Acute Liver FailureAcute Liver Failure

30 year old woman presents to hospital with a 30 year old woman presents to hospital with a two day history of nausea, vomiting, and right two day history of nausea, vomiting, and right upper quadrant pain.upper quadrant pain.

She has been healthy and denies any She has been healthy and denies any medication use.medication use.

She recently traveled to Vietnam where she She recently traveled to Vietnam where she twisted her ankle while bungee jumping. The twisted her ankle while bungee jumping. The pain has been well controlled with over the pain has been well controlled with over the counter and natural remedies.counter and natural remedies.

On examination, she is slightly confused to On examination, she is slightly confused to date and in moderate distress from the date and in moderate distress from the pain.pain.Vital signs are: 123/41, heart rate 109, Vital signs are: 123/41, heart rate 109, respiratory rate 24, and saturations 95% respiratory rate 24, and saturations 95% on room air.on room air.She is has diffuse abdominal tenderness She is has diffuse abdominal tenderness and palpable liver edge with a scleral and palpable liver edge with a scleral icterus.icterus.

What is the most likely cause of this patient’s What is the most likely cause of this patient’s presentation?presentation?

What are the common etiologies of acute liver What are the common etiologies of acute liver failure?failure?– Consider:Consider:

A – acetaminophen, hepatitis A, autoimmuneA – acetaminophen, hepatitis A, autoimmune

B – hepatitis BB – hepatitis B

C – cryptogenic, hepatitis CC – cryptogenic, hepatitis C

D – hepatitis DD – hepatitis D

E – esoteric causes such as Wilson’s and Budd-ChiariE – esoteric causes such as Wilson’s and Budd-Chiari

F – fatty infiltration such as fatty liver of pregnancy and ReyeF – fatty infiltration such as fatty liver of pregnancy and Reye

Initial bloodwork comes back:Initial bloodwork comes back:– ALT 3826, AST 4826, TBili 59, Alk Phos ALT 3826, AST 4826, TBili 59, Alk Phos

283,INR 4.2, creatinine 436, pH 7.31283,INR 4.2, creatinine 436, pH 7.31

What in the history gives us clues to the What in the history gives us clues to the cause?cause?– Travel: hepatitis virus?Travel: hepatitis virus?– Over the counter drugs: acetaminophen?Over the counter drugs: acetaminophen?– Natural remedies: drug or toxin?Natural remedies: drug or toxin?– Childbearing age: fatty liver of pregnancy?Childbearing age: fatty liver of pregnancy?

Obtaining further history, her family tells Obtaining further history, her family tells you that she has been vaccinated against you that she has been vaccinated against hepatitis B because she is a lab tech, she hepatitis B because she is a lab tech, she is not pregnant but do not know what is not pregnant but do not know what medications and remedies she takes.medications and remedies she takes.

You take the history from the family You take the history from the family because the patient is rapidly becoming because the patient is rapidly becoming unresponsive.unresponsive.

What is the definition of fulminant hepatic What is the definition of fulminant hepatic failure?failure?– Severe acute liver injury with impaired synthetic Severe acute liver injury with impaired synthetic

function and encephalopathy in a person with a function and encephalopathy in a person with a normal liver or well-compensated liver disease.normal liver or well-compensated liver disease.

What are the grades of encephalopathy?What are the grades of encephalopathy?

The patient has become completely The patient has become completely unresponsive with posturing to stimulation. You unresponsive with posturing to stimulation. You rapidly intubate and resuscitate her and obtain rapidly intubate and resuscitate her and obtain an urgent CT scan.an urgent CT scan.

Head CTHead CT

What has happened?What has happened?

How do you grade hepatic How do you grade hepatic encephalopathy?encephalopathy?

GradeGrade Mental StatusMental Status AsterixisAsterixis EEGEEG

II Euphoria/depressionEuphoria/depression

Mild confusionMild confusion

Slurred speechSlurred speech

Disordered sleepDisordered sleep

Yes/NoYes/No Usually Usually normalnormal

IIII LethargyLethargy

Moderate confusionModerate confusion

YesYes AbnormalAbnormal

IIIIII Marked confusionMarked confusion

IncoherentIncoherent

Sleeping but arousableSleeping but arousable

YesYes AbnormalAbnormal

IVIV ComaComa NoNo AbnormalAbnormal

How do you treat hepatic encephalopathy How do you treat hepatic encephalopathy with and without intracranial hypertension?with and without intracranial hypertension?

What is the role for intracranial monitoring What is the role for intracranial monitoring in this case?in this case?

After appropriate resuscitation and After appropriate resuscitation and treatment, the patient is more stable. The treatment, the patient is more stable. The family approaches you for more family approaches you for more information. They want to know whether information. They want to know whether she is going to need liver transplant.she is going to need liver transplant.

What do you tell them and how do you What do you tell them and how do you know? know?

Acetaminophen-induced disease Acetaminophen-induced disease

Arterial pH <7.3 (irrespective of the grade of encephalopathy) Arterial pH <7.3 (irrespective of the grade of encephalopathy)

OROR

Grade III or IV encephalopathy AND Grade III or IV encephalopathy AND

Prothrombin time >100 seconds AND Prothrombin time >100 seconds AND

Serum creatinine >3.4mg/dL (301 µmol/L) Serum creatinine >3.4mg/dL (301 µmol/L)

All other causes of fulminant hepatic failure All other causes of fulminant hepatic failure

Prothrombin time >100 seconds (irrespective of the grade of encephalopathy) Prothrombin time >100 seconds (irrespective of the grade of encephalopathy)

OROR

Any Any threethree of the following variables (irrespective of the grade of encephalopathy) of the following variables (irrespective of the grade of encephalopathy)

1. Age <10 years or >40 years 1. Age <10 years or >40 years

2. Etiology: non-A, non-B hepatitis, halothane hepatitis, idiosyncratic drug 2. Etiology: non-A, non-B hepatitis, halothane hepatitis, idiosyncratic drug reactions reactions

3. Duration of jaundice before onset of encephalopathy >7 days 3. Duration of jaundice before onset of encephalopathy >7 days

4. Prothrombin time >50 seconds 4. Prothrombin time >50 seconds

5. Serum bilirubin >18 mg/dL (308 µmol/L) 5. Serum bilirubin >18 mg/dL (308 µmol/L)

•By the way, what are By the way, what are some of the drugs some of the drugs that can cause that can cause fulminant hepatic fulminant hepatic failure?failure?

AcetaminophenAcetaminophenAlcoholAlcoholAmiodaroneAmiodaroneCarbon tetrachlorideCarbon tetrachlorideDideoxyinosineDideoxyinosineGoldGoldHalothaneHalothaneIsoniazidIsoniazidKetoconazoleKetoconazoleMAO inhibitorsMAO inhibitorsMethyldopaMethyldopaNSAIDsNSAIDsPhenytoinPhenytoinPoison mushrooms (Amanita Poison mushrooms (Amanita phalloides)phalloides)PropylthiouracilPropylthiouracilRifampinRifampinSulfonamidesSulfonamidesTetracyclineTetracyclineTricyclic antidepressantsTricyclic antidepressantsValproic acidValproic acid

Next patientNext patient

68 year old man with known chronic liver 68 year old man with known chronic liver dysfunction from NASH.dysfunction from NASH.

He presents to his family doctor with increasing He presents to his family doctor with increasing confusion. He admits the patient to hospital and confusion. He admits the patient to hospital and consults you because of persisting fevers.consults you because of persisting fevers.

On assessment, he is febrile, slightly jaundiced On assessment, he is febrile, slightly jaundiced with signs of chronic liver disease and with signs of chronic liver disease and abdominal tenderness.abdominal tenderness.

Blood cultures come back positive for E. coliBlood cultures come back positive for E. coli

What is the most likely problem?What is the most likely problem?

How is the diagnosis of spontaneous How is the diagnosis of spontaneous bacterial peritonitis made?bacterial peritonitis made?

A paracentesis reveals a WBC count of A paracentesis reveals a WBC count of 375 cells/mL with 95% PMNs.375 cells/mL with 95% PMNs.

What is the appropriate treatment of What is the appropriate treatment of spontaneous bacterial peritonitis?spontaneous bacterial peritonitis?

The next day, the patient feels better but his The next day, the patient feels better but his urine output has been poor.urine output has been poor.His creatinine is 242, last level 6 months ago His creatinine is 242, last level 6 months ago was 109.was 109.What are the possible causes of this problem?What are the possible causes of this problem?– Consider:Consider:

Volume depletion from paracentesisVolume depletion from paracentesisAbdominal compartment syndromeAbdominal compartment syndromeATN from nephrotoxins such as aminoglycosidesATN from nephrotoxins such as aminoglycosidesInterstitial nephritis from B-lactamsInterstitial nephritis from B-lactamsHepatorenal syndromeHepatorenal syndrome

How would you investigate this?How would you investigate this?

There is no change in renal function after There is no change in renal function after fluid challenges and his urine sodium is < fluid challenges and his urine sodium is < 10 mmol/L.10 mmol/L.

What is the criteria for hepatorenal What is the criteria for hepatorenal syndrome?syndrome?

What is the pathophysiology behind What is the pathophysiology behind hepatorenal syndrome?hepatorenal syndrome?

The diagnosis of HRS is confirmed. The The diagnosis of HRS is confirmed. The family asks you what this means. He has family asks you what this means. He has refused transplant workup and long term refused transplant workup and long term dialysis.dialysis.What do you tell the family?What do you tell the family?What is the role of albumin in HRS?What is the role of albumin in HRS?What is the role of vasopressors such as What is the role of vasopressors such as midodrine/octreotide or midodrine/octreotide or levophed/vasopressin in HRS?levophed/vasopressin in HRS?

Questions??Questions??