1. Acute on Chronic Liver Failure
Ulva Yogia Guslaf
1
SMF/Bagian Ilmu Penyakit Dalam Fakultas Kedokteran Universitas Syiah Kuala
Rumah Sakit Zainoel Abidin Banda Aceh
2021/2022
6. 6
The clinical course of cirrhosis
Arroyo et al. Acute‐on‐chronic liver failure in cirrhosis. 2016
7. 7
Common multiple organ dysfunctions in acute-on-
chronic liver failure
Alam A et al. J Biomed Res, 2017
8. 8
Role of liver histology in ACLF
Alam A et al. J Biomed Res, 2017
Liver biopsy is helpful in patients where the
presence and stage of underlying chronic liver
disease and/or the cause of chronic liver disease
are not clear
Liver biopsy can identify stage of fibrosis, measure
in prognostic and outcome, and distinguish ACLF
from Decompensated Cirrhosis
9. 9
Scoring System in Determining the Grading of Liver
Failure
Sarin et al. Hepatology International. 2019
10. 10
Scoring System in Determining the Grading of Liver
Failure
Sarin et al. Hepatology International. 2019
11. • Jaundice (serum bilirubin > 5 mg/dL [> 85 lmol/L]) and coagulopathy (INR > 1.5 or
prothrombin activity < 40%) are mandatory parameters to assess liver failure
• Ascites and/or encephalopathy as determined by physical examination also
reliably reflect significant hepatic functional impairment
• Liver failure score (AARC score) which includes total bilirubin, INR, grade of HE,
plasma lactate and serum creatinine reliably predicts the disease severity and
outcome
• Grading of liver failure as per AARC score I (5–7), II (8–10), III (11–15) effectively
prognosticates and guides the therapy
• Coagulation anomalies
11
Defining the liver failure in ACLF
Sarin et al. Hepatology International. 2019
12. 12
Golden Window Period of ACLF
Sarin et al. Hepatology International. 2019
SIRS needs consideration for organ support,
antibiotics for occult sepsis and prioritization for
definitive therapy, i.e., liver transplan
C-reactive protein
and procalcitonin,
The most frequent
infections are SBP,
pneumonia, UTI, and
bacteremia
Routine examination of
blood and body fluids is
recommended
13. • The diagnosis of invasive fungal infection can be proven, probable or
possible, depends on mycological evidence, and clinical evidence
• Invasive pulmonary aspergillosis (IPA) is increasingly recognized as a
cause of morbidity and mortality in patients with ACL
• Prophylaxis with fluconazole followed by echinocandins needs to be
evaluated in ACLF patients
• Biomarkers such as galactomanan or B–D Glucan can be used for
supporting diagnosis if there is invasive fungal infection in ACLF.
13
Invasive fungal infection in ACLF
Sarin et al. Hepatology International. 2019
14. • AKI criteria (defined as an absolute increase in serum creatinine of 0.3 mg/dl within 48 h
or by percentage increase in serum creatinine of more than 50% from baseline, which is
known, or presumed, to have occurred within the previous 7 days
• A cutoff value of 1.1 mg/dl is a reliable marker of significant renal dysfunction and 1.5
mg/dl of kidney failure in patients with ACLF
• Initiate RRT emergently when life-threatening changes in volume overload,
hyperkalemia, hypernatremia and worsening metabolic acidosis not responding to
conservative management. The threshold for initiating RRT should be lowered when AKI
occurs as part of multi-organ failure, or in non-oliguric patients if the daily fluid balance
cannot be maintained.
• Biomarkers of tubular damage, urine NGAL and IL-18 need to be evaluated for a role in
patients with ACLF to determine the need for early RRT or artificial liver support
14
Defining the Renal failure in ACLF
Sarin et al. Hepatology International. 2019
15. • HE, including grade 1-2 HE (organ dysfunction) and grade 3-4 HE (organ failure), is present in
about a third of the ACLF patients
• Ammonia is a simple surrogate marker for HE in ACLF and correlates with severity of HE/cerebral
failure
• Lactulose, rifaximin, NH3-lowering strategies remain the main therapy for HE in patients with
cirrhosis
• Patients need to be characterized as bleeding or thrombosis phenotype by clinical assessment of
major bleeding and d-dimer assay, respectively
15
Defining the HE in ACLF
Sarin et al. Hepatology International. 2019
16. • ACLF is a hypocoagulable state and this can get escalated with the development
of SIRS and sepsis
• Traditional coagulation measures, including prothrombin time (PT), activated
partial thromboplastin time (aPTT), international normalized ratio (INR),
fibrinogen levels and bleeding time (BT) do not measure bleeding risk in ACLF
• Patients need to be characterized as bleeding or thrombosis phenotype by clinical
assessment of major bleeding and d-dimer assay, respectively
16
Coagulation in ACLF
Sarin et al. Hepatology International. 2019
17. 17
Summary
Definition Acute decompensation of cirrhosis
previous decompensation
AND
Multi organ failure
AND
High short-term mortality
Acute decompensation of
cirrhosis ± previous
decompensation (due to
infection)
AND
Extrahepatic organ failure (2 or
more of respiration, brain,
coagulation, and circulation)
AND
High short-term mortility (30 day)
Acute hepatic injury in
chronic liver disease ±
compensated cirrhosis
(development of jaundice
and coagulopathy)
AND
Ascites ± HE within 4 weeks
from onset
Acute hepatic injury in
chronic liver disease ±
compensated cirrhosis
(development of jaundice
and prolonged INR)
AND
Extrahepatic organ failure (1
or more)
AND
High short-term mortility
Criteria for Organ
Failure
Liver : sBr > 205 𝜂mol/L
Coagulation : INR >2.5
Renal : sCr 177 𝜂mol/L or RRT
Brain : HE grade 3 or 4
CVDs : Vasopressors
Respiratory Pa02/Fi02 < 200 or
Sa02/Fi02 <214
Renal : RRT
Brain : HE grade 3 or 4
CVDs : MAP < 60 or fall in SBP of
40 from baseline
Respiratory : MV
Liver : sBr > 205 𝜂mol/L
Coagulation : INR > 1,5
Renal : AKI
Brain : HE grade 3 or 4
Grading Grade 1 : Single renal failure, Single
liver, coagulation, Circulatory or
respiratory failure + sCr 133-168
205 𝜂mol/L +/- HE 1-2. Single brain
failure + sCr 133-168 𝜂mol/L
Grade 2 : 2 or more organ failures
Grade 3 : 3 or more organ failures
