Acute-on-chronic liver failure: Pathogenesis, prognostic factors and management

Table 1 Chronic liver failure-sequential organ failure assessment score

Organ failure	0	1	2	3	4
Liver (Tbil, mg/L)	< 1.2	≥ 1.2 to < 2.0	≥ 2.0 to < 6.0	≥ 6.0 to < 12	≥ 12.0
Kidney (cr, mg/dL)	< 1.2	≥ 1.2 to < 2.0	≥ 2.0 to < 3.5	≥ 6.0 to < 12	≥ 5.0
	Or use of renal replacement therapy
Cerebral (HE grade)	No HE	I	II	III	IV
Coagulation (INR)	< 1.1	≥ 1.1 to < 1.25	≥ 1.25 to < 1.5	≥ 1.5 to < 2.5	≥ 2.5 or PLT ≤ 20 × 109/L
Circulation (MAP, mmHg)	≥ 70	< 70	DA ≤ 5 or DOB or Terlipressin	DA > 5 or E ≤ 0.1 or NE ≤ 0.1	DA > 15 or E 0.1 or NE > 0.1
Lung PaO2/FiO2	> 400	> 300 to ≤ 400	> 200 to ≤ 300	> 100 to ≤ 200	≤ 100
Or SpO2/FiO2	> 512	> 357 to ≤ 512	> 214 to ≤ 357	> 89 to ≤ 214	≤ 89

This score is used to categorize patients into grades of ACLF. ACLF: Acute-on-chronic liver failure; CLIF: Chronic liver failure; SOFA: Sequential organ failure assessment; Tbil: Total bilirubin; cr: Serum creatinine; HE: Encephalopathy; INR: International normalized ratio; PLT: Plateletes; DA: Dopamine; DOB: Dobutamine; E: Epinephrine; NE: Norepinephrine; PaO₂: Partial pressure of arterial oxygen; FiO₂: Fraction of inspired oxygen; SpO₂: Pulse oximetry saturation. Data from Moreau et al[12].

Table 2 Grades of acute-on-chronic liver failure according to the number of organ failure and the type of organ

No. ACLF
ACLF grade 1	Single- organ failure (coagulation, liver, circulation, lungs) in patients with sCr 1.5-1.9 mg/dL and/or grades 1-2 HE or braine failure with sCr range from 1.5-1.9 mg/dL
ACLF grade 2	Two organ failures
ACLF grade 3	Three or more organ failures

Data from the CANONIC study[12]. ACLF: Acute-on-chronic liver failure; OF: Organ failure.

Table 3 Summary of predicting factors

High levels of bilirubin	Gustot et al[148], López-Velázquez et al[206], Cordoba et al[90]
Age and high INR	Shi et al[155], Cordoba et al[90], Garg et al[146], Kumar et al[151], Moreau et al[152]
Decreased serum thyroid-stimulation hormone (TSH) levels	Wu et al[207]
Low free T3 levels	Agiasotelli et al[208]
Systemic haemodynamic changes	Garg et al[146]
Iron metabolism and transport	Maras et al[209]
Neutrophil-lymphocyte ratio (NRL)	Lin et al[210], Liu et al[211]
Presence of SIRS	Katoonizadeh et al[177], Thabut et al[108]
Infection and sepsis	Sargenti et al[212], Bruns et al[164], Linderoth et al[213]

No well-established prognostic indicators are available for predicting ACLF outcome. Ambiguity in the diagnostic criteria has limited researches into the identification of clear indicators of severity. According to diverse population under study and definition of the syndrome, different indicators have been proposed. ACLF: Acute-on-chronic liver failure; INR: International normalized ratio.