Liver Failure

Hepatic failure is when the liver loses the ability to regenerate or repair so that decompensation occurs. It is marked by:

• Encephalopathy
• Haemorrhagic diathesis
• Ascites
• Jaundice

Fulminant hepatic failure is defined as when the failure occurs within 8 weeks of the onset of the underlying illness. Late onset hepatic failure, also called subacute fulminant hepatic failure, is when there has been a gap of 8 to 26 weeks. The difference may not be immediately obvious as the underlying disease may have been present for a long time but undiagnosed. If the latent period is over 6 months it is chronic decompensated hepatic failure.

There is no sex difference in incidence. In the UK over 600 liver transplants a year are performed¹ but that figure is said to be low compared with the rest of Europe and 60 people a year die waiting.

There are many causes of hepatic failure and the following represent just a few.

• Paracetamol overdose. This can occur at a lower level than expected in chronic alcohol users
• Drug toxicity² including co-amoxiclav, ciprofloxacin, doxycycline, erythromycin, isoniazid, nitrofurantoin, halothane, statins, cyclophosphamide, methotrexate, disulfiram, flutamide, gold, propylthiouracil to name just a few.
• One of the various forms of viral hepatitis, especially if there is also infection with hepatitis B. Hepatitis D requires pre-existing hepatitis B to permit infection.
• Hepatitis E is similar to Hepatitis A in that it occurs mainly by contamination of food and water. It is common in India, Asia, Africa, Middle East and Central America. It may cause acute hepatitis but not normally severe, long term disease. The exception is in pregnancy when it may cause miscarriage at any stage and if caught in the last trimester it is fatal in 20% of cases.
• Adenovirus, Epstein Barr virus, Cytomegalovirus and viral haemorrhagic fevers
• Progression of cirrhosis of various causes including alcoholic cirrhosis and Wilson's disease
• Hepatocellular carcinoma or metastatic carcinoma
• Poisoning by various substances including mushrooms or chemicals including carbon tetrachloride and other organic solvents and phosphorus
• Illicit drugs including Ecstasy and cocaine
• Herbal remedies including ginseng, pennyroyal oil, Teucrium polium, chaparral or germander tea³
• Acute fatty liver of pregnancy and about half develop severe pre-eclampsia
• Reye's syndrome
• Ischaemia, veno-occlusive disease, Budd-Chiari syndrome
• Metabolic disease including alpha-1-antitrypsin deficiency, fructose intolerance, galactosaemia and tyrosinaemia
• Autoimmune liver disease

The cause remains unknown in 15%.

Mental faculties may be so impaired that history from someone close may be required. There may be hallucinations. Haematemesis or melaena may complicate gastrointestinal bleeding.

• Ask about date of onset of jaundice and encephalopathy
• Alcohol use
• Medication including prescription medicines, illicit drugs and alternative medicines
• Family history of liver disease (Wilson's disease or haemochromatosis)
• Exposure risk factors for viral hepatitis (travel, transfusions, sexual contacts, occupation, body piercing)
• Toxin ingestion (mushrooms, organic solvents, phosphorus contained in fireworks)
• Past medical history

• Mental state shows drowsiness and possibly confusion
• Jaundice
• Hyperdynamic circulation with multiple organ failure may mimic septic shock
• Abdominal distension and abdominal masses, including:
  • Possible massive ascites and anasarca due to fluid redistribution and hypoalbuminaemia
  • A dehydrated patient may not show much ascites
  • Hepatomegaly and splenomegaly but not invariably
• Cerebral oedema with increased intracranial pressure (ICP), may produce papilloedema, hypertension, and bradycardia
• Liver palms are red and a hepatic flap, also called asterixis may be present
  • Hyperextend the fingers and wrist, gently pushing back and a slow clonic movement is the liver flap

• Structural lesions or space occupying lesions in the brain
• Cerebral infection, bacterial or viral
• Drug or alcohol intoxication
• Delirium tremens or Wernicke's encephalopathy
• Metabolic upset such as hypoglycaemia, ketoacidosis, electrolyte imbalance, hypoxia, hypercapnia

Blood

• FBC may show thrombocytopenia.
• INR will be raised. Although these are sensitive tests they may indicate other causes such as vitamin K deficiency or disseminated intravascular coagulation.
• Transaminases are very markedly raised but alkaline phosphatase may be slightly high or normal.
• Bilirubin is raised.
• Pseudocholinesterase is low.
• Ammonia levels are high. This should preferable be estimated on arterial blood.
• Glucose can be dangerously low and must be monitored.
• There may be elevated lactate, hypoxia and raised creatinine, especially if there is hepatorenal syndrome or acute renal failure.
• Blood cultures. They are very susceptible to infection.
• Viral serology may indicate the infection that precipitated the hepatic failure.
• Tests for specific conditions include free copper for Wilson's disease and paracetamol levels in case of poisoning.

Imaging

• Doppler ultrasound may establish whether or not the hepatic vein is patent (Budd-Chiari syndrome) as well as looking for primary or secondary carcinoma and checking for ascites.
• CT or MRI may demonstrate the hepatic anatomy and to exclude other pathology, particularly if there is massive ascites, obesity or if transplantation is considered. Avoid contrast in case it damages the kidneys.
• Imaging of the head may demonstrate cerebral oedema.
• EEG may help define level of encephalopathy.
• Liver biopsy should be avoided with compromised coagulation although a transjugular approach is sometimes used.

Early recognition of the diagnosis and transfer to a specialist unit is required. The possibility of liver transplant should be considered at an early stage.

• Poisoning with drugs such as paracetamol or mushrooms may require specific interventions.
• Lactulose, often with neomycin, is given to reduce ammonia production.
• Protein restriction may not be as important as is traditionally taught.⁴
• Mannitol may reduce intracranial pressure. Try to avoid sedatives as they make assessment difficult. Intracranial pressure monitoring is sometimes required.
• Cerebral oedema often leads to brain herniation and death. A possible treatment that is being assessed is hypothermia.⁵
• Renal failure may require haemodialysis or continuous arteriovenous haemofiltration as the former can drop BP to a dangerous level.
• Coagulation deficits require fresh frozen plasma and platelets, often in large amounts.⁶
• Monitor glucose and other biochemical parameters. Large amounts of IV glucose may be required.
• Liver transplantation may be life-saving if a graft becomes available.⁷ Various artificial liver devices have been developed and they may bridge the gap until transplant or spontaneous recovery.⁸ They include a bio-artificial liver.⁹

• Infection is a great problem. Spontaneous peritonitis is common as is infection of one of the access lines. Opportunistic infection and pneumonia may occur
• Cerebral oedema may require intervention including intubation to permit hyperventilation to lower ICP¹⁰
• Haemorrhage can be a considerable problem. Oesophageal varices may require attention. If large transfusion requirements exceed apparent blood loss consider retroperitoneal haemorrhage
• The major complications that cause death, even after transplantation are bleeding, sepsis, cerebral oedema, renal failure, and respiratory failure.¹¹

Prognosis is dependent upon the cause of the hepatic failure.

• Hepatitis A has a good prognosis with a 50 to 60% survival. It accounts for around 20% of paediatric liver transplants.
• Features indicating poor prognosis include arterial pH under 7.3, prothrombin time above 100 seconds, bilirubin above 300μmol/L, more than 7 days jaundice before encephalopathy and age under 11 or over 40.¹¹
• When Wilson's disease presents as fulminant hepatic failure it is almost invariably fatal unless transplantation can be performed.
• In the USA in 1995 it was reported that 7% of all liver transplants were for fulminant hepatic failure and that the survival rate at 1 year was 63% compared with 78% for non-fulminant hepatic disease.¹²
• Figures from England suggest a 75% survival at 1 year compared with a 90% mortality for liver failure without transplantation.¹³
• When comparing figures for survival it is important to compare like with like in terms of case mix. It seems that 3 and 12 months survival are similar,¹⁴ suggesting that most deaths occur in the first 3 months.