Liver failure
Hyper - acute liver failure
Acute liver failure
Greatest risk of cerebral
oedema, CVS failure
Greatest chance of
spontaneous survival
Sub - acute liver failure
Lowest risk of cerebral
oedema/ encephalopathy
Easily confused with CLD
Ascites
Lowest chance of
spontaneous survival
Principle Causes of Acute Liver Failure
Cause Agent responsible
Viral Hepatitis A, B, D E, others
Drug related Idiosyncratic and dose related
Toxins Carbon tetrachloride, Phosphorous
Amanita phalloides
Vascular events Ischemic hepatitis, Budd-Chiari, VOD, heat
shock liver
Other Pregnancy related, Wilson disease, lymphoma
No previous liver disease
Various definitions
Jaundice or symptoms to encephalopthy
• Decompensated chronic liver disease
– Decompensation with sepsis
· Bacterial peritonitis : Rx as “peritonitis”
· Bacteraemia, chest, urine
– Variceal bleed : frequently septic, endoscopic skills ± TIPS
– Encephalopathy
– Hepatorenal failure
– Alcoholic hepatitis : steroids, pentoxifylline, feed, delta bilirubin
Differential with ALF :
History
Pattern of LFT‟s
Imaging : ultrasound, CT scan
Biopsy : vary rarely indicated
• Liver trauma
Multi system disease
Coagulopathy
· INR important prognostic indicator in established ALF
· Platelet dysfunction DIC - rare
Metabolic
· Insulin resistance : Clarke et al Hepatology
· Hyperlactataemia :Bernal et al Lancet 2002 : useful to track
· Liver net producer of lactate Murphy et al Crit Care Med 2001
· P04, Mg, Na, glucose, K, pH
· High incidence of pancreatitis
Nutrition
· Frequent poor recent oral intake ± vomiting
· No evidence for protein restriction in either acute or CLD
· Gastric prophylaxis
· Increased metabolic requirements Walsh et al CCM
2000;28(3):649-54
Renal failure
• Common 45% of all cases
• Multifactorial - frequently pre renal, ATN rather than
HRS
• Role of intra-abdominal pressure
• Specific associations with viral disease, alcohol,
auto-immune
• CRRT or slow haemodialysis is ideal
• Anticoagulation
– epoprostenol, heparin, regional anticoagulation,
citrate
Infection : ALF
• Impaired innate and cellular immunity
• Bacterial infection 335 of 887 patients (550 episodes)
• Severe sepsis 58% mortality
• Septic shock 98% mortality
• Fungal infection 99 of 887 : 11% : 64% mortality
• Rolando et al Hepatology 2000 32:734, 31(4):872
• Components of SIRS associated with encephalopathy
• Rolando et al Hepatology 2000;32:734-9, Vaquero et al Gastroenterology
2003;125:755-64, Shawcross D et al J Hepatol inpress
• Cultures +++
• Antibiotics : broad initially - 5/7 course Antifungals
• No benefit to routine prophylaxis or Selective gut decontamination
• Rolando et al Semin Liver Dis 1996;16:389-402, Rolando et al Liver Trans
Surg 1996;2:8-13
Vasopressors in ALF
• What mean arterial pressure ?
– Clinical examination ….invasive
– Determined by JV saturation and ICP : autoregulating or not ?
• Which drug?
– Determine fluid responsiveness initially
· Whatever you can get your hands on
– In sepsis and MOF epinephrine may be detrimental
· increases splannchnic V02 : glucose turnover Meier Hellman et al 1997
Crit care Med
– Phenylephrine : decreased flow with decrease in spl V02 Reinelt
Crit Care Med 1999,27:325
– Norepinephrine as first choice
– Vasopressin may be potentially detrimental : cerebral
complications and potential splanchnic ischaemia
Results stratified according to blood pressure on day of SST
Harry et al Hepatology 2002
–57% of patients have abnormal synacthen response
–hypotension associated with lower baseline and increment (p65 : frequently not autoregulating - need to measure ICP
• Treat “ICP” - pupillary abnormalities
– Mannitol 150 ml 20% (osmolarity 150, pressors, fever, hyperacute and acute, pupilllary
abnormalities
• Temperature - avoid fever : hypothermia should not be undertaken routinely
Currently available…
Phase III study with BAL Demetriou et al Ann Surg 2004;239 660-670
MARS Therapy
Mitzner et al Liver Transpl 2000;6:277-286, Heemann et al Hepatology 2002;36:949-58
24 patients with CLD and „acute liver injury‟
• MARS group: reduced bile acids, bilirubin, encephalopathy
• Controls: biochemistry static, worsening
encephalopathy
– MARS 11/12 , SMT 6/12 (P90, pressors, 8/30 30 day survival (median 21)
Clinical jaundice > 92% 1month Ventilated survival 0/15
Mortality vs 11% in those with 3.0 day 2 or > 4.0 thereafter INR >1.8
oliguria and/or elevated creatinine oliguria/renal failure
altered conscious level encephalopathy
hypoglycaemia hypoglycaemia
shrinking liver size
300 µmol/l
Budd Chiari
Pregnancy related
Paracetamol Non-Paracetamol
pH 6.5
within 24 hrs
PT > 100 INR > 6.5 any 3 of :
Creatinine > 300 µmol/l seronegative hepatitis or
grade 3 - 4 encephalopathy drug related / halothane
Bilirubin > 300 µmol/l
Low P04 : good prognosis
Alpha feta protein INR > 3.5
Age 40 yrs
Lactate : 4 hrs > 3.5 OR 43 p 7 days
Lactate : 12 hrs > 3.5 OR 63 p 30
Children - coagulopathy INR > 4.5 Encephalopathy +
Factor V 30 yrs of age
The future:
Increasing liver disease
alcohol, HCV, NAFLD
HCC
Treatment changing
Innovative treatment options
liver support systems - further
Controlled trials required
Transplantation is a real option
Early discussion
Assume fluid deplete: time is tissue
Infection is common
Agitation=HE
Close observation
julia.wendon@kcl.ac.uk