10 - Hepatic Encephalopathy and Acute Liver Failure Flashcards
If the liver recovers
It regenerates completely
If the liver fails acutely
Patient dies within 4 - 7 days
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!!!!
Acute Liver Failure - Syndrome
Altered Mentation (Hepatic Encephalopathy) Coagulopathy (INR >- 1.5) Acute Illness (
Acute-on-Chronic Liver Disease
Never has cerebral edema
Refers to when someone with chronic liver disease has an acute failure.
Acute Liver Failure - Management
Establish Diagnosis (INR, AMS, new hepatic illness) Determine Etiology (history, Labs) Estimate Severity (Exam, Labs)
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
Acute Liver Failure - How do we estimate severity?
ICU Monitoring / Management
Supportive Care
Transplant evaluation / Planning (start early!)
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
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
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
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
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%
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.
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
It’s not hepatorenal
If they don’t have massive portal HTN (either ascites or acute - vessel thrombosed or acute liver failure)
How do we make Acute Liver Failure-induced Renal Failure worse?
CT Contrast (dangerous!)
Aminoglycosides
NSAIDS
Flood them with fluids! - Leads to cerebral edema!!
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
Indication for dialysis in acute liver failure
Normal CVP
Not making urine
What happens if you fill an Acute Liver Failure patient who has developed Renal Failure with fluids?!
Cerebral Edema
Complications in Acute Liver Failure that resolve on their own if the liver is transplanted
Infection
Renal Failure
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!!!
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.
Acute Liver Failure - Contraindications to Transplant!!
Multi-Organ Failure
Cerebral Edema
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!
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
Median waiting time of a Status 1 on the transplant list in the USA
1 1/2 days
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.
Indications for OLT in Fulminant Hepatic Failure
King’s College Criteria:
Acetaminophen-Induced (higher rate of spontaneous recovery)
vs
Not Acetaminophen
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
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
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
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
Liver Transplant - Relative Contraindications
Cholangiocarcinoma (bile duct cancer)
Age > ???
HIV Seropositivity?!
AIDS
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
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
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
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)
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
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
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
Hepatic Encephalopathy - Classification
Minimal/Covert - Neurophysiological or neuropsychological testing necessary to detect
Overt - Clinically evident
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
Grading of Hepatic Encephalopathy - West Haven Criteria - Grade 0
No Abnormalities
Grading of Hepatic Encephalopathy - West Haven Criteria - Grade 1
Trival lack of awareness Euphoria or anxiety Shortened attention span Mild asterixis Day/night reversal
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
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
Grading of Hepatic Encephalopathy - West Haven Criteria - Grade 4
Coma (Unresponsive to verbal or noxious stimuli)
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
Stupor
When not stimulated, they fall asleep. Stimulation wakes them up, but once stimulation is done, they fall back asleep!
Hepatic Encephalopathy - Treatment Strategies
Correct precipitating factor: Infection/Inflammation GI Bleed Psychoactive medications (benzodiazepines, opioids) Hyponatremia Renal failure Dehydration Constipation
Lower ammonia levels
Ammonia lowering strategies
Decrease intestinal load
Decrease portal-systemic bypass
Increase consumption by ammonia detoxifying organs (liver, muscle)
Direct removal
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
Decreasing portal systemic bypass to lower ammonia
Evaluate and close spontaneous portal-systemic shunts
Reduce size of TIPS
Increasing ammonia clearance to lower ammonia
L-Ornithine L-Aspartate
Direct Removal to lower ammonia
Albumin Dialysis
MARS (Molecular Adsorbent Recirculating System)
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
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.
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
