acute-liver-failure-accs_june_2018 (1).ppt

acute liver disease

1. Acute Liver Failure
ACCS ST1
Alain Sauvage

2. Topics
Definitions of failure and classification
Aetiology- Acute versus acute on chronic
Basic diagnostic workup
Treatment of complication
Hepatic encephalopathy
Coagulopathy
Specialist centre referral
Organ support

3. The mortality rate for acute liver failure
ranges between 56% and 80%

4. UK incidence of cirrhosis 17 per 100,000
Prevalence of cirrhosis is 76 per 100,000
ALF incidence is 1-6 per million per year

5. Formal diagnosis of acute liver failure
An increase in PT by 4-6 seconds
(INR>1.5)
And the development of hepatic
encephalopathy (HE).
In a patient without pre-existing cirrhosis
and with an illness of less than six months
duration.

6. Definition; Jaundice to HE
Hyperacute- <7days
Acute - >7days <21days
Subacute- >21days <6months
FHF- not used

7. 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.

9. Worldwide cause varies

10. Diagnostics:
Good history- difficult
if HE

11. 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

12. 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)

13. Initial Laboratory Analysis
Ceruloplasmin level
Pregnancy test (females)
Ammonia (arterial if possible)
 Autoimmune Markers (ANA, ASMA,
Immunoglobulin levels )

14. 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

15. 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)

16. Aetiology outcome for ALF
Transplant free survival >50%
Hepatitis A, FLDP, paracetamol
Transplant free survival <25%
Autoimmune, HEB, Wilsons, mushroom,
idiosyncratic drug

17. All Liver transplants
CLD – 60%
Malignancy- 10%
ALF- 10% ( Paracetamol)
Cholestasis - 10-20%

18. King’s College Criteria LT
Acetaminophen-Induced ALF:
 Strongly consider OLT listing if:
arterial lactate >3.5 mmol/L after early fluid
resuscitation
 List for OLT if: pH<7.3 Or
 arterial lactate >3.0 mmol/L after adequate fluid
resuscitation
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
3- Creatinine >3.4 mg/dL

19. 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

20. Case 1
21yo presents with N&V
Found to be tender at RUQ
History of paracetamol OD 24g 3/7 ago
ALT 2,200, PT 22sec, albumin 30
What next?

21. 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

22. When to pick up the phone
D2-
pH <7.3
INR>3
Cr >200
Hypoglycaemia
D3-
HE
Cr>200
INR >4.5
D4-
Any rise in INR
Cr >250
HE

23. Following phone call, transferred to a
liver specialist intensive care

24. Encephalopathy

25. HE- Four compatible theories
Cerebral vasomotor dysfunction
Oedema secondary to ammonia toxicity
Inflammation due to SIRS
putative benzodiazepine-like molecules

26. 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

27. Cerebral Edema
Degree of encephalopathy correlates w/
cerebral edema
Grade I-II: rare
Grade III: 25-35% risk risk
Grade IV: 65-75% risk
Uncal herniation
Compromises cerebral blood flow 
hypoxic brain injury

28. 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

29. GCS –HE correlation
Grade1- GCS 14-15
Grade2- GCS 11-13- HDU
Grade3- GCS 8-11 (Stupor or precoma)
Grade4- GCS<8 (Coma)

30. 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.

31. 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.

32. 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

33. 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.

34. 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)
United States ALF study group- overall was 70% vs
66%

35. Artificial liver??

36. Extracorporeal Liver Assist Device
(ELAD)
Hepatocyte bioreactor- hepatoma cells
cultivated on the exterior surface of
semipermeable hollow fibres
MARS (molecular adsorbent
recirculating system)

37. ELAD
Both reduce the level of bilirubin, bile salt
ammonia etc
However no of patients dying or
requiring liver transplant did not improve
Devices remain experimental and large-scale phase two
and three trials are awaited

38. Case 2
55yo Male, builder bricklayer
PMH
Alcohol abuse (abstinent)
Recurrent ascites
Oesophageal varices
Meds
Thiamine, vit B12, furosemide/amiloride,
lactulose, propranolol

39. 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 ?...

40. 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.

41. 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)

42. For patients with ACLF
Young age
First presentation
Reversible pathology- sepsis, GI
bleeding or severe hepatitis
A trip to ITU is a life changing
experience to some ‘alcoholics’

43. 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

44. Reference ALF
FS Cardoso, P Marcelino, L Bagulho.
Acute liver failure: An up to date
approach; Jn critical care 39(2017)25-30

45. 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/PMC5889153/
DynaMed Plus www.dynamed.com (check with your library if your hospital has an
account, it is a less flashy/organised version of uptodate)