Acute hepatic failure

PB Sherren ST7 ICM

Learning Objective

• Understand the different types of Acute hepatic failure (AHF)• Acute Liver Failure (ALF)• Acute-on-Chronic Liver Failure (AoCLF)• Post-hepatectomy liver failure

• Appropriate therapies and support of the liver

• Role of transplantation and other advanced support

ALF definition

Development of severe hepatic dysfunction within 6 months of the onset of symptoms in the absence of chronic liver disease• Acute Hepatitis with elevation AST/ALT• INR>1.5• Encephalopathy

Hyperacute, Acute or Subacute

ALF

Common causes of ALF

AoCLF

Acute hepatic insult manifesting as jaundice and coagulopathy, complicated within 4 weeks by ascites +/- encephalopathy in a patient with previously chronic liver disease

Bil >85 μmol/L and INR >1.5 mandatory

AoCLF vs end stage CLF

AoCLF

Precipitants of AoCLF

Post hepatectomy liver failure

Impaired ability of the liver to maintain its synthetic, excretory and detoxifying functions characterised by impaired coagulation and hyperbilirubinaemia on or after postoperative day 5.

50/50 definition - PT >50% and Bilirubin >50μmol/L

Grade A, B and C

Caring for the liver patient

Don’t forget the basics!

History and Examination

Send bloods ++• FBC• Coag, fibrinogen, TEG/ROTEM• Biochemistry• LFTs and GGT• Paracetamol/salicylate level• Arterial ammonia• Blood gases (Lact/glucose)• β-HCG• Viral hepatitis serology• Autoimmune screen, copper and caeruloplasmin• AFP• HIV test

Other investigations

• Liver US and doppler ASAP

• +/- CT/MRI

• Liver Bx?

Management

Good ICU Housekeeping• Stop hepatotoxic drugs• Optimise haemodynamics for oxygen delivery• Steriods?• CVC/Vascath/arterial line early with US. PAC?• Invasive ventilation +/- neuroprotection?• 30o head up• Early enteral nutrition (protein 1-1.5g/kg/day)• Stress ulcer prophylaxis (PPI)• Aperients• Antimicrobials• Glycaemic control

Specific Rx

• Paracetamol – NAC• Budd Chiarri – Anticoagulation/TIPS• Autoimmune – Steroids• Acute Fatty Liver of pregnancy – Delivery

baby•Wilsons – Chelating agents• Lamivudine and Aciclovir

Paracetamol OD• Common poisoning

• <1% cases of OD result in significant hepatotoxicty

• CYP450 convert paracetamol to NAPQI

• NAPQI EXTREMELY hepatotoxic

• Usually conjugated with hepatic glutathione

Paracetamol OD

• Bad• Malnutrition, ETOH abuse, enzyme inducing drugs• Large staggered OD• Delayed presentation and initiation of NAC

• N-acetylcysteine augments glutathione levels

• NAC highly effective if delivered within 8-12hrs

• Prescott normogram used to determine risk

Cardiovascular• Hyperdynamic and hypervolaemic

•Moderate incidence adrenal dysfunction

• CO monitoring and fluid responsiveness

• PAC • Right ventricular cardiomyopathy• Hepatopulmonary shunt and pulm Ht

• Noradrenaline

Variceal bleed• Restore Blood volume• Correction of coagulopathy• Reduce portal vascular resistance• Terlipressin/octreotide• 5/7 Abx (Tazcoin/cephalosporin)

• PPI?• OGD• Banding• Glue• Stenting

• Sengstaken• TIPS

Coagulopathy• Coagulation• Low fibrinogen• Low levels of II, V, VII, IX, X, APC, Protein C/S• Mixed fibrinolytic/antifibrinolytic effects

• ‘Auto-anticoagulation’ vs prothrombotic• NO routine correction of INR (incl for lines)• Thromboelastometry helpful (TEG vs ROTEM) • Everything changes if bleeding • Generally platelets/fib 1st• FFP/cyro vs PCC/FCC• TXA and Calcium

Ventilation

• Hepatopulmonary syndrome and shunting• Pulmonary hypertension may need ↓PVR• IAH/IACS

• Early intubation for Grade III/IV HE• Neuroprotection vs standard ARDsnet• LRTI/VAP common, low threshold for Abx• Consider paracentesis in IACS

Encephalopathy and cerebral oedema

• Common in ALF and grade III/IV HE and NH4 >150• Cytotoxic and vasogenic/hyperaemic in origin• Poor autoregulation• ICP>25mmHg and CPP<50mmHg bad prognosis• Sepsis/SIRS detrimental• Reverse Jugular venous oximetry • ICP bolt risk vs benefit• TBI like ICP management• NO evidence for neuromonitoring• CRRT/plasma exchange

Hepatorenal Syndrome• Not the commonest cause of AKI in AHF• ATN/nephrotoxic drugs/glomerulonephritis/IACS

• HRS diagnosis of exclusion• Type 1 vs Type 2• Results from reduced perfusion• Splanchnic vasodilation• Poor autoregulation • ↓ renal prostaglandin synthesis and other vasoactive mediators

• HAS/terlipressin• Early CRRT

Renal Replacement Therapy• Haemofiltration vs HD/HDF?

• Some low level evidence for NH4+ clearance

• Start early

• Esp if Grade III/IV HE and NH4+>150

• Aim for dose of 35ml/kg/hr (Calculated vs actual dose received?)

• No evidence for high volume haemofiltration

Microbiology• Highly susceptible to infection (LRTI/SBP/urinary/lines/wounds)

• SIRS/hyperdynamic/endotoxin translocation vs Bacteraemia

• Proven rates of 80% bacterial and 30% fungal

• Gram +ve in 1st 3-4 days followed by gram –ve and fungal infections

• Prophylaxis offers no mortality benefit

• Maintain high vigilance

• Refer to local guidelines and micro team

ALF transplant Criteria• Paracemol vs non paracetamol• King’s college criteria

• Paracetamol• pH <7.3 >24hrs post overdose• Grade III/IV HE + Creat >300 + PT >100s

• Non Paracetamol• pH <7.3 or PT >100s• HE III/IV with any 3 of the following

• Age <10 or >40• Bil >300• Jaundice to HE time <7 days• PT >50s• Seronegative hepatitis or drug induced

Transplant• Multidisciplinary decision

• Specialised service managed at supraregional centres

• If in doubt=refer/discuss

• Outcomes from transplant depend on ALF vs AoCLF vs CLF

• Live donor vs DBD vs DCD. Orthotopic and Domino Tx

• Complex anaesthetic+++

• Protocolised ICU post op management • TEM guided coagulation (balance bleeding vs HA/anastomosis flow)• Antibiotics• Immunomodulation• Early US and dopplers• MDT approach

Artificial Liver Support• Bridge to transplant or recovery?

• Evidence?

• Detoxifying systems• Albumin dialysis• MARS (albumin dialysis/detoxifying and de-ionising columns)• Plasmaphoresis with FFP promising in ALF

• Bioartificial Systems• Extracorporeal liver perfusion old technology• Other systems using hepatocytes• ELAD study pending publication

Questions?

Conclusion

• Don’t forget the basics• Resuscitate the patient • Good ICU house keeping• ALF vs AoCLF vs CLF• Antidotes/Specific Rx where appropriate• Complex/systemic disease with multi-organ

effects • EARLY referral/discussion with a liver unit