acute liver failureacute liver failure definition rapid deterioration of liver function resulting in...

Aliakbarian M, M.D

ACUTE LIVER FAILURE

Acute Liver Failure

Definition

Rapid deterioration of liver function

resulting in altered mentation and

coagulopathy in a patient without

preexisting cirrhosis and with an illness of

less than 26 weeks duration.

Acute Liver Failure….

• Fulminant hepatic failure

• Fulminant hepatitis

• Subfulminant liver failure

• Subacute hepatic necrosis

• Subacute liver failure

• Hyperacute liver failure

Index of Suspicion for ALF

• Clinical signs of moderate to severe hepatitis

• Laboratory findings including an increase in the prothrombin time of 4-6sec.(INR ≥ 1.5).

• Altered sensorium

INR ≥ 1.5 + Altered Mental Status = ALF

Suspect ALF?..........Admit to ICU

ALF

Etiologies

• Viral

• Drug

• Poisoning

• Ischemia

• VOD

• Malignant Infiltrate

• Wilson’s Disease

• Microvesicular

steatosis

• AIH

• Hyperthermia

• OLT

• Partial hepatectomy

Viral

• Acute Hepatitis A-E

• Reactivation of HBV

Chemotherapy

Immunosuppresion

• Herpes simplex

• Varicella-Zoster

• EBV

Acute HAV and ALF

• ALF uncommon

• Frequency 0.01% - 0.1% in

jaundiced patients

• ALF occurs early

• Survival (transplant- free) 75%

• Age related survival

Acute HBV and ALF

• HBV alone or with HDV co-infection

(rare)

• Transplant-free survival is 23%

• Overall survival 77% because of

transplantation

Drug Induced ALF

• Many drugs implicated

Acetaminophen

Halothone and derivatives

INH/ Rifampin

Tricyclics/ MAO inhibitors

Phenytoin/ NSAID

• Increased risk: acetaminophen (as little as

2gms) + ETOH median dose: 13 gm

• Increased risk if drug continued after

jaundice appears

Poisoning and ALF

• Amanita mushrooms (amanatoxins)

- LD = 50 gms (3 mushrooms)

- Toxins not destroyed by cooking

- Rapid onset of HE in 4-8 days

following severe emesis and diarrhea

• Solvents - chlorinated hydrocarbons

• Herbal remedies

• Yellow phosphorus

Obstruction of Hepatic Veins

and ALF

• Budd-Chiari syndrome

and thrombosis of hepatic

veins

• VOD - Post BMT

Chemotherapy, Irradiation

Other Etiologic Causes of ALF

• Wilson’s Disease

can be presenting feature

usually in patients <20 yrs

can occur if patient discontinued

D-penicillamine for a few years

Other Etiologies (2)

• Microvesicular steatosis

Acute fatty liver of pregnancy

Reye’s syndrome

Drug Induced - Valproic acid

• AIH

May appear as an acute hepatitis

on initial presentation

More common if anti-LKMI antibody present

ASMA usually not present

Other Etiologies (3)

• Hyperthermia (Heat stroke)

Direct thermal injury

Hepatic ischemia due to

-DIC

-Perfusion defect

• OLT

Poor presentation of donor liver

Acute graft rejection

Thrombosis - hepatic artery, hepatic

vein, portal vein

• Partial hepatectomy

Removal of 80% or more of healthy liver

Removal of 50% or less in hepatic dysfunction

Evaluation & Diagnosis

of Impending ALF

History! History! History!

Sexual contacts

IDU

Risk Factors

Pregnancy Mushrooms

Medications Travel Toxic exposures

HISTORY

• Family members with liver disease?

• Recent cold sores

• Onset of jaundice

• Work environment- toxic agents

• Hobbies

• Herbal products/dietary supplements

Physical Exam

Determine presence or absence

of pre-existing liver disease

Hepatic tenderness

Hepatic decompensation

Laboratory Tests

(1)

Drug screening

ALT, AST, Alk Phos, Glu,

Bilirubin

Lytes, Albumin, Mg, Phos.,

CBC with differential

Coags: PT, PTT

Anti HAV IgM

Anti HBc IgM/ Anti HBsAg/

Anti-HCV

Laboratory Tests

(2) If under 35 years of age

Ceruloplasmin

Serum & urine copper

Arterial blood gas

Arterial lactate

Pregnancy test

Autoimmune markers – ANA, ASMA, Ig levels

HIV status

Amylase & lipase

Liver Biopsy

Reserved for diagnostic

dilemma -

AIH, HS

(Transjugular approach)

Diagnosis of ALF

Hallmarks - occurs simultaneously or in

succession

• Altered mentation Clinical

EEG

Arterial Ammonia

• Coagulopathy

PT 4 sec prolonged (INR≥ 1.5)

• Arterial pH<7.3 if acetaminophen ingested

(cause for immediate transfer for OLT)

Management of ALF

(1)

• Directed towards prevention of complications

• ICU setting Central line(s)-10% dextrose

Pulmonary artery pressure and CO

• Inform Transplant Service and transfer with

onset of HE

• Monitor VS and urinary output (Foley)

strict I&O

• Laboratory Testing every 4-6hr electrolytes, BUN, creatinine, CBC, platelets,

PT, PTT, ALT, AST, T. bilirubin, Alk Phos, Albumin

Management (2)

• Maintain gastric pH above 5

- protonix IV

• Preparation for endotracheal intubation

• Prepare to initiate monitoring intracranial

pressure

• Enteral feeding tubes for grade 3 or 4 coma

Cerebral Edema

Cerebral Perfusion Pressure

Mean Arterial Pressure – ICP = Cerebral

Perfusion Pressure (CPP)

Ideal ICP<20-25mm Hg Ideal CPP>50-60mm Hg

Imazaki, et al

When CPP<40 for 2 hrs. 0 of 7 patients recovered

When CPP>50 6 of 8 patients recovered

Improved ICP first sign of spontaneous recovery

Management (3)

Cerebral Edema & Intracranial Hypertension

(Most serious complications of ALF)

Clinical signs of elevated ICP (Intracranial

Pressure)

-sluggish pupillary response

-increased limb-muscle tone

-none

Monitoring ICP

-usually reserved for grade 3 or 4 coma

-awaiting OLT

Management (4)

Cerebral Edema - General Measures

-quiet environment

-elevate head 10°-20°

-avoid sedation (use restraints)

-avoid Valsalva-like maneuvers

-mental status assessments q1-2h

-mannitol if signs of impending

uncal herniation (0.5mg/kg, lolus q4-8h)

when ICP<30-40mm

-assisted ventilation (in all grade 3 and 4)

Multiple Organ Failure

Hepatic damage increased risk

of infection

Failure of

clearance

Endotoxemia

Gut leak

MOF Activation of

macrophages

Tissue Circulating Release of

Hypoxia changes cytokines

TNF, IL-1, IL-6

Williams, Sem Liver Dis, Vol 16, No.4, 1996

Management (5)

Hemodynamic Complications include:

Hypotension, tachycardia, vascular volume decrease

with capillary leak and vasodilation

•Volume expansion (central line)

•FFP or 4.5% albumin, 10% dextrose

•Maintain pulmonary capillary wedge

pressure 12mm-14mm Hg

•Minimize salt solutions (ascites,

interstitial accumulation)

•Inotropic/pressor support(epi, norepi, dopamine),

but not vasopressin.

Management (6)

Coagulopathy/Bleeding Diathesis

• FFP or platelets given in presence of bleeding

• Conventional treatment of GI bleeding

• DIC thrombocytopenia

Metabolic Complications

• Prevent hypoglycemia

• Phosphate and magnesium levels

monitored - replace early

• Enteral feeding, 60gm protein/24 hrs

• No role for high branched-chain AA

• Monitor for lactic acidosis secondary to

tissue hypoxia, sepsis

Management (7)

Renal Failure

- In 42% to 82% of ALF

poor prognostic sign

- Rising creatinine and oliguria

- Metabolites of acetaminophen

are nephrotoxic leading to acute

renal failure similar to ATN and

loss of phosphate

-HRS

Additional Complications

• ARDS

• Sepsis

- Severe complement deficiency

- Decreased PMN motility

- Decreased Kupffer cell function

and removal of endotoxins

- Increased levels of TNF and IL-6

Prognostic Factors

• Dependent on Etiology

• Younger patients do better (<40 and >10)

• Presence of cerebral edema

• Delay between jaundice and HE of more

than 3 weeks - poorer prognosis

• MOF - poor prognosis

Current Treatment

Transplantation

OUTCOME RESULTS U.S. ALF

STUDY GROUP

308 Patients

Spontaneous

Survivors

n=132

(43%)

Transplanted

N=89

(29%)

Died before

Transplantation

n=87

(28%)

Transplanted

N=89

(29%)

Alive

N=75

(84%)

Died

N=14

(16%)

Approach to Suspected ALF

• Etiology and Pathogenesis

• Evaluation and Diagnosis

• Complications

• Management

• Prognosis

• Current and future treatment

approaches