Lactate levels provide additional prognostic value beyond existing scoring systems for predicting mortality in critically ill cirrhotic patients. A multinational study assessed lactate levels and lactate clearance in 584 ICU patients with cirrhosis. Lactate levels on admission were associated with increased short and long-term mortality. The study derived a modified CLIF-C ACLF score incorporating lactate (CLIF-C ACLFsLact) that showed improved discrimination for predicting 28-day, 90-day, and 1-year mortality compared to the original CLIF-C ACLF score or MELD score. The CLIF-C ACLFsLact also showed better prediction of mortality in a validation cohort of 250 patients.

1. BY
Dr. (Maj) Ajay Kandpal
MD, DNB
DM PG
STANLEY MED COLLEGE CHENNAI INDIA
kandykilroy@gmail.com
JOURNAL CLUB

2.  Lactate improves prediction of short-term
mortality in critically ill patients with cirrhosis:
A multinational study
 JOURNAL OF HEPATOLOGY 69, VOL 1 2019,
AASLD

3. BACKGROUND
 ACLF as common cause of mortality
 Limited mortalility predictors for a case of ACLF
comparatively viz AP
 Interesting metabolism of lactate in cirrhosis
 Lactate as a bed side test
 No formal large scale study of use of lactate
levels in cirrhotic patients

4. Whats ACLF

5. Definition APASL: acute hepatic insult in patient with
(diagnosed or undiagnosed) chronic liver disease
(without or with cirrhosis) causing bilirubin > 5 mg/dL
and INR >1.5, complicated within 4 weeks with ascites
and/or encephalopathy.
This acute rapid deterioration of liver function is
accompanied by subsequent rapidly evolving multiple
end organ failure in a patient with previously well
compensated liver disease due to the effects of a
precipitating event
DEFINITION OF ACLF

6. SOUNDS LESS
COMPLICATED!!!

7.  Definition EASL-CLIF: Acute decompensation (AD)
of chronic liver disease (without or with cirrhosis) with
development of large ascites,encephalopathy, GI
hemorrhage and/or bacterial infection.
 associated with at least 2 organ failures, with one
being kidney with a creatinine > 1.5 mg/dL,
 leading to a 28-day mortality >/= 15% in study
 Group at highest risk: Patients with compensated
cirrhosis or recently decompensated cirrhosis in the last 3
months.
 Patients without prior decompensation develop more severe
ACLF

8. ACLF-1 :(28-d mort 22.1%)
 renal failure (creat > 2 mg/dL), or
 Non renal organ failure associated with: creatinine 1.5-
1.99 mg/dL and/or
 grade I-II encephalopathy
 ACLF-2 : 2 organ failures (28-d mort 32%)
 ACLF-3 : 3-6 organ failures, (28-d mort 73%)
 48% had >/= 2 organ failures
GRADES OF ACLF

9.  Two categories of prognostic models are commonly
used:
1)those evaluating the severity of illness:
a) Acute Physiology and Chronic Health Evaluation
(APACHE) II andIII,
b)Simplified Acute Physiology Score (SAPS) II, and
c)Mortality Prediction Model II,
2) models quantifying organ dysfunction and failure
a)Logistic Organ Dysfunction System,
b)Multiple Organ Dysfunction Score,
C)Organ System Failure(OSF), and
d) Sequential Organ Failure Assessment (SOFA)
Prognostic scores for ACLF

10.  Six organs (respiration,coagulation, liver,
cardiovascular, CNS, and renal) are studied dynamically
each day to develop a score that can range between 0
and 24
 chronic liver failure– sequential organ failure
assessment (CLIF–SOFA) score to identify diagnostic
criteria of ACLF in European patients with acute hepatic
decompensation
Sequential Organ Failure
Assessment (SOFA)

12. LACTATE MEABOLISM

14. AIM
 PRIMARY
 The aim of this study was to assess the prognostic
performance and clinical applicability of lactate
levels and lactate clearance in critically ill patients
with liver cirrhosis admitted to the ICU.
 SECONDARY
 Assessing whether incorporation of lactate into
current scoring systems for patients with cirrhosis
and ACLF may yield additional prognostic
information.

15. DESIGN
 Retrospective cohort study.
 Derivation cohort
 Validation cohort

16. PLACE & DURATION
 The study was performed at ICU (11) Intensive
Care Medicine at the University Medical Center
Hamburg-Eppendorf between January 2009 and
January 2015.

17. INCLUSION CRITERIA
 All ICU admitted cirrhosis
 Lactate done within 2 hrs of admission

18. EXCLUSION
 Not specified
 Not meeting inclusion criteria

19. Methodlogy
 Six hundred seventy-eight patients with cirrhosis
admitted to the ICU were identified
 94 patients (14%) were excluded (VBG)
 18 patients (3%) were excluded (No sample)
 Validation cohort of 250 critically ill patients with
liver cirrhosis collected at the Medical University
of Vienna

20.  Baseline characteristics noted
 Sequential organ failure assessment (SOFA)
score,Model for End-Stage Liver Disease (MELD)
score,chronic liver failure-sequential organ failure
assessment (CLIF-SOFA) score, and Chronic
Liver Failure Consortium acute-on-chronic liver
failure score (CLIF-C ACLFs) were calculated as
previously described on ICU admission

21.  Twenty-eight-day-mortality, 90-day-mortality, and
1-year mortality was assessed on site or by
contacting the patients or their attending
physicians

22. STAT ANALYSIS
 Data are presented as median and interquartile
range
 Categorical variables were compared via chi-
squared analysis or Fisher’s exact test
 Metric variables were compared via Mann-
Whitney U test.
 Receiver operating characteristic (ROC) analyses
were performed to assess the discriminative
ability of different metric variables on 28-day
survival.
 Areas under ROC curves (AUROC) were
compared by a nonparametric approach

23. RESULTS

26.  Seeing the data with serum lacate in background

32. Deriving CLIF-C ACLFsLact
 Based on the results obtained from the
multivariable proportional hazards model, a
lactate-adjusted, modified formula prepared
 CLIF −C ACLFsLact
=10× 0.33×CLIF −C
OFs+0.04×Age+0.63×ln(WBC)+0.8×ln(lactate)−2.
7
 CLIF −C ACLFsLact
=CLIF −C ACLFs+8×ln (lactate)−7

33. CLIF-C ACLFsLact in derivation
cohort
 AUROCs for CLIF-C ACLFsLact in prediction of
28-day, 90-day, and 1-year mortality (0.79, 0.77,
and 0.77) were significantly higher than those
obtained for conventional CLIF-C ACLF (0.75 [P =
0.0001], 0.73 [P < 0.0002], and 0.73 [P =
0.0007]).

34. CLIF-C ACLFsLact in validation
cohort
 AUROC for CLIF-C ACLFsLact (0.79) in
prediction of 28 than for conventional CLIF-C
ACLFs (AUROC 0.75 [P < 0.05]) in the validation
cohort.
 Although AUROCs for CLIF-C ACLFsLact were
higher than those observed for CLIF-C ACLFs in
prediction of 90-day and 1-year mortality, these
difference failed to reach statistical significance.

37. Overall (Derivation and Validation
Set,
n = 816)
 Overall, AUROCs for CLIF-C ACLFsLact in
prediction of mortality was significantly higher
than those for CLIF-C ACLFs and MELD,
respectively, at all time points (P < 0.01 for all).
 This applied to both patients with cirrhosis (n =
816) and those with ACLF (n = 635).
 Accordingly, as compared with CLIF-C ACLFs,
CLIF-C ACLFsLact improved mortality prediction
by up to 18.5% in patients with ACLF.

38. CONCLUSION
 Serum lactate is as relevant in cirrhosis as in
other ICU patients
 Both short term and long term mortality prediction
 Development of CLIF-C ACLFsLact score

39. RECOMMENDATIONS
 Incorporation of CLIF-C ACLFsLact score in CLIF
ACLF consortium scoring system

40. Thank you…