long-term survival (Fig. 37-3).³

Biliary Atresia

Biliary atresia is a congenital disorder of infants, occurring in about 1 of 15,000 births, that is characterized by biliary obstruction resulting from obliteration or discontinuity of the extrahepatic biliary system resulting in progressive hyperbilirubinemia, cirrhosis, and hepatic failure. Other anatomic anomalies can also be coassociated with this disorder such as a preduodenal portal vein. The etiology is not completely defined yet is the most common indication for hepatic transplantation in pediatric patients. Standard treatment includes creation of a portoenterostomy (Kasai procedure), if this can be done before 3 months of age. After this point, success rates diminish markedly. Response to the portoenterostomy procedure is highly variable. Patients may develop cirrhosis within the first 6 months of life or live into their twenties before developing synthetic dysfunction and portal hypertension. Approximately 75% of children will require transplantation by 6 years of age.

It is critical that these patients are managed by an experienced pediatric gastroenterologist so that the correct window for effective transplantation can be identified and so they receive appropriate attention to their specialized nutritional needs. Specifically, deficiencies of fat-soluble vitamins that depend on bile for absorption are common and treatable. Transplantation is appropriate when children manifest growth and nutritional failure, when ascites develops, and when portal hypertension progresses to the point of variceal hemorrhage. Recurrent cholangitis is also thought to be an indication for liver transplantation. Transplantation for this population overall has had excellent results with >85% 10-year survival being achieved in the United States.⁴¹ Factors that have been associated with improved survival include living donor transplants and older recipient age. Patients with significant growth failure generally have poorer outcomes.

Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC), thought to be autoimmune in nature, is characterized by gradually increasing serum bilirubin levels, progressive fatigue, and cirrhosis. Early stages of the disease are usually asymptomatic, and disease progression may evolve over 20 years. Treatment with ursodeoxycholic acid appears to slow the progression of the disease, but immunosuppression does not. It was once thought that PBC does not recur, however, histologic analysis has shown that the incidence of recurrence is approximately 15% within 5 years of transplantation.⁴² Eventual progression to graft failure requiring retransplantation is possible, though rare.

Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is an autoimmune disease that is characterized by gradually progressive inflammation of the biliary tree, eventually resulting in cirrhosis. It is associated with ulcerative colitis, but removal of the colon does not affect progression of the disease. In most cases, colectomy for associated inflammatory bowel disease is done after successful transplantation because the failing liver makes the patient a poor candidate for a large abdominal procedure. PSC is also associated with the development of cholangiocarcinoma. Patients who experience a course that becomes rapidly progressive should be examined by endoscopic retrograde cholangiopancreatography (ERCP) with brushings to evaluate for cholangiocarcinoma. In addition to the usual considerations about the timing of transplantation, it is important to note that these patients are susceptible to bacterial cholangitis, which can cause systemic sepsis and rapid hepatic decompensation. Episodes of cholangitis that do not respond to suppressive antibiotic therapy should prompt early consideration for transplantation. Overall, patients with PBC or PSC experience the best outcomes with transplantation when compared to adults with other liver diseases, however, disease recurrence remains higher in PSC patients than in PBC patients.^3,43

Inherited Metabolic Disorders

Numerous inherited metabolic disorders are treatable by liver transplantation (Table 37-3). Some enzymatic deficiencies in this group result in destruction of the liver, so transplantation may resolve the liver failure as well as supply the missing enzyme. Disorders in this category include Wilson disease, alpha-1 antitrypsin deficiency, tyrosinemia, and type I glycogen storage disease. In other cases, the liver is not affected by the disease, either structurally or functionally. In these circumstances transplantation is undertaken solely as enzyme replacement therapy. Diseases that have been cured by hepatic transplantation in this category include hemophilia A or B, homozygous familial hypercholesterolemia, Niemann–Pick disease, oxalosis, familial amyloid polyneuropathy, and numerous enzymatic deficiencies of urea cycle metabolism.⁴⁴ Determination of eligibility for transplantation depends on determining that transplantation will cure the disease, or at least halt its progression, and that the consequences of the disease without transplantation are devastating, making transplantation appropriate.

Budd–Chiari Syndrome

Budd–Chiari syndrome is characterized by obliteration of the hepatic veins. It may be due to congenital webs of the hepatic veins or suprahepatic cava or may be caused by spontaneous thrombosis of the hepatic veins. The latter condition is associated with polycythemia vera and other hypercoagulable states. Diagnosis is made by inferior vena cavagram or magnetic resonance venography. The classic presentation is a triad of right upper quadrant pain, hepatomegaly, and ascites. Patients may present with FHF during acute Budd–Chiari and have symptoms of encephalopathy and coagulopathy, or they may present in a more indolent fashion with ascites as the predominant feature. The natural history of the indolent form of Budd–Chiari syndrome is the eventual development of cirrhosis.

Patients who present with intact hepatic function should undergo an assessment to determine whether the liver has evidence of cirrhosis. A transjugular intrahepatic portosystemic shunt (TIPS) is the preferred therapy for patients who do not have evidence of synthetic failure and have not yet developed cirrhosis. Transplantation is reserved for cases where portal decompressive shunting is not possible or for patients who have advanced cirrhosis. Long-term anticoagulation to prevent recurrent hepatic vein thrombosis in the liver graft is routinely recommended.

Other Considerations

HPS and PPHTN are two other manifestations of cirrhosis whereby transplantation is justified. Similar to HCC, these two diseases can occur in cirrhosis despite overall preserved hepatic function and appear to involve dysregulation of vasoactive mediators such as nitric oxide. Therefore, MELD exception scores are often sought when either HPS or PPHTN are present.¹² HPS is diagnosed on the basis of unexplained hypoxia in the presence of cirrhosis along with a positive “bubble” study for pulmonary shunt on echocardiography. PPHTN is diagnosed on the basis of pulmonary hypertension in the setting of cirrhosis without any other explainable etiology such as underlying pulmonary pathology. Recipient selection and management is critical to achieve reasonable success with liver transplantation. Patients with HPS experience the best outcomes if preoperative PaO₂ is greater than 50 mm Hg.⁴⁵ Patients with PPHTN likewise must have mean pulmonary artery pressures less than 35 mm Hg with or without medical therapy to experience a reasonable chance of recovery following liver transplantation.^46,47

In addition to isolated liver disease, liver transplantation is occasionally considered along with other solid organ transplantation. The two most notable examples are combined kidney and liver transplantation as well as combined liver and intestine transplantation.⁴ Intestine transplantation is usually performed in cases where intestinal failure is present along with progressive cholestatic liver failure secondary to hyperalimentation.⁴⁸ Since HRS frequently occurs with advanced cirrhosis and also frequently resolves with successful liver transplantation, the indications for combined liver and kidney transplantation are more controversial.⁴⁹ It is widely accepted that pre-existing end-stage renal disease along with significant cirrhosis or the existence of HRS requiring eight or greater weeks of renal replacement therapy warrant consideration of combined liver and kidney transplantation. Ongoing investigations are required to define patients with HRS who are less likely to recover renal function following liver transplantation.

LIVER TRANSPLANTATION: SURGICAL PROCEDURE

Anesthetic Management

An anesthesiologist with experience in liver transplantation is invaluable to the transplant team and liver transplant anesthesiology is rapidly becoming a subspecialty. Proper anesthetic management and effective communication between the surgery and anesthesiology teams is necessary to optimize patient care during the surgical procedure. While an extensive outpatient preoperative evaluation is usually performed, including cardiac risk stratification, many liver candidates report from home when a liver becomes available. If adequate time for fasting has not occurred, consideration of rapid sequence induction should be given to prevent aspiration. After induction and intubation, general anesthesia is maintained with a combination of inhalational agents as well as the administration of paralytic agents and analgesics. For adult patients, cardiac monitoring is often performed either by pulmonary artery catheterization or intraoperative transesophageal echocardiography. An arterial catheter is placed for blood pressure monitoring. Adequate vascular access, often including central venous catheters, is required for the administration of blood products and the potential for rapid resuscitation in the case of massive blood loss. A device for rapid infusion and the ability to warm blood products or intravenous fluids is required. Low central venous pressures maintained during the hepatectomy phase of the procedure may help avoid excess bleeding.

Intraoperative Management of Coagulopathy

Liver transplantation has the potential for massive blood loss for several reasons. Liver transplant candidates with cirrhosis often have synthetic deficiencies in circulating coagulation factors as well as severe portal hypertension associated with thrombocytopenia and extensive venous collaterals. Intraoperative coagulopathy may be worsened during the anhepatic phase of the procedure. Finally, liver transplantation involves extensive dissection of major vascular structures including the inferior vena cava, portal vein, and hepatic artery, all with an inherent risk for torrential bleeding.

Intraoperatively, coagulation is monitored by frequent determination of standard parameters including prothrombin time, partial thromboplastin time, platelet count, and fibrinogen. Abnormalities of these laboratory values associated with intraoperative bleeding are often corrected with fresh frozen plasma, platelets, or cryoprecipitate. Normal coagulation is also helped by maintaining normal pH, calcium levels, and normothermia. While the administration of recombinant factor VII intraoperatively can rapidly and effectively stop nonsurgical bleeding, its use has a theoretical risk of postoperative thrombotic complication including hepatic arterial thrombosis. In addition, no definitive data has been demonstrated to decrease the need for intraoperative blood transfusions.^50,51 Therefore, its use is only recommended in emergent situations.

Following reperfusion of the donor liver, a fibrinolytic state may be encountered. This is related to the lack of production of fibrinolysis inhibitors during the anhepatic phase and the inability of the liver to metabolize profibrinolytic compounds. This state may be identified either by thromboelastography, recurrence of bleeding where hemostasis had been previously obtained (such as the wound edge), or by extensive and refractory bleeding after revascularization. This state may be treated with the use of antithrombolytic agents including ε-aminocaproic acid, tranexamic acid, or aprotinin.

Surgical Technique

Transplantation of the liver is among the most technically demanding surgical procedures. During induction and placement of the appropriate monitoring lines by the anesthesiology team, the donor liver is prepared on the back table for implantation (Fig. 37-4). Bench preparation includes resection of the donor diaphragm and adrenal gland off of the bare area of the liver and vena cava. Meticulous ligation of tributaries from the vena cava (adrenal vein, phrenic vein, and lumbar branches) is performed. The artery is dissected free from the Carrel patch of the aorta up to the gastroduodenal artery. Dissection near the right or left hepatic arteries is avoided to prevent unnecessary injury. The portal vein is circumferentially dissected free. The gallbladder may be removed at this stage or following reperfusion. Tissues surrounding the common bile duct are left intact to avoid injury of the blood supply.

Following this, the recipient’s abdomen and bilateral groins are prepped and draped in a standard fashion. The most commonly used incision is a unilateral or bilateral subcostal incision with a midline extension to the xiphoid process (Fig. 37-4). After dividing the fascia, ascites, which can occasionally be present in a large volume, is evacuated. The ligamentum teres hepatis is carefully divided between clamps and ligated because a large recannulized umbilical vein is often present in patients with severe portal hypertension. After dividing the falciform ligament with cautery, a mechanical retractor is used to retract the bilateral costal margins anteriorly and superiorly for excellent exposure of the upper abdomen. The abdominal cavity and liver are then inspected for any abnormalities including unsuspected malignancy, particularly within the cirrhotic liver which is a risk factor for HCC. Following this, liver transplantation occurs in three stages: (1) recipient hepatectomy, (2) anhepatic phase, and (3) postrevascularization.

Recipient Hepatectomy

During the recipient hepatectomy phase, the liver is mobilized from its ligamentous attachments and the porta hepatis is skeletonized. Attention is first directed to dissecting and skeletonizing the structures of the portal triad. The peritoneum overlying the portal triad is divided with electrocautery near the liver edge. The right and left hepatic arteries are dissected free, ligated, and divided leaving adequate length to form a branch patch for the arterial anastomosis. The proper hepatic artery is also dissected free to the level of the gastroduodenal artery allowing enough length for clamping during the anastomosis. Because portal venous flow of blood to the liver may be hepatofugal (away from the liver), division of the artery may leave the patient functionally anhepatic. If a prolonged period of time is expected for mobilization of the liver, such as when extensive adhesions are present, the artery may be dissected free but left in continuity to allow whatever synthetic capacity the native liver has to continue. A replaced or accessory right hepatic artery, which arises as a branch of the superior mesenteric artery and travels in a posterior position to the common bile duct and lateral to the portal vein, can usually be palpated if present and can be ligated and divided. When the replaced right hepatic artery is relatively large and the proper hepatic artery is diminutive in size, the replaced right hepatic artery can be left long and used for arterial inflow for the donor liver. A replaced or accessory left hepatic artery arises from the left gastric artery if present and can be identified by inspection of the pars flaccida of the lesser omentum along the lesser curvature of the stomach (Fig. 37-5).

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