Laboratory Testing for Liver Disease

Poynard, Thierry; Imbert‐Bismut, Françoise

doi:10.1016/b978-1-4377-0881-3.00014-0

Cited by 6 publications

(5 citation statements)

References 161 publications

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“…These two proteins show the highest correlation (0.72 and 0.79 Spearman R, respectively) with the neutrophil-to-lymphocyte ratio (NLR), a prognostic marker for COVID-19 ( Lian et al., 2020 ; Liu et al., 2020a ). We further report a strong correlation ( Figure 1 C) of alkaline phosphatase and gamma-glutamyl transferase activities, both characteristic of biliary disorders ( Poynard and Imbert-Bismut, 2012 ), with plasma levels of the polymeric immunoglobulin receptor (PIGR). We notice that cholangiocytes (bile duct epithelium cells) express ACE-2 and can be directly infected with SARS-CoV-2 ( Zhao et al., 2020 ), potentially leading to host viral response-induced expression of PIGR and cell destruction ( Schneeman et al., 2005 ; Turula and Wobus, 2018 ).…”

Section: Resultssupporting

confidence: 52%

A time-resolved proteomic and prognostic map of COVID-19

Demichev¹,

Tober‐Lau²,

Lemke³

et al. 2021

Cell Systems

146

164

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COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.

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Section: Resultssupporting

confidence: 52%

A time-resolved proteomic and prognostic map of COVID-19

Demichev¹,

Tober‐Lau²,

Lemke³

et al. 2021

Cell Systems

146

164

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show abstract

“…We further report a strong correlation (Fig. 1c) of alkaline phosphatase and gamma-glutamyl transferase activities, both characteristic of biliary disorders 24 , with plasma levels of the polymeric immunoglobulin receptor (PIGR). We note that cholangiocytes (bile duct epithelium cells) express ACE-2 and can be directly infected with SARS-CoV-2 25 , leading to host viral response-induced expression of PIGR and cell destruction 26 .…”

Section: Introductionsupporting

confidence: 56%

A time-resolved proteomic and diagnostic map characterizes COVID-19 disease progression and predicts outcome

Demichev¹,

Tober‐Lau²,

Nazarenko³

et al. 2020

Preprint

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COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. There is an urgent need for predictive markers that can guide clinical decision-making, inform about the effect of experimental therapies, and point to novel therapeutic targets. Here, we characterize the time-dependent progression of COVID-19 through different stages of the disease, by measuring 86 accredited diagnostic parameters and plasma proteomes at 687 sampling points, in a cohort of 139 patients during hospitalization. We report that the time-resolved patient molecular phenotypes reflect an initial spike in the systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution and immunomodulation. Further, we show that the early host response is predictive for the disease trajectory and gives rise to proteomic and diagnostic marker signatures that classify the need for supplemental oxygen therapy and mechanical ventilation, and that predict the time to recovery of mildly ill patients. In severely ill patients, the molecular phenotype of the early host response predicts survival, in two independent cohorts and weeks before outcome. We also identify age-specific molecular response to COVID-19, which involves increased inflammation and lipoprotein dysregulation in older patients. Our study provides a deep and time resolved molecular characterization of COVID-19 disease progression, and reports biomarkers for risk-adapted treatment strategies and molecular disease monitoring. Our study demonstrates accurate prognosis of COVID-19 outcome from proteomic signatures recorded weeks earlier.

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“…Although the specific causes of hepatic disease of dogs in the HLEA group were not determined in this study (no liver histopathology), dogs within this group had high serum cholesterol concentrations. Hypercholesterinemia in liver disease in humans and animals is related to cholestasis 10 , 13 , as well as to increased hepatic synthesis and decreased lecithin-cholesterol acyltransferase 13 . Moreover, while concentrations of most lipoproteins were also elevated in dogs with HLEA, they remained normal or low in dogs with cPSS compared to the Control group.…”

Section: Discussionmentioning

confidence: 99%

“…Congenital portosystemic shunts (cPSS) are commonly seen vascular liver anomalies in young dogs 6 and cats 7 , but occur very rarely in children 8 , 9 . In addition, there are many acquired acute and chronic hepatic diseases in humans and animals related to infectious, inflammatory, degenerative, vascular, neoplastic, drug- or toxin-related processes, as well as hepatopathies of idiopathic origin, which are associated with high serum liver enzyme activities 10 – 13 . Of major human public health concerns are acute and chronic hepatitis virus A to E infections and alcohol-related liver diseases 14 , which are not recognized in dogs 15 .…”

Section: Introductionmentioning

confidence: 99%

Metabolomic serum abnormalities in dogs with hepatopathies

Imbery

Dieterle

Ottka

et al. 2022

Sci Rep

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Hepatopathies can cause major metabolic abnormalities in humans and animals. This study examined differences in serum metabolomic parameters and patterns in left-over serum samples from dogs with either congenital portosystemic shunts (cPSS, n = 24) or high serum liver enzyme activities (HLEA, n = 25) compared to control dogs (n = 64). A validated targeted proton nuclear magnetic resonance spectroscopy platform was used to assess 123 parameters. Principal component analysis of the serum metabolome demonstrated distinct clustering among individuals in each group, with the cluster of HLEA being broader compared to the other groups, presumably due to the wider spectrum of hepatic diseases represented in these samples. While younger and older adult control dogs had very similar metabolomic patterns and clusters, there were changes in many metabolites in the hepatopathy groups. Higher phenylalanine and tyrosine concentrations, lower branched-chained amino acids (BCAAs) concentrations, and altered fatty acid parameters were seen in cPSS dogs compared to controls. In contrast, dogs with HLEA had increased concentrations of BCAAs, phenylalanine, and various lipoproteins. Machine learning based solely on the metabolomics data showed excellent group classification, potentially identifying a novel tool to differentiate hepatopathies. The observed changes in metabolic parameters could provide invaluable insight into the pathophysiology, diagnosis, and prognosis of hepatopathies.

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Laboratory Testing for Liver Disease

Cited by 6 publications

References 161 publications

A time-resolved proteomic and prognostic map of COVID-19

A time-resolved proteomic and prognostic map of COVID-19

A time-resolved proteomic and diagnostic map characterizes COVID-19 disease progression and predicts outcome

Metabolomic serum abnormalities in dogs with hepatopathies

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