Acute Liver Failure - ALFAcute Liver Failure - ALF

Yaakov Maor M.DYaakov Maor M.D..

Department of Gastroenterology and HepatologyDepartment of Gastroenterology and Hepatology

Sheba Medical Center, Tel-HashomerSheba Medical Center, Tel-Hashomer

פרשת מקרה

, יליד ישראל51בן

חודשים בהודו6מנכ"ל חברה נימצא •

שבועות הרגשה רעה, חוסר תיאבון, בחילות3•

לפני שבועיים שתן כהה ובהמשך צהבת•

מיומיים "שינוי בהתנהגות" וישנוניות•

הוטס לארץ ישירות לחדר מיון•

פרשת מקרהבבדיקה:

ישנוני אך ניתן להערה•

c37.3, חום 100/60 לדקה, ל"ד 100דופק •

צהבת בולטת בלחמיות ובעור•

Flapping Tremorרעד מסוג •

ללא סימני מחלת כבד כרונית•

בטן רכה, הכבד נמוש בקצהו, הטחול אינו •מוגדל

פרשת מקרהבבדיקות מעבדה:

•Bilirubin-15 mg/dL•ALT-1800 IU/L; AST-1200 IU/L; ALP-220 IU/L•Glucose-80 mg/dL; Creatinine-1.2 mg/dl•INR-2.9•Hb-12.8 g/dL; WBC-4,300; PLT-133,000•pH-7.43; Lactate-21 mg/dL•Ammonia-90 µg/dL

Acute Liver Failure• Definition – Accurate diagnosis of the syndrome

• Etiology – Determine prognosis and specific treatment

• Initial resuscitation and treatment of complications

• Timely transfer to a Transplant Center!!!

Definition

• Rapid development of hepatocellular dysfunction – Coagulopathy (INR 1.5), Jaundice • Encephalopathy!!! • Absence of a prior history of liver disease (Wilson’s disease, autoimmune hepatitis)

Definition

• Interval between the onset of illness and ALF <26 weeks (US ALF Study Group)

• Jaundice-to-encephalopathy interval (Prognosis): - Hyperacute liver failure – Within 7 days

- Acute liver failure – 7 – 21 days

- Subacute liver failure – 21 days – 26 weeks

Etiology

• Viral infection – HAV, HBV (HDV), HCV?, HEV

• Acetaminophen – Predictable, Direct (ETOH)

• Idiosyncratic Hepatotoxicity – Halothane, Anti-TB

• Idiopathic (15-44%) – Occult viral infection?

• Rare: Autoimmune hepatitis, Wilson’s disease, Budd-Chiari syndrome, Pregnancy related, Toxins - Amanita Phalloides, Cancer

•

0

20

40

60

80

100

120

140

160

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Wils

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B.C

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Tx. Free survival

Transplanted

Died Before Tx.

68%

50% 50%

13%

0%0% 25%11%

50%

12%

63%

17%

Transplant-Free Survival Rate

Unfavorable • Idiopathic• Drugs (not ACPA)• HBV (acute on chronic)• Wilson

Transplant-free survival –

11% (0-25%)

Etiology

Etiology-Specific Therapies

• Acetaminophen - N-Acetylcysteine

• Hepatitis B – Lamivudine

• Pregnancy-associated – Urgent delivery

• Budd-Chiari syndrome - Angioplasty

• Amanita Phalloides - Penicillin, Silibinin

פרשת מקרה

Anti HAV IgMלחולה נימצאו נוגדנים: •

חריפה!Aאובחנה הפטיטיס •

Natural History of ALF:N

ause

a

Jaundic

e

LFT’s

Coagulo

path

y

DEATH

Acute Hepatitis SIRSAcute Liver Dysfunction

Acute Liver Failure

Ence

phalo

path

y H

ypogly

cem

ia M

. aci

dosi

s

Infe

ctio

n M

O F

Cere

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החייאה וניהול ראשוני – ביחידה לטיפול ניטור מצב הכרה וסימנים חיוניים • נמרץ

החייאת נוזלים ומעקב תפוקת שתן• מעקב ומתן גלוקוז - היפוגליקמיה•אנזימי כבד • כולל: מעקב בדיקות דם•

בילירובין• גלוקוז• קראטינין ואלקטרוליטים•• INRפקטור ,V לקטט• גאזים• אמוניה עורקית• ס.ד•

Encephalopathy – Precipitating Factors

Non-neurological:• Sepsis and SIRS!

• Hypoglycemia • Hypoxemia

• Renal failure

Neurological:• Occult seizures - 33% stage 3 – 4 encephalopathy

• Cerebral edema

Stages of Encephalopathy

• Stage 1 – Affect, insomnia, concentration • Stage 2 - Drowsiness, disorientation, confusion, Agitation! Asterixis appears • Stage 3 - Marked somnolence and incoherence • Stage 4 - Coma

Encephalopathy - Management• Quient enviroment! • Maintain the patient's head at a 30° to improve jugular venous outflow

• Sedative-hypnotic drugs should be avoided – Clinical monitoring – Use Propofol!!!

• Treat reversible conditions e.g., hypoglycemia

• Patients encephalopathy stage 3 – 4 – intubation: - airway protection - Intra Cranial Pressure – ICP

Encephalopathy - Management

• Brain CT - Mass, intracranial hemorrhage, and evidence of brainstem herniation • Correlation between CT evidence of cerebral edema ande ICP is imperfect • Monitor and treat deeply sedated patients with phenytoin for sub-clinical seizure?

ICP Monitoring

• Most accurate way to detect intracranial hypertension

• Should be limited to specialized units and to patients awaiting LTS with stage 3 – 4 encephalopathy

• Has not been shown to increase survival • Aims: - ICP <20-25 mm Hg - Cerebral perfusion pressure (CPP) = Mean Arterial Pressure (MAP) – Intra Cranial Pressure (ICP) >50-60 mm Hg

ICP Monitoring

• Requires correction of underlying coagulopathy – Prognostic factor • Portal of entry for infectious organisms • Can precipitate intracranial hemorrhage • Trans-cranial Doppler has not been validated for ICP monitoring

Treatment of ICP

• Osmotherapy Mannitol – IV bolus of 0.5 to 1 g/kg 20% solution – May be repeated until plasma osmolarity reaches 320m Osm/L • Therapy with mannitol requires preserved renal function (or hemofiltration)

• Hypertonic NaCl 30% – Maintain serum Na+ levels of 145-155 mEq/L

Treatment of ICP

• Hyperventilation - Cerebral vasoconstriction - CBF

• New therapies: - N-Acetylcysteine (In non-acetaminophen ALF) Recently: Patients with early encephalopathy showed higher spontaneous survival rate

- Mild hypothermia (32C - 34c) ICP via CBF

• Not in use !!! - Lactulose – No proven benefit

- Barbiturate

Coagulopathy

• Avoid plasma/PLT administration: - Index of hepatic function - Volume overload

• Indications: - Bleeding - Invasive procedures - Prophylactic: PLT count <20,000; INR >7

• aFVII may be advantageous

Coagulopathy

• Monitor INR q 6-12 h (Obtain Factor V when INR> 2.5)

DayINR

# 23

# 3 4

# 4 5

Transfer to transplant Center

InfectionsInfections

• Develop in 80% of patients

• Accounts for 25% of patients who are excluded from liver transplantation

• Clinical recognition of infection is difficult: SIRS may occur without infection

• Infection may be without fever/leukocytosis in 30%

• High level of suspicion for infection should be maintained with a low threshold for administration of antibiotics!!!

Management - General

• ICU admission and supportive treatment • Timely transfer to a Transplantation Center • Liver transplantation – The Only Established & Definitive Treatment

Predictors of Prognosis

Patients with ALF fall into two categories: • Intensive medical care enables recovery of hepatic function – Allow time for regeneration!!! • Require liver transplantation to survive

Predictors of PrognosisPredictors of Prognosis

Determinant of prognosis: • Regeneration

• Liver dysfunction

• Encephalopathy and Brain edema

• Multi-Organ Failure – MOF

Predictors of PrognosisPredictors of Prognosis

Avoid the following two scenarios: • Death of the patient despite intensive medical care without consideration of transplantation

• Unnecessary liver transplantation when recovery would have occurred spontaneously – Surgical mortality, lifelong immunosuppression

Liver Transplantation

• Clinical decision making aided by prognostic markers

• Before the era of liver transplantation – <50% survival

• Liver transplantation for ALF – 63% - >70% (Lower than other etiologies)

King’s College Hospital Criteria

ALF secondary to acetaminophen overdose:

• pH <7.30 (irrespective of encephalopathy grade) or

• Hepatic encephalopathy grade III-IV• INR >6.5 • Creatinine >3.4 mg/dL

• Arterial Lactate >27 mg/dL

King’s College Hospital Criteria

ALF with other causes:

• INR >6.5 (irrespective of encephalopathy grade)

or any three of the following ) irrespective of encephalopathy grade(

• Age <10 or >40 years• Non-A, non-B hepatitis or drug-induced origin• Duration of jaundice before encephalopathy >7 days• Bilirubin >17.6 mg/dL• INR >3.5  

Clichy CriteriaClichy Criteria

Stage III-IV encephalopathy associated with:

• Factor V level <20% in patients <30 years

• Factor V level <30% of normal in patients >30 years

(Based on cohort of patients with acute hepatitis B)

Predictors of Prognosis

• Model for End-Stage Liver Disease (MELD) Score – (Bilirubin; INR; Creatinine)

• Elevated Alpha-Fetoprotein (Indicator of regeneration)

• APACHE II

Liver Transplantation • Contraindications to transplantation:

- Irreversible brain damage (CPP <40 mm Hg) - Active extra-hepatic infection - Multiple-organ failure syndrome – MOF

• Consider living-related liver transplantation

פרשת מקרה

מ"ג לק"ג N-Acetylcysteine 6הוחל טיפול ב- •לשעה

אבל...

II-IIIמצב הכרה – ישנוני יותר – שלב אנצפלופתי •

Propofolהונשם ומקבל •

•INR -פקטור ;6 עלה ל V- 15%

mg/dl 1.9קראטינין עלה ל- •

העברה למרכז השתלות

קשר טלפוני ראשוני •

:העברה כאשר • אנצפלופתיה דרגה •IIחמצת, לקטטמיה, • היפוגליקמיה• קואגולופתיה •

מטפסת

Intensive careEtiology – specific Rx.Consultation with LTS center

Contraindication for LTS

No

YesContinue intensive support

Transfer to LTS center – National

status oneRe-assess for recovery or

contraindication for LTS

Ongoing intensive

care

Liver Transplantation

No

Yes

פרשת מקרה

נוצר קשר עם מרכז השתלות בבלגיה•

הועבר בהטסה להמתנה להשתלת כבד•

Experimental Therapy • Provide a bridge to liver transplantation/ Spontaneous regeneration and recovery

• Auxiliary liver transplantation

• Extracorporeal liver support devices: - Hemodiadsorption systems - Bioartificial liver devices

• Nonhuman liver transplantation

• Hepatocyte transplantation