When to call a Liver Unit

1
When to call a Liver Unit

• Chronic Liver Disease
• Acute Liver Failure
• Hepatobiliary Surgery Issues
• Trauma
• RTAs, liver Bx,

2
Acute on Chronic liver Failure ACLF

• Acute Liver dysfunction
• No pre-existing liver disease
• No encephalopthy at that time
• ALF
• No pre-existing liver disease
• Symptoms / jaundice to onset encephalopathy lt 12
  -24 weeks\
• ACLF
• ..patients with previously well compensated
  chronic liver disease in whom an acute
  decompensation of liver function occurs due to
  the effects of a precipitating event..
• Sen et al Liver 200222(S2) 5-13.

3
ACLF trends
Leon et al Lancet 200636752-56
4
Natural History Chronic Liver Disease.
Christensen et al Scand J Gastro 198924999-1006
J Hepatology 200644217-231
5
Assessment of liver function severity
MELD score Mayo clinic
Child -Pugh score
1 2 3 Encephalopathy 0 I/II III/IV Ascites
Absent Mild gtModerate Bilirubin
µmol/Llt34 34-51 gt51 Albumin g/L gt35 28-35 lt28
INR lt1.3 1.3-1.5 gt1.5 grade A lt6 B 7-9 C
gt10 !!!
6
MELD and Prognosis
After Kamath et al Hepatology 200133(2)464-70
7
Varices Management
Vasopressin Westaby Gut 1988 29(3)372Gimson
Hepatology 1986

• Cochrane analysis 8 trials 864 cases
• Significant decrease mortality (RR0.73)
• Antibiotics
• Airway management
• Vasoactive agents Terlipressin

When to call Failure to achieve
haemostasis Gastric varices and no glue
experience Consider for CP C Rebleed Ask the
question Is this a Tp candidiate ?
8

• Call a liver unit
• Potentially life saving !
• 12 hours use (24 hours max)
• Pressure necrosis may occur at GOJ
• 50 re-bleed when tube deflated
• High complication rate - 25
• serious - 15
• Traction to skin or helmet
• (basket ball or cricket helmet)
• Intubated patient

Gastric balloon inflated 150 - 250 ml of fluid
20 contrast 80 water
9

• 116 patients with cirrhosis and variceal bleed
• HVPG measured within first 24 hours lt or gt 20
  mmHg
• If gt 20 randomized to TIPS or medical Rx

Monescillo et al Hepatology 2004 40793
Rx failure
CP B and C consider referral
Mortality
10
(No Transcript)
11
N67 to N 46
Rx maximum 2 weeks
Type I and II HRF
12
MAP increased 16 16mmHg in N grp (9212) 19
11mmHg in R grp (8316) Creatinine - useless
measure! Creatine produced in liver Decreased
muscle mass
13
Glasgow Alcoholic Hepatitis Score (GAHS)

• Multicenter, retrospective
• Score 5-12
• Derived from 241 patients with ASH
• Verified in 195 patients
• GAHS correctly predicted 28 day outcome in 81
• DF only 51

Forrest et al. Gut 2005
14
GAHS, steroids 28 day mortality

• 188 patients with ASH (Glasgow, KCH, Newcastle)
• All DF gt32 GAHS gt 9 in 64
• Patients with GAHS lt9 have an excellent prognosis
  without treatment
• GAHS gt 9 poor prognosis when steroids not
  given for whatever reason
• Other Rx to consider
• Pentoxyfylline
• Feeding

Forrest et al. J Hepatol 2007
15
CLD - Who to consider for Transplant
May be considered for transplanted with one
organ failure from intensive care

• Encephalopathy
• Ascites - difficult to control
• Hyponatraemia
• Renal dysfunction
• Variceal bleed
• Poor synthetic function
• HCC lt 5 cm (extended criteria 7 cm)
• Episode of SBP
• PBC - Bili gt 100
• Hepatopulmonary syndrome and portopulmonary
  hypertension are indications
• Should be abstinent from alcohol for 6 mnths

16
ALF Basic Handling And When To Refer

• Initial management and outcome of illness
• Make the diagnosis
• Consider Aetiology some treatable may need
  trans jugular liver Bx
• Progression to ALF?
• Prevention of encephalopathy (HE)?
• Limitation of severity of liver injury?
• Limitation of extra-hepatic organ failures?
• Maximise possibilities
• Spontaneous recovery
• Successful transplantation

17
(No Transcript)
18
Basic Handling And When To Refer
Liver ITU Kings College Hospital March
2006-February 2007 847 telephone discussions 579
patients
19
Prevent if possible
Schmidt et al Hepatology 200235876-882

• N-acetyl cysteine (NAC)
• Very safe Benefits from later
  administration ?
• Very effective if given within 16 hours of OD
• Other aetiologies? AASLD 2007 , Vergani et al
  2008

NAC in non paracetamol Grade I/II benefical
Gluathione Repletion Role in cerebral
oedema glutamine metabolism in
mitochondria Mitochondria NO interaction
Complex I
20
Survival by aetiology without transplantation
Grade III/IV, Kings College Hospital 1999-2003
Importance of Aetiology
21
Post partum RUQ / R chest pain - may be
heparinized
AST 2500, lactate 3 ARF, metabolic acidosis
AST 200, increased BP, RUQ/pleuritic pain Hb
fell, BP fell, AST 3000
Pregnancy related liver disease vasculopathy
and liver rupture
22
Hyponatraemia is a poor prognostic marker ALF
and CLD
23
Encephalopathy
Outcome of ALF/AHD at Kings College Hospital
1994-2004. n1544 All etiologies
Bernal 2007 Unpublished
24
Grade III/IV coma Young people Haemodynamic
instability Fever, SIRS, low Na Elevated NH4
(gt150) Renal failure Non-Acetaminophen 33/170
(19) Acetaminophen 55/210 (26)
Bernal W Hepatology 2008 2007
Who to monitor ?
SIRS HE 63 mortality vs 23 without
SIRS Schmidt et al Crit Care Med 200634337
25
Severity of Liver Injury
Outcome of ALF/AHD at Kings College Hospital
1999-2005. Paracetamol Etiology only. n390
INR on Admission
Bernal 2007 Unpublished
26
Severity of Liver Injury
INR gt 1.8 also separates groups
Outcome of ALF/AHD at Kings College Hospital
1999-2005. Non- Paracetamol Etiology only. n281
Admission Bilirubin (mMol/l)
Bernal 2007 Unpublished
27
Guidelines for referral
Paracetamol

• Arterial pH lt 7.30
• INR gt 3.0 day 2 or gt 4.0 thereafter
• oliguria and/or elevated creatinine
• altered conscious level
• Hypoglycaemia
• Elevated P04 (lt1.2 at Day 2 / 3)
• Hyponatraemia

Early acidosis (within 24 hours of ingestion) is
usually a drug effect and resolves seen in
association with high paracetamol levels
28

• Non-Paracetamol
• pH lt 7.30
• INR gt1.8
• oliguria/renal failure
• Encephalopathy
• Hypoglycaemia
• factor V lt 40
• shrinking liver size/ascites
• Na lt 130 mmol/L
• Bilirubin gt 300

Diagnostic issues Is it CLD Is it subacute
liver failure
Children (young) do not develop HE Pregnancy
related HE, AST gt 1000, low glu, INR
gt2 Budd-Chiari HE or renal dysfunction Wilson
HE, coagulopathy, haemolysis
29
Paracetamol Non-Paracetamol

• pH lt 7.30 pHlt7.3
• all 3 of the following INR gt 6.5
• within 24 hrs
• PT gt 100 INR gt 6.5 any 3 of
• Creatinine gt 300 µmol/l seronegative hepatitis
  or
• grade 3 - 4 encephalopathy drug related /
  halothane
• Bilirubin gt 300 µmol/l
• 
  INR gt 3.5
• 
  Age lt 10 yrs or gt 40 yrs
• 
  J - E gt 7 days

Lactate 4 hrs gt 3.5 OR 43 plt0.001 Lactate 12
hrs gt 3.5 OR 63 plt0.001
30

• Low P04 good prognosis
• Alpha feta protein
• MELD gt 30
• Liver volume lt 1000 ml
• Children - coagulopathy INR gt 4.5
• Budd Chiari renal failure HE
• Encephalopathy III/IV
• Plus Factor V lt 20 or lt 30 if gt 30 yrs of age

31
Cases

• 50 yr old lady unwell 2/12 Jaundiced 2 weeks
• Bili 280 AST 400 diagnosis provisional of Hep
  A (no virology)
• 2 weeks later admitted hospital
• alcohol wine 1 -2 glasses wine / night
• Bili 400 AST 300 INR 2.4 Ferritin 6000
• Immunoglobulin G 15, A 2 M 1.2 INR 1.8
• Autoantibodies and Hepatitis serology all
  negative
• Ultrasound heterogenous liver , spleen 13 cm,
  small amount free fluid
• 2 weeks later
• Bili 500, AST 120, INR 4.2

32
Liver Bx formation of arterio-portal fistula
bleeding
33
Pseudo-aneurysms and Bile leaks
ERCP and stent
Embolization
Haemodynamic collapse Malaena Haematemesis
Fever
34
Contacting a Liver Unit Early Appropriate
person Improving outcome Safe
transfer julia.wendon_at_kcl.ac.uk
35
(No Transcript)
36
When to call a Liver Unit

• Early
• . and speak with an appropriate person

37
Case

• 19 year old medical student
• 1 day history of jaundice
• 3 week history of malaise
• 3-4 day history of
• Lethargy
• Anorexia /Night sweats
• Arthralgia/ Myalgia
• Nausea
• Ultrasound- coarse texture, spleen 14 cm

• At referring hospital 2 days later
• Na 135 131 135-145 mmol/L
• Cr 168 163 45-120 µmol/L
• T Bili 216 526 3-20 µmol/L
• ALP 60 25 30-130 IU/L
• GGT 373 306 1-55 IU/L
• AST 39 23 10-50 IU/L
• ALB 28 25 35-50 IU/L
• HB 10.6 7.1 13.0-16.5 g/dl
• WCC 13.4 15.3 4-11.0
• PLT 229 240 150-450
• INR 2 2.2 (post vitamin K)

Whats the diagnosis? Whats the plan ?
38
Extra-Hepatic organ dysfunction
Outcome of ALF/AHD at Kings College Hospital
1999-2003. All Etiologies. n343
Bernal 2007 Unpublished
39
(No Transcript)
40
Teams make things work .
41
Principle Causes of Acute Liver Failure
ALF encephalopathy in a patient with NO previous
liver disease
Cause Agent responsible Viral
hepatitis Hepatitis A, B, D E, CMV, HSV,
Seronegative hepatitis (14 - 25 of cases in
UK) Drug related Paracetamol, Anti tuberculous
drugs, lipid therapies Recreational drugs
Idiosyncratic reactions anticonvulsants, NSAI,
cyproterone etc, etc Toxins Carbon
tetrachloride, Amanita phalloides Vascular
events Ischaemia VOD, Budd-Chiari
Heatstroke Other Pregnancy related liver
disease, liver rupture Wilson disease,
lymphoma, carcinoma, trauma
Paracetamol adducts - role in seroneg (30),
viral (10)
42
Transplantation for ALF - KCH
N236

• Survival
• 90-Day 1 Year
• Overall 73 71
• 1994-99 66 63
• 2000-04 81 79

plt0.01
Surgical techniques, immunosupression General
care, patient selection, organ preservation
43
ICH and Age
n380 plt0.0002
All Patients
Developing ICH
Ware et al Gastroenterology 197161(6)877-84
Age Group (years)
44
Model for End-stage Liver Disease MELD

• www.unos.org/resources/meldPeldCalculator.asp
• Predictive of 3/12 mortality
• Widely validated
• Basis of US transplantation listing

Malinchoc et al Hepatology 200031864-71
45
Clemmensen et al Hepatology 1999 29648-653
Bernal W Hepatology 2007
NH4 cut off 124 pH, cerebral oedema NH4
predict outcome Bhatia V Gut 2005
46
TIPSS vs surgical shunt
Technically successful in gt90 Controls acute
haemorrhage gt95 Rebleeding in up to 30 long
term reimaging and dilation Encephalopathy in
25 Diastolic dysfunction on echo - poor
prognosis Cazzaniga et al Gut 2006 Baveno
criteria Must assess CVS status Drop in portal
pressure requires normal RA function and
pressure Portal pressure lt 12, drop of 20
47
Initial Management

• Clinical monitoring Assessment
• Setting Staff
• Vital signs
• Conscious level neurology
• Urine output
• Blood glucose
• Arterial blood gas Lactate
• Low threshold invasive CVS monitoring

48
Adverse Etiology
Outcome of ALF/AHD at Kings College Hospital
1994-2004. n1544
Bernal 2007 Unpublished
49
Incidence of cerebral oedema Reviewed 229
patients Grade III/IV coma 1999-2002 Hyperacute
24 Acute 23 Subacute 9
NH4 Inflammatory response SIRS
HE 63 mortality vs 23 without SIRS Schmidt et
al Crit Care Med 200634337
Varies between sleepy and above Clinical state
may change very rapidly
50
Histoacryl Glue
140 patients 6 patients had radiographic
evidence PE 4.2 vs 1.8 ml injected Hwang et al
J Comput Assist Tomog 2001 Cerebral and coronary
emboli Endoscopy 2000 Pediatr radiol 2000,
Endoscopy 1998
Rebleed TIPS vs glue 15 vs 30 Longer in
patient stay 18 vs 13 days Mahadeva Am J
Gastroenterology 200398
51
GFR
Definitions may be problematic Creatine produced
in the liver Decreased muscle mass with
progressive liver disease
52
Role of Sodium in outcome from Liver
Transplantation
MELD gt 40 increased post -op mortality 2 of
cohort Role of early RRT
53
Treatable causes of liver failure

• Drug induced - withdraw the drug
• HSV Acylovir
• Hepatitis B lamivudine especially pre
  chemotherapy
• Mushroom poisoning penicillin / sylabarin
• Budd-Chiari anticoagulation /TIPS find treat
  cause
• Lymphoma chemotherapy
• Ischaemic hepatitis Rx underlying cardiac cause
• Auto-immune steroids aza Tacrolimus pre
  HE/MOF only
• Wilsons Penicillamine / Zinc/Trientene
  screening Not if ALF
• Pregnancy delivery
• Trans - jugular Bx - may be needed to exclude
  aetiologies