Acute liver failure is characterized by acute liver injury, hepatic encephalopathy, and elevated INR within 26 weeks without previous liver disease. Common causes include acetaminophen toxicity, viral infections, and idiosyncratic drug reactions. Patients present with symptoms like fatigue, nausea, and jaundice. Complications include cerebral edema, renal failure, electrolyte imbalances, coagulopathy, and infections. Treatment focuses on supportive care, treating encephalopathy, and consideration of liver transplantation for eligible patients. Prognosis depends on the degree of encephalopathy and presence of other risk factors.

1. Acute
liver
failure
By: Ram Gopal
Maurya

2. ACUTELIVER FAILURE
• INTRODUCTION
• ACUTE LIVER FAILURE IS CHARACTERIZED
BY
1. ACUTE LIVER INJURY,
2. HEPATIC ENCEPHALOPATHY,AND
3. AN ELEVATED PROTHROMBIN TIME/INTERNATIONAL
NORMALIZED RATIO (INR)
• IT HAS ALSO BEEN REFERRED TO AS
 fulminant hepaticfailure,
 acute hepaticnecrosis,
 fulminant hepatic necrosis,and
 fulminant hepatitis.

3. DEFINITION
• Acute liver failure refers to development of
 sever acute liver injury
 encephalopathy
 coagulopathy (international normalized ratio
[INR] > 1.5)
 within 26 weeks
 with no previous history of underlying liver
disease.

5. Sub-classification for acute liver failure

6. Etiology and epidemiology

8. • Viral hepatitis remains the most common
identifiable cause of FHF in the developing
world, whereas acetaminophen toxicity and
idiosyncratic drug reactions remain the most
frequent apparent causes of FHF in the United
States and Europe.

9. Acetaminophen Toxicity
• Dose dependent hepatotoxic.
• the recommended maximum dose of acetaminophen was
reduced from 4 to 3.25 grams daily.
• The bulk of acetaminophen metabolism involves the
formation of nontoxic sulfated conjugates, which are
excreted in the urine. About 10% form a toxic metabolite
that is capable of producing oxidant cell injury. This ,toxic
metabolite is removed by conjugation with glutathione, an
intracellular antioxidant. When the daily dose of
acetaminophen exceeds 4 grams, the sulfated conjugation
pathways become saturated, which diverts acetaminophen
metabolism to the pathway with the toxic metabolite.
when glutathione stores fall to 30% of normal, the toxic
acetaminophen metabolite can accumulate and promote
hepatocellular damage.

10. • Doses considered nontoxic (<4 g/day in adults)
may cause hepatotoxicity if other concurrent
factors exist, such as alcohol ingestion, fasting,
or malnutrition.
• Hepatotoxicity usually develops 1 to 2 days
after the overdose, and circulating alanine
aminotransferase (ALT) levels and INR values
peak around day 3.
• N- ACETYLCYSTEINE AS ANTIDOTE IN 16HOURS

11. VIRAL INFECTION
1) HAV-RELATED ALF:
2) HBV-RELATED ALF:
3) HEPATITIS D:
4) HEPATITIS E:
5) HSV-1, 2, AND 6, VARICELLA-ZOSTER VIRUS,
EBV, CYTOMEGALOVIRUS, AND PARVOVIRUS
B19

13. Pregnancy Related: ALF
• There are two hepatic emergencies which occur
in the 3rd trimester of pregnancy: haemolysis,
elevated liver enzymes and low platelets (HELLP)
syndrome and acute fatty liver of pregnancy
(AFLP).
• AFLP is characterised by extensive hepatic
steatosis and usually presents with abdominal
pain and malaise.
• Transaminases are relatively low.
• Hypoglycaemia is common.
• Maternal mortality is around 20%.

14. • Prompt delivery of the baby in both these
emergency scenarios offers a good outcome,
and emergency LTx is rarely needed.
• Persistent elevation of lactate levels in the
presence of severe HE potentially best
identifies patients at greatest risk of death or
LTx.

15. CLINICAL MANIFESTATIONS
SYMPTOMS
• FATIGUE/MALAISE
• LETHARGY
• ANOREXIA
• NAUSEA AND/OR VOMITING
• RIGHT UPPER QUADRANT PAIN
• PRURITUS
• JAUNDICE
• ABDOMINAL DISTENSION FROM ASCITES

16. • ENCEPHALOPATHY
• INTRACRANIAL HYPERTENSION AND
CEREBRAL EDEMA
• HEMODYNAMIC CHANGES AND CIRCULATORY
FAILURE
• INFECTION
• RENAL FAILURE
• HEMATOLOGIC ABNORMALITIES

18. Suggested algorithm for diagnosis

27. Neurologic Consequences:
Encephalopathy with cerebral edema
• mandatory for a diagnosis of ALF
• classically graded on a scale of 1 to 4
• The briefest period between liver injury and
the development of encephalopathy is 3 to 4
days.
• HE is a reversible neuropsychiatric syndrome
of metabolic disturbance and depressed
consciousness that develops following liver
failure.

28. Clinical Stages of HE in ALF (West Haven
Criteria (WHC), also known as the Conn
score)

29. • Potential
Hypotheses for
Hepatic
Encephalopathy:
Astrocyte swelling
in the
pathogenesis of
HE and cerebral
edema in ALF.

33. Therapeutic Options
• Lactulose: The mainstay of therapy in the
treatment of hepatic encephalopathy.
• The fermentation of lactulose produces an acidic
medium that alters the composition of gut
bacterial flora, lowers colonic pH, and produces
an osmotic diarrhea.
• The ammonium ion unable to diffuse readily
across the lipid bilayer of mucosal cells. This
ammonium ion is “trapped” in the fecal effluent
and eliminated with passage of the bowel
movement.

34. • Rifaximin: Rifaximin is a nonabsorbable
antibiotic derivative of rifamycin with broad
antimicrobial activity and has become an
important adjunct agent along with lactulose
for the treatment of hepatic encephalopathy.

35. • Benzodiazepine Antagonists:
There have been several randomized controlled trials of short-
term administration of flumazenil in the treatment of
hepatic encephalopathy.
In some studies, flumazenil was superior to placebo in
improving the grade of encephalopathy; 30% to 60% of
encephalopathic patients improved after administration of
flumazenil, and EEG changes paralleled this improvement.
In other studies, however, flumazenil was no better than
placebo in ameliorating the symptoms of encephalopathy,
and EEGs did not improve.
Overall, flumazenil has a limited role in the treatment of
hepatic encephalopathy.

36. L-Ornithine-L-Aspartate (LOLA) and
Ammonia Scavengers
• LOLA increases the activity of hepatic urea cycle
enzymes and also increases the rate of glutamine
production within skeletal muscle.
• Neomycin: second-line therapy
Neomycin has a limited entrance to the circulation,
with the goal of therapy being to alter the
bacterial composition of the colonic flora.
The main disadvantage is that nephrotoxicity may
occur despite its poor absorption

39. • Short-acting barbiturates and the induction of
hypothermia to a core body temperature of 34-
35°C may be considered for intracranial HTN
refractory to osmotic agents as a bridge to LT(II-
3).
• Seizure activity should be treated with phenytoin
and benzodiazepines with short half-lives.
Prophylactic phenytoin is not recommended (III).
• Corticosteroids should not be used to control
elevated intracranial pressure in pts with ALF (I).

44. Renal and Electrolyte Disturbances
• AKI occurs in 40% to 80% of pts with ALF.

45. Hepatorenal syndrome
• HRS is a reversible functional renal impairment that
occurs in patients with advanced liver cirrhosis or those
with fulminant hepatic failure.

46. DIAGNOSTIC CRITERIA

47. MANAGEMENT

50. Electrolyte Disturbances
• Hyponatraemia is also relatively common in pts
with ALF, especially hyperacute cases. Free water
retention occurs early, resulting in dilutional
hyponatremia, which can contribute to cerebral
edema, mandating immediate correction.
• Hypokalemia accompanies hyponatremia, due to
GI losses, diuretics, and alkalosis.
• Hypokalemic alkalosis occurs early in the course
of ALF, whereas hyperkalemic acidosis dominates
the late stages.

51. • Hypophosphatemia also occurs commonly, and results
from a shift of phosphate from the extracellular to the
intracellular compartment in response to glucose
infusions and possibly due to use in ATP synthesis by
regenerating hepatocytes.
• Hypophosphatemia is a favourable prognostic sign
and appears to be associated with liver regeneration.
• Hypocalcemia and hypomagnesemia may present
concurrently and interfere with the correction of
hypokalemia; these abnormalities should be corrected
by iv replacement.

52. Acid – base changes
• Respiratory alkalosis is due to hyperventilation, probably
related to direct stimulation of the respiratory centre by
unknown toxic substances.
• Respiratory acidosis can be caused by elevated ICP and
respiratory depression, or pulmonary complications.
• Acidosis, increased circulating lactate and reduced
bicarbonate are common features in pts with hyperacute
and acute ALF, and are multifactorial in pathogenesis, with
increased systemic production and reduced hepatic
clearance reported [1,2,3].
• Lactic acidosis develops in about half of the pts reaching
stage 3 coma. It is related to inadequate tissue perfusion
due to hypotension and hypoxaemia.

53. • The development of AKI is a marker of poor
prognosis and greatly complicates fluid and
electrolyte, acid-base disorder, hemodynamic,
and ventilator management of the patient
with ALF.
• Once oliguria develops, continuous renal
replacement therapy (CRRT) should be
considered.

54. Hematologic Disturbances

55. • Replacement therapy for thrombocytopenia
and/or prolonged PT is recommended only in
the setting of hemorrhage or prior to invasive
procedures .

57. Factors Contributing to Infection in ALF

58. • The most common microbial pathogens are
grampositive bacteria (Staphylococcus aureus,
enterococci), enteric gramnegative bacilli (Escherichia
coli, Klebsiella spp.), and Candida spp.
• Prevention of infection is thus an important objective
of the medical MX of ALF, and general guidelines to
avoid nosocomial transmission of organisms should be
strictly enforced.
• Daily blood and urine cultures should be sent
especially early in the course of ALF to obtain antibiotic
sensitivities in case of future infection.

59. Main organ specific complications in
ALF

62. Investigation
• Microbiology
Blood culture, aerobic and anaerobic Urine
culture and microscopy Sputum culture and
microscopy
• Paracetamol level
• Pregnancy test
• USG abdomen
• Ct head
• Liver Biopsy: rare

63. Prognosis
• Encephalopathy degree: strong predictor of
outcome.
Patient with grade 2 HE have a 65% to 70%
chance of survival.
 patient with grades 3 and 4 have a 30% to
50% and a 20% chance of survival.

65. • In patients with nonacetaminophen associated
FHF, the presence of a single factor is associated
with a mortality rate of 80% whereas the
presence of any three factors is associated with
a 95% mortality rate.
• In patients with acetaminophen hepatotoxicity
and FHF, a single risk factor is associated with a
mortality of55% and the presence of severe
acidosis confers a 95% mortality.

66. Clichy criteria
• Based on a French prospective study of pts
presenting with acute viral hepatitis, in which pts
identified as having the lowest survival without
LT included those with HE and low factor V levels.

68. Liver Transplant for ALF
• LT is the definitive treatment for those who meet the
criteria.
• 1 yr. and 5 yr . survival of patients undergoing OLT for
ALF is about 20% lower than cirrhotics.
• The most common technique is orthotopic
transplantation, in which the native liver is removed
and replaced by the donor organ in the same anatomic
position as the original liver.
• Auxiliary transplantation uses a partial left or right
lobe from the donor which acts as temporary support
for the recipient's injured liver, which remains in place.
Once the native liver recovers, immunosuppression is
withdrawn and the graft is either surgically removed or
is allowed to atrophy naturally.

71. Liver Support / Assist Devices

72. Molecular Adsorbent Recycling System
MARS