Liver transplantation in acute liver failure: Dilemmas and challenges

Table 1 Prognostic scoring systems for patients with acute liver failure

Prognostic model/marker	Parameters included	Predictive values	Remarks/drawbacks
KCC[25,26]	Age, INR, serum bilirubin, icterus-encephalopathy interval, drug toxicity	For NAALF, Pooled Sn and Sp are 68% and 82%, respectively. For AALF, Pooled Sn and are 58.2% and 94.6%, respectively	Major limitation is poor sensitivity, only 58% in recent studies (after 2005). Perform better with advanced HE which is a late event. Combining lactate with the KCC improves sensitivity but reduces specificity
MELD score[34,37]	Serum bilirubin, serum creatinine and INR	For NAALF, DOR, Sn, and Sp of MELD scores > 30 are 8.42, 76%, and 73%, respectively. For AALF, DOR, Sn, and Sp of MELD scores > 30 are 6.6, 80%, and 53%, respectively	The discriminatory cut-offs and predictive values vary across the studies. Laboratory variations in the determination of serum bilirubin, creatinine and INR
Clichy criteria[38]	Advanced HE with factor V levels < 20% in patients < 30 years and < 30% in patients ≥ 30 yr	For NAALF, Sn 69%, Sp 50%, PPV 64%, and NPV 55%. For AALF, Sn 75%, Sp 56%, PPV 50%, and NPV 79%	Inferior to KCC and MELD in validation studies. Poor Sp and PPV. Factor V level assay is not a routine parameter
Arterial ammonia[51,52]	Baseline arterial ammonia > 124 mol/L	Sn 78.6%, Sp 76.3%, and DA 77.5%	Ammonia levels can be influenced by renal impairment, sepsis, bleeding, haemolysis, drugs etc. Not validated at LT centres. Persistent hyperammonemia is better predictor, but decision is delayed[52]
Blood lactate[28]	Post-resuscitation arterial lactate cut-off 3.0 mmol/L in AALF	Sn 76%, Sp 97%, PLR 30, and NLR 0.24	Variability in the timing of lactate measurements. Contradictory results with regard to its performance in NAALF
Serum phosphate[43,54]	Level of 1.2 mmol/L at 48 to 96 h after acetamenophen overdose	Sn 89%, Sp 100%, PPV 100%, and NPV 98%	Such results could not be replicated in subsequent studies[43]
Serum Gc globulin[53]	A cut-off level of 80 mg/L in the NAALF	Sn 49%, Sp 90%, PPV 85%, and NPV 43%	Poor sensitivity and NPV. Lacks validation studies
Cytokeratin 18-based modification of the MELD[55]	CK18 M65, INR, MELD. A baseline cut-off of 53.5 modified MELD	Sn 81%, Sp 82%, PPV 65%, and NPV 91%	Reported to be better than MELD and KCC, but lack validation studies
APACHE II[46]	Multiple parameters. APACHE II >15	Sn 82% and Sp 98% for AALF	Not specific to liver disease. Lacks validation studies. Cumbersome for routine clinical use
SOFA[45]	SOFA score of > 6 by 72 h post-acetamenophen overdose	Sn 90%, Sp 69%, PPV 42%, and NPV 96% for AALF	Not specific to liver disease. Relatively lower specificity and PPV. Difficulties in calculating the neurological component in intubated patients
Monocyte HLA-DR expression[50]	Monocyte HLA-DR expression 15% or less in AALF	Sn 96%, Sp 100%, DA 98%	Lacks validation studies. Reduction in monocyte HLA-DR expression was not associated with outcome in NAALF
BiLE score[49]	Bilirubin, lactate, and etiology	Sn 79% and Sp 84%	Scores derived from retrospective analysis. No validation study
ALFED model[27]	Over 3 d values of arterial ammonia, serum bilirubin, INR, and advanced HE	AUROC for ALFED: 0.92. ALFED score of ≥ 4 had a PPV 85% and NPV 87%	Needs further validation. Decision will be delayed. Patients died before 3 d were excluded from analysis. Advanced HE is a late feature
ALFSG index[47]	Coma grade, INR, serum bilirubin and phosphorus levels, and log(10) M30	Sn 85.6% and Sp 64.7%	Requires additional laboratory testing and costs for M30. Found better than MELD and KCC, but requires validation studies

AALF: Acetaminophen-associated acute liver failure; ALFED: Acute liver failure early dynamic; ALFSG: Acute liver failure study group; APACHE: Acute physiology and chronic health evaluation; AUROC: Area under receiver operating characteristic; DA: Diagnostic accuracy; DOR: Diagnostic odds ratio; INR: International normalized ratio; KCC: King’s college criteria; MELD: Model of end stage liver disease; NAALF: Non-acetaminophen-associated acute liver failure; NPV: Negative predictive value; PPV: Positive predictive value; Sn: Sensitivity; Sp: Specificity; SOFA: Sequential organ assessment score; HE: Hepatic encephalopathy.