Dataset Information

Multivariate metabotyping of plasma predicts survival in patients with decompensated cirrhosis.

ABSTRACT:

Background & aims

Predicting survival in decompensated cirrhosis (DC) is important in decision making for liver transplantation and resource allocation. We investigated whether high-resolution metabolic profiling can determine a metabolic phenotype associated with 90-day survival.

Methods

Two hundred and forty-eight subjects underwent plasma metabotyping by (1)H nuclear magnetic resonance (NMR) spectroscopy and reversed-phase ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOF-MS; DC: 80-derivation set, 101-validation; stable cirrhosis (CLD) 20 and 47 healthy controls (HC)).

Results

(1)H NMR metabotyping accurately discriminated between surviving and non-surviving patients with DC. The NMR plasma profiles of non-survivors were attributed to reduced phosphatidylcholines and lipid resonances, with increased lactate, tyrosine, methionine and phenylalanine signal intensities. This was confirmed on external validation (area under the receiver operating curve [AUROC]=0.96 (95% CI 0.90-1.00, sensitivity 98%, specificity 89%). UPLC-TOF-MS confirmed that lysophosphatidylcholines and phosphatidylcholines [LPC/PC] were downregulated in non-survivors (UPLC-TOF-MS profiles AUROC of 0.94 (95% CI 0.89-0.98, sensitivity 100%, specificity 85% [positive ion detection])). LPC concentrations negatively correlated with circulating markers of cell death (M30 and M65) levels in DC. Histological examination of liver tissue from DC patients confirmed increased hepatocyte cell death compared to controls. Cross liver sampling at time of liver transplantation demonstrated that hepatic endothelial beds are a source of increased circulating total cytokeratin-18 in DC.

Conclusion

Plasma metabotyping accurately predicts mortality in DC. LPC and amino acid dysregulation is associated with increased mortality and severity of disease reflecting hepatocyte cell death.

SUBMITTER: McPhail MJW

PROVIDER: S-EPMC4876170 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multivariate metabotyping of plasma predicts survival in patients with decompensated cirrhosis.

McPhail Mark J W MJW Shawcross Debbie L DL Lewis Matthew R MR Coltart Iona I Want Elizabeth J EJ Antoniades Charalambos G CG Veselkov Kiril K Triantafyllou Evangelos E Patel Vishal V Pop Oltin O Gomez-Romero Maria M Kyriakides Michael M Zia Rabiya R Abeles Robin D RD Crossey Mary M E MME Jassem Wayel W O'Grady John J Heaton Nigel N Auzinger Georg G Bernal William W Quaglia Alberto A Coen Muireann M Nicholson Jeremy K JK Wendon Julia A JA Holmes Elaine E Taylor-Robinson Simon D SD

Journal of hepatology 20160118 5

<h4>Background & aims</h4>Predicting survival in decompensated cirrhosis (DC) is important in decision making for liver transplantation and resource allocation. We investigated whether high-resolution metabolic profiling can determine a metabolic phenotype associated with 90-day survival.<h4>Methods</h4>Two hundred and forty-eight subjects underwent plasma metabotyping by (1)H nuclear magnetic resonance (NMR) spectroscopy and reversed-phase ultra-performance liquid chromatography coupled to time ...[more]

PMID: 26795831

Similar Datasets

Project description:Background & aimsThe latest Baveno VII consensus has provided guidance for identifying patients who have truly recompensated from those with hepatic decompensation. This study aimed to evaluate patients' transplant-free survival in three different stages of cirrhosis.MethodsAll patients with chronic HBV infection and liver cirrhosis treated with oral nucleos(t)ide analogues from March 2006 to December 2022 were identified from a territory-wide database in Hong Kong. Patients with follow-up duration of <1 year were excluded. Participants were classified into three mutually exclusive groups: (1) no decompensated events (i.e. compensated group); (2) decompensated events occurred (i.e. decompensated group); or (3) decompensated events occurred followed by recompensation according to Baveno VII criteria (i.e. recompensated group). A time-dependent Cox proportional hazard model was adopted for evaluation. The follow-up period was 5 years.ResultsA total of 4,701 patients with cirrhosis and HBV who were treated with entecavir, tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide fumarate (TAF) were identified. During a median follow-up of 5 years (interquartile range 3.7, 5 years), 3,327 (70.8%), 1,347 (29.2%), and 265 (5.6%) patients had compensated, decompensated, and recompensated cirrhosis, respectively, at least once before the end of the study. In the time-dependent multivariable model, the recompensated group had similar transplant-free survival compared with the compensated group (adjusted hazard ratio 1.16; 95% CI 0.72-1.86; p = 0.536). The 5-year transplant-free survival rate was 89.3% for the compensated group, whereas it was 76.0% for the recompensated group, reflecting a minimal difference between the two groups.ConclusionsThe clinical significance of recompensation of cirrhosis in improving patient outcomes for individuals with CHB infection was highlighted in this study. Early identification and treatment with nucleos(t)ide analogues might promote hepatic recompensation and thus reduce mortality in patients with CHB.Impact and implicationsThe latest Baveno VII consensus introduces the new concept of hepatic recompensation, which refers to the reversal of the structural and functional changes of cirrhosis after removal, cure, or suppression of the aetiology of cirrhosis. It is essential to investigate the transplant-free survival rates of patients who are able to achieve hepatic recompensation, as this has significant implications for the medical resources required to manage liver failure and transplantation. This study features the clinical significance of hepatic recompensation by comparing patient outcomes of those who achieve it to those who do not. The early identification and use of antiviral treatment with nucleos(t)ide analogues is a pivotal strategy to promote hepatic recompensation, which has the potential to significantly reduce mortality rates in patients with chronic HBV infection and ultimately aid in the elimination of hepatitis.

Dataset Information

Multivariate metabotyping of plasma predicts survival in patients with decompensated cirrhosis.

Background & aims

Methods

Results

Conclusion

Publications

Multivariate metabotyping of plasma predicts survival in patients with decompensated cirrhosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets