Term
| What is the clinical definition of ALF? |
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Definition
1) Altered mental status
- Coagulopathy in a patient without pre-existing liver chronic liver disease
- Liver-illness (jaundice) begins at least 8 weeks before patient presents. |
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Term
Patient presents in a confused and agitated state. He explains that he has not experienced any prior symptoms, except for noticing a yellowing hue to the whites of his eyes for the past 3 months.
On PE, you notice coagulopathy in his legs.
What should be on your initial differential? |
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Definition
Sounds like AFL (altered mental status and coagulopthy in a patient with >8 weeks of prior liver-disease)
Acetaminophen is most likely and most likely to survive.
Major etiologies of AFL
1) Acetaminophen- Dominant in US and UK
2) Viral hepatitis (not HCV)
3) Hypo-perfusion or "shock" liver (CHF)
4) Wilson's disease (copper overload)
5) Pregnancy (HELLP syndrome, acute fatty liver)
6) Idiosyncratic drug reactions. |
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Term
| How does acetaminophen toxicity produce AFL? |
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Definition
CYPE1 (Phase 1) produces NAPQI (highly-reactive intermediate), which can cause hepatocyte damage (forming adducts, covalently binding other proteins and causing derangements of apoptosis)
**Antibiotics are another major cause (40%), as are herbals |
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Term
25 year old female patient presents with altered mental status and coagulopathy, as well as jaundice.
You suspect AFL and run some labs.
ALP and Uric acid are very low, and you document hemolytic anemia.
What else should you look for on PE?
What is probably going on? |
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Definition
WIlson's (RARE)- Look for Kayser-Fleischer rings (can be absent)
High mortality rate without liver transplant. |
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Term
Which of the following in INCORRECT description of AFL in the U.S
1) Affects more women than men
2) 2/3 survive with supportive care along
3) Infectious complications are common even after transplant
4) Older patients have decreased survival rates |
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Definition
4!
All etiologies are more common in women (aspirin being the most common), and 2/3 survive on their own. |
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Term
| What are the major predictors of "non-survival" from AFL due to acetaminophen? |
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Definition
King's College Criteria
1) Acetaminophen
- Arterial pH <7.3 OR one of the following
- Serum creatinine > 3.4 mg/dL
- PTT >50 seconds
- Stage 3 or 4 hepatic encephalopathy.
2) Non-Aspirin
- PTT >50 sec OR THREE of:
- Age <10 or >40
- etiology: NANB, halothane, drugs
- Jaundice to encephalopathy >7 days
- INR >3.5
- Bilirubin >300 nmol/L (>17.5 mg/dL) |
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Term
| What are the major neurological complications of ALF? |
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Definition
1) Cerebral hypo- or hyper-perfusion (edema is #1 cause of death)
2) Intracranial hypertension from edema (brainstem compression)
3) Seizures
4) Hemorrhage
5) Hepatic encephalopathy (3 or 4 after aspirin is BAD news)
- 0 (normal)
- 1 (Altered sleep, orientation, affect)
- 2 (Drowsy, confused, slurred speech, asterixis)
- 3 (Stupor, hyper-reflexia)
- 4 (Unresponsive, coma) |
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Term
| How should hepatic encephalopathy be managed in ALF? |
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Definition
1) Airway protection with intubation (grade 3 or 4)
2) Controlled use of CNS sedatives
3) Lactulose (remove NH3), ion trapping (NH3 to NH4+ to prevent colonic absorption)
4) Neomycin to inhibit urea-splitters
5) Flumazenil to antagonize "false neurotransmitters" |
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Term
| How is Neurological status monitored in ALF? |
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Definition
1) Cerebral blood flow determination
2) ICP measured with "bolt" in epidural, subdural or intracranial spaces.
3) Relieve ICP
- 30-degree head elevation
- Avoid suctioning
- Hyperventilation
- Mannitol
- Hypothermia |
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Term
| What are the 4 major indications for liver T/X? |
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Definition
1) Acute liver failure
2) Advanced cirrhosis
- Encephalopathy
- Refractory ascites
- Spontaneous bacterial peritonitis
- Recurrent variceal bleeding
- Hepatocellular carcinoma
3) Metabolic diseases
- Primary hyperoxalosis
- Amyloidosis (variant transthyretin)
4) Congenital disorders
- Congenital biliary atresia |
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Term
| How is the donor priority determined for liver T/x? |
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Definition
Definitive treatment for acute and chronic liver failure (only real solution for AFL that does not resolve)
Patients can have cirrhosis, but they de-compensate (ascites, encephalopathy or variceal bleed), they need it!
MELD criterion (7 is minmum and 40 is maximum to list)
**does not apply for HCC and AFL, or hepatopulmonary syndrome**
1) Parameters (BCINR)
Serum bilirubin
Serum creatinine
International normalized ratio (INR)
2) Calculation:
[0.957 X loge (creatinine) + 0.378 X loge (bilirubin) + 1.12 X loge (INR) + 0.64] X10
Status 1A: local... regional
MELD ≥15: local...regional
MELD <15: local... regional
National: 1A |
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Term
| What kinds of graft rejections occur from liver t/x and how can they be prevented? |
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Definition
1) Hyperacute rejection
- preformed alloantibodies, within 1-2 days
2) Acute (cellular) rejection
- commonest type, usually within first 3 weeks
3) Chronic (ductopenic) rejection
IMMUNOSUPPRESSION
1) Corticosteroids
- Global anti-inflammatory & immunosuppressive effect
2) Calcineurin inhibitors (cylosporine, tacrolimus)
- Inhibits IL-2 synthesis & release
3) Mycophenolate mofetil
- Inhibits purine synthesis
4) Anti-thymoctye globulin
- T cell lysis |
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Term
| What are the 4 major immunosuppressive strategies available to prevent liver graft rejection? |
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Definition
Future therapies may aim to promote "tolerance" prior to t/x
1) Corticosteroids
- Global anti-inflammatory & immunosuppressive effect
2) Calcineurin inhibitors (cylosporine, tacrolimus)
- Inhibits IL-2 synthesis & release
3) Mycophenolate mofetil
- Inhibits purine synthesis
4) Anti-thymoctye globulin
- T cell lysis |
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