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
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