The most common diagnosis for liver impairment is alcohol-related liver disease which accounts for well over a third (37%) of all deaths from liver disease. Furthermore, 22% of deaths due to liver disease are from primary liver cancer, the majority of which will have alcohol-related liver disease as the underlying cause. Other major causes of liver disease include:

• Non-alcoholic steatohepatitis (NASH) or “Fatty Liver” associated with obesity
• Viral hepatitis
• Other chronic liver diseases
• Hepato-biliary disorders
• Pancreatic disorders

Many patients with advanced liver disease experience repeated episodes of deterioration, otherwise termed ‘decompensation’. This is when one or more of the sequelae of liver disease (e.g. ascites, oedema, encephalopathy, jaundice, bleeding) become more progressive, leading to a decline in the patient’s ability to function.

Symptoms may fully or partially resolve, either spontaneously or as a result of medical intervention, leading to an improvement in the patient’s ability to function. Some patients experience an episode of decompensation from which they do not recover and death follows. Several factors may influence whether a particular episode leads to terminal decompensation, including:

• The patient’s physiological reserve (‘fitness’)
• Presence of multiple symptoms
• Presence of added complications such as infection or kidney failure
• Timing, appropriateness and vigour of medical intervention
• The patient’s preferences and engagement with active treatment

Patients with end stage liver disease experience significant symptom burden, either through the impact of their deranged liver function or through complications to which they are particularly vulnerable. These can include:

• Fluid retention
  • Generalised oedema, secondary to reduced serum albumin levels
  • Ascites, leading to abdominal distension, gastric compression and breathlessness
• Muscle wasting and cramps, secondary to protein calorie malnutrition
• Hepatic encephalopathy (HE) , causing delirium and confusion: a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction and portal-systemic shunting diagnosed after exclusion of other known brain diseases. It affects 30% to 45% of patients with cirrhosis, and its presence and degree of progression signify poor prognosis and high mortality. It can be exacerbated by:
  • Infection
  • Constipation: an increased bowel transit time may cause increased ammonia absorption and precipitate encephalopathy. Non-absorbable disaccharides such as lactulose have traditionally been the mainstay of treatment, Non-absorbable antibiotics such as rifaximin may also be used.
  • Opioid analgesics and sedatives
  • Worsening liver function
• Jaundice and itching, secondary to reduction in the breakdown of bilirubin
• Nausea and vomiting due to:
  • Ascites causing gastric compression
  • Increase in circulating toxins
  • GI bleeding and associated raised 5HT3
• Gastrointestinal bleeding due to oesophageal varies, secondary to reduced synthesis of clotting factors, reduced absorption of vitamin K and portal hypertension
• Increased risk of spontaneous bacterial peritonitis
• Fatigue
• Anxiety and depression

Prescribing for a patient with liver disease can be complex as it is affected by the specific cause of the liver disease and the degree of liver damage. As the hepatic reserve is large, liver disease must be severe before changes in drug metabolism occur. Traditionally, markers such as raised bilirubin, raised INR/prothrombin time, raised ALT, low albumin, and the presence of ascites, encephalopathy or jaundice are principally used to assess disease severity. However, there are no adequately sensitive biochemical markers or formulae that can accurately predict drug clearance and there is a lack of reliable information on drugs commonly used in palliative care.

Advice regarding drug treatment therefore, should be individualised to each patientand prescribing should be kept to a minimum where possible. Known hepatotoxic drugs should be avoided if possible.