Acute liver failure

ACUTE LIVER FAILURE
PRESENTATION
BY
DR SAQIB PERVEZ
MEDICAL `C`
LRH PESHAWAR
ACUTE LIVER FAILURE (AASLD 2011)

INTRODUCTION
ALF is a rare condition in which rapid
deterioration of liver function results in altered
mentation and coagulopathy in individuals
without known pre-existing liver disease.
ALF often affects young persons & carries a
high morbidity & mortality

DEFINITION
Evidence of coagulation abnormality , usually an
INR ≥ 1.5, & any degree of mental alteration
(encephalopathy) in a patient without pre-
existing cirrhosis & with an illness of < 26 weeks
duration.
Patients with wilson disease , vertically acquired
HBV, or AIH may be included in spite of the
possibility of cirrhosis if their disease has only
been recognized for < 26 weeks.

ACUTE LIVER FAILURE
A number of other terms have been used for
this condition , including fulminant hepatic
failure & fulminant hepatitis or necrosis.
“Acute liver failure” is a better overall term that
should encompass all durations upto 26 weeks.

CLASSIFICATION
ALF is classified in to three subcategories ,
depending upon the time lapsed b/w the
appearance of jaundice , to the development of
encephalopathy.
 1) Hyper acute : < 7 days
 2) Acute : 7 – 21days
 3) Sub acute : > 21 days & < 26 weeks

PATHOPHYSIOLOGY
 Loss of normal function of hepatic tissue which
occurs over a short period of time.
It results in the loss of the metabolic , secretory ,
& regulatory effects of the liver cells.
This results in the rapid accumulation of toxic
substances , which then manifests in the patient
as an altered sensorium , cerebral edema ,
hemodynamic abnormalities & even multiorgan
failure.

CAUSES OF ALF
Viral hepatitis Hep A, B, E, D, HSV, VZV, CMV
Drugs Dose-related : Acetaminophen
Idiosyncratic : antibiotics, anti TB, .
. anticonvulsants, NSAIDs
Toxin Mushroom poisoning, CCl4
Vascular Ischemic hepatitis, Budd-Chiari syndrome,
veno-occlusive disease
Metabolic Wilson disease
Pregnancy Acute fatty liver, Eclampsia, HELLP
syndrome
Misc Malignant infiltration, sepsis, AIH
Indeterminate

VIRAL HEPATITIS
Viral hepatitis may lead to ALF.
Hepatitis A & B account for most of these cases.
Hepatitis C rarely causes ALF.
Hepatitis D, as a co-infection or super infection
with HBV can lead to ALF.
Hepatitis E (often observed in pregnant women)
in an endemic area is an imp cause of ALF.

VIRAL HEPATITIS
Atypical causes of viral hepatitis & ALF include:
HSV
CMV
EBV
Hemorrhagic fever viruses
Paramyxoviruses

ACETAMINOPHEN
HEPATOTOXICITY
Acetaminophen is a dose related toxin, most
ingestion leading to ALF exceed 10gm/day
(150mg/kg).
However severe liver injury can occur rarely
when doses as low as 3-4 gm/day are taken.
Very high ALT levels are typically seen , serum
levels exceeding 3500 IU/L are highly correlated
with acetaminophen poisoning.

ACETAMINOPHEN
HPATOTOXICITY
Because acetaminophen is the leading cause of
ALF (at least in the US & Europe) & there is an
available antidote, acetaminophen levels should
be drawn in all patients presenting with ALF.
Specific indication that acetaminophen may be
the culprit include very high ALT & low bilirubin
levels, in the absence of apparent hypotension
& cardiovascular collapse.

MUSHROOM POISONING
There is no available blood test to confirm the
presence of these toxins, but this diagnosis
should be suspected in patients with a history of
severe GI symptoms (nausea, vomiting,
diarrhea, abdominal cramping), which occurs
within hours to a day of ingestion.

DRUG INDUCED LIVER INJURY
Drugs other than acetaminophen rarely cause
dose-related toxicity.
Most examples of idiosyncratic drug
hepatotoxicity occurs within the first 6 months
after drug initiation.
Classes of drugs commonly implicated include
antibiotics, NSAIDs & anticonvulsants.

DRUG INDUCED LIVER INJURY
Certain herbal preparations, weight loss agents
& other nutritional supplements have been
found to cause liver injury, so inquiry about such
substances should be included in a complete
medication history.

Uncommon cause of ALF.
Typically occurs in young patients,
accompanied by the abrupt onset of Coombs
negative hemolytic anemia with serum bilirubin
levels >20 mg/dl.
Kayser-Fleischer rings are present in about 50%
of patients
WILSON DISEASE

WILSON DISEASE
Serum ceruloplasmin is typically low, but may
be normal in upto 15 % of cases & is reduced in
῀ 50% of other forms of ALF.
High urinary & plasma copper levels as well as
hepatic copper measurement will confirm the
diagnosis.
Very low serum ALP & uric acid levels.
A high bilirubin (mg/dl) to ALP (IU/L) ratio ( >
2.0) is a rapid (indirect) indicator.

Acute hepatic vein thrombosis
Abdominal pain, ascites and striking
hepatomegaly are often present.
Diagnosis confirmed with hepatic imaging
studies (computed tomography, Doppler
ultrasonography, venography, magnetic
resonance venography) & testing to identify
hypercoagulable conditions (polycythemia,
malignancies).
BUDD CHIARI SYNDROME

ACUTE ISCHEMIC INJURY
Shock liver: cardiac arrest; significant
hypotension/hypovolemia; severe CHF
Drug induced hypotension/hypoperfusion: long
acting niacin; cocaine; methamphetamines
Documented hypotension not always found
Transaminases often > 1000-2000 mg/dL;
Simultaneous renal insufficiency and/or muscle
necrosis often found

AIH patients that develop ALF represent the
most severe form of the disease.
Auto-antibodies absent (up to 30% of cases)
Liver biopsy should be considered if
autoimmune hepatitis is suspected and
autoantibodies are negative.
AUTOIMMUNE HEPATITIS

 Acute Fatty Liver of Pregnancy/HELLP (Hemolysis,
Elevated Liver Enzymes, Low Platelets) Syndrome.
 A small no. of women near the end of pregnancy will
develop rapidly progressive hepatocyte failure associated
with increased fetal or maternal mortality.
 A variety of presentation may be seen generally confined
to the last trimester.
 Triad of jaundice, coagulopathy, and low platelets
 Hypoglycemia and features of pre-eclampsia are
common.
ALF IN PREGNANCY

MALIGNANT INFILTRATION
Malignant infiltration of the liver may cause ALF.
Acute severe hepatic infiltration occurs with
breast Ca, small cell lung Ca, lymphoma,
melanoma & myeloma.
In patients with ALF who have a previous
cancer history or massive hepatomegaly,
consider underlying malignancy & obtain
imaging & liver biopsy to confirm or exclude the
diagnosis.

INDETERMINATE ETIOLOGY
If the etiological diagnosis remains elusive after
extensive initial evaluation , liver biopsy may be
appropiate to attempt to identify a specific
etiology that might influence treatment strategy.
Causes of cases believed to represent
indeterminate ALF , & subsequently recognized
include acetaminophen, AIH , & malignancies.

CLINICAL MANIFESTATIONS
Many of the initial symptoms in patients with
ALF are non-specific : (fatigue, malaise,
anorexia, nausea, vomiting, abdominal pain,
lethargy).
As the liver failure progress, patients who were
initially anicteric may develop jaundice, & those
with subtle mental status changes (e.g lethargy,
difficulty sleeping) may become confused or
eventually comatose.

CLINICAL MANIFESTATIONS
The presence of hepatic encephalopathy is one
of the defining characteristics of ALF.

CNS disturbances
– Hepatic encephalopathy
– Cerebral edema
– Seizures
Infections
Coagulopathy and bleeding
Renal failure & hemodynamic collapse
Metabolic derangements
COMPLICATIONS

DIFFERENTIAL DIGNOSES
Acute decompensation of cirrhosis
Alcoholic hepatitis with underlying cirrhosis
Sepsis with MOF
Eclampsia & pre-eclampsia
Severe liver involvement of systemic infections
(malaria, typhoid, leptospirosis, riketsial
infection etc)

DIAGNOSIS
History
Physical examination
Investigations

HISTORY
Date of onset of jaundice & encephalopathy.
Alcohol abuse
Medication use (prescription & recreational)
Herbal or traditional medicine use
Family hx of liver disease (wilson disease)
Exposure to hepatic toxins (mushroom, organic
solvents)

HISTORY
Exposure to risk factors for viral hepatitis (travel,
transfusion, sexual contacts, occupation, body
piercing)
Evidence of complications (e.g renal failure,
seizures, bleeding, infections)

PHYSICAL EXAMINATION
Mental status examination & grading of HE.
Search for stigmata of CLD (usually absent)
Jaundice
RUQ tenderness
Hepatomegaly (viral hepatitis, malignant
infiltration, CHF, Budd Chiari syndrome)

PHYSICAL EXAMINATION
Rapid development of ascitis in ALF patient,
accompanied by abdominal pain suggest the
possibility of BC syndrome.
Clinical signs of elevated ICP (systemic
hypertension, bradycardia & irregular respiration
_cushing triad & other neurologic changes such
as pupillary dilatation or decerebrate posture)

INITIAL INVESTIGATIONS
Coagulation studies PT / INR
CBC Thrombocytopenia
LFTs Elevated levels of ALT, AST, ALP, Bilirubin
RBS May be low
Serum electrolytes Including HCO3, Ca, Mg, Phosphorus
RFTs Creatinine may be elevated
Blood group & screen
Pregnancy test
ABGs May reveal hypoxemia
Ammonia Elevated
Arterial lactate Often elevated

ETIOLOGY SPECIFIC
Viral hepatitis Anti-HAV IgM
HBsAg, anti-HBc IgM
Anti-HCV, HCV RNA
Hepatitis D virus IgM
Anti-HEV
HSV1 IgM, VZV
Wilson disease Ceruloplasmin, serum & urinary copper
Autoimmune hepatitis ANA, ASMA, Immunoglobulin levels
Budd Chiari syndrome Hepatic doppler USG, Abd CT or MRI
Drugs and toxins Acetaminophen level
Toxicology screen
Indeterminate Liver biopsy

MANAGEMENT
Therapy of ALF consist of general supportive
measures (complications), specific therapies for
some of the etiologies, liver transplantation &
other methods of temporary liver support.

LIVER TRANSPLANTATION
It remains the only effective therapy for ALF
patients who fail to recover spontaneously.
king`s College criteria is used to select the
patient that should be referred to a transplant
center for transplantation.

KING`S COLLEGE CRITERIA

LIVER SUPPORT SYSTEMS
Are support devices which help in resting the
liver to provide it sometime to recover.
There are two kinds of devices, sorbent based
artificial systems & cell based bio-artificial
systems.
There is no good evidence showing a decrease
in mortality with their use in ALF.
They are not currently recommended outside of
clinical trials.

PROGNOSIS
Cause of ALF: most significant predictor of
outcome
Acetaminophen, Hepatitis A, shock liver,
pregnancy related with > 50% OLT free
survival
All others < 20% OLT free survival
Degree of encephalopathy: Grade I-II with 65-
70% spontaneous recovery; Grade III-IV < 20%
Age: > 40 yr or < 10 yr have worse outcome

SUMMARY
Patients with ALF should be hospitalized &
monitored frequently, preferably in an ICU.
The precise etiology of ALF should be sought to
guide further management decisions.
NAC may be used in the setting of non-
acetaminophen ALF including, e.g DILI &
hepatitis B.

SUMMARY
The development of cerebral edema is the
major cause of morbidity & mortality in patients
with ALF.

Acute liver failure

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