Acute liver failure Flashcards
Hyperacute liver failure timescale
Encephalopathy within 7 days of onset of jaundice
Acute liver failure time frame
8-28 days jaundice o encephalopathy
Subacute liver failure timescale
Hepatic encephalopatjy 5-12 weeks after jaundice
Severe acute liver injury vs failure
Injury - elevated transferases, prolonged PT and jaundice
NO hepatic encephalopathy
Timescale of chronic liver disease encephalopathy
> 28 weeks initial presnetation -> encephalopathy
Presentation and clinical signs chronic liver disease encephalopathy
Jaundice, coagulopathy, HE
Portal HPTN
Platelets <150 - hypersplenism
Imaging
Signs of decompensating liver disease
- Jaundice
- HE
- Ascites/peripheral oedema
- Haematemesis or melaena
- Bruising/bleeding
Full liver screen
Viral serology - all heps, CMV, HSV1+2, HIV
Autoantibody screen - AMA (PBC), ASMA/ana (ai HEP), pANCA (PSC)
Immunoglobulins
IgA, IgG, IgM
Ferritin and transferrin sats
Sopper/caeruloplasmin
Alpha1 antitrypsin
What is used to screen for HCC, hpeB+C?
Alphfetoprotein
What is elevated IgA ass with
NAFLD, ALD
Elevated IgM ass wit
PBC
Elevated IgG ass with
AI hepatitis
What is US used to identify
- Degree dilatation biliary tree
- Stones in gallbladder
- Size, patency and flow of hepatic portal veins
- Spac occupying lesions >1cm
NOT good - degree fibrosis, stones in CBD
CT benfits in liver pathology
- Can use contrast eg to highkight hepatic artery
- Good at charcterising liver lesions eg mets vs abscess vs HCC
- Identifies vascular problems including bleeding, hepatic artery thrombosis or portal vein thrombosis
- Complications of biliary and gallbladder disease
- Bile duct dilatation, intra hepatic BD tumours, pancreatic tumours, level f biliary obstruction
- Doesnt always visulaise biliary stones
MRI in liver pathology summary
- Blood vessels, ducts, hepatic tissue
- Diffuse liver disorders
- Haemochromatosis, NAFLD
- Assess focal lesions
- Haemangioma, HCC, metastasis
- CI - metal implants etc
- Less of abdomen visible
MRCP summary
- Detailed images of hepatobiliary and pancreatic systems
- Detailed view of biliary dilatation and intra-ductal stones with up to 95% sensitivity
ERCP what can do, risk
- Endoscopic invasive rocecdure - tissue smapling and therapy, stone removal, dilating ducts, stent placement
- Diagnosis - cholangiogram
- High risk - pancreatitis, perforation, bleeding
Liver biospy benefits, risks
Targetes or non targeted - lesion or general parenchyma
Diagnsoiss+ assess severity
Bleeding high risk
What approach can use in liver biopsy if high risk bleeding
Transjugular approach - avoid puncturing liver capsule
What is definition of acute liver failure
No underlying chronic liver disease
Biochemical evidence of liver injury
Impaired liver function
AND hepatic encephalopathy (within 8 weeks of first illness)
Hepatic encephalopathy grade I
Conscious level - sleep reversal, restless
Personality - forgetful, agitated, irritable
Neuro - tremor, apraxia, incoordination, impaired handwriting
EEG - Triphasic waves (5Hz)
Grade 2 hepatic encephalopathy
Conscious level - lethargy, slowed
Personality - disorientated, loss inhibition, innapropriate behaviour
Neuro signs - asterixis, dysarthria, ataxia, hyporeflexes
EEG - triphasic waves (5Hz)
Grade 3 hepatic encephalopathy
Conscious level - sleepy confused
Personality - aggressive, disorientation
Neuro = asterixis, muscular rigidity, extensor planters, hyperreactive reflexes
EEG = triphasic waves (5Hz)
Grade 4 hepatic encepahlopathy features
Coma
Decerebrate positioning
EEG - Delta slow waves
Signs of acute liver failure
Raised ALT/transaminitis
Acutely deranged LFTs, jaundice, INR >1.5
Hyperacute liver failure signs on investigations
Significantly elevated PT
Low to mod rise in bilirubin
Marked increase INR
Rapid progression
V severe coagulopathy + jaundice+ IC HPTN
Causes of hyperacute liver failure
Paracetamol
HAV, HEV
Ischaemia
Acute liver failure causes
Pregnancy, HBV
Subacute liver failure investigations
V high bilirubin
Low transaminases
less marked or later onset coagulopathy
Splenomegaly
Causes - drug induced liver injury non paracetamol, indeterminate, hep E
Drugs causing acute liver faulure
- paracetemol (most comon in UK)
- herbals
- Anti-TB
- Chemotherapy
- Statins
- NSAIDs
- phenytoin
- Carbamazepine
- Ecstasy
- Flucloxacillin
Toxins causing acute liver failure
- Amanita phalloides (mushroom poisonning)
- Phosphorous
- Other toxins
- Wilsons disease
- AI
- Lymphoma
- Malignancy (infiltration typically by breast or lympohoma origin)
- HLH
Viruses causing acute liver failure
- Hep B, A, E (less frequent CMV, HSV, VZV, dengue)
- Hep C does not cause acute liver failure
Causes of acute liver failure in pregnancy
- Pre-eclamptic liver rupture
- HELLP
- Fatty liver of pregnancy
Vascular causes of acute liver failure
- Budd chiari syndrome
- Thrombosis
- Hypoxic hepatitis
What increases risk of kidney injury and cerebrak iedena in acute liver injury
ALT in 1000s
High lcatate
How much paracetamol can be toxic
10-15g
Paracetamol toxic metabolite and counteractives
N-acetyl-p-benzoquinoneimine ->
- Direct oxidative stress
- Mitochondrial dysfunction
- Immune reaction
in 24-72 hours -> hepatocyte necrosis and apoptosis
Glutathione naturally limits toxicity but in large overdoses depleted -> Nacetylcystine produces gluathione
What weight halves the maximum paracetamol level that can be taken a day
50 kg
>50kg = 4g, under = 2g (500mg per dose)
Complications of acute liver failure
- Hypoglycaemia
- Lactic acidosis
- Loss of hepatocyte metabolic function
- Coagulopathy
- HE
- massive systemic inflam response synrome →
- Multi organ failure rapidly
Symptoms of paracetamol toxicity <8 hours
Nausea/vomitting
Metabolic acidosis
Coma if paracetamol >800mg/L
Symptoms of paracetamol in 12-36 hours
Usually none occassionally abdo pain, RUQ pain
Sympotms 24-72 hours after paracetamol overdse
- hepatic failure,
- coagulopathy
- deranged LFTs
- hypoglycaemia
- RUQ pain, jaundice
- N+V
- renal failure
Drugs need to be cautious of for liver induced injury
Anti TB
Antibiotics - nitrofurantoin, flucloaxacillin, co-amoxiclav
Antiepileptics - phenytoin, valproate
NSAIDs
Cocaine and MDMA - ishcaemic inury
Which virus causes highest mortality in acute liver failure
HBV
What investigations do in acute liver failure sus AI cause
IgG and autoantibody screens - ANA and ASMA
Esp if female, personal or FH of AI disease
Liver biospy required
What resolves acute liver failure in pregnancy
Prompt delivery of placenta
First line investigations for ALF
Aetiology:
- Blood for Paracetamol serum level
- Urinary tox screen
- Viral serological screen
- Hep A, B, E
- HBsAg, anti-HBc IgM, HDV if +
- anti HAV, HEV IgM
- Herpes simplex (anti-HSV IgM)
- VZV (PCR + anti IgM)
- CMV
- EBV
- pARVOVIRUS
- Hep A, B, E
- AI markers
- ANA, ASMA, immunoglobulins
- Ultrasound - exclude chronic disease
6 hrly monitoring in ALF
PT/INR
Liver enzymes esp bilirubin, ALT
Renal function - urine output, urea, creatinine
ABG+lactate
Lipase/amylase for pancreatitis as complications
How long give N-acetylcysteine for in paracetamol overdose
PT<20 or up to 5 dyas
Acute treatment paracetamol overdose
N-acetylcysteine
Aggressive fluid resus - 3-4 litres crystalloid first 24 hours
glucose infusions if hypo
Intubate and ventialte if encephakopathy threat AW
Broad spectrum antibiotics and antifungals
Intotropes if hypotensive
Early CVVH - control acidosis/ammonia
Stress ulcer prophylacis
What electrolyte disturbances see in ALF
- Hypoglycaemia
- Hyponatremia
- Hypophosphatemia
- Hypokalemia
Complications of ALF
Electrolyte and glucose low
Renal damage
Pulmonary - oedema, ARDS, penumopathy
Infetion - septicaemia, pneumonia, UTI
Haemodynamic _/- coag/haemosatsis - hyperkinetic sydnrome, arrhythmia, thrombocytopenia and prolonged PT
Neuro - cerebral oedema -> intracranial HPTN -> brain death
Risk factors for IC HPTN if ALF
Hyperacute failure
Renal impariment
Need for inotropic support
Persistent elevation of arterial ammonia >150-200
NAC efficacy
100% effective under 8 hours
Drops dramatically with time over 8 hours
What to do if side effects from NAC
Anithistamines, slow infusion rate
Treatmetn for AI liver failure
Steroids IF no HE
Increase risk of sepsis
Specific treatments for Hep B and Hep E in ALF
Hep B - nucleotide analogues
Hep E - ribavarin
Budd chiari syndrome management
TIPS, hepatic vein stenting, thrombolysis
Criteria for paracetamol induced ALF for transplant referral
Arterial pH <7.3 or HCO3 <18
INR >3 day 2 or >4 thereafter
Oliguria and/or elevated creatinine
Altered LOC
Hypoglycaemia
Elevated lactate unresponsive to fluid resuscitation
Non paracetamol criteria for transplant referral ALF
pH <7.3 or HCO3<18
INR >1.8
Oliguria/renal failure ir Na<130mmol/l
Encephalopathy, hypoglycaemia or metabolic acidosis
Bilirubin >300 umol/l OR 17.6mg/dl
Shrinking liver sie
Kings college criteria for paracetamol transplant liver after fluid resus
pH<7.3
Lactate >3
Following 3:
-HE >grade 3
Serum creatinine >300
INR >6.5
Kings college criteria non paracetamol ALF for transplatn
INR >6.5
3/5 of:
-Aetiology - indeterminate, hepatitis, DILI
-Age <10 years or >40 years
Interal jaundice encepahlopathy >7 dyas
Bilirubin >300
INR >3.5
Medical CIs to liver transplantation
Untreated or progressive infection
Extrahepatic or metastatic malignancy
Progressive hypotension, resistant or vasopressor support
Clinically significant ARDS, Fi02>0.8
Fixed dilated pupils > 1 hours
Sev coexistent cardiopulmonary isease
HIV AIDS
Psychiatrics CIs to transplantation
Multiple episodes self harm >5
Active IV drug abuse or oral polydrug abise
Alcohol dependence or abuse
Established pattern of non compliance with treatment
Consistently stated wished to die
Chronic refractory schizophrenia resistant to therapy
Incapacitiating dementia or mental retardation
