Fulminant hepatitis by pengtt

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									                                 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 (p<0.05)
    1500
                                               Marik 2005 CCM 53;1254
             NS       P<0.01       P   <0.05
                                               • LDL cholesterol did separate groups
    1000                                          – 8.2±7.6 vs 28.4±14
                                               • Mortality 39% vs 56%
                                               • 75% of those on pressors had abnormal
     500
                                                 response

       0
           Baseline    Increment       Peak
 mortality associated with lower baseline and increment (p<0.05)
                                           * P<0.001

 –correlates with APACHE III and SAPS
 –No correlate with other parameters other than cholesterol
      Encephalopathy             Portal Systemic Encephalopathy
                                 Portal systemic shunt
                                    – spontaneous collateral
                                    – Surgical
                                    – TIPPS
                                 Not at risk of cerebral oedema


                                 Precipitating factors
                                    – Sepsis
                                         · SBP Rx fluids ++
                                         · Albumin
HE of Acute Liver Failure
                                         · Avoid renal failure
Hepatocellular failure
                                     – CNS active drugs
Rapid onset
                                     – Electrolyte abnormalities
Cerebral oedema
Myoinositol levels not reduced       – Diuretics - over use
Cytotoxic and vasogenic              – Gastrointestinal bleeding
                    Hepatic encephalopathy in CLD
•   Not a cause of death ……. Providing the airway is managed
• Treat precipitating cause : sepsis screen, fluids…….
•   Association of SIRS with encephalopathy
•   Feed - std protein, high calorie, fibre content ideally vegetable based
•   Lactulose and enemas - cleaning or acidification
     – Als-Nielson BMJ 2004 ; 328: 1064
•   Non-absorbable antibiotics
•   Decreasing ammonia therapies
     – (i) ornithine and (ii) benzoate

•   Benzodiazepine antagonists - no efficacy Pomiers-Layrargues
    Hepatology 1989 10;969

•   Sedation - real risk in ward environment
     – Yes, they are a menace : up all night, climbing into the wrong bed,
       shouting
                                                     Incidence of cerebral
                                                     oedema

                                                     Reviewed 229 patients
                                                     Grade III/IV coma
                                                     1999-2002

                                                     Incidence
                                                     Hyperacute : 24%
                                                     Acute : 23%
                                                     Subacute : 9%

Progressive neuropsychiatric syndrome,
progressive neural inhibition
                                                 NH4
Occurs in both acute and chronic liver disease
                                                 Neurosteroids
Clinical state may change very rapidly
                                                 Inflammatory response
                                   Shawcross Lancet 365 2005
Larsen Neurochem International 2004 (44)
Increased ammonia in cerebral deaths :
splanchnic ammonia production Larsen et
al Hepatology 1998
NH4 cut off 124 .pH, cerebral oedema +
NH4 predict outcome Bhatia V Gut 2005

Partial pressure NH4 correlates with level
of encephalopathy Kramer Hepatology
2000:21
CBF variable : loss of autoregulation to
pressure

Terlipressin in ALF Shawcross et al;
Hepatology 2004;39(2):464-70
                              N=14




Jalan et al Gastroenterology o
2004;27:1338 Cooled to 32-33 C            PRE       POST n=7
                               ICP   45 (25-49)     16 (13-17) *
                               CBF   103 (25-134)   44 (24 -75) *
                               CPP   45 (37-56)     70 (60-78) *
                               CI    9.8 (7-13)     5.1 (4.3-6.1) *

                             •Arterial NH4 343 (109 - 490) to 259 (100-453
                             •Uptake 2.6 ( 0.6-6.3) to -0.3 (-3.1 - 1.4)
                                              Reduced risk of intracranial
                                              hypertension (p<0.05)




Reduction in ICP in treatment group
(p<0.005)




  Murphy et al Hepatology 2004;39(2):464-70
• Agitation and airway management
   – Grade III : Intubate ventilate and sedate with opiate and propofol
   – Control ventilation - avoid alkalosis
• Position - 10 to 20 degrees head up
• Insert reverse jugular line: JV sat 55 to 80%
• Tight control of glucose, K, pH, Na (145-150 mmol/L) Murphy et al Hepatology
  2004;39(2):464-70
• Ammonia : early CRRT
• MAP >65 : frequently not autoregulating - need to measure ICP
• Treat “ICP” - pupillary abnormalities
   – Mannitol 150 ml 20% (osmolarity < 320) or hypertonic NaCl (30%) : 20 ml
     Indomethacin 0.5 mg/kg
• Hyperventilation - only for ICP in association with high JV satn
• ICP trigger:-
   – JV saturation, ammonia >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 (P<0.05)
   – 6 mnth survival 6/12 MARS vs 4/11

Coagulopathy and
MARS treatment in CLD
Doria et al Clinical transplantation 2004;18:365
Single Pass Albumin Dialysis (SPAD)
Clearance of bilirubin, bile acids, NH4 : improved
Sauer Hepatology 2004;39:1048
                                       MARS
         Nathan et al Liver Transplant 2004;10:1109 Lai W et al Int Care Med 2005


• 18 patients with alcohol related AoCLD randomized to MARS or SMT over 7 days
• Significant improvement in encephalopathy
• No change in renal function or creatinine
• No change in ammonia or cytokine levels (TNF, IL-6, IL-10, IL-8), MDA, MELD fell
  in both groups


    10 patients with ALF grade III/IV coma Treated 8 hours on 2 consecutive days
    Increase SVRI on first Rx 1114±196 to 1432±245, changes not significant by end
       of second Rx
    No change in ICP 14.5 (7-25) to 14 (3-25)


MARS+ SMT vs. SMT Acute on Chronic Liver Disease n=70
Significant improvements in encephalopathy grade
No differences in survival        Hassanein et al AASLD 2004
                                                143 patients :observational study,
       Outcome of CLD in ITU
    Wehler et al Hepatology 2001;34:255-261




                                              30 patients with HRF
Apache III>90, pressors,                      8/30 30 day survival (median 21)
Clinical jaundice > 92% 1month                Ventilated survival 0/15
Mortality vs 11% in those with < 3            Non-ventilated survival 8/15
criteria
420 patients                                  No difference INR/alb/pressors
                                              J Gastroenterology and Hepatology
                                              Witzke et al 2004 19;1369
Gildea Chest 2004;126:1598
Accuracy of ICU scoring systems
                                      Graphical representation of LITU mortality and the
                                       Sequential Organ Failure Assessment System.
    Child Pugh 0.72
                                            100
    MELD       0.72                          90
                                             80

    APACHE II 0.78                Mortality
                                             70
                                             60
                                             50
                                  (Percent)
    SOFA       0.80                          40
                                             30
                                             20
                                             10
                                              0
                                                  1     2        3        4        5   6
                                                            No. of organ failure




                              PSE+CVS+RENAL failure =
                              98% Mortality
                              SOFA score cut off : 13

                             363 patients with
                             CLD admitted to LITU
               Guidelines for referral

    Paracetamol                                 Non-Paracetamol
Arterial pH < 7.30 or HC03 < 18                pH < 7.30 or or HC03 < 18
INR > 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
                                              < 1000 ml need OLT
                                              Na < 130 mmol/L
Children - coagulopathy
                                              Bilirubin > 300 µmol/l

Budd Chiari

Pregnancy related
 Paracetamol                           Non-Paracetamol
 pH < 7.30                                pH<7.3
                                                        Liver volume
 all 3 of the following                   INR > 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 < 10 yrs or > 40 yrs
Lactate : 4 hrs > 3.5 OR 43 p<0.001       J - E > 7 days
Lactate : 12 hrs > 3.5 OR 63 p<0.001
                                           MELD > 30
Children - coagulopathy INR > 4.5          Encephalopathy +
                                           Factor V < 20% or
Budd Chiari : renal failure + HE           < 30% if > 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

								
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