ACLF is acute liver failure resulting from an acute insult in a patient with chronic liver disease or cirrhosis. It can develop from reactivation of hepatitis B, hepatitis E infection, alcohol consumption, drug-induced liver injury, variceal bleeding, or bacterial infections in cirrhotic patients. ACLF severity is classified from grades 1 to 3 based on the number of organ failures. Treatment involves nutritional support, antibiotics for infections, albumin administration, and renal replacement therapy for kidney failure. Liver transplantation or artificial liver support devices may be considered for severe cases, though overall mortality remains high.

2.  ACLF is a clinical syndrome manifesting as acute and
severe hepatic dysfunction resulting from varied insults.
 An acute severe hepatic insult in a healthy liver can lead
to ALF.
 with aggressive critical care, a non-transplantation
survival of up to 60% can be achieved in ALF.
 In the presence of CLD, an acute insult can lead to
rapid and progressive liver failure, with a high short-term
mortality.

4. The concept of the hepatic reserve and ACLF

7.  Development and progression of ACLF
broadly depends :
 the nature and severity of the acute insult,
 the stage of underlying CLD or cirrhosis,
 the rapidity and degree of liver failure.

8.  HBV-related ACLF generally develops in
two clinical scenarios:
 First, HBV reactivation on a background of
chronic HBV infection and CLD and
 second, acute HBV infection on a
background of CLD of any aetiology.

9.  Hepatitis E virus (HEV) infection is a leading
cause of ALF in Asia and Africa, with a median
incidence of 21%.
 HEV infection is associated with a more
severe form of ACLF with higher mortality than
with HAV.
 Super-infection with hepatitis A virus and HEV
lead to the development of ACLF.

10.  The dose and duration of alcohol consumption
determines the stage of CLD.
 Recent alcohol intake and/or binge drinking
behaviour is what contributes to rapid liver
failure.
 The presence of obesity and/or diabetes
mellitus increases disease severity.

11.  Most data relates to drug-induced ALF and information
on ACLF is limited.
 In a multinational Asian study of 660 patients, DILI
contributed as an acute insult in 9.1% of patients and in
53.3% of these patients the acute insult was attributed
to anti-tubercular drugs.
 Antibiotics and anti-epileptic drugs account for >60% of
patients with DILI in the West.

12.  Liver failure in patients with acute variceal
bleeding is mainly due to:
 hepatic ischaemia,
 increased bacterial translocation from the gut.
 was considered a precipitating event in
13.8% of patients in the CANONIC study.

13.  Bacterial infections are more frequent in patients with cirrhosis than in
the general population.
 Cirrhosis-associated immune deficiency syndrome, an emerging
concept, relates to a relative inefficiency of the innate and adaptive
immune system.
 Whether sepsis is a consequence or a cause of liver failure is not clear
from the current data.
 One viewpoint considers sepsis as a common extrahepatic precipitant
of ACLF (I-ACLF).
 The other school of thought supports the concept that sepsis is a result
of liver failure(concept of golden window)

14.  In a patient with Child–Pugh stage B or C
cirrhosis and HCC, acute deterioration
leading to ACLF can develop after TACE or
RFA.

15.  Is difficult unless previously confirmed or when
overt signs of cirrhosis are present.
 History,
 Signs of portal hypertension
 Laboratory test results
 Endoscopic or radiological investigations are
required to confirm the diagnosis.
 If these parameters are not conclusive, a
histopathological evaluation, often by transjugular
biopsy, is recommended.

16.  The earlier definition of ACLF from EASL and
the American Association for the Study of
Liver Disease (AASLD) in 2011 included only
patients with cirrhosis.
 Now it is proposed to include patients with or
without cirrhosis in three categories;
type-A (patients with ACLF but without cirrhosis)
type-B (patients with cirrhosis and ACLF)
type-C(patients with ACLF, cirrhosis and prior hepatic
decompensation)

17.  Liver failure in ACLF is multifactorial and self-perpetuating.
 The acute insult or pathogen (inducer), directly or indirectly
activates different cell types (sensors) and inflammatory
cytokine pathways (mediators).
 Tissue damage as a result of infection is caused by three
factors:
 first, direct action of virulence factors that induce
marked alterations in tissue homeostasis;
 second, an excessive host immune response; and
 third, failed host immune-mediated tolerance
mechanisms.

19. Organ system score:1 Score:2 Score:3
Liver
(Bilirubin)
<6mg/dl ≥6 and <12mg/dl ≥12mg/dl
Kidney
(creatinine)
<2md/dl ≥2 and 3.5 mg/dl ≥3.5 mg/dl
Brain
(Encephalopathy)
0 1-2 3-4
Coagulation INR < 2.0 INR ≥ 2 and <2.5 ≥2.5
Respiratory
(PaO2/FiO2)
>300 ≤300 and >200 ≤200
SpO2/FiO2 >357 >214 and ≤357 ≤214
Circulatory MAP ≥ 70mmhg MAP < 70mmhg use of vasopressosrs

20. Grade of ACLF Organ failure 28 day mortality 90 day mortality
1 Single kidney failure
Single ‘non-kidney
failure’
22.1% 40.7%
2 Presence of 2 organ
failures
32.1% 52.3%
3 Presence of ≥3 76.7% 79.1%

21. Nutrition
 Anorexia adds to nutritional compromise
and poor outcomes.
 A target of 1.5–2.0 g protein/kg per day and
39 kcal/kg per day has been shown to
improve hepatic encephalopathy and
overall survival

22.  Patients with ACLF need close monitoring
to detect the development of SIRS,
hypotension and shock.
 Use of prophylactic antibiotics might help
in prevention of infection if given at the
onset of SIRS.

23.  Patients with ACLF and septic shock are
extremely ill with mortality exceeding 80%.
 Septic shock is fluid responsive in only ~12%
and vasopressor responsive in 50% of
patients
 Terlipressin alone or in combination with
noradrenaline helps reverse septic
shock,reduce the risk of variceal bleeding and
SBP.

24.  The use of albumin is suggested to improve
intravascular volume, and prevent and manage acute
kidney injury (AKI) and infections.
 PGE2 is one of the main drivers for immunosuppression
in patients with acute decompensation of cirrhosis and
its level increased in ACLF.
 Albumin binds to PGE2 and reduces its bioavailability,
which in turn increases circulating TNF levels, reduces
monocyte anergy and reduces the risk of infections.

25.  About 40% of patients with ACLF develop hepatic encephalopathy and require
intensive care.
 Although little evidence exists at present for targeted ammonia reduction
therapies, such as lactulose and rifaximin, they can be given empirically.
 Renal impairment occurs in about one-quarter of patients.
 Use of terlipressin with albumin is effective at treating AKI in only 35% patients
and the responders do have a survival advantage.
 Nonresponders to terlipressin treatment might require renal replacement
therapy in the form of intermittent haemodialysis, slow low-efficient dialysis or
continuous renal replacement therapy.

26.  N-acetyl cysteine, modulation of gut
flora,anti-TNF agents and faecal microbial
transplantation are emerging therapeutic

27.  At present, there are two main devices providing ALSS;
 the Molecular Adsorbent Recirculating System (MARS® (Gambro, Sweden) and
 the Fractionated plasma separation and adsorption (FPSA; the Prometheus
System® (Fresenius Medical Care, Germany).
 RELIEF study using MARS® reported a decrease in serum creatinine and bilirubin levels
with improvement of hepatic encephalopathy on the fourth day of treatment, but without
survival benefits.
 The FPSA (Prometheus System®) device used in the HELIOS study (n = 145) reported a
notable reduction in serum bilirubin levels.
 The survival benefit was limited to patients with type I HRS and a MELD score of >30

29.  G-CSF therapy substantially enhances the mobilization of bone marrow HSCs
with homing of these cells in the hepatic parenchyma .
 Is associated with a reduction of Child–Pugh, MELD and SOFA scores,
reduced sepsis, hepatorenal syndrome and hepatic encephalopathy, and
improved survival .
 In very ill patients with a MELD score of >30, G-CSF therapy should, however,
be considered only if liver transplantation is not feasible and preferably by
specialists experienced in this therapy.
 This approach should not be used in patients with ACLF in the presence of
AKI, ongoing sepsis, significant haemolysis or macrophage activation
syndrome