Vivek Kaul Kenneth D Rothstein Santiago J Munoz Jorge Ortiz and Cosme Manzarbeitia

2.1. ORGAN MATCHING

The outcome of organ transplantation is an extremely complex phenomenon, being the result of an interaction between two different biological systems, those of the donor and the recipient. It is logical, therefore, that any discussion that attempts to describe the process of recipient evaluation must be initiated with a comprehensive assessment of donor and recipient variables. The benefits of "matching" donors to recipients are manifold. Stratifying prospective donor-recipient combinations provides valuable insight into the probable outcomes of individual patients and the analysis of factors that determine those outcomes. In addition, stratifying makes it possible to describe study populations stratified according to risk, and it allows for a uniform comparison of outcomes.

The United Network of Organ Sharing (UNOS) establishes policies regarding organ allocation based on a broad consensus and periodically amends these policies. The process of "matching" begins when a donor organ becomes available in the local area and is offered to patients on the waiting lists of the local transplant centers. In general, a donor is matched to the potential recipient on the basis of several factors (Table 2.1). Recipients are chosen primarily based on medical urgency and the time waiting on the list within each blood group. Using these criteria, if a donor organ cannot be matched locally to a recipient, then it

TABLE 2.1. Variables Involved in Organ Matching

ABO blood type Identical > Compatible > Incompatible

Wailing time on list Highest priority to candidate waiting longest

Degree of medical urgency Status I > Status 11 A > Status II B > Status 111

Body size Determined by transplant surgeon becomes available to patients outside the local area (e.g., regional). Conversely, local transplant centers also receive organs from distant areas if an acceptable match was not possible at the distant centers.

In addition to these variables, studies have attempted to identify potential donor and recipient factors that may have a bearing on graft and patient outcome and use this information for better matching. Several variables have been analyzed: Donor and recipient age, gender, body mass index (BMI), renal function, length of ICU (intensive care unit) stay, a history of cardiopulmonary resuscitation (CPR), and donor liver size have been studied with respect to graft and patient outcome. A study by Ploeg et al. (Transplantation 1993;55(4):807-813) indicated that reduced-size livers, older donor age, renal insufficiency before transplantation, and prolonged cold ischemic time were independently associated with a higher incidence of primary graft dysfunction. Several studies have shown the reduced graft survival seen in the subset of patients where a female donated a graft to a male recipient, but its clinical significance is questionable.

Unlike renal transplantation, liver transplantation (LT) is routinely performed successfully across major human leukocyte antigen (HLA) differences between donor and the recipient. In some studies, surprisingly, HLA matching has been shown to produce an unfavorable graft outcome.

2.2. CANDIDATE SELECTION

The overall goals of LT are to prolong life and to improve the quality of life. The selection of appropriate patients for LT to achieve these goals is a difficult task. Uniform minimal listing criteria that propose listing patients when their estimated survival with liver disease is less than that expected after LT were recently proposed and have generally been accepted. The salient features of this consensus statement are as follows:

• Agreement that only patients in immediate need of LT should be placed on the waiting list.

• Patients should not be placed in anticipation of some future need for such therapy.

• The most important non-disease-specific criterion for placement on the transplant waiting list was an estimated 90% or less chance of surviving 1 year (translates into a Child-Pugh-Turcotte [CPT] score of 3= 7, Classes B and C) (Table 2.2).

• Cirrhotic patients who have experienced gastrointestinal bleeding caused by portal hypertension or a single episode of spontaneous bacterial peritonitis would meet the minimal criteria irrespective of their CPT score.

• Patients with fulminant hepatic failure, regardless of etiology of the onset of stage 2 hepatic encephalopathy, should be placed on the waiting list.

• A requirement for 6 months abstinence from alcohol before placement on the transplant waiting list was considered appropriate for most patients with alcoholic liver disease.

• The concept of "regional review boards" to review candidacy for LT in "exceptional" cases.

Allocation and distribution regulations of the UNOS have also recently undergone changes to balance the principles of utility (i.e., the overall benefits of LT to society) and justice (i.e., the needs of the individual patient).

In most transplant centers, a candidate selection committee comprises the transplant surgeon(s), hepatologist(s), psychiatrists, nurse coordinators, social workers and others, who determine the suitability and general priority for transplantation of potential candidates. Candidate selection is becoming an extremely challenging task with the need to continuously consider newer (and often, controversial) indications for transplantation, a virtually stagnant donor pool, and ever-

TABLE 2.2. Child-Pugh-Turcotte (CPT) Scoring System to Assess Severity of Cirrhosis, as Adopted by UNOS

Points

TABLE 2.2. Child-Pugh-Turcotte (CPT) Scoring System to Assess Severity of Cirrhosis, as Adopted by UNOS

Points

Parameter

1

2

3

Albumin

> 3.5

2.8-3.5

< 2.8

Total bilirubin

< 2

2-3

> 3

Protime (t seconds) or INR"

1-3

4-6

> 6

Ascites

None

Controlled medically

Uncontrolled

Encephalopathy (grade)''

0

I—IT

lll-IV

For primary biliary cirrhosis, primary sclerosing cholangitis, and/or other cholestatic diseases: bilirubin (mg/dL)

< 4

4-10

> to

NoteCVX score 5-6: Child's Class A; CPT score 7-9: Child's Class B; CPT score 10-15: Child's Class C. "The CPT Score includes either the prothrombin time (in seconds) or the International Normalized Ratio (INR). 'Encephalopathy is classified into four stages according the definition of Trey and Davidson.

NoteCVX score 5-6: Child's Class A; CPT score 7-9: Child's Class B; CPT score 10-15: Child's Class C. "The CPT Score includes either the prothrombin time (in seconds) or the International Normalized Ratio (INR). 'Encephalopathy is classified into four stages according the definition of Trey and Davidson.

TABLE 2.3. Criteria for Patient Selection for Liver Transplantation

I. Accepted indications for liver transplantation a. Advanced chronic liver disease b. Fulminant hepatic failure c. Metabolic liver disease d. Alcoholic liver disease"

e. Hepatoma'1

II Controversial indications for liver transplantation a. HIV disease b. Older age (> 75 years)

HI. No alternative form of therapy available

IV. No absolute contraindication to liver transplantai ion present1

V. Willingness and ability to accept liver transplantation and comply with follow-up care VI. Ability to provide for the costs of liver transplantation and pos(transplant care

"Documented abstinence and rehabilitation prior to listing for transplatation (usually a period of 6 months). ^Single lesion less than 5 m or up to three lesions, each < 2 cm in size.

"^Uncontrolled systemic infection, current extrahepatic malignancy, AIDS, advanced cardiac/pulmonary disease, multisystem organ failure, and so on.

constricting health care budgets. The clinical, biochemical, psychosocial, and financial information regarding a patient referred for LT is first reviewed to determine if the patient meets the global selection criteria, highlighted in Table 2.3.

2.2.1. Workup of Candidates

The process of evaluating a patient in consideration for LT needs to address several key issues:

• What is the etiology of the liver disease?

• Does the patient meet minimal listing criterion for LT?

• Are there any contraindications to LT?

• Does the patient have any "severity of disease" indications for LT? (Table 2.4)

• Does the patient have any "quality-of-life" indications for LT? (Table 2.5) What is the psychosocial profile of the patient?

• What are the patient's social support systems?

• Is the patient willing and motivated to undergo a liver transplant?

A transplant hepatologist and surgeon, transplant nursing coordinator, social worker, and a financial counselor evaluate all patients referred for transplantation. If deemed appropriate, a psychiatric consultation is also requested. Once it is determined that the patient appears to be a suitable candidate for listing and

TABLE 2.4. Severity of Disease Indications for Liver Transplantation

I Chronic (hepatocellular) liver disease a. Hepatorenal syndrome b. Spontaneous bacterial peritonitis C. Serum albumin < 2.5

d. Prothrombin time > 5.0 see prolonged c. Serum bilirubin > 5.0 mg/dL It. Cholestatic liver disease

Serum bilirubin > 10 mg/dL

transplantation, laboratory, imaging, and other pertinent evaluations are carried out, as detailed in Table 2.6. Routine upper endoscopy is recommended to document the presence of gastroesophageal varices, portal gastropathy, and to rule out peptic ulcer disease and/or malignancy. Routine colonoscopic examination is not recommended but should be performed in patients with a history of unexplained weight loss and iron deficiency anemia. In patients with primary sclerosing cholangitis (PSC), for example, colonoscopy with biopsy of suspicious lesions is imperative to exclude high-grade dysplasia and/or malignancy. The individual patient's specific medical history and condition dictate any further investigations. For instance, patients with cholestatic liver disease should have a DEXA (dual energy X-ray absorptiometry) scan to exclude significant osteoporosis. These and any other special considerations that may impact posttransplant care are discussed in an ongoing fashion at the transplant selection committee meetings at most institutions.

TABLE 2.5. Quality-of-Life Indicators for Liver Transplantation

!. Chronic liver disease a. Intractable ascites b. Spontaneous encephalopathy c. Varieeal bleeding d. Incapacitating fatigue II Cholestatic liver disease a. Intractable pruritus b. Recurrent ( > 2) episodes of biliary sepsis (cholangitis)

c. Metabolic bone disease with fracture d. Xanthomatous neuropathy

TABLE 2.6. Evaluation of Potential Liver Transplant Recipients

Laboratory investigations

Complete blood counl, Prothrombin time, partial thromboplastin time (PTT) Chemistry (18) panel

Cúmplete LFT (liver function tests) panel Hepatitis A, B. and C serologies: HIV (Elisa)

Cytomeglovirus (CMV), Epstein-Barr virus (EBV), and herpes simplex virus (HSV) serologies Autoimmune hepatitis markers (antinuclear antibody test (ANA), smooth muscle antibody (SMA).

immunoglobulin profile, antimitochrondial antibody (AMA) if applicable) Ceruloplasmin (age < 50 years), alpha-l-anlilrypsin level Ferritin, total iron-binding capacity (TIBC). and serum iron Alpha-fetoprotein Thyroid function tests Urinalysis Lipid profile Drug and alcohol testing

Radiology Chest X-ray

Hepatobiliary sonogram with Doppler study of portal system ( 1 of abdomen for liver volume estimation

Cíirdin VOSCuia r

Electrocardiogram (EKG)

Echocardiogram if patient > 40 years of age

Dob ti lamine echocardiogram^ her stress tests if indicated

Pulmonary

ABG (arterial blood gases) test Pulmonary function tests (F*FTs), if indicated Chest X-ray

Once the pretransplant evaluation is complete, the patients are generally assigned to one of the following four categories:

Suitable and ready for transplant; to be listed for a donor organ.

• Suitable but not in immediate need of transplant; may be listed if he or she meets minimal listing criteria.

Potentially reversible current/active contraindication; recategorization at later date after treatment and reevaluation. Absolute contraindication; transplant denied.

The more common indications and contraindications for LT are listed in Table 2.7.

TABLE 2.7. Common Indications and Contriandications for Liver Transplantation

Indication: Acute or chronic liver failure related to:

Contrai nd ¡calions

Chronic hepatitis (e.g.. hepatitis B. hepatitis C, or autoimmune hepatitis) Cholestatic disorders: primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC). and extrahcpatic biliary atresia Alcoholic liver disease Mctaboiic disease (e.g.. Wilson's disease, hereditary hemochromatosis, alpha-1 antitrypsin deficiency, nonalcoholic steatohepatitis [NASHD Cryptogenic cirrhosis Fulminant hepatic failure of any cause Hepatocellular carcinoma Polycystic liver disease Budd- C'lliari syndrome and hepatic \ end inclusive disease

Severe cardiopulmonary disease Uncontrolled systemic infection Current exlrahepalic malignancy Severe psychiatric or neurological disorders Absence of viable splanchnic venous inflow system

Lack of adequate financial/social support system HIV infection

Active alcoholism and/or illicit drug use Any anatomic abnormality precluding liver transplantation

2.2.2. Waiting Lists and Waiting Period

It is estimated that about 26,000 deaths occur annually from liver disease in the United States. Of these, about 1,300 occurred while waiting on the liver transplant list. Although the absolute number of donors has increased in the past years, the number of potential recipients listed for transplantation has overwhelmed it. Most recent UNOS data reveal that more than 13,000 patients are currently awaiting LT in the United States. With a relatively fixed donor pool of around 4,500 per year, this ever-increasing disparity between available donors and potential recipients has led to lengthening waiting periods and a burgeoning waiting list. The increased success and popularity of living donor liver transplantation (LDLT) programs across the country may help to correct this disparity to some extent. Although the overall death rate on the waiting list has decreased during the last decade, the death rate for the most urgent medical status patients (statuses 1 and 2A) remains very high and unacceptable.

In this context, the importance of the timing of referral for transplantation cannot be emphasized enough. Patients with cirrhosis should be referred for transplantation even before they develop evidence of synthetic dysfunction, experience their first major complication (ascites, spontaneous bacterial peritonitis, variceal bleed, etc.) or develop malnutrition. CPT Class A cirrhotics are best served by early referral to a transplant center, before they develop complications of cirrhosis. Lifestyle changes such as cessation of smoking and alcohol use can be introduced early in order to prevent cardiac and pulmonary complications. Patients can be entered into a screening program to monitor for development of hepatocellular carcinoma (hepatoma), with biannual ultrasounds and alpha-fetoprotein determinations. Early and timely referral for transplantation affords patients a reasonable and fair chance to outlive the long waiting period on the list.

2.3. OPTIMAL TIMING OF LIVER TRANSPLANTATION

Liver disease is the tenth leading cause of mortality in the United States. In 1997, it was responsible for 25,000 deaths. Since the advent of improved surgical techniques, intensive care monitoring, and immunosuppressive regimens, LT has evolved into a viable treatment modality for a large percentage of patients in liver failure. In 1999,4,698 LTs were performed in this country. However, there are over 16,000 patients awaiting transplants, while the number of donors has essentially reached a plateau. The waiting list is estimated to increase by over 200% in the coming years. Currently, waiting-list mortality ranges between 15% and 30%. Although the use of extended donors, living related donation, and split liver modalities has marginally increased the donor pool, it is incumbent upon the transplant center to maximize scarce resources further by transplanting patients at the proper time. In addition, in order for LT to be successful, it should be offered to patients at a stage in which they are able to tolerate it from the physiological point of view. Before offering transplantation, we should give the native liver the opportunity to recover. It is important to transplant patients at a point in their illness when their likelihood of long-term survival without transplantation is low, yet they are physiologically sound enough to withstand a major operation and immunosuppression. This utilitarian approach is driven by medical as well as ethical and financial concerns. When properly timed, LT is medically and ethically rewarding, and financially prudent. This is the gist of the National Institutes of Health (NIH) consensus of 1983. The decision about when to proceed with LT centers around three particular clinical instances. These include the acute or fulminant hepatitis cases, the chronic or cirrhotic cases, and, finally, the issue of retransplantation.

In the late 1970s and early 1980s, the option of LT was thought of as a lastresort effort. Evolving throughout the 1980s, with the advent of cyclosporine, and into today, with even newer immunosuppressants, the frame of mind has dramatically changed. LT has evolved into a viable therapeutic option with good results. In the past, the patient was allowed to deteriorate to the point of being on life support in the ICU. Today, the option of LT should be thought of much earlier. The progression of the disease to the point of irreversible deterioration is so unpredict able, and sometimes so rapid, that transplantation should be thought of early in the course of liver disease. Proper timing of LT must take into account the etiology and natural history of the disease. Thus, different rules apply for acute or fulminant failure versus chronic liver failure. Additionally, retransplantation presents a number of ethical and physiological variables that must be addressed in order to serve the patient as well as the health care system properly.

2.3.1. Fulminant Hepatic Failure

Fulminant hepatic failure (FHF) is defined as acute liver failure complicated by encephalopathy in a patient with no prior history of liver disease. Two thousand patients per year develop acute liver failure in the United States. Irrespective of the cause, FHF causes sudden, massive necrosis of the liver in patients without any evidence of preexisting chronic liver disease. This term is not used for preexisting chronic liver disease or for acute Wilson's disease. Natural recovery happens in about 5-20% of cases. Before the era of cyclosporine, transplantation of the liver did not compare favorably with medical management alone. However, with today's overall survival rate of 88% for LT, FHF is an accepted indication for transplantation of the liver. The etiology of FHF remains largely undiagnosed, with up to 40% of cases being cryptogenic in origin. Other known etiologies include fulminant hepatitis A or B, toxic hepatitis due to acetaminophen or idiosyncratic drug reactions, and mushroom poisoning.

The decision to proceed with LT must be made expeditiously. The workup must be shortened and include essential blood work such as HIV and hepatic serology status, confirmation of diagnosis by repeated frequent liver function, and an ultrasound of the liver to determine patency of the portal vein and overall condition of the liver. The latter usually shows a shrunken liver with a patent portal vein. Successful determination of these parameters, as well as the etiology of FHF, will determine the final outcome with or without transplantation in this population. Poor prognostic signs include the existence of grade 3 or 4 encephalopathy, a severe coagulopathic state, and a rapid shrinkage of the liver as documented by ultrasound (or, whenever possible, computerized tomography [CT] scan). Other bad prognostic signs include metabolic acidosis, cardiovascular instability, or septicemia. It is important to monitor the progression of the brain dysfunction in FHF adequately to avoid transplantation of patients who otherwise are brain dead. Direct intracranial pressure monitoring and cerebral perfusion pressure have been utilized successfully. Transcranial Doppler ultrasound measuring cerebral perfusion pressure has also been used with variable results.

Mortality is therefore dependent on a number of factors, including etiology and proper timing of transplantation. A significant percentage of patients (3550%) improve with intensive medical management alone. It is therefore important to identify those patients that will not respond to medical therapy but are still physiologically sound enough to tolerate transplantation. The King's College criteria (with some modifications) have emerged as the gold standard employed when evaluating the suitability of a patient for transplantation. Negative prognostic indicators for resolution of illness without transplantation (and therefore indications for transplant) include the following:

• Duration of jaundice greater than 7 days before the onset of encephalopathy.

• Factor V level < 20%, if younger than 30 years of age.

Factor V level < 30%, if older than 30 years of age.

• Prothrombin time > 50 seconds.

• Less than 50% viable hepatocytes on liver biopsy.

These criteria vary slightly depending on the exact etiology of the acute liver failure. Generally, if a patient continues in the ICU with obvious signs of liver failure such as coagulopathy, altered mental status, hemodynamic compromise, and the aforementioned negative prognostic indicators, urgent workup should be initiated.

Unfortunately, patients lose their opportunity for transplant when contraindications arise in the end stages of their acute liver failure. Usually, these are infectious or neurological in nature. Pneumonias, urinary tract infections, and line sepsis are fairly common in this patient population. Active infection, whether from fungal or bacterial sources, is a contraindication to transplant. If the intracranial pressure (ICP) is greater than 50 mmHg, with a cerebral perfusion pressure of less than 40 mmHg (usually measured by placement of an intracranial monitoring device), or if signs of uncal herniation are seen clinically or on CT scan, the patient is generally not salvageable. Renal failure and acute respiratory distress syndrome (ARDS) are not contraindications. However, they present significant obstacles in the postoperative period.

The planning of transplantation in this particular population is problematic. If transplantation is performed across the board, many livers that would otherwise recover would be removed unnecessarily, subjecting patients to the risks of surgery and immunosuppression. However, waiting too long may expose the patient to septic and neurologic complications, as well as increase in overall mortality. In general, survival rate for transplantation for FHF ranges anywhere from 60% to 80%. This compares very favorably with the most advanced medical management techniques today. Thus, an early referral to a liver transplant center, the implementation of an aggressive evaluation protocol, and an early decision for liver replacement is the best algorithm for management of these patients. How ever, one should not underestimate aggressive medical management, as emphasized by King's College unit in London. The proper use of mannitol and hyperventilation to prevent brain swelling, as well as antibiotic prophylaxis, can bring many of these patients around without liver replacement. Other authors have successfully applied the use of prostaglandin El (PGE1) for cases of fulminant hepatic failure with varied success.

Certain causes of FHF, such as Wilson's disease or acute Budd-Chiari syndrome, should be treated with LT as soon as possible, because the prognosis with medical intervention alone is dismal. In the latter, a thorough evaluation for the presence of hypercoagulable states or malignancy should always be done.

2.3.2. Chronic Liver Disease

The vast majority of transplants are performed for patients with chronic liver disease. Indications may be infectious (e.g., hepatitis B and C), oncologic (e.g., hepatocellular carcinoma, metastatic neuroendocrine tumors), cholestatic (e.g., primary biliary cirrhosis, sclerosing cholangitis) or metabolic (e.g., amyloidosis, Wilson's disease). Although indications have expanded exponentially, the donor pool has remained relatively stable. In 1988,36% of recipients waited more than 6 months for a graft. That number increased to 69% by 1997. In 1988, 22% of recipients spent more than 1 year waiting. By 1997, that number more than doubled to 48.3%. Therefore, scarce resources must be utilized optimally by maximizing the proper timing of transplantation.

All cirrhotics do not need transplantation. If well compensated (CPT Class A), their 1-year survival with optimal medical, radiologic (e.g., TIPS), and surgical (e.g., Sarfeh or Warren shunts) management exceeds that of transplant recipients. In cases of chronic liver disease, the patient should have an obvious indication for hepatic replacement, such as episodes of variceal bleeding, malnutrition, decrease in hepatic function, severe coagulopathy, spontaneous bacterial peritonitis, severe osteodystrophy, intractable pruritus, intractable ascites, severe encephalopathy, or any combination of the above. These patients are in the stage of hepatic decompensation. The expected 1-year survival of a decompensated cirrhotic is 10%. Each variceal bleed carries a 50% mortality rate. Patients with refractory ascites have a 50% chance of survival and a 25% chance of 1-year survival. Since decompensation can erode into the general well-being of the patient, he or she should still be physically strong enough both to participate in the recovery process and tolerate the procedure overall. Thus, the decision to proceed with transplantation includes close collaboration among the referring physician, the hepatologist at the transplant center, and the transplant team itself. The tip-of-the-iceberg effect of liver disease in certain patients, in which manifestations only typically happen in the late stages and in a sudden dramatic fashion, should alert referring physicians and the medical community at large about the importance of liver disease in the population. This can manifest as subtly as a progressive loss of intellectual capacity (subclinical encephalopathy) or lead to frequent hospitalizations for the aforementioned complications for liver disease. Growth and development problems are common in children with liver disease. These signs should alert the physician to refer for liver transplantation before development of the end-stage complications leading to death.

Recently developed, minimal listing criteria for transplantation includes a CPT score of greater than 7. However, different etiologies of liver failure are confounding variables when considering the optimal timing of transplantation. For patients with predominantly hepatocellular dysfunction, such as postnecrotic cirrhosis, hepatic function is lost well ahead of excretory function. In this group, the presentation is often with several complications, including coagulopathy, low albumin, malnutrition, ascites, and so on. In these cases, the clinician must take into account the following:

1. In alcoholic liver disease, abstinence should be maintained for a minimum of 6 months in order to lesson the risk of postoperative recidivism, to allow development of support systems and attendance of rehabilitation programs, and to allow the liver an opportunity to regenerate.

2. In cases of hepatocellular carcinoma, which frequently develops in cir-rhotics, transplantation should be performed before the lesion metastas-izes, becomes greater than 5 cm in size, or three in number.

3. In hepatitis B, transplantation should ideally be performed while there is no sign of active infection. Those patients transplanted with actively replicating hepatitis B DNA have a dismal prognosis. However, those transplanted with no signs of ongoing replication do extremely well with the addition of lamivudine and hepatitis B immune globulin both pre- and postoperatively.

4. Patients with Budd-Chiari syndrome who demonstrate cirrhosis or fibro-sis on biopsy should be transplanted early, because their chances of extended survival without a new liver are small. However, prior to transplant, shunt options should be exhausted, especially in the acute situation.

5. Those patients with autoimmune hepatitis being treated with cortico-steroids should be transplanted before the onset of extensive osteoporosis.

For patients with predominantly cholestatic disorders, a predominantly cho-lestatic picture with preservation of synthetic hepatic function till late in the course of the disease is the rule. The most studied model of disease staging and its relationship to posttransplantation outcome has been done in cholestatic diseases such as primary biliary cirrhosis, using the Mayo model. This complex evaluation takes into account age, bilirubin, albumin, prothrombin time, and edema. The life expectancy without transplantation can be predicted. This model allows prevent ing early transplantation in the patient who is still healthy and predicts the outcome with and without transplantation. However, this model is unique to cholestatic diseases, and few, if any, noncholestatic disease permit the application of this model in a more generalized fashion. As a general rule, the consensus is that transplantation should be done in the early stages of the disease, before the catastrophic complications of liver disease occur. Similarly, a PSC patient with the aforementioned negative prognostic indicators and recurrent cholangitis should be considered for transplantation. Because of the risk of cholangiocarcinoma in patients with PSC (about 10%), meticulous surveillance and expeditious workups should be performed.

Procrastination prior to referral to transplantation centers has resulted in undue mortalities both before and after transplantation. This should be avoided in those settings of chronic liver disease in which response to medical therapy is not well documented. In one study, 12% of candidates died while waiting, and most of these patients had been referred for transplantation while they were on ventilators, bleeding, coagulopathic, with hepatorenal syndrome, aspiration pneumonitis, sub-acute bacterial peritonitis, or a combination of these, as well as other added endstage complications. In these cases, the outlook after transplantation is demon-strably degraded. One-year survival after liver transplant exceeds 85% in most centers. Patients who are transplanted before being placed on disability are more likely to return to work postoperatively. Those that receive livers while physiologically less sound have diminished survival rates. Therefore, consideration of transplantation should be an early, and not a late, decision. Sometimes rapid, unexpected deterioration occurs in patients with chronic liver failure. This is more frequently seen in those with parenchymal disorders. In these patients, extensive medical clearance is not possible. Those patients who develop progressive en-cephalopathy, hemodynamic instability, renal insufficiency, spur cell anemia, and coagulopathy unresponsive to the administration of clotting factors have an extremely poor survival rate and should be transplanted as soon as possible, before the development of medical contraindications or death.

Finally, an increasing number of diagnoses are being accepted for transplantation, such as polycystic kidney disease, neuroendocrine tumors of the liver, and inborn errors of metabolism. Expansions of several disease entities that affect the liver to the point of potential transplantation indications may further shrink the donor pool. Because of this, consideration of early listing of the potential hepatic transplant candidate is indicated.

Generally, it is important to optimize a candidate medically so that he or she can benefit most from transplantation. Electrolyte disturbances such as hypo-natremia should be resolved outside of the operating room. Infectious issues (urinary infections, pneumonia, spontaneous bacterial peritonitis, tuberculosis, etc.) should be cleared before transplantation. Proper cardiopulmonary clearance is essential. Asthma and respiratory compromise secondary to ascites should be treated before surgery. Coronary artery disease should be addressed with proper screening and medical or surgical intervention when appropriate. In persons with a history of malignancy, meticulous workup should be performed to rule out recurrent disease. Generally, at least a 2-year waiting period after treatment of non-hepatic malignancy is recommended before proceeding with transplantation. Dietary habits, tobacco abuse, nutritional status, exercise tolerance, and psychosocial profiles should all be addressed prior to listing for transplantation.

2.3.3. Retransplantation: Whether or Not?

Before cyclosporine was available, retransplantation was a rare event. However, because of the increased survival rates and improved outcome, as well as the LT experience showing that patient survivals are consistently 10-15% higher than graft survivals, retransplantation is an option. A word of caution, however: It is obvious that these patients take priority in the current system by drawing organs from the pool of donors and removing them from those patients who have not yet received a transplant. Because the overall survival of patients with retransplanted livers is about 10% lower than those with primary grafts, the issue of whether this would be an acceptable algorithm still remains under much debate. Another reason why retransplantation becomes a less than desirable option to discourage is the fact that, if retransplantation were not widely available, most surgeons would opt not to use the so-called expanded donors. This would greatly limit the availability of current organ donors and have a bleak effect on transplantation today.

The overall retransplantation rate varies between 9% and 21%. The most common reasons for this procedure are chronic rejection (69%), primary graft nonfunction (36%), hepatic artery thrombosis (15%), acute rejection (22%), portal vein thrombosis, hyperacute rejection, bile duct necrosis, cholangitis, and recurrent diseases. In the tacrolimus era, retransplantation for rejection is less common than in previous time periods. Overall survival rates are approximately 20-30% inferior to those achieved in patients receiving primary transplants.

The timing of retransplantation in the immediate postoperative period is crucial because retransplants performed between days 1 and 4 after initial surgery are more successful than those performed between days 5 and 30. Data from the University of California at Los Angeles (UCLA) are similar, showing a significant decrease in survival in patients whose transplants were performed between 8 and 30 days postoperatively. Those patients with four organ system failures or the requirement of more than three transplants do not benefit from more grafts. Therefore, when a patient's graft shows poor function, manifested in continued acidosis, blood product requirement, hemodynamic instability, and encephalopa-thy, it is prudent to proceed to retransplant before infectious complication and multiple organ system failure ensues. If a biopsy shows more than 50% necrosis, a retransplant is indicated. Poor prognostic indicators are serum creatinine greater than 4, elevated serum bilirubin, age, need for mechanical ventilation, and greater than 12-hour donor ischemia time.

When transplant recipients show signs of graft failure later in their course, they should be listed when their CPT score is greater than 7, if no medical contraindications have arisen since their previous procedure. When performed electively, retransplantation can have results approaching those of primary transplantation. Anecdotal evidence shows that retransplantation for hepatitic C is best performed before the bilirubin is greater than 8 or renal failure ensues.

Because of the donor organ shortage and diminished survival associated with retransplantation, it is important to time the procedure appropriately. If contraindications have arisen, if the patient is not physiologically sound, and if the donor organ is not optimal, the likelihood of success is small. Therefore, the decision to intervene should be made prudently.

This page intentionally left blank

4 Steps To Permanent Weight Loss

4 Steps To Permanent Weight Loss

I can't believe I'm actually writing the book that is going to help you achieve the level of health and fitness that you always dreamed of. Me, little scrawny sickly Darlene that was always last picked in gym class. There's power in a good story here so get this book now.

Get My Free Ebook


Post a comment