Journal of Gerontological Nursing

Clinical Concepts 

Liver Transplantation in Older Adults

Lissi Hansen, PhD, RN

Abstract

Liver transplantation is the only definitive treatment therapy for end-stage liver disease. In the United States, approximately 15% of annual liver transplant recipients are 65 or older. The most common postoperative complications are infection, acute graft rejection, and acute renal failure. To prevent complications, recipients are treated with immunosuppressive medications and anti-infective agents. The long-term complications of liver transplantation are a consequence of long-term use of immunosuppressive medications and recurrence of the original disease in the liver. Nurses play a critical role in supporting and educating recipients and their primary support persons about post-transplant follow-up care, including laboratory test schedules, medication management, and infection prevention. Strict compliance with follow-up care provides the greatest possibility of avoiding complications or organ rejection. [Journal of Gerontological Nursing, 40(9), 8–13.]

Dr. Hansen is Associate Professor, Oregon Health & Science University, Portland, Oregon.

The author has disclosed no potential conflicts of interest, financial or otherwise.

Address correspondence to Lissi Hansen, PhD, RN, Associate Professor, Oregon Health & Science University, SN-ORD, 3455 S.W. U.S. Veterans Hospital Road, Portland, OR 97239-2941; e-mail: hansenli@ohsu.edu.

Abstract

Liver transplantation is the only definitive treatment therapy for end-stage liver disease. In the United States, approximately 15% of annual liver transplant recipients are 65 or older. The most common postoperative complications are infection, acute graft rejection, and acute renal failure. To prevent complications, recipients are treated with immunosuppressive medications and anti-infective agents. The long-term complications of liver transplantation are a consequence of long-term use of immunosuppressive medications and recurrence of the original disease in the liver. Nurses play a critical role in supporting and educating recipients and their primary support persons about post-transplant follow-up care, including laboratory test schedules, medication management, and infection prevention. Strict compliance with follow-up care provides the greatest possibility of avoiding complications or organ rejection. [Journal of Gerontological Nursing, 40(9), 8–13.]

Dr. Hansen is Associate Professor, Oregon Health & Science University, Portland, Oregon.

The author has disclosed no potential conflicts of interest, financial or otherwise.

Address correspondence to Lissi Hansen, PhD, RN, Associate Professor, Oregon Health & Science University, SN-ORD, 3455 S.W. U.S. Veterans Hospital Road, Portland, OR 97239-2941; e-mail: hansenli@ohsu.edu.

Mr. J, a 65-year-old man, was admitted to the intensive care unit (ICU) with acute renal failure caused by contrast material given during a computerized tomography scan. Mr. J has long-term end-stage liver disease (ESLD) and is a liver transplant candidate at the top of the liver transplant waiting list. He has a history of alcohol and substance abuse and hypertension. Mr. J is accompanied to the ICU by his brother, with whom he is very close; his brother is his primary support person. Mr. J is miserable and exhausted. He has symptoms of decompensated liver disease, with an enlarged abdomen due to ascites and edematous lower extremities. He is getting frequent paracenteses. Mr. J has a right groin dialysis catheter in place and is receiving hemodialysis. He is unable to move and get into a comfortable position. Because of episodes of hypotension during dialysis, Mr. J stays in the ICU. He is worried and anxious that he will not receive a transplant in time to save his life. The liver transplant team is also worried. They are concerned with his high risk for infection because of his invasive catheters. Any infection would prevent him from receiving a transplant.

Liver Transplantation in the United States

In June 2014, more than 15,750 patients with ESLD in the United States were waiting for liver transplantation (U.S. Department of Health and Human Services [USDHHS], 2014a). Of these patients, 3,030 were individuals 65 or older. In 2013, 6,455 U.S. patients received a liver transplant; 966 were adults 65 and older (604 men, 362 women). Of the 966 transplantations, 942 were from deceased donors, and 24 were from living donors (USDHHS, 2014c).

Etiology of Liver Problems

Despite significant improvements in the management and treatment of chronic liver disease, the disease will inevitably progress to end-stage, complete liver failure, and death without transplant. Liver transplant is the only definitive therapy for ESLD. Liver transplantation is indicated for acute and chronic liver failure, cirrhosis, hepatocellular carcinoma (HCC), and other hepatic cancers. For adult patients on the liver transplant waiting list, the primary causes of ESLD are hepatitis C virus (HCV), alcoholic liver disease, and cholestatic disease (USDHHS, 2012). In a study of liver transplantation in older adults by Ballarin et al. (2011), the second listed indication for transplantation after HCV was HCC.

The Ethical Question of Liver Transplantation in Older Adults

Advances in liver transplant technology, the development of immunosuppressive medications, and improvements in postoperative management have contributed to the success of liver transplantation and broadened its indications. At the same time, demand for transplant is growing due to an aging population, obesity, and increasing prevalence of liver cirrhosis and HCC (Merion, 2010; Nensi & Chandok, 2012). The demand for liver transplantation is rising, whereas the availability of donor organs has remained static. This growing shortage of organs engenders the ethical question of transplanting older adults due to their shorter postoperative survival rates, fewer years of potential life, and fewer years in the workforce (Nensi & Chandok, 2012). For these reasons, older adult transplant recipients have been subjected to scrutiny.

However, when Ballarin et al. (2011) matched patients 65 and older to patients 64 and younger on pre-liver transplant pathology, severity of illness, and transplant indication, the patients’ short- and middle-term survival expectancy and morbidity were the same. Other researchers have found similar results when older adult liver transplant candidates were carefully selected (Bilbao et al., 2008). Therefore, local Liver Transplant Selection Committees’ decisions about whether to evaluate older adults for liver transplantation should be based on physiology, not chronological age (Ballarin et al., 2011; Cross et al., 2007; Filipponi et al., 2001). Although no established cutoff age exists for liver transplantation, transplant centers have developed policies excluding patients 70 or older from being evaluated for transplant and listed on the liver transplant waiting list (Ballarin et al., 2011).

The Liver Transplant Waiting List

The United Network for Organ Sharing (UNOS) maintains a national list of patients waiting for organ transplants. UNOS, a private non-profit organization, was developed after the National Organ Transplant Act was enacted in 1984 when the U.S. Congress established the Organ Procurement and Transplantation Network (OPTN) (UNOS, 2014). UNOS raises awareness about organ donation, establishes equitable policies, and facilitates transplantations. UNOS was awarded the initial OPTN contract and has administered it since. The OPTN secure database contains the transplant waiting list, as well as information on organ donation, matching, and transplantation.

After an extensive liver transplant evaluation, patients may be accepted, deferred, or declined listing on the transplant waiting list. An individual who is deferred will need further testing and/or treatment before a decision about candidacy can be made by a Liver Transplant Selection Committee. An individual who is declined does not meet criteria due to medical and/or psychosocial reasons, such as advanced cardiac or pulmonary disease, lack of social support, or psychiatric instability.

The length of time individuals wait for a liver transplant varies widely based on their Model for End-Stage Liver Disease (MELD) score, blood type, body size, and the regional availability of donor organs (Genentech Transplantation, 2009), and 15% die while waiting for a transplant (USDHHS, 2014c). In 2013, 1,495 patients died while waiting for a transplant, and 1,493 were too sick to undergo transplantation (USDHHS, 2014b). The MELD score predicts pretransplant mortality risk from liver disease and is calculated using patients’ values for serum bilirubin, serum creatinine, and international normalized ratio for prothrombin time (Kamath et al., 2001; Kamath & Kim, 2003). The higher the MELD score, the higher the priority for the patient to receive a transplant. Patients with high MELD scores (who are at the top of the liver transplant waiting list) need to arrive at the transplant center within 6 hours from the time when they are called in for a transplant. If they are unable to arrive within that window, they may need to move closer to the center. Donor livers, which are viable for 8 hours, are transported in a preservative to the transplant center (Ignatavicius, 2010).

Post-Liver Transplantation Course

After liver transplant surgery, patients are transferred to the ICU. The surgery varies in length, from 4 to 12 hours, but averages 9 hours (Genentech Transplantation, 2009). Patients’ lengths of stay in the ICU vary depending on how quickly they recover from the anesthetic and how sick they were pretransplant. The average length of stay in the ICU is 3 days. During this time, patients require aggressive monitoring and care. It is particularly important for ICU nurses to assess patients for pain, emotional responses, and early postoperative complications. After the surgery, many patients experience varied emotions; some feel anxious and/or depressed, whereas others feel relief that the surgery is over (Nåden & Bjørk, 2012). Some patients experience no postoperative pain, whereas others experience a great deal of pain (Nåden & Bjørk, 2012). Because of invasive and monitoring devices, patients are restricted in their ability to move, which cause them discomfort (del Barrio, Lacunza, Armendariz, Margall, & Asiain, 2004). They may have difficulty orienting themselves in time and may experience confusion, causing nights and days to blend together. Patients have reported dreaming and nightmares, which may be an effect of the high dose of intravenous corticosteroid agents given immediately after transplant (K. Sparks, personal communication, June 30, 2014; Nåden & Bjørk, 2012). The presence of family members may help patients settle, as family members can be an important source of support. Many patients find the ICU to be an organized place, and being there may provide them with a sense of security (del Barrio et al., 2004).

Early Postoperative Complications

Although older adults receive liver transplantations based on their physiology and not their chronological age, it is critical that nurses promote goal-directed interventions to prevent postoperative complications in this population. The normal aging process is associated with a decrease in physiological reserve (Menaker & Scalea, 2010). Nurses should keep in mind that age-related changes may alter postoperative responses in older adults, such as delayed wound healing.

The most common early postoperative complications include infection, acute graft rejection, and acute renal failure (Ignatavicius, 2010). Indicators of infection depend on its location and can occur at any time during the post-liver transplantation course. Infection can be located in the lungs, urine, wound, bile, and peritoneum. Therefore, patients’ temperatures are monitored frequently. Acute graft rejection can occur at any time and may be manifested by fever, right upper quadrant (RUQ) pain, jaundice, changes in color of stool and urine, and increased weakness or fatigue (Ignatavicius, 2010). Acute renal failure is manifested by changes in urine output and may have several causes, including hypotension, anti-infective agents, and all immunosuppressive medications. To monitor for complications, laboratory values are drawn every 8 hours during patients’ ICU stays. Increased levels of serum bilirubin, transaminases, and alkaline phosphatase, as well as prolonged prothrombin time, are indicative of acute graft rejection and require treatment with high doses of corticosteroid agents and potentially other potent antirejection medications (Ignatavicius, 2010). Increased blood urea nitrogen and creatinine levels are early indicators of renal failure and require a detailed assessment of potential causes for the failure, such as nephrotoxic medications (e.g., cyclosporine). Some of these medications require close laboratory monitoring of patient serum levels.

Other hepatic complications include bile leakage, abscess formation, and hepatic thrombosis. These complications may be manifested by decreased bile drainage, increased RUQ pain, abdominal distension, nausea, vomiting, and changes in the color of stool and urine. In addition to close monitoring of patients for postoperative complications, nurses should assess patients’ psychological well-being. Patients may experience a sense of lack of control, and the possibility of a graft rejection may leave them feeling frustrated, defeated, having depressive thoughts, and being afraid of dying (Nåden & Bjørk, 2012).

When patients are stable, they are transferred from the ICU to a liver transplant unit, where they will stay, on average, for 7 to 10 days. During this time, nurses continue to monitor patients for complications and teach them about signs and symptoms of graft rejection and infection, how to prevent infections, and about medications, clinic appointments, and the schedule for laboratory tests after hospital discharge. Immunosuppressive medications include calcineurin inhibitors (tacrolimus or cyclosporine), purine inhibitors (azathioprine), and corticosteroids (prednisone) (K. Sparks, personal communication, June 30, 2014). Medications to prevent infections include antibiotics (trimethoprim or sulfamethoxazole), antifungals (fluconazole), and antivirals (valganciclovir or acyclovir). Patients will also be on a proton pump inhibitor (omeprazole) to protect from gastric irritation and ulceration. Other medications patients may require include insulin, antihypertensive agents, and/or medications for electrolyte imbalances (magnesium oxide).

Nurses’ assessment of patients’ ability to be compliant with the post-transplant medication regimen is crucial, as the best thought out regimen will fail without patient compliance. Failure to be compliant will often result in organ rejection. The regimen will include therapeutic medication monitoring via serum levels, monitoring for adverse drug reactions, and attention to drug–drug interactions. Calcium channel blockers and ranitidine are examples of medications that increase serum levels of immunosuppressive medications, and anticonvulsant agents will decrease their levels.

Before discharge, it is critical that nurses assess whether patients and their primary support persons are knowledgeable about when to call the transplant coordinator, contact a physician, or go to the hospital for potential complications. Contacting a health care provider or going to the hospital should occur as soon as patients experience fever of 100° F or higher, severe abdominal pain, shortness of breath, vomiting, blood in stools and/or vomit, and confused thinking. After discharge, the transplant team will determine when patients are stable enough to return to their local health care provider for regular care. Liver transplant hepatologists will follow patients and monitor their graft. The local provider will manage other aspects, such as hypertension and diabetes, meaning that patients who do not live locally may have to arrange for housing for 2 to 3 months to be followed closely post-transplant by their hepatologist. To monitor for complications, the first month after the transplantation, patients may have blood drawn twice per week, then once per week for up to 6 months, and then every 2 weeks for 6 months. After 1 year, blood draws may occur every month (K. Sparks, personal communication, June 30, 2014).

Long-Term Complications

In general, liver transplant recipients experience improvements in their physical, social, and emotional well-being and quality of life (Butt, Parikh, Skaro, Ladner, & Cella, 2012; Karam et al., 2003; Pieber et al., 2006; Sainz-Barriga et al., 2005; Santos, Miyazaki, Domingos, Valério, & Silva, 2008). However, their quality of life scores remain more than a standard deviation below that of the general population (Russell, Feurer, Wisawatapnimit, Salomon, & Pinson, 2008). Some recipients experience excess morbidity (Butt et al., 2012); others experience long-term complications of liver transplantation. The primary long-term complications are consequences of the long-term use of immunosuppressive medications and include hypertension, chronic kidney disease, diabetes mellitus, and dyslipidemia (Singh & Watt, 2012). Up to 30% of patients develop obesity after the transplantation (Richards, Gunson, Johnson, & Neuberger, 2005). Another complication is the recurrence of the original liver disease. HCV re-infection in patients after liver transplantation is approximately 50% within 1 year, and up to 30% develop cirrhosis (Gane et al., 1996; Neumann et al., 2004). However, the statistics of re-infection will change for patients with HCV. The new direct-acting antiviral therapies simeprevir and sofosbuvir have shown high cure rates among those with genotype 1 of the virus (“Simeprevir and Sofosbuvir Cure Hep C,” 2013). Toso et al. (2008) found a recurrence rate of 10% to 13% in patients who underwent transplantation for HCC.

Psychosocial Aspects

Despite liver transplant recipients’ improvements in their quality of life, emotional well-being shows less improvement than physical well-being and functional capacity (Russell et al., 2008; Santos et al., 2008). Anxiety and depression are prevalent in preliver transplant candidates. Post transplant, the severity of these emotions decreases (Russell et al., 2008). However, in a sample of adult transplant recipients, post-transplant depression was reported to be related to medical complications, viral recurrence, and potential retransplantation (Santos et al., 2008). Gorevski et al. (2011) found depression to be significantly associated with unemployment. In the liver transplant population, returning to work activities is a common hope.

In patients who undergo transplantation because of alcoholic liver disease, concern exists about recidivism. Patients who resume alcohol consumption have a worse 10-year survival rate compared with patients who are abstinent (Cuadrado, Fábrega, Casafont, & Pons-Romero, 2005). However, the two groups were found to be similar in regard to therapeutic compliance, the occurrence of graft rejection and infection, and associated comorbidities (Cuadrado et al., 2005). To be considered a liver transplant candidate, one criterion may require patients to abstain from alcohol and/or substance abuse for at least 6 months.

The concern of recidivism, psychological symptoms, and social challenges facing adult and older adult liver transplant recipients speaks to the need for long-term psychological assessment and follow up.

Survival Post Transplantation

In three groups of patients with chronic liver disease who underwent liver transplantation, 1-year survival in patients 65 and older was 82%, in comparison to 86% in patients between the ages of 60 and 64 and 83% in patients between the ages of 18 and 59 (Cross et al., 2007). Five-year survival in the groups was 73%, 80%, and 78%, respectively. Patients 65 and older may experience less chronic graft rejection than younger liver transplant recipients (Cross et al., 2007), which may be due to a diminished responsiveness of the immune system in older adults. At the same time, this diminished response may be reflected in the most common cause of death in this group—cancer. Cancer accounts for approximately 11% of all deaths after liver transplantation (Jain et al., 2000). Cardiovascular disease and sepsis are the most common causes of deaths in patients younger than 65 (Cross et al., 2007).

Individual Example Update

For Mr. J, the hardest part of the liver transplant process was the presurgical period due to hemodialysis and a 2-week stay in the ICU, during which he felt tied to the bed. After the transplant surgery, Mr. J’s new transplanted liver started to respond immediately, and after 3 to 4 weeks, his kidneys began to work, which resulted in a remarkable loss of excess fluid. This specific time was the real turning point for him. Mr. J felt that he had come close to dying but believed that we all have to have hope until we take our last breath. He felt his strength was slowly coming back and looked forward to continued improvement. Most of all, he was grateful to the family who made the organ donation and the individual who gave him life.

Summary and Nursing Implications

When older adult liver transplant candidates are carefully selected, their post-transplant short- and middle-term survival expectancy and morbidity are similar to patients 64 and younger. Most liver transplant recipients experience improvements in their quality of life. However, research shows that they experience smaller improvements in emotional well-being than in their physical well-being. Nurses play a critical role in assessing and addressing both pre- and post-transplantation symptoms and complications, as well other health-related and social challenges; as a result, they help (a) enhance older adult liver transplant recipients’ emotional and physical quality of life and (b) prevent complications.

Nurses’ knowledge about age-related changes and the role these changes play as surgical risk factors in older adults is important. Nurses should assess for such changes, including delayed wound healing, fatigue, and confusion (Buis, Wiesner, Krom, Kremer, & Wijdicks, 2002; Zalon, 2004). Research has shown that episodes of acute confusion are more frequent in patients transplanted for alcoholic liver disease than for patients with HCV (Buis et al., 2002). During these episodes, the support person should be supported, and the older adult should be reoriented to the surroundings, provided a safe environment, and not exposed to excessive stimulation with light, noise, or questioning.

Equally important is nurses’ role in educating patients and their primary support persons about post-transplant follow-up care and assessing their level of comprehension of the importance of this care. Such care includes laboratory test schedules, medication management, infection prevention, and other health-related concerns, such as anxiety, depression, recidivism, and recurrence of the original liver disease. Verifying that patients and primary support persons understand all aspects of care surrounding liver transplantation is essential to enhance compliance and provide the greatest possibility for patients to resume the best life after liver transplantation.

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