Palliative care can be helpful at various stages of the transplant process and is currently underused. A recent prospective observational study of palliative care consultation for liver transplant service patients in the surgical intensive care unit demonstrated improved communication and consensus around goals of care. Importantly, palliative care was not associated with any increase in mortality (Lamba et al. 2012). Such integrated interventions and education about palliative care, triggers for palliative care consults, and active case finding are all potential approaches to increase palliative care services for liver transplant patients (Walling et al. 2015).

Patients waiting for transplant face unique challenges. Health-related quality of life has been shown to be significantly impaired in patients awaiting orthotopic liver transplant (Younossi et al. 2000). While 5,921 liver transplants were performed in the USA in 2013, 1,767 patients died while on the waiting list due to organ shortages (Kim et al. 2015). Patients should be prepared for the possibility that they might not receive an organ or that they might be delisted if their disease progresses and they no longer meet criteria. They also must be prepared for the potentially devastating complications that can occur during or after transplant. It can be difficult to discuss these issues when patients and families are hoping for the long-term survival and improved quality of life that transplant can offer. Palliative care specialists can help facilitate these discussions and introduce a “hope for the best while planning for the worst” approach (Back et al. 2003).

Given the increasing success of liver transplantation, more patients are living for longer periods after transplant. 59,000 patients were living with liver transplants in 2013 (Kim et al. 2015). Quality of life has been shown to improve considerably after liver transplant, and some studies in patients after liver transplant have even found quality of life that approaches that of healthy populations (Karam et al. 2003). However, a 2007 systematic review showed that patients after liver transplant still have significant deficiencies in most quality-of-life domains (Tome et al. 2008). Re-hospitalizations are common in the first few months after transplant, frequently from surgical complications, malnutrition, and infection (Shankar et al. 2011). For these patients, palliative care can offer continued support as they may struggle to adjust their expectations about their health and quality of life.

Palliative care is essential for patients who are ineligible for transplant or do not wish to pursue transplant yet is greatly underused in this population (Poonja et al. 2014). One thousand two hundred twenty-three patients were removed from the liver transplant list in 2013 after becoming too sick to undergo transplant (Kim et al. 2015). Patients who are removed from the waiting list have high symptom burden and may continue to receive aggressive medical interventions despite a poor prognosis. In a retrospective chart review of 102 patients who were removed from the liver transplant list or who declined transplant, median time from denial of transplant to death was 52 days; patients spent a median of 14 days in the hospital. This same study found a high prevalence of pain, nausea, dyspnea, and other bothersome symptoms prior to death (Poonja et al. 2014). Palliative care can assist with symptom management and facilitate transitions to hospice care for this subset of patients.

Hospice care is a program for patients at the end of life that provides medical care and support services. Medicare covers hospice services, as do most other insurance plans, and care frequently occurs at home. Families using home hospice care report higher satisfaction with end-of-life care and fewer unmet needs compared with those experiencing end-of-life care without hospice services (Teno et al. 2004). Patients with liver disease tend to be referred late to hospice care with 22 % dying within 7 days of enrollment (Christakis and Escarce 1996). Though somewhat controversial, a few hospices will enroll patients who are still on the transplant list if they otherwise meet hospice criteria; patients then de-enroll from hospice if they are called for transplant (Rossaro et al. 2004). In one study of 157 patients who were admitted to hospice while still listed for liver transplant, the hospice and transplant teams were able to successfully integrate palliative goals with disease-directed goals. Six of these patients went on to receive a transplant (Medici et al. 2008).

Severe pain is common in patients with advanced liver disease and is comparable to the severity of pain in patients with lung and colon cancer (Roth et al. 2000). In one study, 77 % of liver transplant candidates reported moderate levels of pain in the previous 24 h (Madan et al. 2012). Pain may be due to various causes such as neuropathy, hepatic capsular stretch, ascites, or arthralgias. After liver transplant patients may experience pain from a variety of causes, such as infection or bleeding. Immunosuppressant therapy may lead to bone pain from osteonecrosis or osteoporosis (Li et al. 2013). Calcineurin-inhibitor-induced pain syndrome, characterized by bony pain and evidence of bone marrow edema on MRI, is theorized to be caused by tacrolimus- or cyclosporine-induced vasoconstriction (Grotz et al. 2001). Compressive peroneal neuropathies have also been described after liver transplant (Singhal et al. 2009). Pain management will depend on the etiology of the pain and a patients’ condition at the time of treatment. Adequate pain control can be challenging due to potential side effects of analgesic medications in patients who are at risk for complications such as encephalopathy, nausea, or constipation. History of addiction can pose an added challenge when choosing a pain treatment regimen. Standard approaches to pain need to be modified for patients with end-stage liver disease (ESLD) due to changes in pharmacokinetics and other disease-specific considerations. Further challenges include the lack of guidelines for analgesic use in this population. Because of these barriers, pain is often undertreated for these patients (Imani et al. 2014). However, a limited body of evidence combined with expert opinion can help guide pain management decisions.

Acetaminophen is the preferred analgesic in patients with mild to moderate nocioceptive pain because of its overall safety profile and may be safely used in limited doses for patients with liver dysfunction (Dwyer et al. 2014). Due to the increased half-life of acetaminophen in liver dysfunction, many experts recommend limiting acetaminophen in patients with cirrhosis to total doses of 2–3 g/day. For patients with active alcohol consumption, some experts recommend a dose of 2 mg/day or less, as depletion of glutathione levels in these patients makes them susceptible to increased drug-induced hepatotoxicity (Chandok and Watt 2010). Nonsteroidal anti-inflammatory drugs (NSAIDs) should generally be avoided due to the potential for reduced renal perfusion and antiplatelet effects (Imani et al. 2014). Aspirin and other NSAIDs are associated with GI bleeding and have been associated with first bleeding episode in patients with cirrhosis (De Ledinghen et al. 1999). Furthermore, because NSAIDs are highly protein bound, patients with hypoalbuminemia may also experience increased serum levels and subsequent toxicity (Chandok and Watt 2010).

Patients with more severe pain may require opioid medications (Table 2). Opioids can all cause sedation, constipation, or respiratory depression and can precipitate encephalopathy; patients should be closely monitored during titration of these medications. Tramadol requires metabolism to its active form in the liver and so may not be effective in advanced liver disease; some experts recommend avoiding it entirely in this population (Rhee and Broadbent 2007). Morphine and hydromorphone have increased bioavailability and an increased half-life in patients with cirrhosis and therefore need to be used with caution (Hasselstrom et al. 1990; Dwyer et al. 2014). Codeine, oxycodone, and hydrocodone are metabolized via CYP2d6 enzyme in the liver to their active form and therefore may have decreased efficacy; they also have impaired clearance and can cause drug accumulation and associated side effects (Dwyer et al. 2014). Fentanyl does not have active metabolites, and its half-life is not altered in patients with cirrhosis; it therefore may be better tolerated than other agents; however, it still may require reduced dosing in patients with hypoalbuminemia because it is highly protein bound (Haberer et al. 1982; Chandok and Watt 2010). Methadone also does not have active metabolites but should only be used with expert consultation due to the potential for drug interactions and its pharmacokinetic variability.

In general, when using opioids in patients with liver disease, a useful approach is to start with decreased dosing and increased intervals of administration and to titrate with caution and attention to any side effects such as constipation or encephalopathy (Imani et al. 2014). Avoidance of long-acting formulations of medications may also be recommended (Dwyer et al. 2014). In patients with successful liver transplants, the pharmacokinetics of opioids can be comparable to the pharmacokinetics seen in healthy populations. In a trial involving six patients before and after liver transplant, the metabolism of oxycodone normalized after transplant and was similar to that of healthy adults (Tallgren et al. 1997).

Adjuvant analgesics can be used to treat neuropathic pain. Tricyclic antidepressants, often used as first-line agents for neuropathic pain, may have impaired clearance in patients with cirrhosis and should be up-titrated slowly. Anticonvulsants such as gabapentin and Lyrica are excreted by the kidney and are generally safe for use in patients with liver dysfunction (Dwyer et al. 2014). Other anti-convulsants can also be helpful in neuropathic pain and have varying hepatic clearances.