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End-stage liver failure: filling the treatment gap at the intensive care unit.

ABSTRACT: End-stage liver failure is a condition of collapsing liver function with mortality rates up to 80. Liver transplantation is the only lifesaving therapy. There is an unmet need for therapy to extend the waiting time for liver transplantation or regeneration of the native liver. Here we review the state-of-the-art of non-cell based and cell-based artificial liver support systems, cell transplantation and plasma exchange, with the first therapy relying on detoxification, while the others aim to correct also other failing liver functions and/or modulate the immune response. Meta-analyses on the effect of non-cell based systems show contradictory outcomes for different types of albumin purification devices. For bioartificial livers proof of concept has been shown in animals with liver failure. However, large clinical trials with two different systems did not show a survival benefit. Two clinical trials with plasma exchange and one with transplantation of mesenchymal stem cells showed positive outcomes on survival. Detoxification therapies lack adequacy for most patients. Correction of additional liver functions, and also modulation of the immune system hold promise for future therapy of liver failure.

SUBMITTER: Chamuleau RAFM

PROVIDER: S-EPMC7228976 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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End-stage liver failure: filling the treatment gap at the intensive care unit.

Chamuleau Robert A F M RAFM Hoekstra Ruurdtje R

Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs 20190918 2

End-stage liver failure is a condition of collapsing liver function with mortality rates up to 80. Liver transplantation is the only lifesaving therapy. There is an unmet need for therapy to extend the waiting time for liver transplantation or regeneration of the native liver. Here we review the state-of-the-art of non-cell based and cell-based artificial liver support systems, cell transplantation and plasma exchange, with the first therapy relying on detoxification, while the others aim to cor ...[more]

PMID: 31535298

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Project description:IntroductionEnd-stage renal disease (ESRD) is associated with an increased propensity for critical illness, but whether ESRD is independently associated with a greater risk of death after major surgical procedures is unclear.MethodsThis was a retrospective analysis of prospectively collected data from all adult (>18 years) patients admitted to a 50-bed surgical intensive care unit (ICU) between January 2004 and January 2009. ESRD was defined as the need for chronic peritoneal dialysis or hemodialysis for at least 6 weeks prior to ICU admission. We used multivariable logistic regression analysis and propensity-score matching to adjust for possible confounders.ResultsIn total, 12,938 adult patients were admitted during the study period; 199 patients had ESRD at ICU admission, giving a prevalence of 1.5%. Patients with ESRD were more likely to be male (72.9% versus 63.0%, P?=?0.004) and had higher severity scores, a higher incidence of diabetes mellitus and cirrhosis, and a lower incidence of cancer at ICU admission than those without ESRD. Patients with ESRD were more likely to have any type of organ failure at ICU admission and during the ICU stay. Patients with ESRD had higher ICU and hospital mortality rates (23.1% and 31.2% versus 5.5% and 10.0%, respectively, P <0.001 pairwise) and longer ICU length of stay (2 (1 to 7) versus 1 (1 to 3) days, P <0.001). In multivariable logistic regression analysis, ESRD was independently associated with a greater risk of in-hospital death (odds ratio?=?3.84, 95% confidence interval 2.68 to 5.5, P <0.001). In 199 pairs of patients, hematologic and hepatic failures were more prevalent, ICU and hospital mortality rates were higher (23.1% versus 15.1% and 31.2% versus 19.1%, P <0.05 pairwise), and ICU length of stay was longer (2 (1 to 7) versus 1 (1 to 7) days, P <0.001) in patients with ESRD.ConclusionsIn this large cohort of surgical ICU patients, presence of ESRD at ICU admission was associated with greater morbidity and mortality and independently associated with a greater risk of in-hospital death. Our data can be useful in preoperative risk stratification.

Project description:IntroductionPediatric acute liver failure is a rare and serious disease. Though liver transplantation is considered as the established treatment option for patients who are unlikely to recover with medical management, however, with the advancement of medical care there has been an increase in spontaneous regeneration of liver, obviating the need for liver transplantation. We identified the etiologies, outcome and prognostic factors of acute liver failure and the validity of the existing liver transplantation criteria to predict the outcome of pediatric acute liver failure.Materials and methodsThis was a retrospective study done from January 2014 to December 2019 in a tertiary pediatric critical care unit in South India. All children aged between 1 month to 18 years admitted with acute liver failure were enrolled.ResultsOf 125 children with acute liver failure, the main etiologies were infections (32%), indeterminate (23%), paracetamol toxicity (21%), metabolic (13%) and others (11%). Dengue was the most common infection (55%). The median pediatric logistic organ dysfunction score at admission was 12 (4-27). Of 125 patients, 63.2% (n = 79) had spontaneous regeneration which was higher in paracetamol induced (92.3%) compared to non-paracetamol induced acute liver failure (55.5%). Only two patients underwent liver transplantation and 35% died. Peak alanine transaminase and use of inotropes significantly predicted the outcome of disease. Of 38 children meeting King's College Hospital criteria for liver transplantation, 57.9% had spontaneous regeneration and 36.8% died. Of 74 children meeting INR > 4 criteria, 54% (n = 40) had spontaneous regeneration and 43.2% died. INR >4 criteria was more sensitive than King's College Hospital criteria for predicting the need for liver transplantation.ConclusionPediatric acute liver failure is caused by varied etiologies and infections were the commonest cause. Despite having a seriously ill cohort of patients, medical management resulted in spontaneous regeneration in the majority of children with acute liver failure. The use of inotropes, advanced hepatic encephalopathy, and peak alanine transaminase were predictors of poor outcome in children with acute liver failure and these patients could be considered for liver transplantation as available. Therefore, we may need to develop better predictors of pediatric acute liver failure in resource limited settings.

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End-stage liver failure: filling the treatment gap at the intensive care unit.

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End-stage liver failure: filling the treatment gap at the intensive care unit.

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