G23- Management of a patient with acute liver failure

Define acute liver failure

• Acute deterioration in liver function in patient (most often) without underlying chronic liver disease

• 2-3x elevation of transaminases (marker of liver damage)

• fulminant hepatic failure = acute hepatic necrosis= fulminant hepatic necrosis= fulminant hepatitis

Define acute on chronic liver failure

• acute deterioration in liver function and extrahepatic organ failures in patients with chronic liver disease with high mortality rate

Define decompensation of cirrhosis

• an advanced stage of liver disease where the liver can no longer function properly due to severe scarring, leading to life-threatening complications

What is fulminant liver failure

• potentially reversible condition- consequence of severe liver injury

• with an onset of encephalopathy within 8 weeks of appearance of the first symptoms and in the absence of pre existing liver disease

What is the treatment of acute liver failure

only transplant

What are teh symptoms of decompensation of liver cirrhosis

• ascites

• hepatic encephalopathy

• renal impairment

• GI bleeding

What is the classification of acute liver failure

Based on time between onset of symptoms and development of hepatic encephalopathy

• hyperacute- HE within 7 days

• acute- 8-28 days

• subacute- 5-12 weeks

Define hyperacute liver failure

• increased transaminase levels/ severe coagulopathy/ increase in bilirubin which usually precedes clinical encephalopathy

• better prognosis with higher incidence of cerebral oedema

• acetaminophen toxicity, ischaemic hepatopathy

Define subacute/ subfulminant

• milder increase in serum transaminases/ deep jaundice/ mild to moderate coagulopathy + splenomegaly, ascites, shrinking in liver volume

• worse prognosis with lower incidence of cerebral oedema, renal failure and portal HT are more frequent

• Wilson’s ddisease

What is the etiological factors of ALF

• metabolic

  • Wilsons

• Drugs

  • tylenol, prescription meds, ecstasy, amanita

• Viral

  • HAV, HBV/HDV, Non A E

• vascular

  • Budd Chiari, ischaemia

• pregnancy

  • HELLP, fatty liver

    • HELLP-syndrome: haemolysis, elevated liver enzymes and low platelet count

• autoimmune

• infiltrative

  • lymphoma, melanoma, TB

What are the main hepatotoxic drugs

• paracetamol, NSAIDs

• amoxicillin- clavulanate, antibiotics

• antituberculotics

• statins

• ketoconazole

• antiepileptics

What is the pathomechanism of acute liver failure

• injurous agent causes hepatocyte damage directly, or by forming free radicals

• → coagulation activation, cytokine release, DAMP release from hepatocytes

• → systemic inflammation, possible infections

• → organ failures

What are the complications of ALF

• CNC disturbances

  • hepatic encephalopathy, cerebral oedema, seizures

• infections

• coagulopathy and bleeding

• renal failure/ hemodynamic collapse

• metabolic derangement

What are the diagnostic steps in ALF

• history

• clinical signs

• PE- liver and spleen

• lab- blood + urine

• abdominal US/ CT/ MRI

  • fibroscan, upper GI endoscopy, echocardiography

• biopsy

What are important during history taking in ALF

• alcohol consumption

• family ihstory of liver disease

• occupation

• sexual contact

• muschroom consumption with unknown origin

• transfusion

• tattoo, piercing

• travelling history

• meal, food

• medication, herbs

What are the symptoms of ALF

• jaundice

• mental confusion, difficulty concentration, disorientation

• RUQ pain

• nausea, vomiting

• pruritus

• fatigue, malaise

• melena/ hematemeses

• ascites

• ankle oedema

• muscle tremors

What are the physical findings in ALF

• icterus- sclera, mucosa, skin

• neurological signs

  • flepping tremour, consciousness

• RUQ tenderness, hepatomegaly, skin bleedings

  • petechia, purpura, echymosis, suffusion

• ascites

• hernias

What are the containdications of liver transplant

• alcohol consumption and alcohol caused chronic liver disease

• recent malignancy

• severe cardiovascular problems

What are the laboratory markers in ALF

- hepatic: AST, ALT, GOT
- cholestatic: GGT, ALP
- total blood count, LDH, coagulation
- bilirubin, ammonia, albumin, glucose
- arterial blood gas
- urine toxicology screen
- viral serology

What are the gradings for hepatic encephalopathy

What are the diagnostic criteria of ALF

1. prolongation of INR >1.5
2. any degree of hepatic encephalopathy
3. no prior evidence of liver disease
4. <26 weeks disease course

What can you see on US

• hepatomegaly

• inhomogeneity

  • check blood supply- differentiate from Budd CHiari

What are the indications for a liver biopsy

• no exact etiology based on lab and imaging tests but

  • specific treatment or conduct can be decided ( AH, DILI, viral infection, mushroom, Wilsons, malignancy)

• to distinguish ALF from chronic liver disease

• Transjugular apprach is prefered

What is the differential diagnosis of ALF

• acute decompensation of cirrhosis

• acute on chronic liver failure

• alcoholic hepatitis with underlying cirrhosis

• eclampsia/ preeclampsia

What are the teratment modalities of ALF

• specific- treat underlying cause

• supporttive- independently from underlying etiology

• decide whether they need ICU or center with active liver transplantation

What are the specific therapies

• Autoimmun hepatitis

  • glucocorticoids-with careful consideration-infection risk!

• Acute hepatitis B

  • antiviral treatment (NA: entecavir, tenofovir)

• Amanita phalloides

  • gastric aspiration, lavage, activated charcoal, silibinin, penicillin G, Nacetylcystein

• Pregnancy-related liver disease

  • pregnancy interruption

• Budd-Chiari syndrome

  • transjugular intrahepatic shunt placement, surgical decompression, thrombolysis

• Acetaminophen intoxication

  • N-acetylcystein

What is the supportive treatment

• haemomdynamic stabilisation

  • fluid, vasopressors, NE, terlipressin, inotropic drugs

• ventilatory support

• AKI

  • renal replacement therapy

    • uraemia, fluid overload, hyperkalemia, acidosis, sodium imbalance, hyperammonemia

• infections

  • bacteria- pneumonia, UTI, BSI, multiresistant

  • fungal

  • routine sampling for cultures, CXR, diagnostic paracentesis

  • broad spectrum antibiotics

• hepatic encephalopathy

  • lactulose, rifaximin

  • severe protein restriction must be avoided

• nutritional

• metabolic abnormalities

  • acidosis, hypokalaemia, hyponatreaemia, hypophosphatemia, hypoglycemia

• coagulation

  • decreased amount

  • thromboelastography- evaluates coagulation phenotype

  • give necessary haemoderivatives

• intracranial HT

  • invasive monitoring- intraparenchymal microtransucers

  • non invasive- transcranial doppler

  • serum sodium must be monitored, mannitol

• extreacorporal support

  • MARS- molecular absorbent recirculation system- albumin dialysis

What are bad prognostic factors for liver transplantation

• >50

• requirement of life support

• BMI >30

• serum creatinin >2mg/dl

• other- reduced organ size, donor age >60, incompatible ABO group, donor liver steatosis

What are the kings college criterias for paracetamol induced ALF

• arterial pH <7.3 after fluid resusucitation, >24 h since ingestion

• or

• lactate > 3 mmol/l

• or

• the 3 following criteria:

  • HE grade>3

  • serum creatinine >300 umol/l

  • INR>6.5

What is the Kings college criteria for non paracetamol induced ALF

• INR>6,5

• or-3 out of the 5 following criteria:

  • aetiology: „indeterminate”, drug induced

  • age <10 years or >40 years

  • icterus HE interval >7 days

  • bilirubin >300 umol/l

  • INR>3.5