Multivariate metabotyping of plasma predicts survival in patients with decompensated cirrhosis

McPhail, Mark; Shawcross, Debbie L.; Lewis, Matthew R.; Coltart, Iona; Want, Elizabeth J.; Antoniades, Charalambos; Veselkov, Kirill; Triantafyllou, Evangelos; Patel, Vishal C.; Pop, Oltin T.; Gómez-Romero, María José; Kyriakides, Michael; Zia, Rabiya; Abeles, R.D.; Crossey, Mary M.E.; Jassem, Wayel; O’Grady, John; Heaton, Nigel; Auzinger, G.; Bernal, William; Quaglia, Alberto; Coen, Muireann; Nicholson, Jeremy K.; Wendon, Julia; Holmes, Elaine; Taylor-Robinson, Simon D

doi:10.1016/j.jhep.2016.01.003

Cited by 82 publications

(74 citation statements)

References 54 publications

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“…Metabolomics studies, while only conducted in small cohorts to date, have showed that plasma metabolites including tyrosine may have high discriminatory value in predicting short-term mortality in both alcoholic hepatitis and decompensated cirrhosis. 35,36 C-reactive protein, frailty indices, and even cardiac function markers have also shown promise in this area. 37 Given the rising prevalence of NASH, some of these markers of more systemic dysfunction might be valuable in gauging the overall health of a listed individual.…”

Section: Discussionmentioning

confidence: 99%

The decreasing predictive power of MELD in an era of changing etiology of liver disease

Godfrey

Malik

Lai

et al. 2019

American Journal of Transplantation

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The field of liver transplantation has shifted considerably in the MELD era, including changing allocation, immunosuppression, and liver failure etiologies, as well as better supportive therapies. Our aim was to evaluate the predictive accuracy of the MELD score over time. The United Network for Organ Sharing provided de‐identified data on 120 156 patients listed for liver transplant from 2002‐2016. The ability of the MELD score to predict 90‐day mortality was evaluated by a concordance (C‐) statistic and corroborated with competing risk analysis. The MELD score's concordance with 90‐day mortality has downtrended from 0.80 in 2003 to 0.70 in 2015. While lab MELD scores at listing and transplant climbed in that interval, score at waitlist death remained steady near 35. Listing age increased from 50 to 54 years. HCV‐positive status at listing dropped from 33 to 17%. The concordance of MELD and mortality does not differ with age (>60 = 0.73, <60 = 0.74), but is lower in diseases that are increasing most rapidly—alcoholic liver disease and non‐alcoholic fatty liver disease—and higher in those that are declining, particularly in HCV‐positive patients (HCV positive = 0.77; negative = 0.73). While MELD still predicts mortality, its accuracy has decreased; changing etiology of disease may contribute.

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Section: Discussionmentioning

confidence: 99%

The decreasing predictive power of MELD in an era of changing etiology of liver disease

Godfrey

Malik

Lai

et al. 2019

American Journal of Transplantation

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“…More commonly, MS-based methods have shown elevations in specific serum bile acids in human liver cirrhosis [128,132,135], together with fluctuations in a broad range of urinary steroids [141]. Another common finding were alterations in serum phospholipids in both human liver cirrhosis [135,139,140] and in animal models [169,170,172]. In both the human and animal model investigations, perturbations in metabolic intermediates, akin to those revealed by NMR, have also been described.…”

Section: Uplc-qtofmsmentioning

confidence: 99%

“…LPC concentrations negatively correlated with the circulating markers of cell death, M30 and M65. Therefore, metabolomic phenotyping ("metabotyping") was said to accurately predict mortality in decompensated cirrhosis, due to LPC and amino acid metabolism dysregulation that reflected hepatocyte cell death [140]. Using LC-MS, a Chinese group profiled 43 steroids in the urine of HV (21), LC (21), and HCC (28) relative to urinary creatinine.…”

Section: Fibrosis and Cirrhosismentioning

confidence: 99%

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Beyoğlu

Idle

2020

Metabolites

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In recent years, there has been a plethora of attempts to discover biomarkers that are more reliable than α-fetoprotein for the early prediction and prognosis of hepatocellular carcinoma (HCC). Efforts have involved such fields as genomics, transcriptomics, epigenetics, microRNA, exosomes, proteomics, glycoproteomics, and metabolomics. HCC arises against a background of inflammation, steatosis, and cirrhosis, due mainly to hepatic insults caused by alcohol abuse, hepatitis B and C virus infection, adiposity, and diabetes. Metabolomics offers an opportunity, without recourse to liver biopsy, to discover biomarkers for premalignant liver disease, thereby alerting the potential of impending HCC. We have reviewed metabolomic studies in alcoholic liver disease (ALD), cholestasis, fibrosis, cirrhosis, nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH). Specificity was our major criterion in proposing clinical evaluation of indole-3-lactic acid, phenyllactic acid, N-lauroylglycine, decatrienoate, N-acetyltaurine for ALD, urinary sulfated bile acids for cholestasis, cervonoyl ethanolamide for fibrosis, 16α-hydroxyestrone for cirrhosis, and the pattern of acyl carnitines for NAFL and NASH. These examples derive from a large body of published metabolomic observations in various liver diseases in adults, adolescents, and children, together with animal models. Many other options have been tabulated. Metabolomic biomarkers for premalignant liver disease may help reduce the incidence of HCC.

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“…Most of the studies published to date are relatively small pilot studies, but larger, externally validated studies are emerging more recently: the study by McPhail et al demonstrating external validation in two independent cohorts of a model for the prediction of survival in decompensated liver cirrhosis patients is a landmark (McPhail et al, 2016). …”

Section: Discussionmentioning

confidence: 99%

From Metabonomics to Pharmacometabonomics: The Role of Metabolic Profiling in Personalized Medicine

Everett

2016

Front. Pharmacol.

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Variable patient responses to drugs are a key issue for medicine and for drug discovery and development. Personalized medicine, that is the selection of medicines for subgroups of patients so as to maximize drug efficacy and minimize toxicity, is a key goal of twenty-first century healthcare. Currently, most personalized medicine paradigms rely on clinical judgment based on the patient's history, and on the analysis of the patients' genome to predict drug effects i.e., pharmacogenomics. However, variability in patient responses to drugs is dependent upon many environmental factors to which human genomics is essentially blind. A new paradigm for predicting drug responses based on individual pre-dose metabolite profiles has emerged in the past decade: pharmacometabonomics, which is defined as “the prediction of the outcome (for example, efficacy or toxicity) of a drug or xenobiotic intervention in an individual based on a mathematical model of pre-intervention metabolite signatures.” The new pharmacometabonomics paradigm is complementary to pharmacogenomics but has the advantage of being sensitive to environmental as well as genomic factors. This review will chart the discovery and development of pharmacometabonomics, and provide examples of its current utility and possible future developments.

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Multivariate metabotyping of plasma predicts survival in patients with decompensated cirrhosis

Abstract: Graphical abstract

Cited by 82 publications

References 54 publications

The decreasing predictive power of MELD in an era of changing etiology of liver disease

The decreasing predictive power of MELD in an era of changing etiology of liver disease

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

From Metabonomics to Pharmacometabonomics: The Role of Metabolic Profiling in Personalized Medicine

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