Acute Liver Failure Brian Kim - PowerPoint Presentation

Slide1

Acute Liver Failure

Brian Kim

USC Transplant Hepatology

October 16, 2018

Slide2

Definition

Acute liver failure (ALF) or fulminant liver failure is most commonly defined as the onset of encephalopathy within 26 weeks (or whatever threshold used) of development of jaundice

Liver injury with encephalopathy and impaired synthetic dysfunction (INR ≥ 1.5) in a patient without known cirrhosis or pre-

exisiting

liver disease

Exceptions can include patient with HBV, AIH, Wilson Disease, but not alcoholic liver disease

Slide3

Acute Liver Failure

Onset

of jaundice to encephalopathy

Hyper-acute

<

7 days

Acute

7-28

days

Sub-acute

5-26 weeks

Slide4

Acute Liver Failure is not

…

Acute on chronic liver failure or decompensated cirrhosis

Preexisting liver disease (cirrhosis)

Bleeding

Infection

Cancer

Acute alcoholic hepatitis

Acute liver injury

Jaundice +/- coagulopathy

Normal mental status

May deteriorate into ALF

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Acute Liver Failure vs. Decompensated Cirrhosis

ALF patients generally present with severe hepatic dysfunction

Hepatic encephalopathy as a result of hepatic necrosis/cytokine release

High INR as a result of hepatic necrosis

Decompensated cirrhotic patients generally present with portal hypertension complications

Variceal hemorrhage

Ascites

Hepatic

encepahlopathy

as a result of portosystemic shunting (macro vs. micro)

Can have considerable overlap

ALF can potentially have considerably higher mortality than patients with decompensated cirrhosis (more on this later)

Slide6

Acute liver failure

Approximately 2000 cases annually in the US

3/4 white

3/4 female

Median age 38 years

ALFSG

Slide7

Causes

Acetaminophen

Other drugs (>400 associated with ALF)

Augmentin

INH

Valproic

acid

Toxins

–

mushrooom

(Amanita

phalloides

)

Viral hepatitisHAVHBV +/- HDVHEVHSVAutoimmune hepatitisWilson diseaseBudd-ChiariShock liverHyperthermiaAcute fatty liver of pregnancyMalignant infiltrationHemophagocytic lymphohistiocytosis (HLH)Reye’s syndromeIndeterminate (15-20%)

Not causes of ALF

Alcohol

Hemochromatosis

NASH

HCV?

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Etiologies of ALF in the US (N=324)

ALFSG

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Clinical Presentation

Symptoms can be nonspecific

Fatigue

Nausea/vomiting

Abdominal pain

Confusion

Physical Exam

Alteration in mental status

Asterixis

, clonus

Evidence of liver injury on labs

Elevated AST/ALT, TB, INR

Renal failure

Pancytopenia

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Diagnostic Work-Up

Thorough history to obtain potential etiologies (

pmh

, family history, medication

hx

, ingestions,

etc

)

Physical exam

Find subtle mental status changes

Signs of underlying chronic liver disease

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Diagnostic Work-up

Labs

LFTs, INR

Viral

serologies

Acetaminophen level

Arterial ammonia

AFP,

phos

pH

Imaging

Ultrasound with

dopplers

Transjugular

liver biopsy

Slide12

Some Etiology Specific Therapies

Acetaminophen

activated charcoal if recent ingestion

N-acetyl-cysteine

HBV

lamivudine,

entecavir

or

tenofovir

HSV

acyclovir

Mushroom poisoning

silibinin

(milk thistle), penicillin G

Wilson diseaseplasmaphresis - temporizingAutoimmune hepatitissteroids?Pregnancy relateddelivery

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How do people die from ALF?

Cerebral edema

Infection/sepsis

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Hepatic encephalopathy

Part of the diagnosis of acute liver failure

Decreased ammonia and false neurotransmitter metabolism

Increased cytokine release from hepatic necrosis

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Grades of Encephalopathy

Changes in behavior with minimal change in level of consciousness

Gross disorientation, drowsiness, possibly

asterixis

, inappropriate behavior

Marked confusion; incoherent speech, sleeping most of the time but

arousable

to vocal stimuli

Comatose, unresponsive to pain, decorticate or

decerebrate

posturing

Slide16

Slide17

Cerebral Edema

Most serious complication of acute liver failure

Combination of cytotoxic and

vasogenic

edema

Osmotic disturbances from cytokine/toxin release

Increased blood flow from impaired cerebrovascular autoregulation

Lead to intracranial hypertension (ICH) with

uncal

herniation

Cerebral edema and ICH seen in 35% of patient with grade III and 75% in grade IV encephalopathy

CT imaging is rarely helpful early

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Cerebral Edema

Grade I/II

Close monitoring

Avoid all sedation

Questionable role of lactulose

–

may make liver transplant difficult

Grade III/IV

Intubation with sedation

Efforts to reduce intracranial pressure (ICP)

Elevated head of bed

Hyperventilation

Mannitol infusion

Hypertonic saline

CRRTHypothermiaICP monitoringCerebral perfusion pressure = MAP – ICP; goal ICP<20mmHg and keep CPP >60mHgcontroversial

Slide19

Infection

Patients at risk for bacterial and fungal infection

Empiric antibiotics do appear to reduce incidence of infection

Start empiric, broad spectrum antibiotics in all patients with hypotension and SIRS

Consider empiric antifungal coverage in patients renal failure

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Bleeding

Risk for DIC/

hyperfibrinolysis

Elevated INR may not reflect bleeding risk

Spontaneous bleeding risk is rare

Routine FFP transfusion not recommended

INR followed for prognosis

Vitamin K is fine

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Management of Other Complications

Continuous renal replacement therapy (CRRT) for volume overload and renal failure

–

especially in patients with advanced encephalopathy and hypotension

Vasopressor support

Glucose drip for hypoglycemia

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Prognosis

Overall mortality 30-40%

Multiple factors influence mortality

Cause of liver failure

acetaminophen has best outcome, >50% survival

idiopathic drug reaction has poorest outcome, <25% survival

Degree of encephalopathy

Important to determine prognosis to determine who needs a liver transplant

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Encephalopathy and Prognosis

Grade

of Encephalopathy

Short-term

transplant-free Survival

Short-term

survival after liver transplant

I-II

52%

77%

III-IV

33%

56%

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King’s College Criteria

Prognostic system developed from King’s College Hospital in London

Predict transplant-free mortality

Meta-analysis shows 68-69% sensitivity, 82%-92% specificity

Two separate criteria

Acetaminophen

Non-acetaminophen

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King’s College Criteria - Acetaminophen

pH <7.3 or arterial lactate >3.0mmol/L after early fluid resuscitation

Or

All three:

Grade III/IV encephalopathy

INR > 6.5

Cr >3.4 mg/

dL

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King’s College Criteria

–

Non-acetaminophen

INR > 6.5

Or

Three of five

Age < 10 or > 40 years

INR ≥ 3.5

TB ≥ 17mg/

dL

Unfavorable etiology

–

Wilson, idiopathic drug reaction, non A, B hepatitis

Development of encephalopathy > 7 days after jaundice

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Management

Supportive care

Follow mental status, transaminases, and INR closely

Early involvement and transfer to transplant center

Liver transplantation

Rapid work-up with thorough psycho-social evaluation

Listed as ”Status 1”

1 year survival is lower than for other

Tx

After 1 year, survival improved

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Future Directions

Better prognostic score

Better monitoring of ICP

Liver dialysis

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Key Points

ALF is marked by rapid deterioration in liver function resulting in encephalopathy and coagulopathy

Early recognition and involvement of transplant hepatology is essential

Determining etiology may help to target early therapy to prevent deterioration

–

especially in acetaminophen

Supportive care is hallmark of ALF treatment

Determining prognosis can help determine who will best benefit from liver transplantation