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1、 Liver failureSub - acute liver failure Lowest risk of cerebral oedema/ encephalopathy Easily confused with CLD Ascites Lowest chance of spontaneous survivalHyper - acute liver failure Acute liver failure Greatest risk of cerebral oedema, CVS failure Greatest chance of spontaneous survivalCauseAgent
2、 responsibleViral Hepatitis A, B, D E, others Drug relatedIdiosyncratic and dose relatedToxins Carbon tetrachloride, PhosphorousAmanita phalloides Vascular events Ischemic hepatitis, Budd-Chiari, VOD, heat shock liverOther Pregnancy related, Wilson disease, lymphomaPrinciple Causes of Acute Liver Fa
3、ilurePrinciple Causes of Acute Liver FailureNo previous liver disease Various definitions Jaundice or symptoms to encephalopthyDecompensated chronic liver disease Decompensation with sepsis Bacterial peritonitis : Rx as “peritonitis” Bacteraemia, chest, urine Variceal bleed : frequently septic, endo
4、scopic skills TIPS Encephalopathy Hepatorenal failure Alcoholic hepatitis : steroids, pentoxifylline, feed, delta bilirubinDifferential with ALF : History Pattern of LFTs Imaging : ultrasound, CT scan Biopsy : vary rarely indicatedLiver traumaMulti system diseaseCoagulopathy INR important prognostic
5、 indicator in established ALF Platelet dysfunction DIC - rareMetabolic 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 pancreatitisNut
6、rition 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 failureCommon 45% of all cases Multifactorial - frequently pre renal, ATN rather than HRS Role of i
7、ntra-abdominal pressure Specific associations with viral disease, alcohol, auto-immune CRRT or slow haemodialysis is idealAnticoagulation epoprostenol, heparin, regional anticoagulation, citrate Infection : ALFImpaired innate and cellular immunityBacterial infection 335 of 887 patients (550 episodes
8、)Severe sepsis 58% mortalitySeptic shock 98% mortalityFungal infection 99 of 887 : 11% : 64% mortalityRolando 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
9、et al J Hepatol inpressCultures +Antibiotics : broad initially - 5/7 courseAntifungalsNo benefit to routine prophylaxis or Selective gut decontaminationRolando et al Semin Liver Dis 1996;16:389-402, Rolando et al Liver Trans Surg 1996;2:8-13Vasopressors in ALFWhat mean arterial pressure ? Clinical e
10、xamination .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 M
11、ed Phenylephrine : decreased flow with decrease in spl V02 Reinelt Crit Care Med 1999,27:325Norepinephrine as first choice Vasopressin may be potentially detrimental : cerebral complications and potential splanchnic ischaemiaResults stratified according to blood pressure on day of SST050010001500NS
12、P65 : frequently not autoregulating - need to measure ICPTreat “ICP” - pupillary abnormalitiesMannitol 150 ml 20% (osmolarity 150, pressors, fever, hyperacute and acute, pupilllary abnormalitiesTemperature - avoid fever : hypothermia should not be undertaken routinelyCurrently availablePhase III stu
13、dy with BAL Demetriou et al Ann Surg 2004;239 660-670MARS Therapy Mitzner et al Liver Transpl 2000;6:277-286, Heemann et al Hepatology 2002;36:949-5824 patients with CLD and acute liver injuryMARS group: reduced bile acids, bilirubin, encephalopathyControls: biochemistry static, worsening encephalop
14、athy MARS 11/12 , SMT 6/12 (P90, pressors, Clinical jaundice 92% 1month Mortality vs 11% in those with 3.0 day 2 or 4.0 thereafterINR 1.8oliguria and/or elevated creatinineoliguria/renal failurealtered conscious levelencephalopathyhypoglycaemiahypoglycaemiashrinking liver size300 mol/lParacetamolNon
15、-ParacetamolChildren - coagulopathyBudd Chiari Pregnancy relatedpH 6.5within 24 hrsPT 100 INR 6.5 any 3 of :Creatinine 300 mol/lseronegative hepatitis or grade 3 - 4 encephalopathydrug related / halothaneBilirubin 300 mol/lINR 3.5Age 40 yrsJ - E 7 daysParacetamol Non-ParacetamolLactate : 4 hrs 3.5 O
16、R 43 p 3.5 OR 63 p 30 Children - coagulopathy INR 4.5Encephalopathy +Factor V 30 yrs of ageLow P04 : good prognosis Alpha feta proteinLiver volumeThe future: Increasing liver diseasealcohol, HCV, NAFLDHCCTreatment changing Innovative treatment options liver support systems - further Controlled trials requiredTransplantation is a real option
