Ability of King's College Criteria and Model for End-Stage Liver Disease Scores to Predict Mortality of Patients With Acute Liver Failure: A Meta-analysis

TL;DR: Based on a meta-analysis of studies, the KCC more accurately predicts hospital mortality among patients with AALF, whereas MELD scores more accurately predict mortalityamong patients with NAALF.

About: This article is published in Clinical Gastroenterology and Hepatology.The article was published on 2016-04-01 and is currently open access. It has received 91 citations till now. The article focuses on the topics: King's College Criteria & Model for End-Stage Liver Disease.

Summary

INTRODUCTION

• Acute Liver Failure (ALF) is a rare, but devastating illness with a high risk of progression to multi-organ failure and death1-3.
• The key clinical issue remains to accurately identify patients with ALF who will die without ELT, and those who will survive with medical management alone.
• One particularly salient difference is the treatment of transplanted patients.
• To date, there have been three meta-analyses23 of the performance of the KCC in ALF.
• The first included only Acetaminophen-induced ALF (AALF) identifying nine studies in total, and concluded that the KCC had limited sensitivity13.

METHODS

• All potential articles were assessed independently by two researchers (HF, MM) according to prospectively defined eligibility criteria, and disagreements were resolved by consensus or consultation with a third author (WB).
• If this was not possible or there was doubt over the 2 x 2 calculation, the study was excluded from the subsequent analysis.
• The DerSimonian-Laird random effects method was used to produce summary estimates of sensitivity, specificity, likelihood ratios (LR) and diagnostic odds ratio (DOR, defined as the ratio of positive to negative likelihood ratios).

NAALF).

• A funnel plot and effective sample size (ESS) regression analysis (the logarithm of the DOR plotted against 1/√ESS) was used to investigate publication bias.
• Data analyses were performed using the freeware Meta-Disc version 1.4 (Universidad Complutense, Madrid, Spain) and Eggers statistic calculated in Excel (Microsoft Corporation, Redmond WA)33.

RESULTS

• The search strategy identified 4,063 potentially relevant studies.
• Subgroup analysis was performed to assess differences in heterogeneity and diagnostic accuracy between the groups specified earlier.
• Furthermore Egger's statistic was not significant again suggesting publication bias was not present.

DISCUSSION

• This meta-analysis confirms that when comparing KCC and MELD for outcome prediction in ALF KCC have lower sensitivity and MELD lower specificity.
• The sROC analysis is therefore a more valid way to pool the results of studies with varying thresholds.
• This is no doubt a consequence of the fact that the KCC were derived from an ALF cohort, whereas MELD was developed from results in chronic liver disease patients undergoing TIPS.
• This may be why KCC is preferred in countries facing such organ shortages and with high rates of AALF.
• Clearly such delays are relatively short but in cases of fulminant hepatic failure it is clearly advantageous to use simpler bedside tests during the evolution of disease.

OLT.

• Information on prothrombin time measurements and assay details were not available in all studies and may have contributed to heterogeneity or threshold effects.
• The potential benefits of combining the specificity of the KCC with the sensitivity of MELD are attractive.
• Such novel methods would require data for each patient rather than summative as presented for publication.
• Many new biomarkers have been proposed in ALF but have failed to be validated in larger studies or are deemed not ready for widespread distribution.
• Neither KCC nor MELD are optimal in all circumstances so there remains an urgent need for more accurate outcome prediction systems in ALF.

Figures

Table 2 Individual and pooled sensitivity, specificity, and diagnostic odds ratios (DOR) for King's College Criteria (KCC) and Model for End Stage Liver Disease (MELD).

Table 1 Characteristics of studies included in the meta-analysis (STARD - standards for reporting of diagnostic accuracy studies, AALF- acetaminophen related acute liver failure, NAALF (nonacetaminophen related acute liver failure, TB – tuberculosis, *midway year of study recruitment).

Table 3: Subgroup analysis of the performance of A) King’s College Criteria (KCC) and B) Model for End Stage Liver Disease (MELD) in predicting outcome in acute liver failure. (STARD – standards for the reporting of diagnostic accuracy studies, AALF acetaminophen related acute liver failure, NAALF non acetaminophen related acute liver failure, LR likelihood ratio, DOR diagnostic odds ratio, CI confidence interval.*midway year of study recruitment

Figure 1: Flow diagram of assessment of studies identified in the systematic review

Frequently asked questions

Q1. What have the authors contributed in "Meta-analysis of king's college criteria and model for end stage liver disease to predict outcome in acute liver failure" ?

The authors assessed the accuracy of King 's College Criteria ( KCC ) versus the Model-forEnd-Stage-Liver-Disease ( MELD ) in ALF through meta-analysis of studies which report the accuracy of both tests. 

Q2. What have the authors stated for future works in "Meta-analysis of king's college criteria and model for end stage liver disease to predict outcome in acute liver failure" ?

The authors hope these data help inform such decisions and future research. A worsening grade of HE can be detected at the bedside and incorporated into KCC without awaiting further biochemical analysis.