Hepatology RoundsACUTE LIVER

FAILURE

ACUTE LIVER

FAILURE

Jose Socrates ‘Dee’ Matuod EvardoneGastro 2

Year Level IICDUH-IM

ACUTE LIVER FAILURE

• SOURCES:

CASE

CASE• PATIENT PROFILE

• G.R. 26 yo• Male• Single• Non-DM• Non-HTN• PTB (maintenance) on HRZE x 2 months• HIV, Hep B• Bisexual orientation

• CHIEF COMPLAINT: Disorientation

CASE• HPI

• 4 weeks PTA,• noted yellowish skin

discoloration• Body malaise• Loss of appetite• Mild epigastric pain• Maculopapular rashes

• Consulted his AP, Labs taken showed elevated SGPT

• Admitted 6 days PTA

• admitted for 4 days, treated as drug induced liver injury secondary to Anti-TB meds,

• with Elevated INR, Elevated SGPT, no encephalopathy

• Discharged 1 day PTA• That night on discharge day,

px noted to be disoriented and became incoherent, thus he was brought back for readmission

• (-) fever, (-)diarrhea, (-) vomiting,

• No Hx of fall, head trauma

CASE

• Maintenance meds1. Phospholipids Essentiale Forte2. Vitamin K3. Fluimucil4. Ursodeoxycholic acid5. Hydroxyzine6. Mycostatin

Physical Exam

Lethargic, incoherent, NIRD, Warm, good turgor and mobility, CRT <2 seconds, Generalized Jaundice, Maculopapular rashes

Icteric sclerae, pink palpebral conjunctivae,

Equal chest expansion, dec BS on the Right lower quadrant

Distinct heart sounds, tachycardic, regular rhythm

Flat, Normoactive bowel sounds, soft, direct tenderness on RUQ, Hepatomegaly, no splenomegaly, no fluid wave

Strong peripheral pulses, no edema,

Neurologic: Lethargic, but arousable, not cooperative

BP: 110/80mmHg, HR: 129bpm, RR: 20cpm, Temp: 36.5°C

CN II, III: Isocoric, round, brisk, OUCN III, IV, VI: n/aCN VII: no facial asymmetryCN XII: n/aSensory: n/aMotor Strength: 5/5Reflexes: +2 DTRs (-) Babinski(-) Meningeal signsNO asterixis

LABSCBC AdmHgb 10.7Hct 31.6WBC Seg Bas Eos Lymph Mono

9.979011010

RBC 4.95Platelet 88.5MCVMCHMCHC

85.62933.9

CHEMISTRY

Creatinine

0.78

Potassium

2.4

SGPT 376Albumin 1.8Globulin 5.7Total Prot

7.5

Prothrombin TimeControl 10.7 secPro Time 85.4 sec% Activity 5.8INR 7.03

CASEIMPRESSION

1. Acute Liver Failure secondary to Anti-TB Medications

2. Hepatic Encephalopathy Grade 1-2, sec to #1

3. Hypokalemia sec to #14. HIV5. Hepatitis B Infection

ACUTE LIVER FAILURE• DEFINITIONS• ETIOLOGY and

EPIDEMIOLOGY• Viral hepatitis• Acetaminophen and other

hepatotoxins• Idiosyncratic drug reactions• Hypoperfusion

• CLINICAL MANIFESTATIONS• Symptoms• Physical examination findings

• - Neurologic examination• - Other physical examination

findings• Laboratory test abnormalities

• - Laboratory findings associated with specific diagnoses

• Imaging and other studies

• DIAGNOSIS• Diagnosing acute liver failure• Determining the cause of

acute liver failure• - Timing of the evaluation• - History• - Physical examination• - Laboratory evaluation• - Imaging studies• - Liver biopsy

ACUTE LIVER FAILURE• APPROACH TO

MANAGEMENT• Overall Strategy• General Measures

• DIFFERENTIAL DIAGNOSIS

• TREATMENT OF COMPLICATIONS• Neurologic Complications• Infection• Hemodynamic Instability and

Hypoxemia• Renal Failure

• Coagulopathy• Metabolic Disorders• Nutritional Deficiencies

• PROGNOSIS• LIVER

TRANSPLANTATION• EXTRACORPOREAL

LIVER SUPPORT

PHYSIOLOGY

The Liver as an Organ

The Liver as an OrganLIVER’S DIFFERENT FUNCTIONS:

(1) FILTRATION AND STORAGE OF BLOOD;(2) METABOLISM OF

a) carbohydrates, b) proteins,c) fats, d) hormones, and e) foreign chemicals;

(3) FORMATION OF BILE; (4) STORAGE OF VITAMINS AND IRON; AND (5) FORMATION OF COAGULATION FACTORS

ACUTE LIVER FAILUREINTRODUCTION

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 hepatic failure, acute hepatic necrosis, fulminant hepatic necrosis, and fulminant hepatitis.

DEFINITION

ACUTE LIVER FAILUREDEFINITIONACUTE LIVER FAILURE REFERS TO THE DEVELOPMENT OF

AND

IN A PATIENT WITHOUT CIRRHOSIS OR PREEXISTING LIVER DISEASE

ENCEPHALOPATHY

impaired synthetic function (INR of ≥1.5)

< 26 WEEKS

SEVERE ACUTE LIVER INJURY

ACUTE LIVER FAILUREDEFINITIONA NUMBER OF OTHER TERMS HAVE BEEN USED FOR THIS CONDITION, INCLUDING FULMINANT HEPATIC FAILURE AND FULMINANT HEPATITIS OR NECROSIS.One categorization based on clinical patterns and outcome described 3 groups based on the time interval between the onset of jaundice and encephalopathy:(8 weeks to 6 months)

A.Hyperacute liver failure (7 days or less),

B.ALF (8 to 28 days), and C.Subacute liver failure (4 to 24

weeks)

ETIOLOGY&

EPIDEMIOLOGY

ACUTE LIVER FAILUREETIOLOGY AND EPIDEMIOLOGY

ACUTE LIVER FAILUREETIOLOGY AND EPIDEMIOLOGY

THREE PATTERNS OF ALF ARE ASSOCIATED WITH DRUGS: 1. DOSE-RELATED,2. IDIOSYNCRATIC, AND 3. HYPERSENSITIVITY REACTIONSdrug-induced liver

injury (DILI)46% were antimicrobials and 15% were central nervous system agents

The mortality rate was 3% to 4%

ACUTE LIVER FAILUREETIOLOGY AND EPIDEMIOLOGYSOME DRUGS, HERBAL PRODUCTS, AND TOXINS ASSOCIATED WITH ACUTE LIVER FAILURE

Abacavir Comfrey He Shon Wu MDMA (Ecstasy) Pyrazinamide

Acetaminophen (paracetamol) Dapsone Herbalife® Methamphetam

ine Rifampin

Alcohol Didanosine Hydroxycut®Monoamine oxidase inhibitors

Senecio

Allopurinol Dideoxyinosine Isoflurane Methyldopa StatinsAmiodarone Disulfiram Isoniazid Nicotinic acid SulfonamidesAmoxicillin Doxycycline Itraconazole Nitrofurantoin TerbinafineAspirin Efavirenz Kava Kava NSAIDS Tetracycline

Carbamazepine Gemtuzumab Ketoconazole Phenprocoumon Tolcapone

Carbon tetrachloride Gold Labetalol Phenytoin Tricyclic

antidep.

Ciprofloxacin Greater celandine LipoKinetix®

Poison mushrooms (Amanita phalloides)

Valproic acid

Cocaine Halothane Ma Huang Propylthiouracil

ACUTE LIVER FAILUREETIOLOGY AND EPIDEMIOLOGY: DRUGSACETAMINOPHEN

-PARTIALLY DOSE-DEPENDENT HEPATOTOXINWITH MORTALITY HIGHEST AT DOSES EXCEEDING 48G

- INCREASED SUSCEPTIBILITY TO ACETAMINOPHEN TOXICITY:

a) Antiepileptic therapy, b) Regular alcohol consumption, and c) Malnutrition

-DIRECT TOXIN TO OTHER ORGANS- N-ACETYLCYSTEINE AS ANTIDOTE IN

16HOURS- MOST COMMON CAUSE OF ALF IN THE UNITED

KINGDOM AND THE UNITED STATES

ACUTE LIVER FAILUREETIOLOGY AND EPIDEMIOLOGY: IDIOSYNCRATIC REACTIONS (DILI)

THE DIAGNOSIS OF DILI IS MADE WHEN THERE IS A TEMPORAL RELATIONSHIP

(DRESS)- DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS

ACUTE LIVER FAILURE

ACUTE LIVER FAILURE

ACUTE LIVER FAILUREETIOLOGY AND EPIDEMIOLOGYVIRAL INFECTIONS1) 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

ACUTE LIVER FAILUREETIOLOGY AND EPIDEMIOLOGY: RARE CAUSES

1. PREGNANCY-RELATED ACUTE LIVER FAILURE--- 0.0008%, 1S T PREG AND MALE FETUS- ALF of pregnancy, preeclampsia, and the HELLP syndrome

2. VASCULAR CAUSES- Hepatic vein thrombosis, or Budd-Chiari syndrome

3. HYPERTHERMIA-cause may be a drug reaction

4. AUTOIMMUNE HEPATITIS- strongly positive autoantibodies and elevated serum IgG

5. WILSON DISEASE- alkaline phosphatase: total bilirubin= < 4 - AST: ALT = > 2.2

6. MUSHROOM POISONINGSevere diarrhea and vomiting , ALF in 4-5 days

ACUTE LIVER FAILUREETIOLOGY AND EPIDEMIOLOGYHYPOPERFUSION

HYPOPERFUSION OF THE LIVER CAN RESULT IN ISCHEMIC HEPATITIS AND ACUTE LIVER FAILURE.

HYPOPERFUSION MAY RESULT FROM:1. SYSTEMIC HYPOTENSION DUE TO CAUSES

SUCH AS CARDIAC DYSFUNCTION, SEPSIS, OR DRUGS.

2. BUDD-CHIARI SYNDROME (HEPATIC VEIN THROMBOSIS),

3. VENO-OCCLUSIVE DISEASE , OR 4. THE USE OF VASOCONSTRICTING DRUGS

SUCH AS COCAINE AND METHAMPHETAMINE. 

CLINICALMANIFESTAT

IONS

ACUTE LIVER FAILURECLINICAL MANIFESTATIONSSYMPTOMS

●FATIGUE/MALAISE●LETHARGY●ANOREXIA●NAUSEA AND/OR VOMITING●RIGHT UPPER QUADRANT PAIN●PRURITUS●JAUNDICE●ABDOMINAL DISTENSION FROM ASCITES

ACUTE LIVER FAILURECLINICAL FEATURES

●ENCEPHALOPATHY●INTRACRANIAL HYPERTENSION AND CEREBRAL EDEMA●HEMODYNAMIC CHANGES AND CIRCULATORY FAILURE●INFECTION●RENAL FAILURE●HEMATOLOGIC ABNORMALITIES

ACUTE LIVER FAILURECLINICAL FEATURES:

ENCEPHALOPATHY-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

ACUTE LIVER FAILURECLINICAL MANIFESTATIONSPHYSICAL EXAMINATION FINDINGS

ACUTE LIVER FAILURECLINICAL FEATURES: INTRACRANIAL HYPERTENSION AND CEREBRAL EDEMA

CEREBRAL EDEMA: HALLMARK COMPLICATION OF ALF, MAJOR CAUSE OF DEATH, AND THREAT TO SUCCESSFUL LTDEVELOPED IN UP TO 80% OF PATIENTS WITH GRADE 3 TO 4 ENCEPHALOPATHY

ACUTE LIVER FAILURECLINICAL FEATURES: INTRACRANIAL HYPERTENSION AND CEREBRAL EDEMATHE CLINICAL FEATURES OF CEREBRAL EDEMA

1. systemic hypertension, 2. decerebrate posturing, 3. hyperventilation, 4. Abnormal pupillary reflexes, and ultimately impairment of

brainstem reflexes and functions

The outcome with medical management is usually either

full recovery or death

ACUTE LIVER FAILURECLINICAL FEATURES:INTRACRANIAL HYPERTENSION AND CEREBRAL EDEMA

ACUTE LIVER FAILURECLINICAL FEATURES:HEMODYNAMIC CHANGES AND CIRCULATORY FAILURE

Hyperdynamic circulation

• increased cardiac output, and reduced systemic peripheral vascular resistance

Circulatory failure

• falling cardiac output• inability to maintain an adequate

mean arterial pressure

Cardiac arrhythmias

• hypo- or hyperkalemia, acidosis, • hypoxia, or• cardiac irritation by a central venous

catheter.

ACUTE LIVER FAILURECLINICAL FEATURES:INFECTION- 2X THE RISK- COMMON CAUSE OF DEATH- DEFECTIVE NEUTROPHIL FUNCTION- GRADE 2 & UP, 80% BACTERIAL, 32% FUNGAL- CULTURE SOURCES

- Blood, Urine, sputum and vascular cannulae- PREDOMINANT BACTERIA

- Staphylococcus aureus, Streptococci, and coliform bacteria

- RISK FACTORS FOR BOTH BACTERIAL AND FUNGAL SEPSIS INCLUDE:- coexisting renal failure, - cholestasis, - treatment with a barbiturate, and - Liver transplant

ACUTE LIVER FAILURECLINICAL FEATURES:RENAL FAILURE- 75% OF PATIENTS FOLLOWING AN

ACETAMINOPHEN OVERDOSE- 30% OF PATIENTS WITH OTHER ETIOLOGIES- RENAL FAILURE AFTER AN ACETAMINOPHEN

- direct renal toxicity and - develops early in the course of the illness and - in parallel with liver injury

- EARLY RENAL DYSFUNCTION MAY ALSO BE SEEN IN- Wilson disease, - mushroom poisoning, and - pregnancy-related syndromes

ACUTE LIVER FAILURECLINICAL FEATURES:

RENAL FAILURE- NON-ACETAMINOPHEN CASES,

PROGRESSING FROM A STAGE OF:- functional, or prerenal, - failure (urinary sodium < 10 mmol/L,

urine/plasma osmolarity ratio > 1.1) - to acute tubular necrosis

ACUTE LIVER FAILURECLINICAL FEATURES:

HEMATOLOGIC ABNORMALITIES-DECREASED CIRCULATING LEVELS OF FIBRINOGEN, PROTHROMBIN, AND FACTORS V, VII, IX, AND X - PARAMETERS:

- prothrombin time, the INR and the individual factor levels- EVIDENCE OF INCREASED PERIPHERAL

CONSUMPTION- OVERT DIC OBSERVED IN PREGNANCY-RELATED

SYNDROMES- DECREASED ANTICOAGULANT PROTEINS:

- proteins C and S, antithrombin- RISK OF BLEEDING IS MUCH MORE CLOSELY LINKED

TO THE PLATELET COUNT- INCREASED LEVELS OF CIRCULATING VON

WILLEBRAND FACTOR

ACUTE LIVER FAILURECLINICAL FEATURES:

HEMATOLOGIC ABNORMALITIES

- PLATELET COUNTS BELOW 100,000/MM3 ARE SEEN IN UP TO 70% OF PATIENTS- A COOMBS-NEGATIVE HEMOLYTIC ANEMIA

IS A CHARACTERISTIC OF WILSON DISEASE- COOMBS-POSITIVE HEMOLYTIC ANEMIA

MAY BE SEEN IN ALF ASSOCIATED WITH AUTOIMMUNE HEPATITIS

- ERYTHROHEMOPHAGOCYTOSIS- POOR PROGNOSIS

DIAGNOSIS

ACUTE LIVER FAILUREDIAGNOSIS

ACUTE LIVER FAILUREDIAGNOSIS

ACUTE LIVER FAILUREDIAGNOSISACUTE LIVER FAILURE IS DIAGNOSED BY DEMONSTRATING ALL OF THE FOLLOWING:

I. ELEVATED AMINOTRANSFERASES (often with abnormal bilirubin and alkaline phosphatase levels

II. HEPATIC ENCEPHALOPATHYIII.PROLONGED PROTHROMBIN

TIME (INR ≥1.5)

ACUTE LIVER FAILURELABORATORY TEST ABNORMALITIES●PROLONGED PROTHROMBIN TIME , RESULTING IN AN INR ≥1.5 (THIS FINDING IS PART OF THE DEFINITION OF ACUTE LIVER FAILURE AND THUS MUST BE PRESENT);

●ELEVATED AMINOTRANSFERASE LEVELS (OFTEN MARKEDLY ELEVATED)

●ELEVATED BILIRUBIN LEVEL

●LOW PLATELET COUNT (≤150,000/MM3)

ACUTE LIVER FAILUREOTHER LABORATORY TEST ABNORMALITIES●ANEMIA●ELEVATED SERUM CREATININE AND BLOOD UREA NITROGEN●ELEVATED AMYLASE AND LIPASE●HYPOGLYCEMIA●HYPOPHOSPHATEMIA●HYPOMAGNESEMIA●HYPOKALEMIA●ACIDOSIS OR ALKALOSIS●ELEVATED AMMONIA LEVEL●ELEVATED LACTATE DEHYDROGENASE (LDH) LEVEL

ACUTE LIVER FAILURELABORATORY FINDINGS ASSOCIATED WITH SPECIFIC DIAGNOSES:ACETAMINOPHEN: • VERY HIGH AMINOTRANSFERASE LEVELS

(>3500 INT. UNIT/L), • LOW BILIRUBIN, • HIGH INR

ISCHEMIC HEPATIC INJURY: • VERY HIGH AMINOTRANSFERASE LEVELS (25

TO 250 TIMES THE UPPER LIMIT OF NORMAL), • ELEVATED SERUM LDH LEVELS

HEPATITIS B: • AMINOTRANSFERASE LEVELS OF TO 1000 TO

2000 INT. UNIT/L • ALT>AST

ACUTE LIVER FAILURELABORATORY FINDINGS ASSOCIATED WITH SPECIFIC DIAGNOSES:

WILSON DISEASE: • COOMBS-NEGATIVE HEMOLYTIC ANEMIA, • AMINOTRANSFERASE LEVELS <2000 INT. UNIT/L, • AST:ALT >2, • NORMAL OR MARKEDLY SUBNORMAL ALKALINE

PHOSPHATASE (<40 INT. UNIT/L), • ALKALINE PHOSPHATASE (INT. UNIT/L) TO TOTAL

BILIRUBIN (MG/DL) RATIO <4, • RAPIDLY PROGRESSIVE RENAL FAILURE, • LOW URIC ACID LEVELS

ACUTE FATTY LIVER OF PREGNANCY/HELLP SYNDROME: • AMINOTRANSFERASE LEVELS <1000 INT. UNIT/L, • ELEVATED BILIRUBIN, • LOW PLATELET COUNT

ACUTE LIVER FAILURELABORATORY FINDINGS ASSOCIATED WITH SPECIFIC DIAGNOSES:

HERPES SIMPLEX VIRUS : • MARKEDLY ELEVATED TRANSAMINASES, • LEUKOPENIA, • LOW BILIRUBIN

REYE SYNDROME, VALPROATE TOXICITY, OR TETRACYCLINE TOXICITY: • MINOR TO MODERATE ELEVATIONS IN

AMINOTRANSFERASE AND BILIRUBIN LEVELS

APPROACH TO

MANAGEMENT

ACUTE LIVER FAILUREAPPROACH TO MANAGEMENTOVERALL STRATEGY

- SURVIVAL RATES IN ALF HAVE IMPROVED DRAMATICALLY

- OVER 60% OF PATIENTS CAN BE EXPECTED TO SURVIVE THE ILLNESS

- THE KING’S COLLEGE HOSPITAL EXPERIENCE FROM 1973 TO 2008 - improvement in care and Liver Transplant - increase in overall survival from 16.7% to

62.2%, with rates of- 86% for those undergoing LT and - 48% for those managed medically

- TIME IS OF THE ESSENCE

ACUTE LIVER FAILUREAPPROACH TO MANAGEMENT: OVERALL STRATEGY

ACUTE LIVER FAILUREAPPROACH TO MANAGEMENTGENERAL MEASURES- ADEQUATE FLUID RESUSCITATION- PARENTERAL VITAMIN K- N-ACETYLCYSTEINE,

- within 15 hours - No benefit for non-acetaminophen ALF- transplant-free survival was significantly better in

patients with grade 1 to 2 encephalopathy - FAST-ACTING ANTIVIRAL DRUGS EFFECTIVE

AGAINST HBV - SILYMARIN- MUSHROOM POISONING- D-PENICILLAMINE – WILSON’S- GLUCOCORTICOID THERAPY – NO BENEFIT

DIFFERENTIAL

DIAGNOSIS

ACUTE LIVER FAILUREDIFFERENTIAL DIAGNOSISA) SEVERE ACUTE HEPATITIS

THE PRIMARY ENTITY IN THE DIFFERENTIAL DIAGNOSIS

HAVE JAUNDICE AND COAGULOPATHY BUT LACK SIGNS OF HEPATIC ENCEPHALOPATHY

B) NEUROLOGIC WILSON DISEASE PRESENCE OF DYSARTHRIA, DYSTONIA, TREMORS,

OR PARKINSONISMBEEN PRESENT PRIOR TO THE ONSET OF THE

HEPATIC MANIFESTATIONS

C) SEVERE ACUTE ALCOHOLIC HEPATITIS OVER THE COURSE OF WEEKS TO MONTHS AST:ALT 2:1DOES NOT EXCLUDE OTHER CAUSES OF ALF

TREATMENT OF

COMPLICATIONS

ACUTE LIVER FAILURETREATMENT OF COMPLICATIONS: NEUROLOGIC

- PROTECTION OF THE PATIENT’S AIRWAY, AND - ENDOTRACHEAL INTUBATION AND MECHANICAL VENTILATION ARE INDICATED ONCE GRADE 3 ENCEPHALOPATHY DEVELOPS- ADEQUATE ANALGESIA AND SEDATION ARE REQUIRED

-PROPOFOL AND FENTANYL - REDUCTION OF THE RISK OF CEREBRAL EDEMA

ARE INSTITUTED- EXPERIMENTAL APPROACHES (NO SURVIVAL

BENEFIT)- branched-chain amino acids, - the benzodiazepine antagonist flumazenil, and- extracorporeal liver support devices

ACUTE LIVER FAILURETREATMENT OF COMPLICATIONS: NEUROLOGIC

- THE MAIN NEUROLOGIC COMPLICATION AMENABLE TO THERAPY IS CEREBRAL EDEMA- Mannitol- hypertonic saline (3%)

- HYPERVENTILATION - ONLY BE USED AS AN EMERGENCY MEASURE IN REFRACTORY CASES

- HYPOTHERMIA (BODY TEMPERATURE REDUCED TO 32° TO 33°C)

- PHENOBARBITAL (OR SODIUM THIOPENTAL) AND IV INDOMETHACIN

- HEPATECTOMY

ACUTE LIVER FAILURETREATMENT OF COMPLICATIONS:

INFECTION-PROPHYLACTIC ANTIBIOTICS

- REDUCTION IN INFECTION RATES - NO BENEFIT

- SMALL BOWEL DECONTAMINATION - Not effective

ACUTE LIVER FAILURETREATMENT OF COMPLICATIONS:

HEMODYNAMIC INSTABILITY AND HYPOXEMIA

- INVASIVE HEMODYNAMIC MONITORING- COLLOID, CRYSTALLOID FLUIDS, AND BLOOD PRODUCTS- VASOPRESSORS

- may cause or aggravate hypoxia- epoprostenol (prostacyclin) infused at a rate of 5 ng/kg/min when

used in conjunction with both norepinephrine and epinephrine

- HYDROCORTISONE- For inotropic resistant, hypoadrenal profile- cosyntropin stimulation test or short tetracosactide test

ACUTE LIVER FAILURETREATMENT OF COMPLICATIONS:

RENAL FAILURE

• AN EARLY FLUID CHALLENGE IS INDICATED IN PATIENTS IN WHOM OLIGURIA OR BIOCHEMICAL EVIDENCE OF RENAL DYSFUNCTION DEVELOPS

• EXTRACORPOREAL RENAL SUPPORT HAS BEEN REQUIRED • 75% of cases of acetaminophen-induced ALF • 30% of cases due to other

• EARLY INTERVENTION WITH HEMODIALYSIS

ACUTE LIVER FAILURETREATMENT OF COMPLICATIONS: COAGULOPATHYFRESH FROZEN PLASMA - PROPHYLACTIC REPLETION

- failed to demonstrate an improvement in survival and - was thought to be detrimental in a minority of patients- interferes with the use of coagulation studies - fluid overload and - hyperviscosity syndrome

- RECOMBINANT FACTOR VIIA - Limited data

- > 50,000 TO 70,000/MM3 PLATELETS - has been recommended

ACUTE LIVER FAILURETREATMENT OF COMPLICATIONS: METABOLIC DISORDERS- HYPOGLYCEMIA

- mistaken for the onset of advanced encephalopathy- METABOLIC ACIDOSIS

- acetaminophen overdose, high mortality of at least 90% if the arterial pH is below 7.30 on the second or subsequent days after the overdose

- HYPERLACTATEMIA- HYPOKALEMIA

- Associated with alkalosis- HYPONATREMIA

- Vomiting, dilutional, intracellular sodium shifts- HYPOPHOSPHATEMIA

- acetaminophen-induced ALF - HYPOMAGNESEMIA

ACUTE LIVER FAILURETREATMENT OF COMPLICATIONS:

NUTRITIONAL DEFICIENCIES- CATABOLIC PROCESS CAN BE PROFOUND- INFLUENCED BY THE THEORETICAL ROLE OF

AMINO ACID RATIOS IN MEDIATING ENCEPHALOPATHY

- ENTERAL NUTRITION IS DESIRABLE - FEEDING IS NORMALLY COMMENCED

WITHIN 24 HOURS OF ADMISSION TO AN ICU

- GOAL OF 25 TO 30 KCAL/ KG/DAY

PROGNOSIS

ACUTE LIVER FAILUREPROGNOSISOVERALL SURVIVAL RATES >60%40% OF PATIENTS SURVIVES W/O NEEDING LT THREE IMPORTANT DETERMINANTS OF OUTCOME - UNDERLYING ETIOLOGY OF ALF, - AGE OF THE PATIENT, AND - GRADE OF ENCEPHALOPATHY

EARLY INDICATOR OF A POOR PROGNOSIS JAUNDICE FOR MORE THAN 7 DAYS BEFORE THE ONSET

OF ENCEPHALOPATHY

MOST SPONTANEOUS SURVIVORSHYPERACUTE CATEGORY OF ALF

ACUTE LIVER FAILUREPROGNOSISPROGNOSTIC MODELS1) KING’S COLLEGE HOSPITAL CRITERIA2) THE CLICHY CRITERIA3) THE MELD SCORE4) SERUM BILIRUBIN, SERUM LACTATE, AND

ETIOLOGY (GERMANY)5) ACUTE LIVER FAILURE STUDY GROUP

INDEX6) THE APACHE II SCORE AND SEQUENTIAL

ORGAN FAILURE ASSESSMENT (SOFA) INDEX

ACUTE LIVER FAILUREPROGNOSIS

LIVER TRANSPLANTATION

LIVER TRANSPLANTATION

LIVER TRANSPLANT IS ONE OF THE MAIN REASONS WHY SURVIVAL RATES FOR ALF HAVE INCREASED FROM LESS THAN 20% IN THE 1970S TO OVER 60% IN THE 2010S

THE DECISION TO PROCEED WITH LIVER TRANSPLANTATION DEPENDS UPON THE PROBABILITY OF SPONTANEOUS HEPATIC RECOVERY

EXTRACORPOREAL LIVER SUPPORTATTEMPTS TO IMPROVE SURVIVAL IN ALF USING EXTRACORPOREALLIVER SUPPORT DEVICES EXTEND BACK TO THE 1970S1. THE EXTRACORPOREAL LIVER ASSIST DEVICE

(ELAD) SYSTEM,2. BASED ON C3A HEPATOCYTES3. THE BIOARTIFICIAL LIVER (BAL) BASED ON PORCINE

HEPATOCYTES4. MOLECULAR ADSORBENTS RECIRCULATING SYSTEM

[MARS]5. SINGLEPASS ALBUMIN DIALYSIS [SPAD]6. CHARCOAL OR RESIN HEMOFILTRATION7. PLASMAPHERESIS

ACUTE LIVER FAILUREDIAGNOSISACUTE LIVER FAILURE IS DIAGNOSED BY DEMONSTRATING ALL OF THE FOLLOWING:

I. ELEVATED AMINOTRANSFERASES (often with abnormal bilirubin and alkaline phosphatase levels

II. HEPATIC ENCEPHALOPATHYIII.PROLONGED PROTHROMBIN

TIME (INR ≥1.5)

THANK YOU

CASE• Managed with:

• Hydration• N acetyl-cysteine Infusion

• KCL drip• Lactulose enema

• Meds:• Lactulose• KCL durule• Omeprazole• UDCA• Phospholipids• Rifaximin

CASE• Discharged with

• Take home Meds:• Lactulose• KCL durule• Omeprazole• UDCA• Phospholipids

ACUTE LIVER FAILUREAPPROACH TO MANAGEMENTOVERALL STRATEGY

ACUTE LIVER FAILUREDEFINITION