Acute Liver Failure Flashcards
What is the weight of the liver ?
It makes up about 2.5% of the body weight
Function of the liver ?
- Bile formation
- Cholesterol & lipoprotein metabolism
- Drug metabolism
- Carbohydrate metabolism
- Fatty acid metabolism
- Ammonia metabolism
- Storage; A,B12,D,glycogen, iron
- Immunology
Characteristics of ALF?
- INR > 1.5
- Hepatic encephalopathy
- Vasoplegic CVS collapse
Classification of liver failure?
- Hyperacute
- Acute
- Subacute
What is hyperacute liver failure ?
This is where encephalopathy occurs within 7 days of jaundice
What is acute liver failure ?
This has an interval of between 8 - 28 days from jaundice to encephalopathy
What is subacute liver failure?
This is when encephalopathy occurs between 28 days - 12 weeks after the onset of Jaundice
What is the most common precipitant of infective ALF?
Hepatitis A,B & E
Risk of ALF is lowest with Hepatitis A
Transplant in secondary liver failure?
Not an option but is only indicated in patients with primary liver failure
Infective causes of ALF?
- Hepatitis - A,B,E & seronegative hepatitis
- HSV, CMV
- Chicken-pox (Immuno-compromised)
Does hepatitis C cause ALF?
This is not a common cause
Hepatitis D infection in ALF?
Hepatitis D requires Hepatitis B co-infection
What are the causes of drug related ALF?
- Acetaminophen
- TB drugs
- MDMA, Cocaine
- Idiosyncratic reactions ( Anticonvulsants, Abx, NSAIDs)
- Aspirin - In kids lead to Reye’s syndrome
- Kava kava root supplement
What are the causes of toxin related ALF?
- Carbon tetrachloride
- Phosphorous
- Amanita Phalloides
- Alcohol
What are the possible vascular events causing ALF?
- Ischaemia
- Veno-occlusive disease
- Budd-Chiari syndrome (Hepatic vein thrombosis)
- Hyperthermic liver injury
Pregnancy related ALF?
- Acute fatty liver of pregnancy
- HELLP syndrome
- Liver rupture
What is the full meaning of HELLP ?
Haemolysis
Elevated liver enzymes
Low platelets
Other rare causes of ALF?
- Wilson’s disease
- Auto-immune
- Lymphoma
- Carcinoma
- Haemophagocytic syndrome
- Trauma
Metabolism of Acetaminophen and pathways in overdose?
Cytochrome P450 converts 5% of Acetaminophen to N-Acetyl Pbenzoquinoneimine (NAPQI) - This is a metabolite
NAPQI detoxification by hepatic glutathione - Conjugation
Hepatic glutathione becomes depleted in overdose, hence NAPQI persists to cause cellular damage
NAC infusion restores the depleted hepatic glutathione . Very effective within 8-12 hrs
factors potentiating depletion of glutathione stores?
- Anorexia
- Malnutrition
- Chronic alcohol use
- Enzyme inducing drugs (Phenytoin & Carbemazepine)
- Cystic fibrosis
- HIV
List some common enzyme inducers?
- Phenytoin
- Carbemazepine
- Rifampicin
- Phenobarbitone
- Chronic alcohol use
What is the composition of the hepatic portal vein?
- Superior mesenteric vein
- Splenic vein
Also receives blood from;
- Inferior mesenteric
- Gastric veins
- Cystic veins
Characteristics of the hepatic portal vein?
- ## About 75% of liver blood supply
what is Wilson’s disease?
- Inherited autosomal recessive
- Defective coding of copper-transporting ATPase
- Insufficient copper excretion in bile
- Accumulation in brain, liver & cornea
- Diagnosis by measuring serum copper & ceruloplasmin
What is the definition of acute decompensated liver failure ?
- New onset ascitis
- Hepatic encephalopathy
- GI bleeding
- Infection - CLD
Acute on chronic liver failure ?
- Acute decompensation
- Organ failure
What are the components of the CLIF-SOFA score ?
- Liver
- Kidney
- Circulation
- Lungs
- Brain
- Coagulation
What are the common organisms causing infection in chronic liver patients?
- E.Coli
- Staph Aureus
- E. Faecalis
- Strep pneumoniae
- Pseudomonas
- Staph epidermidis
- MRSA
- VRE
- ESBL-Producing enterobacteria
List few familial liver diseases?
- Alpha-1-Antitrypsin deficiency
- Haemochromatosis
- Wilson disease
- Cystic fibrosis
List a few genetic metabolic diseases which could cause liver failure in children?
- Reye’s syndrome
- Gaucher disease
- Niemann-pick disease
- Tangier disease
- Fabry disease
- Hurler
Management of haemochromatosis ?
Venesection to prevent liver failure
Common presenting sigs with ALF?
- Jaundice
- Encephalopathy
- Coagulopathy
Distinguishing between the acuity of liver failure?
Understanding the interval from the onset of jaundice to the development of encephalopathy
Underlying pathologies which could cause acute deterioration in patients with CLD?
- Sepsis
- Dehydration
- Electrolyte abnormalities
- Sedative drugs
- Portal vein thrombosis
- Liver tumor
- GI bleed
Checking bilirubin to determine the extent of hemolysis’s contribution to jaundice ?
- Conjugated
- Unconjugated
Laboratory markers specific for the liver?
- ALT
Interpretation of AST & ALT?
In alcohol related ALF, AST is usually twice that of ALT
Coagulation factors produced by the liver ?
I, II, V, VII, IX & X
Hematological changes in ALF?
- Macrocytic Hypochromic erythrocytes
- Pancytopenia
Chronic low-grade blood loss could be caused by?
Hypertensive gastropathy
Other investigations in ALF?
- Plasma immunoglobulin
- Hepatitis serology
- CMV, EBV, HSV, VZ
- Ceruloplasmin
- Copper (Urine & serum) - Pre/post-penicillamine
- Alpha-1-antitryptase
- Iron studies
- Procoagulant profile
- AFP
Significance of AFP in ALF?
- Indication of liver cancer
Picture of laboratory tests for leptospirosis ?
- Elevated bilirubin
- Marginally elevated AST & INR
- Normal GGT
Significance of pancytopenia ?
This will indicate bone marrow depression
Components of hemolysis screen?
- Reticulocyte
- Haptoglobin
- Blood film
List assessment tools for ACLF?
- Child-Pugh score
- MELD ( Model End-stage Liver Disease)
What is the benefit of MELD score ?
- Developed to assess likely outcome in TIPS
- Prognostication 3 months mortality
Components of the CLIF-SOFA score ?
CCLLKC
- Cerebral (HE)
- Circulation (MAP)
- Lungs ( FiO2/PaO2)
- Liver (Bilirubin)
- Kidney (Creatinine)
- Coagulation (INR)
What is the modified-Parsons smith scale of hepatic encephalopathy
See attached
Hepatorenal failure?
Urinary sodium is usually low
Toxins causing ALF and their antidotes?
- Amanita Phalloides - Penicillin or Silibinin
- Wilson’s disease - Penicillamine or Trientene
- Budd-Chiari - Thrombolysis or TIPPS
Management of past HBV infection in patients with ALF?
- Lamivudine
- Entecavir
- Tenofovir
A patient undergoing chemotherapy for lymphoma presents with transaminitis (AST 500 IU/l), jaundice (bilirubin 450 µmol/l (26.3 mg/dl)), alkaline phosphatase 120 U/l (N<150 U/l), INR 2.1 and altered level of consciousness (GCS 10). Is this progressive lymphomatous infiltration? Give reasons.
This may be progressive lymphomatous disease but it is unlikely if the liver function tests have deteriorated rapidly.
Outline other causes of this acute deterioration which require exclusion in this setting?
Veno-occlusive disease associated with chemotherapy; chemotherapy induced cardiomyopathy causing marked hepatic congestion; Budd–Chiari syndrome may be associated with procoagulant disorders, chemotherapy and/or dehydration
Any hepatic disorder which may be triggered by the chemotherapy?
Reactivation of hepatitis B following systemic chemotherapy may be a possibility
Management of decreased splanchnic inflow?
Terlipressin
Indication for TIPPS
- Re-bleeding (Refractory)
- Portal pressures > 20mmHg
- Child-Pugh B/C
Prevention of re-bleeding in oesophageal varices ?
- Non-selective beta-blocker
You are asked to assess a 42-year-old man with major upper GI haemorrhage and haemodynamic compromise (HR 130/min, BP 90/40 mmHg, postural drop). He is known to have auto-immune liver disease and is drowsy. He has ascites and has recently become oliguric. The admitting team wishes to undertake an upper GI endoscopy – what is your advice?
Resuscitation prior to the endoscopy. He is likely to have oesophageal varices
What pre-procedure measure would you consider appropriate in a patient with UGIB?
- Central venous access/large bore cannulae/cross-match blood
- Correction of coagulopathy with blood products and vitamin K
- If drowsiness persists, he is at risk of aspiration, therefore tracheal intubation/ventilation prior to endoscopy likely to be pre-emptively required
- Consider terlipressin/broad-spectrum antibiotics/anti-fungals after blood cultures/septic screen taken.
Investigations used to diagnose sub-clinical encephalopathy?
- EEG
- Evoked potential
Causes of acute encephalopathy ?
- Infection.
- Metabolic disturbances (electrolyte abnormalities, excessive diuretic therapy or fluid restriction, excessive paracentesis, uraemia, alkalosis, anaemia, hypoxaemia).
- Gastrointestinal disturbances (haemorrhage, constipation, excessive protein load).
- Hepatic abnormalities (acute liver necrosis, disease progression, portal vein thrombosis, ischaemia, hepatoma, spontaneous portosystemic shunting that may not be associated with liver disease, TIPS or surgical shunts).
- Psychoactive drugs.
- Medication non-compliance.
Management of encephalopathy associated with CLD may involve
Resuscitative measures e.g. control of airway, support of circulation.
Diagnosis and treatment of the precipitant.
Treat infection and biochemical abnormalities.
Protein intake of 1–1.5 g protein/kg/day depending on level of encephalopathy (can be reduced to 0.5 g/kg/day transiently).
Vegetable protein is preferable to animal protein.
Lactulose/lactilol. The cathartic effect removes endogenous and exogenous ammonia-generating compounds from the bowel and maintains an acidic environment that retains ammonia within the bowel lumen.
Recent studies suggest benefit with rifaximin in preventing encephalopathy in chronic liver disease
The combination of rifaximin and lactulose may be of additional benefit in chronic liver disease
Branch chain amino acids are recommended for refractory HE
Neomycin may have an additive benefit but is not often used because of the risk of oto-and nephrotoxicity.
Zinc supplementation is recommended as zinc is a necessary substrate in the metabolism of ammonia to urea and many patients are zinc deficient.
There is no evidence to support the use of benzodiazepine antagonists.
Use of ammonia lowering agents such as L-ornithine and L-arginine have some role in chronic liver disease but had no beneficial effect on survival when studied in the context of ALF.
Extracorporeal therapies improve severe hepatic encephalopathy. Best data is available for albumin dialysis.
what could cause porto systemic shunt in a patient with no liver dieases?
Portal vein thrombosis
Mechanisms of cerebral oedema in ALF?
- Vasogenic
- Cytotoxic
Cerebral oedema in CLD?
Not seen usually
Intracranial pressure parameters indicative of poor prognosis?
- ICP > 25mmHg
- CPP < 50mmHg
CPP and autoregulation in ALF?
Autoregulation is impaired in ALF
Management of patient with grade III/IV encephalopathy ?
- Tracheal intubation and mechanical ventilation
- Provide adequate sedation – propofol or a benzodiazepine and an opiate
- Normal/high serum sodium with hypertonic saline if necessary
- Prevent fever
- Maintain normocapnia
- Maintain in the head up position
- Maintain normovolaemia.
- Maintain normothermia
- Extracorporeal therapies
Management of increased ICP?
Mannitol bolus: 0.5–1.0 g/kg, normally using 20% (20 g/100 mls) mannitol. Serum osmolality should be monitored and should not be allowed to increase to above 320 mosmol/kg.
Hypertonic saline: slow infusion to maintain sodium levels of 145– 155 mmol/l.
Thiopentone (thiopental)
Hyperventilation
CVS management in ALF?
- Steroids 200-300mg/day if on Norad
Unexplained hypoxia when patients with ALF sit up?
Hepatopulmonary syndrome due to intrapulmonary dilation and shunting.
Indicative or liver transplant
Consequences of CLD?
- Pulmonary HTN (Porto pulmonary HTN)
What is terlipressin?
Splanchnic vasoconstrictor
What is Octreotide?
- Long-acting somatostatin analogue
- Reduces gastric secretion
- Reduces splanchnic blood flow
Management of refractory variceal bleeding ?
- Sengstaken-Blakemore tube
- Only the gastric balloon is inflated
- Oesophageal stents (Most effective)
Risks associated with insertion of Sengstaken-Blakemore tube?
- Oesophageal tear following balloon inflation
- PTX / Surgical emphysema
Diagnosis of hepatopulmonary syndrome?
- Bubble echocardiography
- Bubbles seen after 2-3 cardiac cycles
- Indication for liver transplant
What is The Clichy criteria for liver transplant ? Based on patients with ALF secondary to Hep B
- There is encephalopathy (coma or confusion) and
- Factor V level <20% (if aged <30) or
- Factor V level <30% (if aged 30 or above)
Disease-specific criteria for transplant?
- Budd-Chiari syndrome - HE & RF
- INR > 4.5 in a child
- Acute Wilson’s disease with HE
Management of Budd-Chiari syndrome in patients without HE & RF ?
Hepatic encephalopathy
Renal failure
- Thrombolysis
- TIPPS
Significance of AFP?
Elevated in liver cancer
Outcome for CLD patient undergoing elective liver transplant?`
The outcome is usually very good
ALT:AST ratio if the same?
Usually indicates ischemic hepatitis due to CCF, ischemic necrosis & hepatitis
When there is significantly raised WCC
Myeloproliferative disease should be investigated
Differential diagnosis in ALF?
- Shocked liver (Ischemic hepatitis)
- Haematological malignancies
- Drug toxicity
- Viral hepatitis
what are the specific therapies for unique causes of ALF?
- Paracetamol OD - NAC
- Pregnancy related ALF - Early delivery
- Autoimmune hepatitis - Steroids
What is vasoplegia syndrome?
- Low SVR
- Severe hypotension
- Normal or elevated cardiac index
- Hyperdynamic circulation
Mechanism of vasoplegia ?
- Activation of inducible NOS
- Increased availability of endotoxins
- Portal blood shunted past the liver to system
Risk factors for ICH secondary to cerebral oedema?
- Pts with rapid ALI which progress to HE
- Hyper-acute & acute presentations
- HE grade III/IV
- High serum ammonia > 150
- Young age < 35yo
- Pts with infection / sepsis
- Pts requiring vasopressor or RRT support
What are the kings college criteria for liver transplant?
See attached image
Contraindications for liver transplant?
- Lymphoma
What is hepatic encephalopathy ?
This is brain dysfunction caused by liver insufficiency and /or porto-systemic shunt (PSS)
Classification of HE according to underlying disease?
- Type (A) - ALF (Ass with cerebral herniation and ICH)
- Type (B) - Porto-systemic bypass or shunt
- Type (C) - Cirrhosis
Management of raised ICP?
- Head up
- Normocapnia
- IV Mannitol 0.5-1g/kg
- Controlled hyperventilation
- Hypertonic saline
- Therapeutic hypothermia (32-33 for 8-14h)
- Hypothermia for up to 5 days is acceptable
Target parameters to limit raising ICP in ALF?
- Below 20-25mmHg
- CPP > 50mmHg
what are the characteristics of an exudative fluid ?
- Higher levels of protein
- ## Filtration exceeds lymph flow
What is the normal level of protein in pleural fluid?
about 1.5g/dL or 15g/L
What is the criteria used to differentiate between exudate and transudate ?
Lights criteria
What is the cause of transudative effusion?
- Combination of increased hydrostatic pressures and decreased oncotic pressures
- CCF
- Cirrhosis / Ascitis
- Hypoalbuminaemia / Nephrotic syndrome
Characteristics of exudative effusion?
- Increased capillary permeability
- Pneumonia, cancer, PE, viral, TB
Kings college criteria for liver transplant?
See attached
