Chronic liver failure

Chronic liver failure is a disease process that involves progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis.

Venous flow into the liver decreases due to this, leading to elevated portal pressures. Portal hypertension then leads to splenomegaly, causing anaemia and thrombocytopenia. Ascites, hepatorenal syndrome, hepatopulmonary syndrome, variceal bleeding and hepatic encephalopathy are all recognised complications.

Cirrhotic patients may have stable liver functions for long periods of time. An acute insult in the presence of advanced fibrosis and decreased functional reserve may lead to development of hepatic decompensation. These patients may develop decompensation in two ways:

• The most common is a progressive decompensation resulting in a clinical course of end-stage liver disease.
• Acute liver decompensation resulting from a precipitating event such as variceal bleeding or sepsis.

You may also want to view the Acute liver failure clinical tool.

Aetiology

• Alcohol
• Hepatitis B and C
• Non-alcoholic steatohepatitis (NASH)
• Autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis
• Right heart failure, congestive cardiac failure
• Drugs, for example amiodarone
• Metabolic or genetic, for example Wilson’s disease and haemochromatosis

History

Remember to ask about

• Medications the patient is taking and degree of compliance
• Previous endoscopy and presence of varices
• Anorexia, weight loss, pruritus, fever, abdominal pain, shortness of breath, etc.

Examination

Signs of chronic liver failure

• Vital signs. Heart rate may be low due to beta-blockers (for varices). Blood pressure may be low due to bleeding, dehydration or sepsis. Oxygen saturation may be low due to pleural effusions, splinting of diaphragm or encephalopathy and drowsiness
• Encephalopathy
• Jaundice
• Hepatomegaly (may be tender)
• Splenomegaly
• Ascites
• Peripheral oedema
• Spider naevi
• Bruising
• Liver flap
• Gynaecomastia

Investigations

For patients with advanced disease consider the:

• appropriateness of investigations and interventions
• reversibility of the situation
• prognosis for the patient.

The Child-Pugh score can be used to help determine prognosis.

Investigations to complete

• Full blood count may reveal thrombocytopenia, anaemia, macrocytosis
• Coagulation studies
• Liver function tests. Often elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), low albumin and/or protein
• Bilirubin level may be elevated
• Serum ammonia level may be dramatically elevated. Risk of intracranial hypertension highest when sustained level ammonia 150-200µmol/L (250-340 µg/dl)
• Serum glucose level may be dangerously low
• Lactate is often elevated
• Creatinine level may be elevated
• Electrolytes. Sodium may be low, often dilutional due to fluid accumulation
• Calcium, magnesium, phosphate
• Blood cultures (for patients with suspected infection)
• Pregnancy test
• Lipase
• Chest X-ray
• Electrocardiogram
• If first presentation of chronic liver disease, consider full liver screen including hepatitis A, B, C +/- D, Epstein-Barr virus, bacterial vaginosis, cytomegalovirus, antinuclear antibody test, anti-smooth muscle antibody,1 antitrypsin, copper, paracetamol, thyroid function tests, immunoglobulins, ceruloplasmin, alpha-fetoprotein.

Investigations to consider

• Hepatic Doppler ultrasound
• Abdominal computed tomography
• Brain computed tomography, particularly looking for intracranial bleeds
• Echocardiogram, hypoxic hepatitis can result from myocardial dysfunction
• Electroencephalogram
• Intracranial pressure monitoring

Management

General

Patients with liver failure often deteriorate quickly. If a patient is not unwell enough for a resuscitation bed, they should be placed in a highly visible bed with a cardiac monitor.

Specific

Alcohol

• Supplement thiamine to prevent Wernicke's encephalopathy. Give thiamine prior to glucose load.
• Multivitamins for nutritional deficiencies, replace electrolytes.
• Glucose as have lost gluconeogenic powers. Give thiamine prior to glucose load.
• Alcohol withdrawal scale and benzodiazepine as required.
• Education about abstinence.
• Calculate Maddreys Discriminant Function (MDF) score. Patients with MDF ≥32 have a poor prognosis. Discuss with gastroenterology. The patient may benefit from:
  • Steroids. Minimal data but there is a suggestion that steroids have a protective effect. Start 40mg/day if no contraindications.
  • Anticytokine therapy, pentoxifylline, oral phosphodiesterase inhibitor which decreases production of tumour necrosis factor and other cytokines.

Ascites

• Sodium restriction
• Fluid restriction is not indicated unless there is concomitant hyponatraemia
• Spironolactone +/- frusemide.
• Indications for paracentesis include abdominal pain and shortness of breath.
  • Check for coagulopathy and thrombocytopaenia
  • Relative contraindications such as adhesions, bowel obstruction.
  • Send sample for albumin, cytology, cell count and culture.
  • If a large amount (>6L) to be drained, replace volume with human albumin solution (no evidence for use if less than this). Once paracentesis complete 100mLs 20% albumin / 3L ascites.

Spontaneous bacterial peritonitis (SBP)

• SBP is infection of ascitic fluid without clear source such as perforation or abscess (secondary bacterial peritonitis).
• Diagnosis
  • Ascitic fluid – includes polymorph cell count >250cells/mm³ or positive fluid culture.
  • Typical organisms include klebsiella, E. coli, streptococcus pneumoniae.
• Treatment
  • If SBP suspected, treat empirically with antimicrobials as per local protocol.
  • Stop beta-blockers. Nonselective beta-blockers have been found to increase haemodynamic instability, time of hospitalisation and risks for hepatorenal syndrome and acute kidney injury.

Coagulopathy

• Per oral vitamin K
• Platelet transfusion, if clinically indicated
• Active haemorrhage: fresh frozen plasma +/- recombinant factor VIIa - discuss with haematologist.

Hepatic encephalopathy

• Treat with Lactulose
• Early intubation if required to protect airway. You must first make an assessment about the appropriateness of this intervention.

See MDCalc Hepatic Encephalopathy Grades/Stages.

Variceal bleeding

See Upper GI bleeding clinical tool

Hepatorenal syndrome

• Caused by extreme renal artery vasoconstriction in setting of splanchnic vasodilation, low cardiac output and low effective plasma volume.
• Plasma expansion with albumin +/- haemodialysis plus vasoactive agents like octreotide or noradrenaline.
• Paracentesis has been found to improve renal function in volume resuscitated patients.

Hepatopulmonary syndrome (HPS)

• Tense ascites can cause pleural effusions and splint the diaphragm. However true HPS is a disorder of pulmonary vascular dilatation and shunting.
• Provide supplemental oxygen.
• For refractory hypoxaemia, liver transplant is considered, and higher priority given to those with liver failure and HPS.

Further resources

• Clinical guidance for withdrawal from alcohol and other drugs
  Source: NSW Ministry of Health
• Liver disorders: Ascites
  Source: Therapeutic Guidelines
• Spontaneous bacterial peritonitis
  Source: Therapeutic Guidelines
• State-wide referral criteria: Cirrhosis (suspected or known)
  Source: NSW Ministry of Health
• Liver disorders: Hepatorenal syndrome
  Source: Therapeutic Guidelines
• Kidney impairment in patients with cirrhosis: Hepatorenal syndrome
  Source: Therapeutic Guidelines
• Hepatopulmonary syndrome in adults: Prevalence, causes, clinical manifestations, and diagnosis
  Source: UpToDate
• Hepatopulmonary syndrome in adults: Natural history, treatment, and outcomes
  Source: UpToDate