Emergency presentation

in liver disease

By : DR AbdelRahman A Mokhtar
Professor of Internal Medicine ( Hepatogastroenterology )
Mansoura University …….2013
Presentation At A Glance
 Background on Liver Function
 Review of liver physiology
 Structural components of the liver.

 Normal liver and road map for hepatic

Emergencies.
 Emergency presentation of acute liver disease.
 Emergency presentation of chronic liver disease.
 Jaundiced emergencies.
 Acute presentation post liver transplant.
Let’s Take It From The Top
 A Physiology Review
Functions of the Liver:
 Largest organ in body, integral to most metabolic
functions of body, performing over 500 tasks

Produces over 160 different proteins

Makes clotting factors for the blood
 Only 10-20%detoxifies,
Metabolizes, of functioning
synthesizes liver is required to
sustain life
 Removal of liver will result in death within 24
hours
Functions of the Liver
 Main functions include:
 Metabolism of CHO, protein, fat
 Storage/activation vitamins and minerals
 Formation/excretion of bile
 Steroid metabolism, detoxifier of drugs/alcohol
 Action as (bacteria) filter and fluid chamber
 Conversion of ammonia to urea
 Gastrointestinal tract significant source of ammonia
 Generated from ingested protein substances that are
deaminated by colonic bacteria
 Ammonia enters circulation via portal vein
 Converted to urea by liver for excretion
The Urea Cycle Aspartate Transaminase(AST)

Alanine Transaminase (ALT)

Normal Liver and Road map for hepatic
emergencies
Interrupted liver cell function….HCF.
Interrupted Arterial circulation…ischemic liver.
Interrupted portal circulation…..PH .
Interrupted venous
outflow……Acute BCS.

Interrupted bile flow

cholestatic emergencies.

Disturbed anatomical integrity….traumatic liver injury & post transplant &

oncologic emergencies.

Disturbing other organs : HPS & HRS.

And Now Our Featured
Presentation…
 Emergency presentation of
acute liver disease.
ALF
Definitions
Fulminant hepatic failure….
A potentially reversible disorder due to
Described in 1970 severe liver damage with an onset of
encephalopathy within 8 weeks of symptom
appearance and in the absence of preexisting
liver disease ( Trey & Davidson ,1970 )

Modified in 1993 Considering the interval between the onset of jaundice

and the development of encephalopathy in recognition of the fact that the
jaundice to encephalopathy time is an important prognostic index
N.B
PATHOPHYSIOLOGY :
PATHOPHYSIOLOGY :
 The spectrum of functional derangement.
 Factors determining the severity.
 The initiating events and their clinical
implications .
 The clinical expression.
The spectrum of functional derangement :

CEREBRAL OEDEMA

HAEMODYNAMIC INSTABILITY

RENAL FAILURE

COAGULOPATHY

PROFOUND METABOLIC DERANGEMENT

IMMUNE DERANGEMENT WITH LIABILITY TO

BACTERIAL & FUNGAL SEPSIS
Factors determining the severity & prognosis:

Regegenerative capacity

ALF is still responsible for 6% of mortality from liver

disease.
In earlier reports mortality was around 85% , however in
the era of transplant the one year survival became 60 –
80 % in higher centers.
The initiating events and their clinical implications :
The initiating events and their clinical implications .

 Drug induced ALF ( esp. acetaminophen toxicity ) has surpassed

viral hepatitis as the most common etiology in the states & UK .
The initiating events and their clinical implications :

Unlike other causes of ALF drug induced LF

arises more often in older than younger
patients , especialy 60 yrs old or more.
Acetaminophen toxicity
 The most popular analgesic antipyretic.
 Recommended < or = 4 gm / day.
 Sustained consumption of 4 gm/ day for > 4days may cause
asymptomatic increase of serum liver enzymes with no evidence of
serious liver injury.
 Enhanced liver injury has been described with consumption of
therapeutic doses for symptom relief at the onset of acute liver
disease due to other causes.
 Preexisting conditions as alcohol abuse may influence the liver
susceptibility to lower doses of acetaminophen.
 Compared with all other causes of ALF , patients who had ingested
acetaminophen , had higher rates of spontaneous recovery and
better outcomes.
Viral infections :
 The predominant cause in developing world .
 Hepatitis A , B ,and E accounts for most

cases .
Viral infections :
 HEV:
 The most common cause of ALF in India , Pakistan , China & south east Asia.
 Mortality can exceed 50% if no emergency liver transplant available.

Highest mortality in pregnant females .
 HBV:
 The main cause of ALF in Asia , Sub-saharan Afica and the Amazon basin.
 Follow 4% of acute HBV & markedly decrease after vaccination programs .

 ALF can develop on top of CHBV

In situations where viral status change e.g
 Seroconversion ( from immune tolerance to immune clearance )
 Superinfection with HDV.
 Reactivation whether spontaneous or after drug induced immune suppression which is more
aggressive and more fatal and so prophylactic antiviral should be given for such patients,

 Other viral causes :

 Herpes simplex types 1 & 2 , VZs , EBV , CMV and Parvovirus 19.


HCV is a rare cause .
The initiating events and their clinical implications :
The clinical expression:
 ALF leads to
A unique
combination of
often rapidly
progressive
severe multi
organ failure
with
unpredictable
complications .
Management
Evaluation
History taking
 Symptoms..GI upset , Gen malaise up to confusion.
 Detailed history looking for the cause.

 Physical & Mental examination:

To differentiate acute
from acute on top of CLD.

To identify a possible
cause
Monitoring mental status.
Monitoring mental status.
Laboratory evaluation :
 Evidence of ALF
 Possible cause,
 Evidence of
complications.
Liver biopsy :

 To confirm the etiology if lab results are

inconclusive.
 Transjugular approach is preferred.
TREATMENT
Treatment Principles : 1
 Dealing with the possible
cause :
May limit the severity.

Potentially prevent
progression from isolated
hepatic failure to multi
organ damage,
 2
Treatment Principles :
 Supportive care in ICU

To maintain body
systems & combat
multi organ failure
 3
Treatment Principles :
 Liver transplant when
indicated

This is the only definitive treatment for patients

who failed to have spontaneous
regeneration.

Early identification of those who will not

recover is of utmost importance.

Different selection criteria are used at

different centers
Future directions :
Artificial liver support system now is the most potential.

Bioartificial support systems utilizing hepatocytes …pose a lot

of challenges.

Hepatocyte transplant ..under investigation.

Fruitful directions :
Public health measures to :

Minimize drug – induced ALF.

Vaccination a against A, B and E

viruses,
Normal Liver and Road map for hepatic
emergencies
Interrupted liver cell function….HCF.
Interrupted Arterial circulation…ischemic liver.
Interrupted portal circulation…..PH .
Interrupted venous
outflow……Acute BCS.

Interrupted bile flow

cholestatic emergencies.

Disturbed anatomical integrity….traumatic liver injury & post transplant &

oncologic emergencies.

Disturbing other organs : HPS & HRS.

Emergency presentation of
chronic liver disease.
 Natural Course of chronic liver disease.

Chronic
Chronic
liver Compensated Decompensated
liver cirrhosis Death
disease
disease cirrhosis

Development
Development of
of complications:
complications:

·· Variceal
Variceal hemorrhage
hemorrhage
·· Ascites
Ascites
·· Encephalopathy
Encephalopathy
·· Jaundice
Jaundice
Acute Complications of Cirrhosis Result from
both vascular & LCell decompensation

Variceal
Portal hemorrhage
hypertension Spontaneous
Spontaneous
bacterial
bacterial
Ascites peritonitis
peritonitis

Cirrhosis Hepatorenal
Hepatorenal
syndrome
syndrome

Encephalopathy
Liver
insufficiency
Jaundice
Varices
 Esophagus
 Gastric
 Colo-rectal
 Portal hypertensive gastropathy
 Hepatic
Encephalopathy

 Reversibledecrease in neurological
function secondary to liver disease
PATHOPHYSIOLOGY OF HEPATIC ENCEPHALOPATHY

Hepatic Encephalopathy
Pathogenesis
Toxins

NH33
Shunting
Failure to GABA-BD
metabolize receptors
NH33

Bacterial action
Protein load
load
Hepatic Encephalopathy
Variants

· Type
Type AA
Associated with Acute
liver failure
· Type
Type B
Associated with porto-
systemic Bypass without
intrinsic hepatocellular
disease
· Type
Type C
Associated with Cirrhosis
and porto-systemic
shunting

Ferenci
Ferenci et
et al.,
al., Hepatology
Hepatology 2002;
2002; 35:716
35:716
Characteristics of Type A vs. Type C
Hepatic Encephalopathy
Type A Type C
·Rapid onset ·Gradual onset
·Frequently fatal ·Rarely fatal
·Main cause: ·Main cause:
cerebral edema shunting / toxin
·Precipitant
·Treatment: usually
·Treatment: rarely effective
effective short of
liver transplant
HEPATIC ENCEPHALOPATHY IS A CLINICAL DIAGNOSIS

Hepatic Encephalopathy Is A
Clinical Diagnosis

· Clinical findings and history are important

· Ammonia levels are unreliable
· Ammonia has poor correlation with
diagnosis
· Measurement of ammonia not necessary
· Number connection test
· Slow dominant rhythm on EEG
 STAGES OF HEPATIC ENCEPHALOPATHY

Stages of Hepatic Encephalopathy

Confusion
Confusion

Drowsiness
Drowsiness

Somnolence

Coma
1 2 3 44
Stage
 STAGES OF HEPATIC ENCEPHALOPATHY

Stages of Hepatic Encephalopathy

Stage Mental state Neurologic signs

11 Mild
Mild confusion:
confusion: limited
limited attention
attention Incoordination,
Incoordination,
tremor,
tremor,
span,
span, irritability,
irritability, inverted
inverted sleep
sleep impaired
impaired handwriting
handwriting
pattern

22 Drowsiness,
Drowsiness, personality
personality changes,
changes, Asterixis,
Asterixis, ataxia,
ataxia, dysarthria
dysarthria
intermittent
intermittent disorientation
disorientation

33 Somnolent,
Somnolent, gross
gross disorientation,
disorientation, Hyperreflexia,
Hyperreflexia, muscle
muscle
marked
marked confusion,
confusion, slurred
slurred speech
speech rigidity,
rigidity, Babinski
Babinski sign
sign

44 Coma
Coma No
No response
response to
to pain,
pain,
decerebrate
decerebrate posture
Number
Number Connection
Connection Test
Test Draw
Draw aa star
star
(NCT)
(NCT)
Time
Time to
to
complete____________________
complete____________________

End
End
66 10
10 25
25
44
77 99 23
23
11 11
11
55 Begin
Begin

14
14
33 88 24
24
22 Sample
Sample handwriting
handwriting
13
13
12
12
17
17
15
15 16
16 22
22
18
18 21
21
19
19 20
20
Treatment of Hepatic
Encephalopathy
 HEPATIC ENCEPHALOPATHY PRECIPITANTS

Identify and treat HE Precipitants

Sedatives /
hypnotics
Excess
Excess protein
protein GI bleeding

TIPS
Diuretics

Serum K++
Serum
Temp
Temp Plasma
Plasma volume
volume

Infections
Infections Azotemia
Azotemia
 ACTIONS OF LACTULOSE

Actions of Lactulose

NH
NH33
Decreased pH

NH44++

Lactic
Lactic acid
acid NH
NH33
Lactulose

Urease-producing Increase
Increase
bacteria cathartic
cathartic effect
effect
 HEPATIC ENCEPHALOPATHY – TREATMENT SUMMARY

Hepatic Encephalopathy
Treatment: Summary
Increase ammonia Flumazenil
fixation in liver:
· Ornithine
aspartate
· Benzoate

Shunt
occlusion or
reduction

Decrease
Decrease
ammonia
ammonia
production
production in
in gut:
gut:
·· Lactulose
·· Antibiotics
·· Adjustment in
dietary protein
Jaundiced
Emergencies
 Acetaminophen Toxicity
 Fulminant Hepatic Failure
 Ascending Cholangitis
Ascending Cholangitis
 Pus under pressure
 Charcot’s triad: fever, jaundice, RUQ pain
 All
3 present in 70% of patients, but fever > 95%
 May also present as confusion or hypotension
 Most frequent causative organisms:
 E.Coli, Klebsiella, Enterobacter, Enterococcus
 anaerobes are rare and usually post-surgical
 Treatment:
 Antibiotics:
Levaquin, Zosyn, meropenem
 ERCP with biliary drainage
Ascending Cholangitis
Indications for Urgent ERCP
 Persistent abdominal pain
 Hypotension despite adequate IVF
 Fever > 102
 Mental confusion
 Failure to improve after 12 hours of
antibiotics and supportive care
 Acute presentation post liver
transplant.
Liver Transplant Patient
 7000 liver transplants worldwide
each year
 4000 performed in US
 Number or transplants limited by
# of donors
 Before 1980s, 1 year survival
rates < 30%
 Better immunosuppression,
surgical techniques and patient
selection
 1 year survival=87%
 Post transplant problems high
Postoperative Complications
 Bleeding-most occur in first week, so not seen in ED
 GI bleeding-manage in usual way
 May signal graft dysfunction
 May be accompanied by hypoglycemia, profound
coagulapathy
 Portal HTN should have been reversed by transplant
 Variceal bleeding may indicate portal vein thrombosis
 High dose steroids predisposed to GI bleeding
 CMV, HSV, Candidal infections can cause GI bleeding
Other Vascular Complications
 Less common
 Associated w/ high morbidity, mortality, graft failure
 HAT (hepatic artery thrombosis) most common-occurs
w/in 3 weeks post-transplant
 Incidence b/w 5-40%
 Incidence higher in children (26%)-treated w/ anitplatelet
agents
Vascular Complications
 Portal vein thrombosis less
common= 2-3% of patients
 Dx suggested by variceal
hemorrhage, massive ascites, other
sxs portal HTN
 Tx directed towards reducing
portosystemic pressure gradient
 May need retransplantation
Infection
 Account for most death
 Most patients have at least one episode
 Immunosuppression-induced blunting of inflammatory
response may mask presentation
 Three major infection periods
– <1 month
– 1-6 months
– >6 months
 In first 30 postop days=bacteria and fungi
 Immunosuppression at greatest levels, anastamoses at
most vulnerable
Infection
 Most infections <30 days normal
nosocomial agents in post-op patients
 Opportunistic organisms absent in first
month
 From 1-6 months most
infections=viruses
 EBV from reactivation or donor
transmission
 Or opportunisitic infections
Infection
 After 6 months, incidence of serious
infection declines
 Cholangitis most common
 High index of suspicion
 “Close monitoring is essential, as rapid
deterioration can take place while the
patient is still in the ED”
 MCQ
 Q1. Regarding ALF due to acetaminophen
toxicity the following is true except :

a) Higher rates of spontaneous recovery.

b) N-acetyl cysteine is the pharmacologic antidote.
c) Not the commonest cause in Egypt.
d) It is a rare cause in the western countries.
 Q2. The least possible viral cause of ALF
is :

a) HAV.
b) HBV.
c) HEV.
d) HCV.
 Q3. Physical exam in a case of ALF the
following is true except :
a) Intense hemolytic jaundice suggest Wilson
disease.
b) Tender hepatomegaly and ascites suggest
portal vein thrombosis.
c) Pregnancy suggest acute fatty liver of
pregnancy.
d) Absence of jaundice suggest
acetaminophen toxicity.
 Q4. The best approach for liver biopsy in ALF
is :

 a ) Blind biopsy.
 b) CT guided biopsy.
 c) Transjugular biopsy.
 d) Ultrasound guided biopsy.
 Q5. The definitive treatment for ALF is :
 a ) N-acetyl cysteine.
 b ) Lamuvidine.
 c) Liver transplant.
 d ) Acyclovir.
 Q6. The following are common acute
complications on top of chronic liver disease
( cirrhosis) except :
a) Rupture oesophageal varices.
b) Hepatic encephalopathy.
c ) Acute hepatic venous outflow obstruction.
d ) Spontaneous bacterial peritonitis.
 Q7. Diagnosis of hepatic encephalopathy
is mainly :
a) Radiologic diagnosis.
b) Clinical diagnosis.
c) Histopathologic diagnosis.
d) Laboratory diagnosis.
Q8. The following are precipitating factors
for hepatic encephalopathy except :
a ) Heavy protein diet.
b) Upper gastrointestinal bleeding.
c ) B-blockers.
d ) Sedatives & hypnotics.
 Q9.For Upper GI bleeding post liver
transplant the following is true except :

a) It is uncommon in the first week.

b) May suggest portal vein thrombosis.
c) May signal graft dysfunction.
d)May result from high dose steroid.
 Q10. Regarding post-transplant infection
the following is true except :
a) Accounts for most cases of death.
b) Viral infections are commonest between 1-6
month.
c) Bacterial infections are rare in the first month
postoperative.
d) Serious infections decline after 6 month.
Key answers :
Q 1 d  Q7 b
Q2 d Q8 c
Q3 b Q9 a
Q4 c  Q 10 c
Q5 c
Q6 c