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Journal ArticleDOI

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

01 Apr 2016-Clinical Gastroenterology and Hepatology (Clin Gastroenterol Hepatol)-Vol. 14, Iss: 4, pp 516-525
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 (2 min read)



  • 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.


  • 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).


  • 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.


  • 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.


  • 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.


  • 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.

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Cites background from "Ability of King's College Criteria ..."

  • ...In patients with DILI who developed ALF, the King’s College criteria or the US ALF Study Group criteria for non-APAP ALF can be applied for assessing the prognosis and for timing liver transplant evaluation, but these models are not specific for DILI (73,74)....


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TL;DR: The term acute liver failure (ALF) is frequently applied as a generic expression to describe patients presenting with or developing an acute episode of liver dysfunction, however, it refers to a highly specific and rare syndrome, characterised by an acute abnormality of liver blood tests in an individual without underlying chronic liver disease.

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TL;DR: N-acetylcysteine is recommended for all patients with APAP-induced ALF and it reduces mortality and Liver transplantation should be offered early to those who are unlikely to survive based on described prognostic criteria.

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TL;DR: The challenges with prognostic modeling in PALF are discussed and predictive methods that are currently available and in development for the future are described.

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Cites background from "Ability of King's College Criteria ..."

  • ...,((20)) in their meta-analysis, revealed higher sensitivity of MELD over KCH criteria but at the cost of reduced specificity....


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TL;DR: The current diagnostic and therapeutic approach to acute liver failure is reviewed, especially in the intensive care unit setting, to improve patients' outcomes and selection of patients for liver transplantation.

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Cites background from "Ability of King's College Criteria ..."

  • ...A recent metaanalysis has revealed its prognostic ability in comparison with the MELD score: for acetaminophen-related ALF, sensitivities were 58% and 80%, respectively, and specificities were 89% and 53%, respectively; for non-acetaminophen etiologies, sensitivities were 58% and 76%, respectively, and specificities were 74% and 73%, respectively [73]....


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04 Sep 2003-BMJ
TL;DR: A new quantity is developed, I 2, which the authors believe gives a better measure of the consistency between trials in a meta-analysis, which is susceptible to the number of trials included in the meta- analysis.
Abstract: Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice? Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis. Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4 Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted? A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …

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Frequently Asked Questions (2)
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. 

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.