acute liver failure wih HRS

1. Acute Liver Failure

2. Topics
 Definitions of failure and classification
 Aetiology- Acute versus acute on chronic
 Basic diagnostic workup
 Liver biopsy in the context
 ACLF-Ethical dilemma- HDU admission
 Treatment of complication
 Hepatic encephalopathy
 Renal failure
 GI bleed
 Infection
 Coagulopathy
 Aetiology specific treatment
 Organ support
 Liaison with Transplant centre

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

4. Abnormal LFT is NOT ALF
Dear Doctor
Patient’s bilirubin is 600 and has liver
failure- kindly urgently see
Family was told transplant may be
necessary

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. 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

7. aCLF
This entity is quite common- background
of cirrhosis. Innocent precipitating event
culminates in MOF
Events
Toxins (alcohol!)
Vascular (hypotension- GI bleed,
dehydration, Portal vein thrombosis)
Infection (SBP)
HCC

8. ACLF-Ethical dilemma- HDU admission

9. 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’

10. Few definitions
Hyperacute- <7days
Acute - >7days <21days
Subacute- >21days <6months
FHF- not used

12. Diagnostics:
 Good history- difficult
if HE

13. Initial Laboratory Analysis- general
 Prothrombin Time/INR
 Blood Chemistry
Sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate,
AST, ALT, alkaline phosphatase, GGT, total bilirubin, albumin,
Creatinine, urea
Glucose
 Arterial blood gas
 Arterial lactate
 Full blood count
 Blood type and screen
 Ammonia (arterial if possible)
 HIV status
 Amylase and lipase

14. Diagnostics- specific
 Paracetamol (acetaminophen)
level
 Toxicology screen
 Viral hepatitis serologies
Anti-HAV IgM,
HBSAg, anti-HBc IgM,
anti-HEV,
anti-HCV
CMV
EBV
VZ/HZ
 Ceruloplasmin level
 Pregnancy test
 Autoimmune markers- ANA,
ASMA, Immunoglobulin levels
 Doppler US- ischaemic vs
thrombosis

15. Liver biopsy
Importance of early biopsy- severity and
aetiology
Particularly useful in Hep B, AIH,
Alcoholic hepatitis, differentiate between
ALF and aCLF
Transjugular route

16. www.gastrotraining.com

17. Urgent OLT is the only life saving
therapy
The main role of intensive care therapy
is multi-organ support

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

21.  Phase I – 0-24h
 Anorexia, nausea and vomiting, malaise
 LFT derrangement at 12h
 Phase II – 18-72h
 RUQ pain
 LFT derrangment
 Phase III – 72-96h
 Centrilobar necrosis
 Liver failure
 Phase IV – 4d-3wk
 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. Definition:
HRS
ARF in a patient
CLD, severe alcoholic hepatitis or ALF
from any cause
End-stage of reduction in renal perfusion
induced by increasingly severe hepatic
injury.

24. 1. Sinusoidal portal hypertension, in
the presence of severe hepatic
decompensation
2. Leads to splanchnic and systemic
vasodilatation-role of NO
3. Decreased effective arterial blood
volume
4. Activation of RAS, and vasopressin
aimed at restoring arterial filling
pressure.
5. Renal vasoconstriction increases
counterbalanced by the intrarenal
prostaglandins.
6. When this balance is lost renal
hemodynamics worsens, and
hepatorenal syndrome develops

25. Terlipressin
NSBB

26. HRS
 Major criteria
 Chronic or acute hepatic disease and liver failure with portal
hypertension
 Serum creatinine level >133 micromoles/L
 Absence of shock, ongoing bacterial infection, recent use of
nephrotoxic drugs, excessive fluid or blood loss
 No sustained improvement in renal function after volume
expansion with 1.5 L isotonic saline solution
 No Proteinuria (Protein<500 mg/day) and no ultrasonographic
evidence of renal tract or parenchymal disease
 Minor criteria
 Urine volume <500 mL/day
 Urine sodium <10 mEq/L
 Urine osmolality greater than plasma osmolality
 Urine red blood cell count <50 per high-power field
 Serum sodium <130 mEq/L

27. Classification of HRS
Type I is defined by a rise in creatinine
level to over 221 micromoles/L in less
than 2 weeks
 Median survival of 2 weeks
 Type II is defined as less severe renal
insufficiency; it is principally
characterized by ascites that is resistant
to diuretics.
 Median survival of 3-6 months.

28. Vasoactive Medical treatment
Terlipressin bolus(0.5mg/4h)-increase
every 3 days if no response to 1-2mg/4h
 Given until creatinine normalizes or for 15 days
Albumin 1g/kg on day1( one bag of HAS
contains 20grams)
 20-60g/d thereafter

29. Step by step guide :
 Normal renal us
 Normal urine dipsix –
no RBC cast
 No nephrotoxic drugs
 Fluid challenge
 Spot Na and serum
Na
 Serum and urine
osmolality
 Urine output
PRERENA
L
HRS ATN
Spot Na <10 <10 >30
Urine
sediment
Nil Nil Positive
Fluid
challenge
Responds Nil Nil

30. The stages of HE- West Haven
criteria:
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.

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

32. The pathophysiology of HE
 A large body of work points at ammonia as a
key factor in the pathogenesis of HE.
 Portal ammonia is derived from both the
urease activity of colonic bacteria and the
deamidation 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

33.  Patients with grade II HE should be managed
in a HDU environment.
 Grades III and IV HE requires definitive airway
protection and appropriate monitoring.
 Grade IV HE is strongly associated with
elevated levels of serum ammonia, a high
incidence of raised intracranial pressure and
the development of uncal herniation.

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

35. In acute and chronic liver disease,
increased arterial levels of ammonia are
commonly seen.
However, correlation of blood levels with
mental state in cirrhosis is inaccurate.

36. 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.

37. 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.

38. If patient is refusing oral lactulose prescribe
phosphate enemas TDS!
An excessively sweet taste, flatulence, and
abdominal cramping are the most frequent
subjective complaints with this drug.

39. The coagulopathy of liver disease
 Failure to produce clotting factors II, V, VII and IX
 Failure of the diseased liver to clear activated clotting
factors.
 Degree of hypersplenism and thrombocytopaenia
often adds to the coagulopathy, especially if
disseminated intravascular coagulation (dic) also co-
exists.
 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

40. Sepsis
 Infection may be the initiating event of liver
failure,
 Intercurrent sepsis is also a common problem .
 Impaired immune function, in part secondary
to reduced complement factor production and
 Impaired neutrophil, leukocyte and monocyte
function, can result in delayed presentation of
clinical signs of infection.
 The interventions required for diagnosis and
management of liver disease also increase
patient vulnerability to invasive infection.

41. 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.

42. In presence of sepsis
Choice of antibiotic should be guided by
local microbiological surveillance.
The high incidence of mycoses - low
threshold for antifungal.
Regular microbiological surveillance

43. Role of NAC
 Efficacy of NAC is well established in PCM
induced ALF
 Non PCM ALF – role of NAC is controversial
 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%

44. Artificial liver??

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

46. 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

47. Summary
• The mortality rate for acute liver failure ranges between 56% and
80%
• The main role of intensive care therapy is multi-organ support
• The commonest cause of acute liver failure in the western world
is paracetamol toxicity
• Hepatic encephalopathy is no longer the main cause of death but
it’s detection and management requires sophisticated
cardiovascular and cerebral monitoring
• Hepatorenal failure is due to the complex interplay between
splanchnic, renal and systemic circulatory responses to liver
failure. Terlipressin has been shown to be of use in its treatment
• Novel hepatic replacement therapies are under development but
definitive studies as to their efficacy are, as yet, unpublished.