Acute Liver Failure

Acute Liver Failure
Aboubakr O. Aldhib
Topic
s  Definitions of failure and classification
 Aetiology- Acute versus acute on chronic

 Basic diagnostic workup
 Treatment of complication
 Hepatic encephalopathy
 Coagulopathy
 Specialist centre referral

The mortality rate for acute liver failure
ranges between 56% and 80%
Formal diagnosis of acute liver failure
 An increase in PT by 4-6 seconds

(INR>1.5)
AND
 And the development of hepatic
encephalopathy (HE).
AND
 In a patient without pre-existing cirrhosis
and with an illness of less than six months
duration.
Stages of Hepatic Encephalopathy:
Stage 0. Lack of detectable changes in personality or behaviour.

Asterixis absent.
Stage 1. Trivial lack of awareness. Shortened attention span.

Impaired addition or subtraction. Hypersomnia, insomnia, or
inversion of sleep pattern. Euphoria or
depression. Asterixis can be detected.
Stage 2. Lethargy or apathy. Disorientation.

Inappropriate behaviour.
Slurred speech. Obvious asterixis.
Stage 3. Gross disorientation. Bizarre

behaviour. Semistupor to
stupor. Asterixis generally absent.
Stage 4. Coma.
Routinely consider ALF in patients presenting
with acute encephalopathy.
Worldwide cause varies
Diagnostics:
 Good history- difficult

if HE
Diagnosis and Initial Evaluation ALF
 HISTORY:
 Family members with liver disease?
 Recent cold sores
 Onset of jaundice
 Work environment- toxic agents
 Hobbies/travel
 Herbal products/dietary supplements
Initial Laboratory
Analysis
 Prothrombin time/INR
 Chemistries
 Liver enzymes
 Arterial blood gas
 Paracetamol level, Toxicology screen
 Viral hepatitis serologies (anti-HAV IgM, HBsAg,
anti-HBc IgM, anti-HEV, anti-HCV, HCV RNA ,
HSV1 IgM, VZ/HS, EB, CMV)
Initial Laboratory
Analysis
 Ceruloplasmin level
 Pregnancy test (females)
 Ammonia (arterial if possible)

Autoimmune Markers (ANA,
ASMA, Immunoglobulin G levels )
Liver biopsy for diagnostic dilemma
 Importance of early biopsy- severity and

aetiology
 Particularly useful in Hep B,
Autoimmune, Alcoholic hepatitis,
differentiate between ALF and
ACLF
 Transjugular route
What are the potential
outcomes?
 Recovery because of a successful
intervention
 NAC for paracetamol toxicity
 Antivirals for acute hepatitis B
 Spontaneous recovery with

supportive care
 Death
 Rescue by liver transplant (OLT)

Aetiology outcome for
ALF
Transplant free survival >50%
 Hepatitis A, FLDP, paracetamol
Transplant free survival <25%

 Autoimmune, Wilsons, mushroom,
idiosyncratic drug
All Liver transplants
 CLD – 60%
 Malignancy- 10%
 ALF- 10% (Paracetamol)
 Cholestasis - 10-20%
King’s College Criteria LT
 Acetaminophen-Induced ALF:
 Strongly consider OLT listing if:
 1- Arterial lactate >3.5 mmol/L after early
fluid resuscitation
 List for OLT if: 2- pH<7.3 Or arterial

lactate >3.0 mmol/L after adequate fluid
resuscitation
 3- List for OLT if all 3 occur within a 24-

hour period:
 1- presence of grade 3 or 4 hepatic
encephalopathy
 2- INR >6.5
King’s College Criteria LT
 Non-acetaminophen:
 INR > 6.5 OR
 Any 3 of the following 5:
 Age < 10 or > 40
 Serum bilirubin > 300
 Jaundice to encephalopathy interval > 7 days
 INR > 3.5
 Unfavorable Etiology
 Non-A, non-B hepatitis, halothane, idiosyncratic drug
reaction, Wilson’s
Case 1
 21yo presents with N&V

 Found to be tender at RUQ
 History of paracetamol OD 24g
 ALT 2,200, PT 22sec, albumin 30
What next?
 Stage I – 0-24h
 Asymptomatic
 GI upset
 LFT derangement at 12h
 Stage 2 – 24-48h
 RUQ pain, tenderness
 LFT derrangment, bilirubin, PT
 Stage 3 – 48-96h
 Centrilobar necrosis
 Liver failure
 Stage 4
 Recovery, transplant or death
 No chronic state
Encephalopathy
HE- Four compatible theories
 Cerebral vasomotor dysfunction

 Oedema secondary to ammonia toxicity
 Inflammation due to SIRS
 Putative benzodiazepine-like molecules
The pathophysiology of HE
 Ammonia as a key factor in the
pathogenesis of HE.
 Portal ammonia is derived from both the
 urease activity of colonic bacteria and the
 de-amidation of glutamine in the small bowel.
 The intact liver clears almost all of the portal
vein ammonia, converting it into glutamine and
preventing entry into the systemic circulation.
 Ammonia - astrocyte swelling in brain > Brain
edema > High ICP…
Cerebral Edema
 Degree of encephalopathy correlates w/

cerebral edema
 Grade I-II: rare
 Grade III: 25-35% risk
 Grade IV: 65-75% risk
 Uncal herniation
 Compromises cerebral blood flow 
hypoxic brain injury
Grade III/IV Encephalopathy
 Intubate trachea + ventilate
 Elevate head of bed
 Consider placement of ICP monitoring device
 Immediate treatment of seizures required;
prophylaxis of unclear value
 Mannitol: use for severe elevation of ICP or
first clinical signs of herniation
 Hypertonic saline to raise serum sodium to
145- 155 mmol/L
 Hyperventilation: effects short-lived; may
use for impending herniation
GCS –HE correlation
 Grade1- GCS 14-15

 Grade2- GCS 11-13- HDU
 Grade3- GCS 8-11 (Stupor or precoma)

 Grade4- GCS<8 (Coma)
Lactulose is a first-line
pharmacological treatment of HE.
 Lactulose – reaches colon, where bacteria will
metabolize the lactulose to acetic acid and lactic
acid.
 This lowers the colonic pH
 Formation of the non-absorbable NH4+ from NH3,
 Other effects like catharsis also contribute to the

clinical effectiveness of lactulose.
Lactulose
 For acute encephalopathy, lactulose (ingested
or via nasogastric tube), 45 ml p.o.,
 Is followed by dosing every hour until

evacuation occurs.
 Target -three soft bowel movements
per day
 If response to disachharide is poor- add

antibiotic (metronidazole or rifaximine after
48Hrs) to reduce enteric bacterial mass.
The coagulopathy of liver disease
 Failure to produce clotting factors II, V, VII and IX
 The degree of coagulopathy is a measure of severity of
liver disease and of patient prognosis.
 Routine correction of coaguloapthy is therefore NOT
indicated unless active bleeding or planned interventions
require it
 Vitamin K: give at least one dose
 FFP: give only for invasive procedures or active bleeding
 Platelets: give only for invasive procedures or active bleeding
 Recombinant activated factor VII: possibly effective for invasive
procedures
Role of prophylactic antibiotic
 Only patients who have an episode of

gastrointestinal bleeding
 or an episode of spontaneous bacterial

peritonitis (SBP) have been shown to
have a significant outcome benefit from
prophylactic antibiotics.
Role of NAC
 Efficacy of NAC is well established in
paracetamol induced ALF
 Non PCM ALF – role of NAC is
controversial
 However most recent studies has
improved
outcome
 175 patients of non PCM ALF
received NAC
 Transplant free survival at 3 weeks was 52% in
NAC group compared to 30% in placebo arm ( only
with coma grade of 1-2)
Case 2
 55yo Male, builder bricklayer

 PMH
 Alcohol abuse (abstinent)
 Recurrent ascites
 Oesophageal varices
 Meds
 Thiamine, vit B12, furosemide/amiloride,
lactulose, propranolol
Case 2
 PC
 Tired, fatigued, reversal of sleep wake
pattern, generalized slowness,
 Exam
 Spider naevi, no asterixis, splenomegally,
mild shifting dullness, INR 1.3, plt 115,
Hb 14.5, MCV 101, alb 48, ALP 110, ALT
32
 What next ?...
Stages of Hepatic Encephalopathy:
Stage 0. Lack of detectable changes in personality or behaviour.

Asterixis absent.
Stage 1. Trivial lack of awareness. Shortened attention span.

Impaired addition or subtraction. Hypersomnia, insomnia, or
inversion of sleep pattern. Euphoria or
depression. Asterixis can be
detected.
Stage 2. Lethargy or apathy.

Disorientation. Inappropriate behaviour.
Slurred speech. Obvious asterixis.
Stage 3. Gross disorientation. Bizarre

behaviour. Semistupor to
stupor. Asterixis generally absent.
Stage 4. Coma.
Acute on Chronic Liver Failure
ACLF
 This entity is quite common- background
of cirrhosis. Innocent precipitating event
culminates in Massive Organ Failure
(OF)
 Events
 Toxins (alcohol!)
 Vascular (hypotension- GI bleed,
dehydration, Portal vein thrombosis)
 Infection (SBP)
Summary
• The mortality rate for acute liver failure ranges between 56% and
80%
• Careful history taking and examination of lab results help identify

patients
• The commonest cause of acute liver failure in the western world is

paracetamol toxicity
 Some causes have low survival without OLT, prompt referral…
• Hepatic encephalopathy is no longer the main cause of death but

it’s detection and management requires sophisticated
cardiovascular and cerebral monitoring
• Acute on Chronic Liver Failure

Reference
ALF
 FS Cardoso, P Marcelino, L Bagulho. Acute liver
failure: An up to date approach; Jn critical care
39(2017)25-30
Reference Acute Fatty Liver of
Pregnancy
 Ronen, Shahzeb, Steinberg. Acute Fatty Liver of

Pregnancy: A Thorough Examination of a Harmful
Obstetrical Syndrome and Its Counterparts.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889
153
/
 DynaMed Plus www.dynamed.com .

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Acute Liver Failure

 Aetiology- Acute versus acute on chronic

 Specialist centre referral

 An increase in PT by 4-6 seconds

Stage 0. Lack of detectable changes in personality or behaviour.

Stage 1. Trivial lack of awareness. Shortened attention span.

Stage 2. Lethargy or apathy. Disorientation.

Stage 3. Gross disorientation. Bizarre

 Good history- difficult

 Importance of early biopsy- severity and

 Spontaneous recovery with

 Rescue by liver transplant (OLT)

Transplant free survival <25%

 List for OLT if: 2- pH<7.3 Or arterial

 3- List for OLT if all 3 occur within a 24-

 21yo presents with N&V

 Cerebral vasomotor dysfunction

 Degree of encephalopathy correlates w/

 Grade IV: 65-75% risk

 Grade1- GCS 14-15

 Grade3- GCS 8-11 (Stupor or precoma)

 This lowers the colonic pH

 Formation of the non-absorbable NH4+ from NH3,

 Other effects like catharsis also contribute to the

 Is followed by dosing every hour until

 If response to disachharide is poor- add

 Only patients who have an episode of

 or an episode of spontaneous bacterial

 55yo Male, builder bricklayer

Stage 0. Lack of detectable changes in personality or behaviour.

Stage 1. Trivial lack of awareness. Shortened attention span.

Stage 2. Lethargy or apathy.

Stage 3. Gross disorientation. Bizarre

• Careful history taking and examination of lab results help identify

• The commonest cause of acute liver failure in the western world is

 Some causes have low survival without OLT, prompt referral…

• Hepatic encephalopathy is no longer the main cause of death but

• Acute on Chronic Liver Failure

 Ronen, Shahzeb, Steinberg. Acute Fatty Liver of

 DynaMed Plus www.dynamed.com .

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