Acute Liver Failure

Dr Prakash Sapkota
Resident
Department of Internal Medicine
Dhulikhel Hospital
 PBQ
• A 38 years old male with harmful amount of alcohol consumption presented to
emergency with complain of yellowish discoloration and abdominal distension for
10 months. Patient party gave history of altered sensorium and pain abdomen since
3 days after consuming hepatotoxic drug.
• What is your provisional diagnosis? [1]
• What are the different classification of your likely diagnosis? (2)
• What are the different causes of your likely diagnosis? (2)
• How will you manage this case as an emergency physician? (3)
• List out the possible complication of this patient? (2)
 EASL-AASLD definition of ACLF
European Association for the Study of the Liver (EASL)

• Acute deterioration of pre existing, chronic liver disease usually related to a

precipitating event and associated with increased mortality at 3 month due to
multi-system oragan failure
 INTRODUCTION
• Clinically and pathophysiological distinct syndrome occurs in patients with cirrhosis and is
characterized by:
1. Acute deterioration in their clinical condition
2. occurrence of organ failures,
3. systemic inflammation
4. high short term mortality
• Occurs in 30% of hospitalised cirrhotic patient and requires admission in ICU
• It can occur in any stage of cirrhosis, whether they are previously well, compensated or
decompensated
 Acute Liver Failure
AASLD Definition and Prognosis
Definition Evidence of coagulation abnormality (INR 1.5),
any degree of encephalopathy without
preexisting cirrhosis and with an illness of <26
weeks’duration
Prognosis Prior to transplantation < 15% survival
Currently overall short-term survival (one year)
including those undergoing transplantation is
greater than 65%
5
The presence of encephalopathy is a cardinal feature,
with mental changes progressing from delirium to coma.
The syndrome was originally defined further as occurring
within 8 weeks of onset of the precipitating illness, in
the absence of evidence of pre-existing liver disease.
NEWER CLASSIFICATION

• Hyperacute (<7 days)

Moderate • Acute (7 to 21 days)
• Subacute (>21 days and
Poor <26 weeks)

Poor
 Predicting Outcomes in Acute Liver
Failure
• Important predictive factor: Stage of encephalopathy
• Suggested laboratory markers:
Factor V, AFP, Serum Phosphate,
VII/V ratio > 30, Gc globulin
• Four factors Etiology ofALF INR,
bilirubin
Encephalopathy and brain edema
Multiorgan failure
Variables Used for Prognostic Models of ALF
King’s Clichy MELD Indian

John O’Grady. Clin Liver Dis 11 (2007) 291–303

Acharya SK et al . Hepatology 23: 1996
 Clichy- Villejuif Criteria from France

• Model for End-stage Liver Disease (MELD) Score

Criteria from India

Acharya SK et al . Hepatology 23: 1996

Presence of > 3 factors – 90%

Mortality
Alcoholic hepatitis
Autoimmune hepatitis
Ischemic hepatopathy
Veno-occlusive disease
Acetaminophen and other hepatotoxins
• Most common toxin associated with acute liver failure
• Hepatotoxicity is dose-dependent and rarely occurs at therapeutic doses
 Idiosyncratic drug reactions
• Dose-independent
• Occurs within six months of drug initiation
• Commonly implicated drugs
• Antibiotics
• Nonsteroidal anti-inflammatory drugs
• Anticonvulsants
• Herbal medications and dietary supplements
 Hypoperfusion
• Can result in ischemic hepatitis and acute liver failure
• Hypoperfusion may result from
• Systemic hypotension due to causes such as cardiac dysfunction,
sepsis
• Budd-Chiari syndrome
• Veno-occlusive disease
• Vasoconstricting drugs such as cocaine and methamphetamine
 Clinical assessment
• Cerebral disturbance (hepatic encephalopathy and/or cerebral
oedema) is the cardinal manifestation of acute liver failure
• The initial clinical features are often subtle
• Include reduced alertness and poor concentration
• Restlessness and aggressive outbursts, to drowsiness and coma
• Causing unequal or abnormally reacting pupils, fixed pupils
• Papilloedema
 Jaundice
• May be jaundiced but jaundice may not be present at the outset (e.g.
in paracetamol overdose), and there are a number of exceptions,
including Reye’s syndrome, in which jaundice is rare.
• Occasionally, death may occur in fulminant cases of acute liver failure
before jaundice develops.
• Fetor hepaticus can be present.
 Investigations:
• To determine the cause of the liver failure and the prognosis.
• Hepatitis B core IgM antibody
• Plasma bilirubin, aminotransferase, albumin
• Percutaneous liver biopsy: Contraindicated
• PT
• Factor V levels
• Can be used instead of the PT to assess the degree of liver impairment.
 Other Investigations:
• Neuroimaging : cerebral edema
• Electroencephalogram : seizure activity, even in the absence of clinical signs of seizures
• Pulmonary edema and pulmonary infections develop in about 30 percent of patients
• Liver biopsy may help with the diagnosis of:
• Malignant infiltration
• Autoimmune hepatitis
• Wilson disease
• Hepatitis due to herpes simplex virus
 Laboratory findings associated with
specific diagnoses
• Acetaminophen:
• Very high aminotransferase levels • Hepatitis B:
(>3500 international units/L) • Aminotransferase levels of to 1000 to
• Low bilirubin and High INR 2000 international units/L
• Ischemic hepatic injury: • alanine aminotransferase (ALT) level
• Very high aminotransferase levels (25 that is higher than the aspartate
to 250 times the upper limit of aminotransferase (AST) level
normal)
• Elevated serum LDH levels
 Wilson disease:
• Coombs-negative hemolytic anemia
• Aminotransferase levels <2000 international units/L
• AST to ALT ratio of >2, normal or markedly subnormal alkaline phosphatase
(<40 international units/L)
• Alkaline phosphatase (international units/L) to total bilirubin (mg/dL)ratio <4
• Rapidly progressive renal failure
 Management
• Treated in a high dependency or intensive care unit
• Conservative treatment aims to maintain life in the hope that hepatic
regeneration will occur
• N-acetylcysteine therapy may improve outcome, particularly in patients
with acute liver failure due to paracetamol poisoning.
• Liver transplantation
 Airway Protection and Cerebral Edema

• Patients who are in stage III coma should have a nasogastric tube (NGT) inserted for stomach
decompression and intubation should be performed
• Cerebral edema :
• Ammonia play a pathogenic role
• 25 to 35 %: Grade III encephalopathy
• 75%: Grade IV encephalopathy
• ICP elevation, brain ischemia and hypoxia, and brainstem herniation, which are the most common
causes of death in acute liver failure
• liver transplantation is the only definitive treatment for cerebral edema
 Management of Intracranial Hypertension
• Managed initially with the use of mannitol
• The dose may be repeated once or twice, as needed, provided that serum osmolality has
not exceeded 320 mOsm/L
• Hyperventilation: Temporarily in an attempt to acutely lower the ICP and to prevent
impending herniation
• Other therapies : Hypertonic saline, barbiturates, and hypothermia
 Barbiturate and Hypothermia
• Barbiturate agents may also be considered when severe ICH does not respond to
other measures
• Doses of barbiturates for ICH are
• Thiopental: 5-10 mg/kg IV loading dose, followed by 3-5 mg/kg IV infusion
• Pentobarbital: 3-5 mg/kg IV loading dose, followed by 1-3 mg/kg/h infusion
• Moderate hypothermia (32-34°C) may prevent or control ICH in patients with acute
liver failure
• An external cooling blanket may be used to achieve this goal
Algorithm For ICP Monitoring
 Coagulopathy of ALF & Correction

Vitamin K No Role, At least one dose (AASLD)

Fresh Frozen Plasma Best prognostic indicator ,Prophylactic FFP not recommended
Does not reduce risk of significant bleeding
volume overload
ALFSG recommends aiming for: INR 1.5

Platelets Limited role for prophylactic transfusion

If clinically significant bleeding or < 10 - 20,000/mm3, ALFSG recommends aiming for Plts. 50,000
Cryoprecipitate When fibrinogen <100 mg/dL.
Recombinant VII When FFP fails to correct PT/INR
Risk of thrombotic complication
 Management of Coagulopathy

• FFP: Usually not necessary in the absence of bleeding

• FFP infusion of 15 mL/kg of body weight or 4 units will correct the deficiency.
• Recombinant factor VIIa:
• In patients whose condition is nonresponsive to FFP
• Dose of 4 µg/kg intravenous (IV) push over 2-5 minutes
• PT is normalized in 20 minutes and remains normalized for 3-4 hours.
 Hemodynamic Failure

• Decreased SVR and High Cardiac output

Restoration of hemodynamics

• Correct hypovolaemia with Crystalloids initially

• Once euvolemic, studies show albumin is better
 Hemodynamic Failure

Pressors Noradrenaline is the agent of choice

Vasopressin not recommended as it increases ICP Low-dose
terlipressin
Inotropes Low CO syndromes carry poor prognosis
dopamine or dobutamine,Adrenaline Adrenaline
may compromise HBF
 Renal Issues of ALF
• Avoid nephrotoxic agents
• AKI and Renal Dysfunction common
• Infection and Sepsis Management
Hypovolaemia
• Renal Replacement Therapy
• Hepato-Renal Syndrome
• Renal failure
• Acute tubular necrosis
• Fluid overload
• Protect and maintain renal functions by • Severe hyperammonemia
• Optimize volume • Severe Lactic Acidosis
• Optimize hemodynamics
 Renal Issues of ALF

•CRRT preferred over IRRT If dialysis support is

needed for acute renal
•Anticoagulation
failure, it is recommended
Usually not needed that a continuous mode
Use citrate over heparin rather than an intermittent
mode be used (I).
Monitor ionized calcium
• Bicarb buffer over lactate or citrate buffer
•Avoid hyponatraemia
32
 General Supportive Measures

● Monitor blood glucose 2-hourly and maintain between 140 to 180mg%.

● Monitor serum electrolytes and correct
● Nutrition— Early NG feed with gradual increase in protein
• AASLD : H2 blocking agents or proton pump inhibitors (or sucralfate as a
second-line agent) for acid-related gastrointestinal bleeding associated
with stress (I).
 3
7

n-Acetyle Cystine
AASLD 2011 Recommendation 12 :
NAC may be beneficial for ALF due to drug-induced liver injury (I)
NAC is infused in a 3 stage iv infusion

Total dose of 300 mg/kg of over 20 hours

First Infusion 150mg/kg in 200mL of 5% D over 15 to 60 mins

Second Infusion 50mg/kg
. in 500mL of 5% D over the next 4 Hrs
Third Infusion 100mg/kg in 1 Lof 5% gluc over next 16 Hrs
 NAC Administration
NAC -140 mg/kg orally followed by 70mg/kg every 4 hrs for 72 hrs

Mix 30gm of NAC in 1Lt of 5%Dextrose

Patient treated Patient treated >8hrs

<8hrs after acute after acute ingestion
ingestion

Loading dose 150mg/kg in 1hr Loading dose 150mg/kg in 1hr

Run infusion at 15mg/kg/hr Run infusion at 15mg/kg/hr for

for 4 hrs 44 hrs

Cont. infusion at 7.5mg/kg/hr for 16hrs 35

 Infections

Bacterial (90%): Gram Neg. Empirical ATBs are recommended by ALFSG & AASLD
when:
organisms & Staphylococci
o Surveillance cultures reveal significant isolates
Fungal (30%) o Advanced stage (III/IV) encephalopathy (III)
Prophylactic antibiotics? o Refractory hypotension
o SIRS
Decrease rate of infections
Prophylactic fluconazole - with multiple-site colonization
But no improvement in outcomes with yeast
(III)
 Anti-Viral Treatment Improves the Prognosis
of Fulminant Hepatitis B
AASLD Recommendations

Nucleos(t)ide analogues should be considered

for Hep B- associated ALF and for prevention
of post-LT recurrence.(III)

Patients with known or suspected Herpes Virus or

varicella zoster as cause of ALF should be treated Cumulative Survival for Patients
with acyclovir and may be considered for treated with Lamivudine and
Transplantation (III). without
Int Med 47: 2008
36
 Other Issues

AASLD Recommendations

Steroids
• Patients with coagulopathy and mild HE due to autoimmune hepatitis
may be considered for corticosteroid treatment (prednisone 40-60
mg/day) (III)
• Patients with autoimmune hepatitis should be considered for LT even
while corticosteroids are being administered (III)
Complications of acute liver failure
 Prognosis:
• Survival following liver transplantation for acute liver failure is
improving and 1-year survival rates of about 60% can be
expected.
• A number of artificial liver support systems have been developed
and evaluated for use as a bridge to either transplantation or
recovery.
 4
4

Conclusions

• Transplantation is a definitive treatment for ALF

• Good quality critical care and aggressive transplant programmes have
improved survival of ALF
• Early etiological diagnosis and aggressive management
• Optimal referral to Transplant unit to Improve Survival
• LAD devices are not of proven benefit
 References
• AASLD Position Paper : Introduction to the Revised American
Association for the Study of Liver Diseases Position Paper on Acute Liver
Failure 2011
• Davidson 23rd Edition
• Medscape
• Uptodate
Thank You!!