Download acute hepatic failure

ACUTE HEPATIC FAILURE
Dr Jyoti Khare
FCCCM, Part II
PSRI Hospital, New Delhi
Acute Liver Failure (ALF)
ALF also known as FULMINANT HEPATIC FAILURE
is a rare condition defined as the development
of coagulation disturbance and encephalopathy
in individuals without cirrhosis developing < 26
weeks
duration.
Wilson
disease
and
Autoimmune hepatitis included as intial
presentation is as acute illness.
O’ GRADY CLASSIFICATION
On bases of time from jaundice to encepalopathy
development
1. Hyperacute - <7days
2. Acute - 8 to 28days
3. Subacute – 29 to 8 weeks
ETIOLOGY
(1/2)
1. Acute Viral Hepatitis – Hepatitis A,B,C,E
(common in pregnancy), Cytomegalovirus
,Varicella
Zoster
Virus,
Adenovirus,
Paramyxovirus, Ebsten Barr virus, Herpes
virus (more in 3rd trimester of pregnancy).
2. Metabolic Disorders- Acute fatty liver of
pregnancy, HELLP, Wilson Disease, Reye
syndrome.
ETIOLOGY
(2/2)
3. Cardiovascular disorders- Budd Chairi
syndrome, Ischemic hepatitis, Hyperthermia.
4. Drugs and Toxins –Acetaminophen (most
common), NSAIDS, Isoniazid, Rifampicin,
Cocaine ,Herbal drugs, Halothane, Amanta
phalloides (amatoxins).
5. Malignancy- lymphomas, leukemias
6. Autoimmune with ANA, Antismooth muscle
antibody, Anti LKM1 positive.
SIGNS and SYMPTOMS
1.
2.
3.
4.
5.
6.
7.
8.
9.
Lethargy, Altered mentation
Jaundice
Tachypneic
Hypotension
Fluctuating urine output
Hypoglycemia
Bleeding
Asterxsis
Ascites
EVALUATION and DIAGNOSIS
History!
History!
Sexual contacts
History!
cardiac disease
Risk Factors
Pregnancy
Medications
Mushrooms
Travel
Toxic exposures
TEST
• Routine tests- ABG, CBC, LFT,PT/ INR, Ammonia,
RFT, CxR, Viral makers with Anti HAV,HEV,
Autoimmune markers, Ceruloplasmin levels,
Toxins levels.
• Blood, Urine, ascitic fluid c/s
• USG abdomen.
• CT SCAN Head for Cerebral oedema and
Abdomen.
• EEG
• Echocardiography
Differential Diagnosis
•
•
•
•
•
•
Acute decompensation of cirrhosis
Alcoholic hepatitis with underlying cirrhosis
Autoimmune Hepatitis
Eclampsia
Preeclampsia
Sepsis with multiorgan failure
COMPLICATIONS (1/3)
1. Encephalopathy -
COMPLICATIONS (2/3)
Factors precipitating HE
IGSCALP
• I- INFECTION
• G-GI BLEEDING
• S-SEDATION
• C-CONSTIPATION
• A-ALKALOSIS
• L-LOW K
• P-HIGH PROTEIN
COMPLICATIONS
(3/3)
2. Cerebral oedema may lead to brain herniation.
3. Coagulopathy
4. Renal failure including ATN, Pre-renal renal failure,
Hepato Renal syndrome
5. Metabolic Acidosis ,Hypoglycemia, Lactic acidosis,
hypomagnesimia, hypophosphotemia
6. Infection –Staphylococcus, fungal .
7. Cardiovascular-Distributive shock arterial hypertension.
8. ARDS, Pleural Effusion ,Atelectasis,Intrapulmonary
shunt.
9. pancreatitis
PATHOPHYSIOLOGY OF CEREBRAL
EDEMA (1/3)
Multi factorialHyperammonia - In the brain, ammonia is
detoxified to glutamine via amidation of
glutamate by glutamine synthetase. The
accumulation of glutamine in astrocytes results
in astrocyte swelling and brain edema. The
relationship between high ammonia and
glutamine levels and raised ICH has been
reported in humans.
PATHOPHYSIOLOGY OF CEREBRAL
EDEMA (2/3)
Cytogenic edema - is the consequence of
impaired cellular osmoregulation in the brain,
resulting in astrocyte edema. Cortical astrocyte
swelling is the most common observation in
neuropathologic studies of brain edema in acute
liver failure.
PATHOPHYSIOLOGY OF CEREBRAL
EDEMA (3/3)
Vasogenic factors
An increase in intracranial blood volume and
cerebral blood flow is a factor in acute liver failure.
The increased cerebral blood flow results because
of disruption of cerebral autoregulation. The
disruption of cerebral autoregulation is thought to
be mediated by elevated systemic concentrations of
nitric oxide, which acts as a potent vasodilator and
BBB injury.
TREATMENT (1/4)
1. General measures –identifying the severity,
cause. ICU admission, securing airway, breathing
,circulation ,iv vasopressors.
2. IV antibiotics for sepsis
3. Coagulopathy correction with FFP, Vit K ,factor
VII
4. Correction of Acidosis and hypoglycemia with
IVF, IV dextrose.
5. Seizures control with anti epileptic drugs.
6. Correction of electrolytes.
TREATMENT
(2/4)
7. Renal failure –correcting cause, maintaing BP, avoiding
nephrotoxic drugs and adjusting doses of antibiotics as
per creatinine clearance.
8. Cerebral oedema with raised ICP- HOB 30 degree
– Permissive hypernatremia (145 to 155 mmol/l)
– IV mannitol (0.5 to 1.0 g/kg) and to keep osmolality <320
mosmol to avoid damage to BBB and worsening of vasogenic
edema.
– Hyperventilation to keep Pco2 25 to30 mmHg
– Hypothermia
– IV INDOMETHACIN (0.5mg/kg)
– Phenobarbital, steroids role not very clear.
TREATMENT
(3/4)
9. Hepatic encephalopathyLactulose, L-ornithine and aspartate, non absorable
antibiotic like Rifaximin, neomycin metronidazole
,oral vancomycin and quinolones. High branch chain
amino acid formulae may provide protein
supplimentation.
TREATMENT
(4/4)
Diet
• Patients with acute liver failure are, by necessity, on
nothing by mouth (NPO) status. They may require large
amounts of IV glucose to avoid hypoglycemia.
• When enteral feeding via a feeding tube is not feasible
(eg, as in a patient with paralytic ileus), institute total
parenteral nutrition (TPN). Restricting protein (amino
acids) to 0.6 g/kg body weight per day was previously
routine in the setting of hepatic encephalopathy.
However, this may not be necessary.
• Endoscopic post-pyloric feeding tube in refractory
cases.
ACETAMINOPHEN TOXICITY
• Intentional and Unintentional overdose.
• Dose -150mg/kg
• Patient with LFT derranged can have toxicity
even with low doses.
• Symptoms- nausea ,vomiting with derranged
LFT, coagulopathy, renal failure, hypoglycemia,
shock.
TREATMENT
• ABC
• N-acetylcysteine enchances Glutathione synthesis
and detoxifies N acetyl p benzoquinone imine to
non toxic acetaminophen sulfate and prevent
hepatic damage.
• Dose-IV 150mg/kg over 15 mts followed by
50mg/kg over 4 hrs followed by 100mg/kg over
20 hrs.
• Oral -140mg/kg loading dose followed by17
doses of 70mg/kg every 4hrs for 72 hrs.
• Liver Transplant.
HEPATORENAL SYNDROME
• Is reversible acute kidney injury seen in
Fulminant Liver Failure.
• Renal function worsen in days to weeks.
• Types
– Rapidly progressive form ,doubling of s. Creat >2.5
mg/dl in <2 weeks
– Moderate with slowly progressive course S. creat
1.5 to 2.5 mg/dl mostly associated with refractory
ascites.
TREATMENT
1. Vasoconstrictors- Terlipressin, midodrine (5to
15mg / day), octreotide (100 to 200
microgram SC three times a day)
2. IV albumin (1gm /kg /day for 3 days)
3. Transjugular intrahepati portosystemic shunt
–risk of HE.
4. Heamodialysis
5. Liver transplant.
ALF due to HAV and HEV
• Supportive treatment - Securing airway ,
breathing , maintaining circulation.
• Correction of coagulation parameters,
cerebral oedema.
• Correction
of
electrolytes,
acidosis,
Hypoglycemia, encephalopathy .
• Heamodialysis in case of AKI .
• Liver Transplant.
LIVER TRANSPLANT CRITERIA (1/2)
• Acetaminophen-induced disease
• Arterial pH <7.3 (irrespective of the grade of
encephalopathy)
or
• Grade III or IV encephalopathy, and
• Prothrombin time >100 seconds, and
• Serum creatinine >3.4mg/dl (301 μmol/L)
LIVER TRANSPLANT CRITERIA (2/2)
All other causes of fulminant hepatic failure
• Prothrombin time >100 seconds (irrespective of the grade of
encephalopathy)
• Or
• Any three of the following variables (irrespective of the grade
of encephalopathy)
• Age <10 years or >40 years
• Etiology: non-A, non-B hepatitis, halothane hepatitis,
idiosyncratic drug reactions
• Duration of jaundice before onset of encephalopathy >7 days
• Prothrombin time >50 seconds
• Serum bilirrubin >18 mg/dl (308 μmol/L)
VARIATIONS OF LIVER REPLACEMENT THERAPY
Transplantation: Orthotopic LT
DDLT or LDLT
Auxiliary liver transplant
Split liver transplant
Two-stage procedures:
Hepatectomy followed later by OLT
Non-Transplanta Therapies
Xenotransplantation
Hepatocytetransplantation
Hepatic assist devices
CONTRAINDICATIONS FOR
TRANSPLANT
• Advanced cardiopulmonary dysfunction
• Sepsis
• Extrahepatic malignancy - Active severe
infection outside the liver
• HIV / AIDS
• Cholangiocarcinoma
• Lack of adequate family social support
• Active alcoholism or drug abuse
PROGNOSIS
ALF carries high mortality rate with HEV
infection in pregnancy.
Over all mortality is high in Acute Liver Failure
without Liver transplant.
Thank you