Pulsion, Excalez MAB member

Fresenius, Ashai Kasei consultancy

julia.wendon@kcl.ac.uk

“Liver Failure”

Julia WendonKings College London and Kings College Hospital

London

Disclosure of speaker’s interests

(Potential) conflict of interest

Potentially relevant company

relationships in connection with

event 1

• MAB member of Pulsion and (Excalenz) : no payment

• I have undertaken consultancy work for Fresenius and AshaiKasei

• Pulsion and Baxter supported research through provision of products

What is Liver Failure ?

• Cirrhosis

– Fibrosis, Portal hypertension

• Decompensated Liver Disease

– Ascites, varices, renal dysfucntion

• Acute on Chronic Liver Failure

– Acute event with worsening of liver and other organ function

• Acute Liver Failure

– Previously normal liver : acute, hyperacute, subacute

• Post surgical Liver failure

• Liver dysfunction / failure in critically ill patients

• Post trauma liver dysfunction / failure

Possible points of CC referral

Is this new disease

Is this a homogoenous population

What is AoCLF ?

Asian view

minor fibrosis/ fat + viral, DILI

European / USA view

varices, sepsis, paracentesis, alcohol

Sepsis

Variceal bleed

Paracentesis

Metabolic status / drugs

Alcoholic hepatitis

Surgery

Alastair J. O’Brien Intensive Care Med (2012) 38:991–1000

Definition of organ failureModified SOFA score for Cirrhosis (The SOFA-CLIF SCORE)

Organ/system 0 1 2 3 4

Liver (Bilirubin, mg/dL)

<1.2 ≥1.2 - ≤1.9 ≥2 - ≤5.9 ≥6 - <12 ≥12

Kidney (Creatinine (mg/dL)

<1.2 ≥1.2 - ≤ 1.9 ≥2 - <3.5 ≥3.5 - <5 ≥5

or use of renal-replacement therapy

Cerebral (HE grade)

No HE

1 2 3 4

Coagulation (INR) <1.1 ≥1.1 – <1.25 ≥1.25 - <1.5 ≥1.5 – <2.5 ≥2.5 or Platelets≤20x109/L

Circulation (MAP mm Hg)

≥70 <70 Dopamine ≤5or Dobutamine or Terlipressin

Dopamine >5 or E ≤ 0.1 or NE ≤ 0.1

Dopamine >15 or E > 0.1 or NE > 0.1

Lungs PaO/FiO2: or SpO2/FiO2

>400

>512

>300 - ≤400

>357 - ≤512

>200 - ≤300

>214 - ≤357

>100 - ≤200

>8 - ≤214

≤100

≤89

GASTROENTEROLOGY 2013;144:1426–1437

Acute on chronic liver failure:

Other factors and prognosis

Levesque E et al. J Hepatology 2012, n = 377

Source :

Chest : HE

Ascites

Blood

Urine

MDR organisms / infections

18% overall BUT :

4, 18 and 35 % of community, HCA,

nosocomial

Efficacy of treatment only 40% in

nosocomial sepsis

Mortality of 25% vs 12% for MDR

Multivariate analysis : predictors of mortality ignoring appropriate antiobiotic choice

diagnosis of infection, age, Bilirubin, creatinine,

Multivariate analysis : predictors of mortality considering appropriate antiobiotic choice

diagnosis of infection , appropriate antibiotic choice, age, INR

Alcoholic hepatitis

Lille score

Age

Renal

INR

Bilirubin

Albumin

Delta Bilirubin

Aliment Pharmacol Ther 2014; 39: 721–732, Burroughs

Comparison of 9 scores : no difference in AUC

3.19-0.101*(age)+0.147*(alb day 0)

+0.0165*(change in Bili)-

0.206*(renal insufficiency

{0/1:creat < or > 115 µmol/L)-0.0065

(Day 0 Bili)

Hypoxia and CLD

Common

Hydrothorax : “SBP”

Atelectasis

Sepsis

Interstitial lung disease

Intra-abdominal pressure Ascites

Hepatopulmonary syndromeO2, position

Portopulmonary hypertensionsidenafil, PGI2, bosanten

Aliment Pharmacol Ther 2015; 41: 189-198

Pro-coagulant

Protein C, S, FVIII

and ATIII

Thrombomodulin

resistant

Avoid FFP

Increase anticoagulation

The 4 fluids of lifeJournal of Hepatology 2014 vol. 60 j 1310–1324

Journal of Hepatology 2010 vol. 53 j 397–417

SBP

Endothelial markers TLR4, IL-10

Phagcytosis

Oxidative burst

Albumin for bacterial infections other than

spontaneous bacterial peritonitis in cirrhosis. A

randomized, controlled study.

• J Hepatol. 2012 Oct;57(4):759-65.

• Non SBP infections 100 patients

• Antibiotics ± albumin at diagnosis and day 3

(1.5 and 1 g/kg)

• No difference in survival at 3 mnths

• Improved creatinine and circulation markers –

no difference in HRF ( 1 vs 3)

Journal of Hepatology 2015

62 822–830

Thierry Thévenot

• Resuscitation : Airway

• Coagulation support - as per massive Tf

• Diagnostic endoscopy +

• Therapy

• Vasoactive drugs

• Endoscopic therapy

• banding and glue

• Failed drugs + OGD

• Balloon tamponade

• TIPS

Lactate

Number of endoscopies

CXR – that wasn’t seen before the OGD!

…………….

RRT/ metabolic support : yes or no

Na, brain and outcome

Critical Care 2014, 18:700 Increased ITU stay and mortality

Liver International (2013)

Acute on chronic liver failure:

Prognostication based on scores

Levesque E et al. J Hepatology 2012, n =377

A

B

C

D

The American Journal of GASTROENTEROLOGY 2014 McPhail et al

• A SOFA/CLIF-SOFA score of greater than 13 on Day 1

• 90% mortality rate

• SOFA scores greater than 13 on Day 3 and 7

• 89% and 90% mortality rates respectively

• Lactate level greater than 4 mmol/L on Day 1

• 81% mortality rate

• Lactate level greater than 4 mmol/L on day 3 and 7

• 91% mortality rate and 88% mortality respectively

• The absolute SOFA score on day 3 was a better predictor of mortality than change in

score.

• Delta SOFA score changes

• Increase from day 1 : mortality 51%

• Unchanged : mortality of 42%

• Decrease after Day 1 : mortality was 28%.

Mark J. W. McPhail Clinical Gastroenterology and Hepatology 2014

The Royal Free Hospital Score: A Calibrated Prognostic Model for Patients With

Cirrhosis Admitted to Intensive Care Unit. Comparison With Current Models and CLIF-

SOFA Score

Am J Gastroenterol. 2014 Feb 4.

Burroughs AK

Incorporation of age and wbc : CLIFF C score

Jalan et al Journal of Hepatology

2014 vol. 61 j 1038–1047

Fixing specificity at 95% and estimating sensitivity (bootstrap

method)

A cut-off value of greater than 14 for CLIF-SOFA gives a sensitivity of

32% (26%– 40%)

A cut-off of greater than 12 for SOFA gives a sensitivity of 33 % (26–

39)

Suggests neither score : SOFA or CLIFF SOFA provide an accurate

indicator of futility.

Mark J. W. McPhail Clinical Gastroenterology and Hepatology 2014

Can we predict “Futility”

The right lobe is injured more commonly than the left

(>85% involve segments VI, VII, and VIII)

Deceleration injury

IVC and hepatic veins

Children at increased risk -

flexible ribs and a weaker

connective tissue framework

Grade 3 – laceration >3cm deep Grade 5 – laceration >75% of lobe

juxta-hepatic venous injury

Pseudo-aneurysms

Presentation 2 weeks post trauma

Haemodynamic collapse,

Malaena, Haematemesis

Obstructive liver function

Rare in

those managed with

embolization

Horse kick injury

Failure of stent with ongoing

high volume drain loss

Ileus - consider nasobiliary tube

33% bile leakAll managed with ERCP

Stent placed across sphincter

Bala et al. Scandinavian

Journal of Trauma, Resuscitation

And Emergency Medicine

2012, 20:20

Acute Liver Failure

Bernal et al, Lancet 2010

Bone marrow stained for T cell marker

CD3

in situ hybridization for EBV

Liver Int 2013

Coagulation

Journal of Hepatology

2012 vol. 57 780–786

Mallett et al

Larsen et al J Hepatology 2016

Bernal et al 2016

D1: INR 6.5 rising to 8.5, CK 150K, ALT 9,000 , ARF, lactate 6 - D2 INR 5, lactate 3.0, ALT 7000

Found outside club - fitting – intubated and brought to ED : Temp 41 seizure control : D0

Teams make things workjulia.wendon@kcl.ac.uk

Case : 50 year old man ALD, occasional drinking but remains in full employment

Presents jaundice, oedema, SoB - ?PE Rx clexane - admitted to ward

Day 2 : CT-PA negative BUT now Confused ++, malaena developed

Intubated for OGD in theatre : no bleeding point seen

Extubated - bradycardic, intubated, CPR X 1 cycle

In recovery - annuric, acidotic, adrenaline / noradrenaline infusions

pH 7.06 pO2 8.6 pCO2 8.2 HCO3 13.6 BE-14 Fi02 0.5

Lactate 2.7 mMol/l

Na 135 K 6.8

Urea 30 (N< 7) Creatinine 587 (N < 120)

Bilirubin 100 µmol/L (5.8 mg /dl)

ALP 56 AST 244 GGT 339

WBC 16.4 Hb 12.4 Plt 73

INR 2.94 APTT 2.02

CRP 190

Child Pugh 6-8 (pre)MELD 27SOFA 17CLIFF COF ACLF 3CLIFF C 70 (91% mortality)

Swollen inflammedLeg with area of necrosis

Day 4

Free of pressorsPassing urine Fi02 0.4INR 1.6

Culture negative Rising ASO titre

Discharged to ward day 18

*Patients who fulfil these criteria may still have structural damage such as tubular

damage. Urine biomarkers will become an important element in making a more accurate

differential diagnosis between HRS and acute tubularnecrosis.

Journal of Hepatology 2015

Rare

Most have an AKI

Mark J. W. McPhailClinical Gastroenterology and Hepatology 2014