What Do We Know About the Symptoms and Palliative Care Needs of People Affected by Liver Disease?

Introduction and Scope of the Problem

Worldwide, chronic liver disease (CLD), including cirrhosis and hepatocellular carcinoma (HCC), leads to approximately 2 million deaths annually. The major causes of CLD include viral hepatitis, alcohol-associated liver disease, nonalcoholic fatty liver disease, and autoimmune disorders, and are discussed in detail in Chapter 43 . CLD is a major cause of patient disability, and this population experiences extensive health care utilization, including frequent hospitalizations and readmissions. Small studies at North American liver transplant centers demonstrate that patients with advanced liver disease rarely receive palliative care, even at the end of life. However, there is evidence of a trend toward increasing access to palliative care for this population. This chapter describes the most common symptoms resulting from advanced liver disease and its management, the experience of affected patients and their family caregivers, and how the impact of liver disease translates to palliative care needs in this population.

Relevant Pathophysiology

In this section, common symptoms of advanced liver disease are identified, and the pathophysiology is described. Management strategies are discussed in the second half of the chapter.

Pain

Pain is present in 30% to 79% of patients with CLD, and it is one of the most prevalent and challenging symptoms to manage. Aggressive symptom control may improve quality of life in these patients. While the basic principles of pain assessment and management are applicable to the care of patients with CLD, special considerations are needed in this population due to altered pharmacokinetics from liver dysfunction, hepatic encephalopathy, possible history of and stigma around substance use disorder, as well as provider bias and stigma (see Chapter 4 for a discussion of opioid pharmacology in the setting of liver impairment).

The mechanisms and sources of pain in people with CLD are not well described. The mechanism of chronic pain in this population is not well understood and is thought to be related to inflammation or altered mechanisms in pain processing in the setting of liver disease. In a retrospective cohort study at a large academic transplant center, of 1,286 patients, 34% had pain and 25% received opioid prescriptions. The most common location of pain was the abdomen; other sites included joint, extremity, and back pain. While anatomical reasons for pain may include hepato- or splenomegaly or ascites, many individuals report pain in the absence of advanced or decompensated disease.

Itching

Pruritus is a complication of CLD that adversely affects quality of life by disrupting sleep, daily activities, and personal relationships. Although known to occur in CLD of any etiology, it is more common in patients with cholestatic liver diseases like primary biliary cirrhosis or primary sclerosing cholangitis. The pathogenesis of pruritus in CLD remains elusive, but it is thought to be mediated by pruritogenic substances that accumulate as a result of impaired biliary secretion. These pruritogens (e.g., bile salts, lysophosphatidic acid) may act at the nerve endings at the level of the skin or act centrally to mediate itching.

Cramping

Many patients with advanced liver disease experience muscle cramping, which while minor in some cases, can be debilitating with significant impact on quality of life. Changes at the level of the nerve fiber are thought to contribute, including changes in myelination and increased nerve excitability. Impaired protein synthesis may also contribute, leading to altered amino acid metabolism at the level of the muscle that changes the behavior of ion channels. The cramps experienced by patients can be quite painful, and thus cramping should be included on the differential diagnosis when assessing pain for someone with liver disease.

Fatigue

Fatigue is another common but challenging and poorly understood symptom associated with CLD, with a prevalence of 50% to 85%.

It is most common among patients with cholestatic liver diseases such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), malignancy (hepatocellular carcinoma), and viral hepatitis. Fatigue can be categorized as central (volitional or mental fatigue) or peripheral (neuromuscular dysfunction, physical fatigue). In addition to differentiating central from peripheral fatigue, it is important to distinguish fatigue from liver-related medical conditions and liver disease symptoms with similar features, such as hepatic encephalopathy, anemia, frailty, and depression. Overall, objective tools to measure the complex aspects of fatigue in patients with liver disease are lacking.

Swelling

Patients with liver disease are at risk of experiencing swelling related to fluid overload, third spacing, and portal hypertension. Imbalance of the renin-angiotensin-aldosterone system is associated with portal hypertension and leads to water and sodium retention and splanchnic vasodilation. These phenomena, combined with reduced oncotic pressure from impaired albumin synthesis in the liver, can lead to peripheral edema. Commonly, patients experience abdominal swelling related to the accumulation of ascites, also resulting from portal hypertension, in which transudative fluid “weeps” from the surface of the liver (see Chapter 43 ).

Confusion

Hepatic encephalopathy (HE) has a potentially devastating impact on the quality of life experienced by patients and their family caregivers. Liver insufficiency and portosystemic shunting may trigger the onset of a wide range of neuropsychiatric symptoms such as confusion, delirium, and HE. HE occurs in about 30% to 40% of patients with decompensated cirrhosis. It is classified as overt (West Haven grades II–IV, disorientation to coma) or covert (West Haven grade I; diagnosis may require neuropsychological testing). The course of overt decompensated cirrhosis is unpredictable and often requires hospitalization. HE is the leading cause of readmission and mortality in cirrhotics. The pathophysiology and classification of HE are discussed in Chapter 43 .

Sleep Disturbance and Drowsiness

Sleep disturbance is common in patients with CLD and is strongly associated with anxiety, depression, and diminished quality of life. This can be due to a direct consequence of liver disease (altered melatonin metabolism or the presence of low-grade HE) or other related factors such as pain, medications that may interfere with sleep (e.g., diuretics), pruritus, ascites, and fatigue. Sleep-wake cycle inversion (i.e., restless nights and more daytime sleepiness) occurs in patients with HE. The prevalence of sleep disturbance varies from 27% to 70% to include insomnia, difficulty falling sleep, multiple night awakenings, and daytime sleepiness.

Anxiety and Depression

Depression and anxiety are highly prevalent in patients with chronic liver diseases and may lead to adverse clinical outcomes for complex and multifactorial reasons. One study showed prevalence rates of depression of 30% to 40%, which conferred increased risk of dying while waiting for a transplant. Patients who were suffering from depression had a higher mortality rate than non-depressed patients, and appropriate antidepressant use reverses the effect. It is important also to remember that psychiatric symptoms may be a presentation of HE.

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