This document discusses acute liver failure (ALF), defining it as the rapid development of severe liver injury and encephalopathy in someone who previously had a normal liver or well-compensated liver disease. It describes the development of encephalopathy within different time periods to classify ALF as hyper-acute, acute, or subacute. Common causes, clinical presentation, investigations, complications including cerebral edema, and treatment approaches are summarized.

1. DR JAWAD ALI RESIDENT MEDICINE
KRL HOSPITAL ISLAMBAD

2. DEFINITION
Acute liver failure refers to the rapid
development of severe acute liver
injury with impaired synthetic
function and encephalopathy in a
person who previously had a normal
liver or had well-compensated liver
disease.

3. DEVELOPMENT OF
ENCEPHALOPATHY WITHIN 7 DAYS
OF ONSET OF JAUNDICE
HYPER-ACUTE

4. DEVELOPMENT OF
ENCEPHALOPATHY WITHIN 2TO 28
DAYS OF ONSET OF JAUNDICE
ACUTE

5. DEVELOPMENT OF
ENCEPHALOPATHY WITHIN 5TO 56
WEEK OF ONSET OF JAUNDICE
SUBACUTE

6. Hepatitis viruses
Although hepatitis A is the most common form of acute
viral hepatitis, it is rare for acute infection to progress to
ALF. Hepatitis B is probably the most common viral
cause of ALF.
Hepatitis C virus does not appear to be a significant cause
of ALF.
Other viral etiologies of ALF include hepatitis delta virus
coinfection or superinfection, hepatitis E (especially in
pregnant women in endemic areas), Epstein-Barr virus,
cytomegalovirus, herpes simplex virus, and varicella
zoster.
CAUSES/ETIOLOGY

7. Acetaminophen is the most common toxin
associated with ALF in most reports . Most cases
occur after ingestion of large doses in an attempt
to commit suicide.
AMINATA FUNGAL TOXIN
ISONIAZIDE
HALOTHANE
TOXINS AND DRUGS

8. Vascular causes of ALF include portal
vein thrombosis, Budd-Chiari
syndrome (hepatic vein thrombosis),
veno-occlusive disease, and ischemic
hepatitis.
VASCULAR

9. A number of metabolically-related
disorders have been associated with
ALF including Wilson's disease, acute
fatty liver of pregnancy, and Reye's
syndrome.
METABOLIC

10. ALF has also been reported in patients
with malignant infiltration of the liver,
heat stroke, sepsis, and autoimmune
hepatitis.
MISCILLANEOUS

11. SIGNS:
JAUNDICE
HEPATIC ENCEPHALOPATHY
FETOR HEPATICUS
ASTEREXIS
CONSTRUCTIONAL APRAXIA
SIGNS OF CHRONIC LIVER DISEASE
CLINICAL PRESENTATION

12. BLOOD:
BLOOD CP
URINE R/E
LFTS
PT/APTT
BSR
PARACETAMOL LEVELS
HEPATITIS PROFILE
CMV AND EBV SEROLOGY
INVESTIGATIONS

13. FERITIN
ALPHA 1 ANTITRYPSIN
CERULOPLASMIN
AUTOANTIBODIES (ANTI SMA, AMA, ANTI LKM,
ANA)

14. BLOOD C/S
URINE C/S
ASCITIC FLUID R/E AND C/S
MICROBIOLOGY

15. CXR
ABDOMINAL USG
DOPLER USG OF PORTALVEIN
CT SCAN BRAIN
RADIOLOGY

16. EEG
EVOKED POTENTIALS
NERUROPHYSIOLOGY

17. • ENCEPHALOPATHY
• SEPSIS
• GI BLEED
• CEREBRAL EDEMA
• AKI
• PULMONARY
• METABOLIC
COMPLICATIONS

18. HEPATIC ENCEPHALOPATHY —
Hepatic encephalopathy is a major complication of ALF,
although the precise mechanism remains unclear.
The most widely accepted theory is related to increased
production of ammonia from nitrogenous substances
within the gut lumen.
lactulose, although its use in acute liver failure is
controversial.
it should not be administered orally or per nasogastric
tube to patients with advanced encephalopathy unless
endotracheal intubation is performed.
.
COMPLICATIONS

19. Cerebral edema develops in 75 to 80 percent of
patients with grade IV encephalopathy.
The precise mechanism by which it occurs in ALF
is incompletely understood.
Possible contributing factors include osmotic
derangement in astrocytes
changes in cellular metabolism and alterations in
cerebral blood flow
CEREBRAL EDEMA

20. The consequences of cerebral edema include
elevated intracranial pressure (ICP) and brainstem
herniation, which are the most common causes of
death in ALF.
Cerebral edema also can lead to ischemic and
hypoxic injury to the brain.
The classic signs of elevated ICP include systemic
hypertension, bradycardia, and irregular
respirations (referred to as Cushing's triad).
CEREBRAL EDEMA

21. invasive means of monitoring intracranial
pressure have been recommended, and are
routinely used by more than one-half of liver
transplantation programs
MONITORING OF ICP

22. Four types of catheters have been used to measure ICP:
epidural, subdural, parenchymal, and intraventricular:
Epidural catheters are placed outside the dura mater
Subdural catheters are placed beneath the dura mater
Parenchymal catheters are placed directly into the brain
parenchyma
Intraventricular catheters are placed within a cerebral
ventricle
ICP MONITORING

24. An epidural ICP monitor should be placed in
patients with grade IV encephalopathy or
in patients in whom grade III encephalopathy is
rapidly progressing.
Before an ICP monitor is placed, any existing
coagulopathy should be corrected.
TREATMENT

25. Three parameters should be followed during intracranial
pressure monitoring:
Intracranial pressure
Cerebral perfusion pressure (CPP)
Cerebral oxygen consumption
Cerebral perfusion pressure is the difference between
mean arterial pressure and intracranial pressure
Cerebral oxygen consumption is a function of cerebral
blood flow and the oxygen gradient between arterial and
jugular venous blood.
ICP MONITORING

26. The goals of therapy are to maintain the ICP below 20
mmHg and the CPP above 50 mmHg.
These goals can be accomplished using a combination of
interventions:
Patients should be placed in an environment with minimal
sensory stimulation since stimulation
Placement of a nasogastric tube can cause gagging and
thus their use should be minimized
Similarly, endotracheal suction should be minimized.
ICP TREATMENT

27. Overhydration can elevate ICP. Thus, the
fluid status of patients with ALF should be
closely monitored.
The head of the patient's bed should be
elevated to 30 degrees. However, bed
elevation can also reduce cerebral
perfusion. Thus, patients should remain
supine if the CPP falls below 50 mmHg with
bed elevation.
ICPTREATMENT

28. If no response or relapse is noted, hyperosmotic agents
such as mannitol (0.5 to 1 g/kg) or
hypertonic saline (3 percent) should be administered as
an intravenous bolus and then on an as-needed basis.
ICPTREATMENT

29. If no response or relapse is noted after
mannitol administration
pentobarbital coma should be induced using a
bolus of 3 to 5 mg/kg intravenously.
Dexamethasone has not proven to be effective in
the treatment of cerebral edema caused by ALF
and should not be administered
ICPTREATMENT

30. Prophylactic phenytoin
The observation that patients with
acute liver failure may have subclinical
seizure activity provided the rationale
for a controlled trial of seizure
prophylaxis using phenytoin.
SEIZUREPROPHYLAXIS

31. Acute renal failure complicates ALF in
approximately 30 to 50 percent of patients.
The frequency of acute renal failure is
higher (up to 75 percent) for etiologies of
ALF that are known to independently
damage the kidneys, such as
acetaminophen intoxication
ACUTE RENAL FAILURE

32. Treatment of acute renal failure should focus on
prevention because, once established, the renal
failure is usually progressive and associated with
a grave prognosis without liver transplantation.
Among the preventive measures are ensuring
arterial perfusion by maintaining an adequate
systemic blood pressure, identifying and treating
infections promptly, and avoiding the use of
nephrotoxic agents
TREATMENT OF AKI

33. Patients with ALF are at increased risk of infection and
sepsis from a wide variety of causes.
The most common sites of infection are the respiratory
and urinary tracts and blood .
Localizing signs of infection, such as fever and sputum
production, are frequently absent and the only clues to an
underlying infectious process may be worsening of
encephalopathy or renal function.
Thus, an aggressive approach to diagnosing and treating
infections is necessary.This includes a low threshold for
obtaining frequent blood, urine, and sputum cultures, and
diagnostic radiographs, or for performing a diagnostic
paracentesis.
INFECTION AND SEPSIS

34. The role of prophylactic antibiotics is
controversial.
Empiric broad spectrum antibiotics should be
considered in the following patients
Presence of or the rapid progression to advanced
stages of encephalopathy
Refractory hypotension
Presence of systemic inflammatory response
syndrome
ANTIBIOTICS

35. Common metabolic disturbances in ALF include
acid-base and electrolyte disorders,
hypophosphatemia, and hypoglycemia. Among
the acid-base disorders, alkalosis is more
frequently encountered than acidosis in the early
stages of ALF, and is frequently a mixed
respiratory and metabolic abnormality. As ALF
progresses, patients typically develop metabolic
acidosis (due to lactic acidosis) with respiratory
alkalosis.
METABOLIC DISTURBANCES

36. Correction of hypokalemia, if present, is an
essential component of therapy.
Hypokalemia increases renal ammonia
production; in addition, the often concurrent
metabolic alkalosis may contribute by promoting
ammonia entry into the brain by promoting the
conversion of ammonium (NH4+),
a charged particle which cannot cross the blood-
brain barrier, into ammonia (NH3) which can.
METABOLIC DERANGEMENTS

37. Hyponatremia is more frequently seen
in patients with subfulminant hepatic
failure.Tissue hypoperfusion, leading
to enhanced release of antidiuretic
hormone, and impaired renal function
combine to limit free water excretion.
METABOLIC DERANGEMENT

38. Hypophosphatemia is especially common
in patients with acetaminophen-induced
ALF and those with intact renal function.
METABOLIC DERANGEMENT

39. Prophylactic administration of fresh frozen
plasma is usually not recommended since
it has not been proven to influence
mortality, it can interfere with assessments
of liver function, and it may worsen cerebral
edema. Fresh frozen plasma (FFP) is
indicated only in the setting of active
hemorrhage or prior to invasive
procedures, such as placement of
intracranial pressure monitors.
COAGULOPATHY

40. Small pilot studies have demonstrated that
recombinant human factor VIIa (rFVIIa) has been
associated with improvement or normalization of
the serum prothrombin time and control of
bleeding in such patients
COAGULOPATHY

41. Pulmonary edema and pulmonary infections are
encountered in approximately 30 percent of
patients with ALF.
Mechanical ventilation may be required to ensure
adequate oxygenation.
However, extreme caution must be used with
positive end-expiratory pressure in patients with
ALF since PEEP can worsen cerebral edema.
PULMONARY COMPLICATIONS

42. A number of specific interventions have been studied but
are unhelpful for ALF and should generally not be used.
Glucocorticoids, increase the risk of sepsis, although they
may have a potential role in severe autoimmune hepatitis.
Hepatic regeneration therapy using insulin and glucagon.
UNHELPFULTREATMENT

43. Artificial hepatic assist devices — There has been a
strong interest in developing an artificial hepatic assist
device for ALF that would operate on the same basic
principles as hemodialysis for renal failure.
The major difference between the two is that the liver
performs an incredibly large number of diverse and vital
synthetic functions compared to the kidneys. As a result,
developing a machine that performs the functions of the
liver is inherently more difficult than developing one that
performs the excretory functions of the kidneys.
Extracorporeal assist devices currently under
development use hepatocytes from human or nonhuman
cell lines to provide synthetic capability.
NEWER APPROACHES

44. Auxiliary liver transplantation —
Auxiliary liver transplantation involves placement
of a graft adjacent to the patient's native liver
(auxiliary heterotopic liver transplantation) or in
the hepatic bed
There are also reports of auxiliary liver grafts
being reused in second recipients with chronic
liver disease .
NEWER APPROACHES

45. Xenotransplantation — The role of
xenotransplantation (transplantation of a nonhuman
organ) in the treatment of ALF is currently being
reexamined.
Prior to 1992, only 33 xenotransplants had been
performed in humans
The longest graft survival was only nine months.
Despite the initial disappointing results, this approach is
being reevaluated because of advances in
immunosuppression and the ability to manipulate donor
antigen expression
NEWER APPROACHES

47. only therapy proven to improve patient
outcome in ALF is orthotopic liver
transplantation, which is associated with
one-year survival rates of greater than 80
percent, this is in contrast to patients with
ALF who are managed with supportive
medical therapy alone, in whom survival is
much lower
PROGNOSIS

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