[lecture] acute liver failure

7/27/2019 [Lecture] Acute Liver Failure

1/60

ACUTE LIVER FAILURE


2/60

Acute Liver Failure Acute liver failure = fulminant hepatic

failure

Definition

Acute onset of liver disease with

coagulopathy

Development of hepatic encephalopathy

No prior evidence of liver disease

Friedman and Keeffe EB. Handbook of Liver Disease 2004


3/60

Definitions of ALF in Current UseFrance

(Bernuau et al)UK

(OGrady et al)Trigger event Jaundice JaundiceTerm Fulminant hepatic failure Hyperacute liver failureTime to encephalopathy 2 weeks < 7 daysTerm Subfulminant hepatic

failure Acute liver failureTime to encephalopathy 3-12 weeks 8-28 daysTerm Subacute liver failureTime to encephalopathy 29-84 days

Weinstein WM, Hawkey CJ and Bosch J. Clin Gastroenterol and Hepatol 2005


4/60

Bacon BR and et al. Comprehensive Clin Hepatol 2006


5/60

Etiology of ALFCommon

Hepatitis A

Hepatitis B

Seronegative hepatitis

Acetaminophen Idiosyncratic drug

reactions

Uncommon

Wilson disease

Infections : EBV, CMV,Herpes

Vascular abnormalities Acute fatty liver of

pregnancy

AIH

Malignant infiltration

Ischemic hepatitis Toxins :Amanita

phalloides



6/60

Non-paracetamol-based Drugs Causing Acute Liver Failure

Bernal W et al. Lancet 2010;376:190-201


7/60

Initial Evaluation of ALFHistory

Medications

Recreational drugs

Prodome

Travel

Alcohol

Past medical history

Physical examination

Vital signs

Size of liver

Mental status

Rash



8/60

Clinical Features of ALF

Whole body Systemic inflammatory response

High energy expenditure and catabolism

Liver Loss of metabolic function

Decreased gluconeogenesis leading to hypoglycemia Decreased lactate clearance leading to lactic acidosis

Decreased ammonia clearance leading to hyperammonaemia

Decreased synthetic capacity leading to coagulopathy

Lungs Acute lung injury

ARDS Adrenal gland

Inadequate slucocorticoid production contributing to hypotension

Bone marrow Frequent suppression, especially in viral and seronegative disease



9/60

Clinical Features of ALF

Circulating leucocytes Impaired function and immunoparesis contributing to high risk of sepsis

Brain Hepatic encephalopathy

Cerebral edema

Intracranial hypertension Heart

High output state

Frequent subclinical myocardial injury

Pancreatitis Particularly in paracetamol-related ALF

Kidney Frequent dysfunction or failure

Portal hypertension Might be prominent in subacute disease and confused with chronic liver disease



10/60

Laboratory StudiesTo identify cause of ALF

Anti-HAV IgM

HBsAg, Anti-HBc IgM

Anti-HDV (if HBsAg

positive) Drug screen

ANA, SMA

Serum ceruloplasmin,serum copper

To assess severity PT, bilirubin, albumin

ABG for arterial pH

To assess complications

Serum creatinine

Chest X ray

Electrolytes, blood sugar

Arterial ammoniaLaboratory for OLT listing

Anti-HIV

Anti-CMV, EBV

EKG Blood type and cross-match



11/60

Clinical Stages of HepaticEncephalopathy in ALF

Grade Symptoms Signs EEG0 Normal Normal Normal1 Lack of awareness,short attention span,

altered sleep pattern Tremor, asterixis Symmetric slowing

2 Agitation, lethargy,seizures Asterixis,hyperreflexia Symmetric slowing,triphasic waves

3 Asleep, arousable bypain Hyperreflexia Triphasic waves

4 Unarousable Babinski, ankleclonus, decerebrateposture

Delta (very slow)activity

Boyer TD, Wright TL and Manns MP. Zakim and Boyers Hepatology 2006


12/60

Management

TreatmentEtiology Drug

Acetaminophen N-AcetylcysteineHepatitis B

Lamivudine, Adefovir

Amanita phalloides Penicillin G, N-AcetylcysteineHerpes simplex virus Acyclovir

Acute fatty liver of pregnancy Fetus deliveryHELLP syndrome Fetus delivery

Autoimmune hepatitis SteroidsWeinstein WM, Hawkey CJ and Bosch J. Clin Gastroenterol and Hepatol 2005


13/60

Paracetamol Poisoning

2 forms

Single overdoseexceed 7-10 g

Repeated supratherapeutic ingestion(therapeutic misadventure)

Daily ingestion 10-20 g over three days

Risk: malnourished, heavy alcoholic drinkers,

drugs (phenobarbital, phenytoin, isoniazid,

and zidovudine)


14/60

Paracetamol Poisoning

Categorized into 4 stages

Preclinical toxic effects (normal serum

ALT)

Hepatic injury (elevated ALT)

Hepatic failure (hepatic injury with hepatic

encephalopathy) Recovery


15/60

Metabolism of Acetaminophen


16/60

The Rumack-Matthew Nomogram


17/60

Current FDA-approved Protocols

Oral Acetylcysteine

Loading 140 mg/kg and repeat 70 mg/kg

every 4 hours for a total 17 doses

Intravenous Acetylcysteine

Loading 150 mg/kg over a period of 15-60

minutes, followed by an infusion of 12.5mg/kg over a 4-hour period, and finally an

infusion of 6.25 mg/kg over 16-hour period


18/60

Hepatitis B


19/60

Features to Differentiate Acute

Exacerbation of CHB from Acute HBV

Wong VWS, Chan HLY. J Gastroenterol Hepatol. 2009;24:1179-1186.

Exacerbation of CHB Acute Hepatitis B

Useful Features

History Past or family history ofCHB

Recent sexual, blood,

or percutaneousexposure to HBV

Anti-HBc IgM titerNegative or low

(


20/60

Serologic Profile of Acute HBV

versus Exacerbation of CHB

Kumar M, et al. Dig Dis Sci. 2006;51:594-599.


21/60

Serum HBV DNA in Acute HBV

versus Exacerbation of CHB

Kumar M, et al. Dig Dis Sci. 2006;51:594-599.

0.5 pg/mL 140,000 copies/mL or 25,000 IU/mL


22/60

Features to Differentiate Acute

Exacerbation of CHB from Acute HBV

Wong VWS, Chan HLY. J Gastroenterol Hepatol. 2009;24:1179-1186.

Exacerbation of CHB Acute Hepatitis B

Featur es of Uncertain Value

Basal corepromoter mutation Present Absent

Precore stop codonmutation

Present Absent

Not Useful Features

Symptoms andsigns

Prodromal symptomsJaundice and itching

Abdominal discomfort

Prodromal symptomsJaundice and itching

Abdominal discomfort

ALT levels Very high Very high


23/60

LAM Therapy in Severe Acute HBV

Author, year Patients(no.)

StudyDesign

HBsAgLoss

Anti-HBsGain

Survival

Miyake et al, 2008 10 Retrospective NA NA70% (vs

26%)

Lisotti et al, 2008 5 Prospective 100% 40% 100%

Delic et al, 2009 10 Prospective 90% NA 90%

Schmilovitz-Weiss et al,

200415 Prospective

73% (only 11

tested)

60% (only 9

tested)87%

Tillmann et al, 2006 17Prospective,

historic controls

82% (NA for

historic

untreated)

NA

82% vs 20%

in historic

controls

Kumar et al, 2007 31Prospective,

RCT

92.5% vs

93.5% in

untreated

group at 1 yr

67.7% vs

85% in

untreated

group at 1 yr

100% vs

100% in

untreated

group

Te HS. Curr Hepatitis Rep. 2010;9:119-123.


24/60

AASLD Guideline regarding Treatment

of Acute Severe Hepatitis B

Recommendations for Treatment of Patients with Acute

Symptomatic Hepatitis B:

1. Treatment is only indicated for patients with fulminant

hepatitis B and those with protracted, severe acutehepatitis B.

2. Lamivudine or telbivudine may be used when the

anticipated duration of treatment is short; otherwise,

entecavir is preferred.

3. Treatment should be continued until HBsAg clearance is

confirmed or indefinitely in those who undergo liver

transplantation.

Lok A, McMahon BJ. Hepatology. 2009;50:661-662.


25/60

Wilson Disease


26/60

Wilson Disease Autosomal recessive

Impaired biliary excretion of copper

Progressive accumulation of copper invarious organs include liver, brain, cornea

Prevalence 1:30,00050,000 , equivalentamong all ethnic groups

Gitlin JD. Gastroenterology 2003;125:1868-1877


27/60

Bacon BR et al. comprehensive Clin Hepatol 2006


28/60

Clinical ManifestationHepatic Acute fulminant hepatitis, steatosis, chronic

hepatitisNeurological Extrapyrimidal, cerebellar manifestationPsychiatric Depression, mania, delusionsOcular KF ring, sunflower cataractHematological Hemolysis, thrombocytopeniaMusculoskeletal Osteoporosis, rickets, chondrocalcinosisRenal Renal tubular acidosis, nephrolithiasisCardiac Arrhythmias, cardiomyopathyEndocrine Hypoparathyroidism, delayed puberty


29/60

Clinical Features

40

30

10

20Hepatic

Neurologic

Psychiatric

Mixed form

Knawy BA et al. Hepatology : A practical approach 2004


30/60

Hepatic FormAcute wilsonian hepatitis and fulminant

wilson disease

Indistinguishable from other forms

Female : male = 2-3 : 1

AST, ALTnot increase above 10 times

Coomb s negative hemolysis

Alkaline phosphatasetotal bilirubin ratiobelow 2 suggestive fulminant hepatitis

Bacon BR et al. Comprehensive Clin Hepatol 2006


31/60

Hepatic FormChronic hepatitis

Young patients (8-18 years)

Nonspecific and mimics manifestations ofchronic liver disease due to other causes

Liver biopsymoderate steatosis,glycogen vacuolation of nuclei in periportal



32/60

Neurologic Form Develop in mid teens or in the 20 s

Well documented in 45-55 years

Initialmild tremor, speech and writingproblem then progressive movement

disorder

Common symptomsdysarthria,

dysphagia, apraxia and tremor-rigiditysyndrome



33/60

Psychiatric Form Reduced school or work performance

Depression, very labile mood

Sexual exhibitionism Frank psychosis



34/60

Kayser-Fleischer Rings

Tanner MS. Comprehensive Clin Hepatol 2000; 21.1-21.12

Superior

InferiorLateral

50% in hepaticform

90% inneurologic form


35/60

Tanner MS. Comprehensive Clin Hepatol 2000; 21.1-21.12

Sunflower Cataract


36/60



37/60

Roberts EA and Schilsky ML. Hepatology 2008


38/60

Tests for Diagnosis of WilsonDisease



39/60

Management of Wilson Disease1. Initial therapy

2. Maintenance therapy

3. Non-pharmacologic management4. Family screening

Brewer GJ and Askari FK. J Hepatol 2005;42:S13-S21


40/60

Initial TherapyDrug Dose Side effect

Penicillamine

(plus pyridoxine)1-2 gm/day Hypersensitivity reactions, BMsuppression, SLE,

Goodpastures syndromeTrientine 1-2 g/day Same side effect aspenicillamine, but lessor,

proteinuriaTetrathiomolybdate

(TM) 60-120 mg/day BM suppression

Zinc acetate 150-300 mg/day Gastric irritation



41/60

Diagnosis Established

Patient ClassificationFor Initial Therapy

Neurologic/PsychiatricPresymptomatic

Hepatic

LiverFailure

Treatment Rec.1. Zinc2. Trientine

TransaminaseElevations Only

Mild or Moderate(Nazer scope up to 7) Severe(Nazer scope over 7)

Treatment Rec.1. Trientine + Zinc

2. Penicillamine + Zinc

Treatment Rec.1. transplantation

Treatment Rec.1. TM + Zinc2. Zinc or

Trientine + Zinc

Treatment Recommendations1. Zinc2. Trientine


42/60

Maintenance TherapyFor maintenance and therapy of

presymptomatic and pregnant patient

First choice : Zinc

Second choice : Trientine



43/60

Non-pharmacologic ManagementDiet

Avoid chocolate, liver and shellfish

Drinking water Use water with copper below 0.1 ppm

(parts per million)



44/60

Management

General management

Full hemodynamic monitoring

ET tube for stage 3 encephalopathyAirway protection

Provision of respiratory support

Management of intracranial hypertension

Parenteral glucose (D10 or 20) to prevent

hypoglycemia



45/60

Management

Correct electrolyte and acid-base

disorders

Hyponatremia and hypernatremia

Hypokalemic alkalosis

Hyperkalemic acidosis

Nutritionenteral or parenteral route

Caloric goal : 35-40 Kcal/day

Protein : 40 gm/day



46/60

Management

Prevention of bleeding

Administration of vitamin K

H2blocker, PPI or sucralfate to prevent GI

bleeding

Renal insufficiency: oliguria

Continuous arteriovenous or venovenous

hemofiltration Minimize hypotension, decreased cerebral

edema compare to standard hemodialysis


P ti d M t f


47/60

Prevention and Management ofInfection

50%

22%

12%

16%

Chest

Urinary tract

IV catheter

Blood only


P ti d M t f


48/60

Prevention and Management ofInfection

Prophylactic antibiotics reduce infections

Cultures and microbiological screening

Third-generation cephalosporin IV

Fungal infections were suspected in

patients

High fever unresponsive to antibiotics

Profound leukocytosis



49/60

Management

Hepatic encephalopathy

Lactulose

No improvement and controversy

Volume depletion, electrolyte disturbances

and ileus

Discontinue if no benefit after two enemas



50/60

Management

Cerebral edema and Intracranialhypertension

The most common cause of death

Occur >75% of ALF patients with grade 4encephalopathy

Diagnosed by systemic HT,

hyperventilation, abnormal pupillaryreflexes, muscular rigidity and decerebrateposturing



51/60

Management

Elevate head of bed 20-30o

Hypothermia (32-33o C)

Correct volume overload

Maintain mean BP 50-60 mmHg

Hyperventilate to keep PCO225-30 mmHg

Treat agitation with intubation and sedation

Intratracheal lidocaine before respiratory

suctioning



52/60

Management

Correct hypoxemia

Monitor for and treat seizures Phenytoin IV 15 mg/kg IV loading dose followed

by 100 mg every 8 hrs. Mannitol

IV bolus 1-2 mg/kg and can be repeated

Ineffective in renal failure, serum osmolality > 320

mmol/l 20% of patients have increased intracranial

pressure after administration of mannitol



53/60

Management

Plasmapheresis

Exchanging elements in plasma with normal components

Exchange 10L of plasma: full replacement of the

extracellular fluid compartment

Removal toxins and repletion of factors synthesized by

the liver

Decrease plasma ammonia, improve HE within hours

Mean arterial pressure improved, decreased cardiacindex, increased vascular resistance

Lee WM et al. Hepatology 2007;47:1404-15


54/60

ManagementHepatic assist devices

Non-cell-based detoxification systems

Open-loop approaches - single pass albumin

dialysis system and plasma exchange

Closed loop systemsprometheus albumin

dialysis system and MARS

Cell-based systems (bioartificial liver)


55/60

ManagementNAC

Intraveneous NAC improves transplant-free

survival in early stage non-acetaminophen acute

liver failure 173 patients, multicenter trial

NAC 150 mg/kg/hr of NAC over 1 hour, followed

by 12.5 mg/kg/hr for 4 hours, then continuous

infusions of 6.25 mg/kg NAC for the remaining67 hours


56/60

Intraveneous NAC Improves Transplant-free Survival inEarly Stage Non-acetaminophen Acute Liver Failure

Lee WM et al. Gastroenterology 2009:137:856-64


57/60

Child-Turcotte-Pugh ScoreCriteria Points

1 2 3Total bilirubin

(mg/dl) 3

Albumin (g/dl) >3.5 3.5-2.8


58/60

King s College Criteria for OLTParacetamo l-induced ALF

Arterial blood pH < 7.3

OR all of the following

PT > 100 s (INR > 6.5) Serum creatinine > 300

mmol/L Grade III or IV HE

Non-paracetamol indu cedALF

PT > 100 s (INR > 6.5)

OR any 3 of the following

Age < 10 or > 40 yrs Etiology : non-A/non-Bhepatitis, drug-induced

Duration of jaundice toencephalopathy > 7 days

PT > 50s (INR > 3.5) Serum bilirubin > 300

mmol/L

OGrady JG and et al. Gastroenterology 1989;97: 439-445


59/60

Criteria of Hospital Paul-Brousse, Villejuif Hepatic encephalopathy, and factor V level


60/60

Model for End-Stage Liver Disease(MELD)

9.6 X ln(creatinine mg/dl) + 3.8Xln(bilirubin

mg/dl) + 11.20Xln(INR) + 6.4

Score higher than 20survival benefitwith liver transplantation

[lecture] acute liver failure

Documents