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Dynamic assessments of hepatic encephalopathy and ammonia levels predict mortality in acute-on-chronic liver failure

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Abstract

Background

We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence.

Methods

ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted.

Results

Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I–II in 981 (74.6%) and grades III–IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p < 0.05; each). The progressive course of HE was noted in 10.0% of patients without HE and 8.2% of patients with HE at baseline, respectively. Independent predictors of progressive course of HE were AARC score (≥ 9) and ammonia levels (≥ 85 μmol/L) (p < 0.05; each) at baseline. A final grade of HE was achieved within 7 days in 70% of patients and those with final grades III–IV had the worst survival (8.9%). Ammonia levels were a significant predictor of HE occurrence, higher HE grades and 30-day mortality (p < 0.05; each). The dynamic increase in the ammonia levels over 7 days could predict nonsurvivors and progression of HE (p < 0.05; each). Ammonia, HE grade, SIRS, bilirubin, INR, creatinine, lactate and age were the independent predictors of 30-day mortality in ACLF patients.

Conclusions

HE in ACLF is common and is associated with systemic inflammation, poor liver functions and high disease severity. Ammonia levels are associated with the presence, severity, progression of HE and mortality in ACLF patients.

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Abbreviations

HE:

Hepatic encephalopathy

ACLF:

Acute-on-chronic liver failure

EASL:

European Association for the Study of the Liver

APASL:

Asian Pacific Association for the Study of Liver

DC:

Decompensated cirrhosis

ALF:

Acute liver failure

ICU:

Intensive Care Unit

AARC:

APASL ACLF Research Consortium

HVPG:

Hepatic venous pressure gradient

CTP:

Child-Turcotte-Pugh score

MELD:

Model for endstage liver disease

MELD-Na:

MELD-sodium

SOFA:

Sequential Organ Failure Assessment score

APACHE-II:

Acute Physiology and Chronic Health Evaluation-II

IQR:

Interquartile range

AUROC:

Area under receiver operating curve

SIRS:

Systemic inflammatory response syndrome

SHR:

Sub-distribution hazard ratio

CI:

Confidence interval

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Correspondence to Radha Krishan Dhiman.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Institutional and National) and with the Declaration of Helsinki 1975, as revised in 2008. The AARC registry for ACLF was approved by the Institutional Ethical Review Board at the nodal center, i.e., ILBS New Delhi (vide letter no F/25/5/64/AC2013/912) and all the participating centres also had necessary approval from the respective ethical board.

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Informed consent was obtained from all individual participants or legally acceptable representatives of the participant included in the study.

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Verma, N., Dhiman, R.K., Choudhury, A. et al. Dynamic assessments of hepatic encephalopathy and ammonia levels predict mortality in acute-on-chronic liver failure. Hepatol Int 15, 970–982 (2021). https://doi.org/10.1007/s12072-021-10221-7

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  • DOI: https://doi.org/10.1007/s12072-021-10221-7

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