אי ספיקת כבד חריפה acute liver failure

חריפה כבד ספיקת איAcute Liver Failure

ספדי' ריפעת פרופכבד למחלות היחידה מנהל

" , " ם י כ ע הדסה רפואי מרכז17/2/2013

[email protected]

אי ספיקת כבד חריפהAcute Liver Failure (ALF)

FULMINANT HEPATIC FAILURE:

(FHF)

FULMINANT HEPATITIS:

(FH)


(FHF)

Definition:Definition: Acute hepatic failure within:

• 0-1 week (Hyperacute)• 1-4 weeks (Acute)• 4-12 weeks (Subacute)

Manifestations:Manifestations: Hepatic encephalopathy, INR↑

Hepatic Encephalopathy (HE)

HE is a serious & potentially fatal complication in: Acute liver failure Cirrhosis Portal-systemic Shunt w/o hepatocellular disease Metabolic Defects

Encephalopathy- Grades 1. Minor disturbances of consciousness or motor

function

2. Drowsy but responsive to commands

3. Stuporous but responsive to pain

4. Unresponsive to pain

Seizures may appear at any grade

HE spectrum: Minimal HE (MHE) to overt HE with risk of cerebral edema & death

West-Haven criteriaStage Consciousness Intellect and behavior Neurological findings

0 Normal Normal Normal examination; if impaired psychomotor testing, consider MHE

1 Mild lack of awareness

Shortened attention span Impaired addition or subtraction. Mild asterixis / tremor

2 Lethargic Disoriented; inappropriate behavior

Obvious asterixis; slurred speech

3 Somnolent but arousable

Gross disorientation; bizarre behavior

Muscular rigidity and clonus; hyperreflexia

4 Coma Coma Decerebrate posturing

Coagulopathy

• Low levels of coagulation factors:– Factor 2– Factor 7– Factor 9– Factor 10

• Disturbed vit. K absorption (cholestasis)

• Thrombocytopenia/pathia

FULMINANT HEPATIC FAILURE:MAJOR COMPLICATIONS:

• Cerebral edema• Bleeding• Sepsis• Renal failure• Respiratory failure• Metabolic acidosis• Hypoglycemia• Pancreatitis

•Acetaminophen •Drugs – prescription, recreational•Viral - HAV, HBV, HDV, HEV; CMV, EBV, VZV, HSV, Parvovirus,

Enteroviridae

•Poisoning – Amanita phalloides•Wilson’s disease•Autoimmune hepatitis•Acute fatty liver of pregnancy / HELLP•Budd Chiari Syndrome•Miscellaneous – Acute ischemic injury, malignant infiltration, sepsis.•Indeterminate

ETIOLOGY (With Therapeutic Implications)

AASLD Position Paper: The Management of Acute Liver FailurePolson & Lee, Hepatology 2005; 41: 1179-97

Prescribed medicines

“ACAMOL”


(FHF)

ETIOLOGY

Acetaminophen:

45% suicidal

55% accidental

ETIOLOGY – “OTHER”

FHF- Course:

Fulminant Fulminant HepatitisHepatitis

RecoveryRecovery

DeathDeath

TransplantationTransplantation

Which patients are LT candidates?

ALF

Etiology

Clinical course

Deterioration?

LTx

King’s College Criteria

Progression rate

Rating Scheme for the Strength of the Evidence

Grade I:Grade I: Randomized controlled trials

Grade II-1:Grade II-1: Controlled trials w/o randomization

Grade II-2:Grade II-2: Cohort/ case-control analytic studies

Grade II-3:Grade II-3: Multiple time series, dramatic uncontrolled

experiments

Grade III:Grade III: Opinions of respected authorities,

descriptive epidemiology

Decision-MakingDecision-Making

Diagnosis & Initial Evaluation

• ALF Patients should be admitted & monitored frequently, preferably in an ICU (Grade III).(Grade III).

• Contact with a transplant center & plans to transfer appropriate patients with ALF should be initiated early (Grade III).(Grade III).

• The precise etiology of ALF should be sought to guide further management decisions (Grade III).(Grade III).

דם בדיקות :ביוכימיה

' , ,' כליה ת סוכר אלקטרו TP Albumin: הפטוצליולרים כבד אנזימי ALT AST הפטוצליולרית הפרעה: כולסטטים כבד אנזימי GT ALK-Phos Bilirubin כוליסטטית הפרעה

' קרישה'/ ת סד :מיטבוליTSH Ferritin Ceruloplasmin 1AT ACE : נגיפית /סירולגיה לימפוטרופים היפטו נגיפים אמונית ANA AMA LKM ASMA ANCAסירולוגיה

ASCA IG PEP IEP CELIAC

דם בדיקות: ביוכימיה

' , ,' כליה ת סוכר אלקטרו TP Albumin: הפטוצליולרים כבד אנזימי ALT AST הפטוצליולרית הפרעה

: כולסטטים כבד אנזימי GT ALK-Phos Bilirubin כוליסטטית הפרעה

' /' קרישה ת סד :מיטבוליTSH Ferritin Ceruloplasmin 1AT ACE : נגיפית /סירולגיה לימפוטרופים היפטו נגיפים אמונית ANA AMA LKM ASMA ANCAסירולוגיה

ASCA IG PEP IEP CELIAC

לאבחון זמינים כליםהדמייה:

: חודרנית US /CT /MRI /MRCPלא : חודרנית/ ERCPחודרנית ± אנגיוגרפיה

ביופסיה

... אנדוסקופיות: דליות להערכת

... / עמוקות: מכוונות ביופסיות לפרוסקופיה



ביופסיה

... :אנדוסקופיות דליות להערכת

...לפרוסקופיה: / עמוקות מכוונות ביופסיות



ביופסיה

... אנדוסקופיות: דליות להערכת

... / עמוקות: מכוונות ביופסיות לפרוסקופיה

Role of transjugular liver biopsy in ALFHepatology 1993;18:1370

• 61 ALF pts., 2 to 82 yr, retrospectively analyzed.

• Transjugular biopsy was successful in 60/61.

• 8 minor complications managed conservatively.

• In 34/54 (63%), the presumed clinical diagnosis was confirmed by biopsy.

• In 11 (20%), biopsy clarifies clinical uncertainty

• In 9/54 (17%) the diagnosis was altered by biopsy

אי ספיקת כבד חריפהAcute Liver Failure (ALF)

FULMINANT HEPATIC FAILURE:(FHF)

טיפולTherapy

Hepatic Encephalopathy PathogenesisNHNH33

Hepatic Encephalopathy PathogenesisNHNH33

The Gut Microbiota The Gut Microbiota (Bacterial action)(Bacterial action)

& & Protein loadProtein load

The Gut Microbiota The Gut Microbiota (Bacterial action)(Bacterial action)

& & Protein loadProtein load

Failure to Failure to metabolize metabolize

NHNH33

NHNH33 Shunting Shunting GABA-BD GABA-BD receptorsreceptors

ToxinsToxins

HE TreatmentHE Treatment

↓ ↓ Gut NH3 production:Gut NH3 production: Adjust diet proteinAdjust diet protein Lactulose & Lactilol Lactulose & Lactilol AntibioticsAntibiotics ProbioticsProbiotics

↑ NH3 fixation in liver:• L-ornithine L-asprtate (LoLa)• BCAA • Benzoate

Shunt occlusion or Shunt occlusion or reductionreduction

Flumazenil

nMDR inhibition

Encephalopathy- Aggravating Factors

Gastrointestinal hemorrhageHypovolemiaPotassium depletionHypoglycemiaUremiaInfectionConstipationSedatives and anaestheticsHigh protein intake

Conservative management

Grade I/II Encephalopathy • Consider transfer/listing to liver transplant facility• Brain CTCT: rule out other causes• Avoid stimulation, avoid sedationavoid sedation• LactuloseLactulose: possibly helpful

Hemodynamics/Renal Failure

• Pulmonary artery catheterization • Volume replacement • Pressor support• Avoid nephrotoxic agents • Continuous modes of hemodialysis if needed • Vasopressin: not helpful; potentially harmful

Metabolic Concerns• Follow closely: glucose, K+, Mg++, Phosphate

• Consider nutrition: enteral feedings or TPN

Infection

• Periodic surveillance culturescultures to detect bacterial & fungal infections (Grades II-2, III).

• Antibiotic prophylaxis Antibiotic prophylaxis possibly helpful but not proven (Grades II-2, III).

Coagulopathy

• Replacement therapy (PLT/FFP): • only in the setting of hemorrhage • or prior to invasive procedures (Grade III).

Gastrointestinal (GI) Bleeding• Prophylaxis for bleeding associated with stress

(Grades I, III).

CNS & Intracranial Pressure Monitoring

Grade III/IV Encephalopathy • IntubateIntubate trachea • Consider placement of ICP monitoring• Immediate treatment of seizuresseizures required;

prophylaxis of unclear value • Mannitol:Mannitol: use for severe elevation of intracranial

pressure or first clinical signs of herniation • Hyperventilation:Hyperventilation: effects short-lived; may use for

impending herniation

Acetaminophen Hepatotoxicity

• With known/suspected overdose within 4h, give

activated charcoal just prior to NAC (Grade I).(Grade I).

• Begin NAC promptly in all patients where the quantity of acetaminophen ingested, serum drug level, or rising aminotransferases indicate impending or evolving liver injury (Grade II-1).(Grade II-1).

• NAC may be used in cases of ALF in which acetaminophen ingestion is possible or when knowledge of circumstances surrounding admission is inadequate

(Grade III).(Grade III).

NAC for non-acetaminophen-induced ALF

• MEDLINE search (1966-March 2003)• International Pharmaceutical Abstracts (1970-2003)• Cochrane Library (2003, issue 3) databases.

• All studies were small & do not provide conclusive do not provide conclusive

evidenceevidence that NAC benefits this subgroup of patients. • IV NAC should not be usedshould not be used routinely for treatment of non-acetaminophen-induced ALF.

Ann Pharmacother. 2004 Mar;38(3):498

Viral Hepatitis

HAV, HBV, HEV related ALF must be treated with supportivesupportive care (Grade III).

Lamivudine is safe in patients with severe acute or fulminant hepatitis B, leading to fast recovery with the potential to

prevent liver failure and liver transplantation when administered early enough.

1. Schmilovitz-Weiss H, et al. Lamivudine treatment for acute severe hepatitis B: a pilot study-15. Liver Int. 2004.

2. Tillmann HL, et al. Safety & efficacy of lamivudine in 17 patients with severe acute or fulminant HBV, a multicenter experience. J Viral Hepat. 2006.

Wilson's disease or AIH?

• Patients with AIH may be salvaged by steroid treatment.

• On the contrary, liver transplantation is currently the only life saving therapeutic option available for patients with WD who present with fulminant liver failure

Budd-Chiari Syndrome• BCS with hepatic failure is an indication for liver transplantation, provided underlying malignancy is excluded (Grade II-3).

Mushroom Poisoning

• Consider penicillin G & silymarin (Grade III). (Grade III).

• Should be listed for transplantation (Grade III).(Grade III).

Drug Induced Hepatotoxicity

• Obtain details concerning all drugs, herbs & dietary supplements taken (Grade III).

• Determine ingredients of non-prescription medications whenever possible (Grade III).

• Discontinue all but essential medications (Grade III)

• Steroids?

Kings College selection criteria for transplantation according to etiology of FLF


Aetaminophen:

Arterial pH< 7.3

Or

PT>100 sec & Serum Creatinine > µ300 mol/l when Encephalopathy grade III or IV.

Not Aetaminophen:

PT>100 sec (irrespective of Encephalopathy grade).

Or

Any 3 of the following (irrespective of Enceph. grade):

Age < 10 or > 50 years

Cryptogenic, halothane or other drug toxicity

Jaundice to Encephalopathy interval > 7 days.

Serum Bilirubin > 300 µmol/l


Waiting list:Waiting list:• Air Transportation• Liver support technology• Living related transplantation• Auxiliary liver transplantation

Long-distance transportation of Long-distance transportation of 4343 patients patients with liver diseases is safe & feasiblewith liver diseases is safe & feasible

Liver Transpl 2005;11:650Liver Transpl 2005;11:650 (Grade II-III).

USA, Germany (n=2) 4%

ALF- Referral Centers 1987-1998:Total 46 cases

US

A, C

hina

(n=2

) 10%

ALF- Referral Centers 1999-2006:Total 21

Liver Support Systems:

A variety of systems have been tested to date, with no certain evidence of efficacy.

Sorbent systems: Detoxification, no hepatocyte replacement.

• Such systems, may show loss of platelets & worsening of coagulation across the device.

• Transient improvement of encephalopathy may be observed but no long-term benefit

Hepatocytes (w or w/o sorbents):

• Few controlled trials

• Some reports suggest no benefit to outcome, ±transplantation (HEPATOL 1996;24:1446).

• A multi-center trial did report improved short-term survival with a porcine hepatocyte-based bioartificial liver (Ann Surg 2004;239:660).

• A recent meta-analysis, considering all forms of devices together: no efficacy for bio-artificial liver devices for the treatment of ALF (Kjaergard LL, et al. JAMA 2003;289:217).

Waiting list:• Air Transportation• Liver support technology• Living related transplantation• Auxiliary liver transplantation

Currently available liver support systems are not Currently available liver support systems are not recommended outside of clinical trials; their future recommended outside of clinical trials; their future

remains unclear remains unclear (Grades I, II-1).(Grades I, II-1).

אי ספיקת כבד חריפה acute liver failure

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