Hepatitis

INTRODUCTION
ACUTE LIVER FAILURE (IN THE

ABSENCE OF ANY PRE-EXISTING
LIVER DISEASE)
LIVER
FAILURE...
ACUTE-ON-CHRONIC LIVER FAILURE

(ACLF)
CHRONIC DECOMPENSATION OF
AN END-STAGE LIVER DISEASE
Sarin SK, et all. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific
Association for the study of the liver (APASAL). Hepatol Int 2009;3:269-82
INTRODUCTION
ACUTE-ON-CHRONIC
LIVER FAILURE (ACLF)
...ACUTE HEPATIC INSULT

MANIFESTING AS JAUNDICE
AND COAGULOPHATY,
COMPLICATED WITHIN 4 WEEKS
BY ASCITEAS AND/OR
ENCEPHALOPHATY IN A
PATIENTS WITH PREVIOUSLY
DIAGNOSED OR UNDIAGNOSED
COMPENSATED CHRONIC LIVER
DISEASE...
Laleman W et all. Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical
manifestations and potential therapeutic interventions. Expert Rev Gastroenterol hepatol 2011;5:523-37
INTRODUCTION
REVERSIBILITY
ACLF...
MAIN FEATURES...
HIGH MORTALITY
(UP TO OVER 70%) IN
THE ABSENCE OF
LIVER SUPPORT
SYSTEM DEVICES
AND/OR LIVER
TRANSPLANTATION
Sarin SK, et all. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the
study of the liver (APASAL). Hepatol Int 2009;3:269-82
INTRODUCTION
ACLF...
END-STAGE
LIVER
DISEASE...
...THE MOST IMPORTANT DIFFERENCE BETWEEN

BOTH ENTITIES IS THE POTENTIALLY REVERSIBLE
NATURE OF ACLF IF THE PRECIPITATING FACTOR CAN
BE CONTROLLED...
INTRODUCTION
ACLF...
ACUTE LIVER
FAILURE
(ALF)...
...THE MOST IMPORTANT DIFFERENCE BETWEEN BOTH

ENTITIES IS THE PRESENCE OF UNDERLYING CHRONIC
LIVER DISEASE IN THE PATIENTS WITH ACLF...
INTRODUCTION
ACUTE EVENT IN ACLF
HEPATOTROPIC AND NONHEPATOTROPIC VIRUSES
INFECTIOUS ETIOLOGY
REACTIVATION OF HEPATITIS B OR C
OTHER INFECTIOUS AGENTS AFFLICTING THE LIVER
ACTIVE DRINKING WITHIN THE LAST 4 WEEKS
HEPATOTOXIC DRUGS, HERBS
NONINFECTIOUS ETIOLOGY
FLARE OF AUTOIMMUNE DISEASE

SURGICAL INTERVENTION
VARICEAL BLEEDING
UNKNOWN HEPATOTOXIC ETIOLOGY
INTRODUCTION
THE ACUTE
EPISODES VARY
DEPENDING ON THE
GEOGRAPHIC
REGION AND THE
POPULATION UNDER
STUDY
ALCOHOL AND
DRUGS
CONSTITUTE THE
MAJORITY OF
ACUTE INSULT IN
THE WEST
INFECTIOUS
ETIOLOGIES
PREDOMINATE IN
THE EAST
REACTIVATION OF HEPATITIS B VIRUS

INFECTION IS ONE OF THE MAJOR
CAUSES OF ACLF IN THE ASIAN REGION
INTRODUCTION
DISEASE
QUALIFIELD AS
UNDERLYING
CHRONIC LIVER
DISEASE
COMPENSATED CIRRHOSIS OF ANY ETIOLOGY

CHRONIC HEPATITIS
NASH
CHOLESTATIC LIVER DISEASE
METABOLIC LIVER DISEASE
SIMPLE STEATOSIS IS NOT
INCLUDE
INTRODUCTION
PATHOPHYSIOLOGY...
MULTI-ORGAN
FAILURE PLAYS A
CENTRAL ROLE IN
THE CLINICAL
COURSE OF ACLF
THERE IS A CENTRAL
ROLE OF
INFLAMMATION
AND NEUTROPHIL
DYSFUNCTION IN
ORGAN FAILURE
SIRS CHARACTERIZED BY
A PREDOMINANTLY
PRO-INFLAMMATORY
CYTOKINE PROFILE
(IL-6, TNF), CAUSES
TRANSITION FROM A
STABLE CIRRHOSIS TO
ACLF
Graziadei IW. The clinical challenges of acute on chronic liver failure. Liver International 2011;31:24-6
AIM OF THE STUDY
The aim of our study was to analyze the

clinical, laboratory and etiological
predictors of mortality in patients with
ACLF
...to analyze time of death from the

moment of hospitalization in patients with
ACLF
PATIENTS AND METHODS
JAUNDICE (serum bilirubin 85 mol/L)

AND COUGALOPHATY (INR 1.5)
DEFINING THE LIVER

FAILURE IN ACLF
ASCITES and/or ENCEPHALOPHATY as
determined by physical examination

ABSENCE OF ANY CHRONIC LIVER
DISEASE ON INVESTIGATIONS
KNOWN DECOMPENSATED CIRRHOSIS
PRIOR TO ONSET OF ACUTE HEPATIC
INSULT
THE EXCLUSION
CRITERIA
HEPATOCELLULAR CARCINOMA
PORTAL VEIN THROMBOSIS
AGE MORE THAN 80 YEARS

CLINICAL PRESENTATION, COURSE AND NATURAL HISTORY
COLLECTED DATA INCLUDED:

Patient demographics
Clinical features
Laboratory variables
Assesment of the severity of liver failure
Evaluation of aethiology of acute insult
Underlying liver disease
The presence and degree of one or more
The primary endpoints of the

study were 14-and 30-day
mortality
organ dysfunction
MO-F was defined when 2 or

more organs had failed
besides liver failure

ASSESSMENT OF SEVERITY OF ACLF
THE SEVERITY
SCORES
EVALUATED
FOR
MORTALITY ...
Child-Pugh (CP)
MELD
MELD-Na
SOFA
APACHE II
ACLF
...these were calculated within 48

hours of admission...
OF 1215 PATIENTS WITH

CHRONIC LIVER DISEASE
114 MALE
MEAN AGE 6110.43 YEARS
170 (13.99%) PATIENTS MET THE

CRITERIA OF ACLF'S
56 FEMALES
MEAN AGE 6210.86 YEARS
PARAMETAR
Gender (M:F)
114:56
Age (years) man
6110.43
Age (years) women

Laboratory parameters
6210.86
WBC (103 cells/mm3 )
11.767.98
Platelets
(103 cells/mm3
110.8568.39
Bilirubin (mol/L)
202.35146.11
Serum ALT (IU/L)
120.93301.01
Serums albumin (g/L)
26.394.17
Serum sodium (mmol/L)
133.15.88
Serum potassium (mmol/l)
4.010,92
Creatinine (mol/L)
115.878.96
PV
0.360.16
Demographic
and laboratory
data...
CLINICAL PRESENTATION; THE MOST COMMON REASON

FOR HOSPITALIZATION
Presenting
symptom
Ascites
Bleeding
Encephalophaty
Jaundice
Other
49
(32.03%)
22
(14.38%)
27
(17.65%)
52
(33.99%)
3
(1.96%)
CLINICAL PRESENTATION;
ETIOLOGY OF CHRONIC LIVER DISEASE
ALCOHOL
HEPATITIS B HEPATITIS C
NASH
CRYPTOGENIC
OTHER
MEN
96 (84,96%)
5 (4.38%)
10 (8.77%)
1 (0.87%)
1 (0.87%)
WOMEN
20 (51.28%)
1 (2.56%)
2 (5.12%)
1 (2.56%)
13 (33.33%)
2 (5.12%)
ALL
116 (75.82%)
6 (3.92%)
12 (7.84%)
2 (1.31%)
14 (9.15%)
3 (1.96%)
CLINICAL PRESENTATION;
THE AETIOLOGIES OF ACUTE INSULT
AETIOLOGY OF CHRONIC LIVER
DISEASE
ALCOHOL (N=116)
HEPATITIS B (N=6)
HEPATITIS C (N=10)
CRYPTOGENIC (N=14)
AETIOLOGY OF ACUTE
INSULT
NUMBER (%)
Alcohol hepatitis
Bleeding
Sepsis/other infection
Unknown
Reactivation
Bleeding
Unknown
Reactivation
Sepsis /other infection
Bleeding
Unknow
Sepsis
Bleeding
Unknow
92 (60.13%)
11 (7.19%)
7 (4.58%)
6 (3.92%)
3 (50%)
1 (16.66%)
2 (33.33%)
4 (40%)
3 (30%)
1 (10%)
2 (20%)
3 (21.42%)
2 (14.28%)
9 (64.28%)
COURSE OF ILLNESS
OF WHICH 33%
WITHIN THE FIRST
14 DAYS OF
ADMISSION
OF ALL PATIENTS,
43% OF THEM
DIED WITHIN 30
DAYS
...These data suggest that it is

the first 2 weeks which
determines the outcome in
most patients with ACLF...
IN 72% OF CASES
THE CAUSE OF
DEATH WAS MOF
PREDICTORS OF MORTALITY
Multivariate Analysis
(CUTOFF VALUES)
OR (95%CI)
SERUM POTASSIUM
(<3.9 and >5.1mmol/L)
4.30 (2.84 to 6.52)
P < 0.0001
CRP (> 5 mg/L)
5.74 (2.87 to 11.51)
P < 0.0001
CREATININE (>104mol/L)
3.83 (2.82 to 5.20)
P < 0.0001
BILIRUBIN (>85mol/L)
2.96 (1.99 to 4.39)
P < 0.0001
ENCEPHALOPATHY (NH3>50mol/L)
2.81 (2.01 to 3.91)
P < 0.0001
PERFORMANCE OF SEVERITY SCORES

APACHE
100
Sensitivity: 85,7
Specificity: 85,4
Criterion : >13
Sensitivity
80
60
40
20
0
0
20
40
60
100-Specificity
80
100
Area under the ROC curve (AUC)

Standard Error
95% Confidence Interval
0.894
0.034
0.811 to 0.949
MOF
100
80
Sensitivity
Sensitivity: 74,2
Specificity: 97,7
Criterion : >0
AT ADMISSION 51
PATIENTS HAD MOF
(TWO OR MORE
ORGAN FAILURE) OF
WICH 49 DIED...
60
40
20
0
0
20
40
60
100-Specificity
Area under the ROC curve (AUC)

Standard Error
95% Confidence Interval
80
0.860
0.032
0.794 to 0.910
100
CORRELATION OF NUMBER OF ORGANS FAILED (AT

ADMISSION) WITH IN-HOSPITAL MORTALITY
There was no difference in

outcome duo to age of
patients; the mean age in nonsurvival group was 56.058.8
years and in the survival group
was 59.669.8 years (p=NS)
Patients with alcoholic

underlying chronic liver disease
had better survival compared to
those with non-alcoholic
underlying chronic liver disease
(p< 0.0001).
Patients with infection/sepsis

as an etiology of an acute
insult had the worst overall
prognosis
CONCLUSION
ACLF IS SERIOUS
CONDITION WITH
VERY HIGH
MORTALITY...
MOST OF THE
PATIENTS DIE
BECAUSE OF
MULTI-ORGAN
FAILURE
NECESSARY IDENTIFICATION THOSE WHO ARE AT

RISK AS SOON AS POSSIBLE IN ORDER TO TIMELY
ACT ON AN ACUTE EVENT DUE TO THE
REVERSIBILITY OF THIS CONDITION.
THANK YOU...

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INTRODUCTION

ACUTE LIVER FAILURE (IN THE

ACUTE-ON-CHRONIC LIVER FAILURE

...ACUTE HEPATIC INSULT

...THE MOST IMPORTANT DIFFERENCE BETWEEN

...THE MOST IMPORTANT DIFFERENCE BETWEEN BOTH

FLARE OF AUTOIMMUNE DISEASE

UNKNOWN HEPATOTOXIC ETIOLOGY

REACTIVATION OF HEPATITIS B VIRUS

COMPENSATED CIRRHOSIS OF ANY ETIOLOGY

AIM OF THE STUDY

The aim of our study was to analyze the

...to analyze time of death from the

PATIENTS AND METHODS

JAUNDICE (serum bilirubin 85 mol/L)

DEFINING THE LIVER

PATIENTS AND METHODS

PORTAL VEIN THROMBOSIS

AGE MORE THAN 80 YEARS

PATIENTS AND METHODS

COLLECTED DATA INCLUDED:

The primary endpoints of the

MO-F was defined when 2 or

PATIENTS AND METHODS

...these were calculated within 48

PATIENTS AND METHODS

OF 1215 PATIENTS WITH

170 (13.99%) PATIENTS MET THE

Age (years) man

Age (years) women

WBC (103 cells/mm3 )

Serum ALT (IU/L)

Serums albumin (g/L)

Serum sodium (mmol/L)

Serum potassium (mmol/l)

CLINICAL PRESENTATION; THE MOST COMMON REASON

...These data suggest that it is

4.30 (2.84 to 6.52)

CRP (> 5 mg/L)

5.74 (2.87 to 11.51)

3.83 (2.82 to 5.20)

2.96 (1.99 to 4.39)

2.81 (2.01 to 3.91)

PERFORMANCE OF SEVERITY SCORES

Area under the ROC curve (AUC)

Area under the ROC curve (AUC)

CORRELATION OF NUMBER OF ORGANS FAILED (AT

There was no difference in

Patients with alcoholic

Patients with infection/sepsis

NECESSARY IDENTIFICATION THOSE WHO ARE AT

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