10 - Hepatic Encephalopathy and Acute Liver Failure Flashcards Preview

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1

If the liver recovers

It regenerates completely

2

If the liver fails acutely

Patient dies within 4 - 7 days

3

What do you see in halothane-induced hepatic failure?

Massive Necrosis
Little bile ducts re-forming!
Sadly, most patients don't make it long enough for the regeneration!!!!

4

Acute Liver Failure - Syndrome

Altered Mentation (Hepatic Encephalopathy)
Coagulopathy (INR >- 1.5)
Acute Illness (

5

Acute-on-Chronic Liver Disease

Never has cerebral edema
Refers to when someone with chronic liver disease has an acute failure.

6

Acute Liver Failure - Management

Establish Diagnosis (INR, AMS, new hepatic illness)
Determine Etiology (history, Labs)
Estimate Severity (Exam, Labs)

7

Acute Liver Failure - How do we treat different etiologies?

Acetaminophen? --> Tx = N-Acetyl Cysteine
Mushrooms (not the magic kind. The dad kind.) ? --> Tx = Penicillamine/silibinin antidote
Wilsons? (Elevated bilirubin, low AP, Increased Ucu)? --> Tx = OLTx
Drug-Induced/Viral/Indeterminate? --> Tx = Good Intensive Care

8

Acute Liver Failure - How do we estimate severity?

ICU Monitoring / Management
Supportive Care
Transplant evaluation / Planning (start early!)

9

Fulminant Hepatic Failure - Etiologies

Viruses (HAV, HBV, HDV, HEV)
Other viruses you can't find (they are hepatotrophic)
Drugs (Acetaminophen)
Toxins (Amanita Mushrooms)
Metabolic Diseases (Wilson's)
Ischemia (Budd-Chiari)
Others (AFLP, Heat Stroke, Autoimmune)
Cryptogenic

10

Fulminant Hepatic Failure - Acetaminophen

Billion dollar product - OTC more than 300 brands
Unique dose-related toxin
100,000 calls to Poison Control annually
50,000 ER visits/year
10,000 hospitalizations/year
500 deaths/hear
Current assay measures only the acetaminophen parent compound, not the toxic metabolite

11

Acute Liver Failure - Other Drugs

Anti-TB Drugs
8 INH without other anti-TB drugs
2 with other non-TB drugs
5 INH + rifampin + pyrazinamide
1 INH + Ethambutol
2 rifampin + pyrazinamide

Sulfa-related drug
TMP-Sulfa
Sulfadiazine
Sulfasalazine

Other antibiotics
1 Amox-clavulanate
6 Nitrofurantoin
1 Ciprofloxacin
1 Doxycycline
1 Itraconazole

Misc
Phenytoin 6
Valproate 1
PTU 4
Disulfiram 4
Atorvastatin 1
Cerivastatin 2
Bromfenac 4
Troglitazone 4
Herbals and/or dietary supplements 9
(including 2 Kava-Kava
HAART 2
Halothane/Isoflurane 2

12

Fulminant Hepatic Failure - Therapy

ICU
Correct Complications
Avoid FFP, sedatives until decision on transplant reached
Short trial of lactulose may help
Transfer to transplant center before complications develop

13

Fulminant Hepatic Failure - Infection

Happens in MOST patients!! (80% of patients)
Documented bacteremia in 20 - 25%
Secondary to gut translocation, decreased ReticuloEndothelial function and instrumentations
Gram negatives, Staph, Strep with fungal infection in up to 33%

14

Fulminant Hepatic Failure - Infection Plan

Culture all patients broadly with a low threshold for empiric antibiotics
Prophylactic antifungals if renal failure or on abx already.

15

Fulminant Hepatic Failure - Renal Failure

Occurs in up to 33% of patients
Often multifactorial - Volume depletion, ATN, hepatorenal
Urine sodium may be helpful (if it's low)
Avoid CT contrast, empiric aminoglycosides
Since patients tolerate volume overload poorly, CVP or PA monitoring is important!
If oliguria persists with normal CVP --> CVVH

16

It's not hepatorenal

If they don't have massive portal HTN (either ascites or acute - vessel thrombosed or acute liver failure)

17

How do we make Acute Liver Failure-induced Renal Failure worse?

CT Contrast (dangerous!)
Aminoglycosides
NSAIDS
Flood them with fluids! - Leads to cerebral edema!!

18

What is the only imaging you should order in the case of Acute Liver Failure?!

Ultrasound with doppler examination of the hepatic vessels

Unless you suspect that the reason is massive malignant infiltration of the liver

19

Indication for dialysis in acute liver failure

Normal CVP
Not making urine

20

What happens if you fill an Acute Liver Failure patient who has developed Renal Failure with fluids?!

Cerebral Edema

21

Complications in Acute Liver Failure that resolve on their own if the liver is transplanted

Infection
Renal Failure

22

Complications in Acute Liver Failure that DON'T resolve on their own if the liver is transplanted!!!!

Multi-Organ Failure
and
Cerebral Edema

Contraindications to Transplant!!!

23

Multi-Organ Failure

Can give ARDS, ATN, Peripheral Vasodilatation with Hypotension, and DIC

Difficult to separate from Sepsis

Can be a contraindaction to OLT (particularly ARDS)
Treatment is supportive only.

24

Acute Liver Failure - Contraindications to Transplant!!

Multi-Organ Failure
Cerebral Edema

25

Fulminant Hepatic Failure - Cerebral Edema

Most common cause of death in patients with Acute Liver Failure
Present in up to 80% of patients DYING with FHF
The remaining 20% died of septic shock.
Difficult to diagnose with CT, early monitoring essential
If untreated, leads to herniation. Transplantation is the only "cure" but it takes 48 hours to reduce the edema!
Barbiturates, mannitol, hyperventilation & elevation of the head MAY halp!

26

Fulminant Hepatic Failure - Timing of Transplantation

80% of patients with fulminant hepatic failure who survive successful liver transplants have them in the first 48 hours
Early transfer to transplant center is key
Role of extracorporeal liver assist devices inconclusive

27

Median waiting time of a Status 1 on the transplant list in the USA

1 1/2 days

28

Pediatric Acute Liver Failure

Syndrome same as adults
Etiology is different:

52% are indeterminate (probably non-A-through-C viral hepatitis)

Acetaminophen Origins - Often through therapeutic mistakes. Infant tylenol is more concentrated than children's tylenol. Also suicidal teens.

29

Indications for OLT in Fulminant Hepatic Failure

King's College Criteria:

Acetaminophen-Induced (higher rate of spontaneous recovery)

vs

Not Acetaminophen

30

Indications for OLT in Fulminant Hepatic Failure - King's College Criteria for Acetaminophen-Induced

Systemic pH 100 seconds
AND
Creatinine > 3.5 mg/dL in patient with Stage III or IV coma

31

Indications for OLT in Fulminant Hepatic Failure - King's College Criteria for Not-Acetaminophen

PT > 100 seconds

OR

Any three of the following:
PT > 50 seconds
Age 40 years
Not Hep A or Hep B
Jaundice > 7 days before onset of encephalopathy
Bilirubin > 17 mg/dL

32

Liver Transplant - Indications

Patient with End Stage Liver Disease who meets UNOS listing criteria with NO significant comorbidities:
Acute Liver Failure
Any form of Chronic Liver Failure

Complications or predicted 1 year survival

33

Liver Transplant - Contraindications

Cancer outside the liver
Active substance abuse/noncompliance
No social support
Diseases that won't be fixed by a transplant or that will make surgery too high risk

34

Liver Transplant - Relative Contraindications

Cholangiocarcinoma (bile duct cancer)
Age > ???
HIV Seropositivity?!
AIDS

35

Liver Transplant - Timing of Referral

Consider disease's natural history
Consider MELD scores in our area
>17,000 patients are waiting for a liver transplant
Waiting list priority is based on severity (MELD), not waiting time, but you still benefit from an early visit
Referrals should be when 1 year survival dips below 90% without transplant

36

MELD Score

Based on the bilirubin (jaundice), INR (clotting time) and creatinine (kidney function)
Uses logarithms (so not linear)
Best predictor of 3 month risk of dying on waiting list

37

Transplant Evaluation - Mandatory Tests

Ultrasound with Dopplers
HCC Screening (Usually CT or MRI)
CXR & EKG
Echocardiogram +/- Saline Contrast (bubble echo)
ABG +/- Pulmonary Function Tests
Laboratory tests inlcuding HIV & ABO blood type
PPD
Pregnancy Test
Recent PAP Smear

38

Transplant Evaluation - Additional Tests for SOME

Thallium stress test (Over 45, risk factors)
Mammogram (Women over 40)
Heart catheterization (Abnormal heart tests)
Screening colonoscopy (over 50)

39

Transplant - Listing

Once evaluation is completed and discussed
UNOS - Organs allocated locally, THEN nationally
Organs matched by blood type and size
Priority based on MELD first, THEN by time on list

40

MELD exceptions

Stage II HCC, Meld >= 22 + Additional points every 3 months (most common exception, increasing value for HCC screening)

Hepatopulmonary Syndrome

Familial Amyloidosis

Ascites with TIPS failure

Recurrent Cholangitis

Regional Review Boards vote on priority

41

Hepatic Encephalopathy

Only in Chronic Liver Disease!!

Reflects spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction and/or portal systemic shunting
After exclusion of other known brain disease

42

Hepatic Encephalopathy - Classification

Minimal/Covert - Neurophysiological or neuropsychological testing necessary to detect

Overt - Clinically evident

43

Diganosis of Minimal Hepatic Encephalopathy

Neuropsychological Testing
Across multiple neuropsychological domains
Focus on attention and fine motor function
Most used tests - NCT-A, NCT-B, digit-symbol and block-design tests

Neurophysiological Testing
Evoked potentials
EEG
Critical Flicker Frequency

>=2 Abnormal Tests
>=2 SD below the mean

44

Grading of Hepatic Encephalopathy - West Haven Criteria - Grade 0

No Abnormalities

45

Grading of Hepatic Encephalopathy - West Haven Criteria - Grade 1

Trival lack of awareness
Euphoria or anxiety
Shortened attention span
Mild asterixis
Day/night reversal

46

Grading of Hepatic Encephalopathy - West Haven Criteria - Grade 2

Lethargy or apathy
Minimal disorientation for time or place
Personality change
Inappropriate behavior
Slurred speech
Asterixis

47

Grading of Hepatic Encephalopathy - West Haven Criteria - Grade 3

Somnolence to semi-stupor
Responsiveness to verbal stimuli
Confusion and/or gross disorientation
Bizarre behavior
Asterixis absent
Clonus Present

48

Grading of Hepatic Encephalopathy - West Haven Criteria - Grade 4

Coma (Unresponsive to verbal or noxious stimuli)

49

Asterixis

Loss of concentration leading to the inability to multitask.

You forget your hand is flexed, and it starts to slack. You notice, and you flex again.

Falling asleep head bob is a form of asterixis

50

Stupor

When not stimulated, they fall asleep. Stimulation wakes them up, but once stimulation is done, they fall back asleep!

51

Hepatic Encephalopathy - Treatment Strategies

Correct precipitating factor:
Infection/Inflammation
GI Bleed
Psychoactive medications (benzodiazepines, opioids)
Hyponatremia
Renal failure
Dehydration
Constipation

Lower ammonia levels

52

Ammonia lowering strategies

Decrease intestinal load
Decrease portal-systemic bypass
Increase consumption by ammonia detoxifying organs (liver, muscle)
Direct removal

53

Decreasing Intestinal Load to lower ammonia

Disaccharides (Lactulose, Lactitol)
Lactulose remains gold-standard by reducing transit. Competes for digestion, so less protein is digested. Byproducts are methane and H+, acidifying the colon and turning ammonia into ammonium.

Poorly absorbable antibiotics (neomycin, rifaximin)
Rifaximin reduces risk of having a recurrent episode of HE by 50% in 6 months

Changes in intestinal flora towards non-ammoniogenic bacteria (probiotics, synbiotics)
Not proven

54

Decreasing portal systemic bypass to lower ammonia

Evaluate and close spontaneous portal-systemic shunts
Reduce size of TIPS

55

Increasing ammonia clearance to lower ammonia

L-Ornithine L-Aspartate

56

Direct Removal to lower ammonia

Albumin Dialysis
MARS (Molecular Adsorbent Recirculating System)

57

Hepatocellular Carcinoma management pre-transplant

Screen every 6 months with imaging (ultrasound, CT or MRI) +/- blood test (AFP) CRITICAL

UNOS extra points for HCC if 1 lesion 2-5cm or 3 lesions less than 3cm

Every 3 months patients move up the point scale

58

Therapies for HCC on the transplant list

Localized interventions - Chemoembolization, radiofrequency ablation to control or downsize tumors

Chemotherapy (Sorafenib/Nexavar) not yet standard of care for patients on the list.

Need scans every 3 months to assess spread of disease while waiting for liver transplantation.

59

Pre-Transplant Potpourri

Baseline bone density - Increased risk of osteopenia or osteoporosis in all cirrhotics
Vaccinations for Hep A, B, Flu, Pneumovax, Swine Flu
Exucation, strong psychosocial support
Good communication between patient, team, local GI MD, PCP, specialists