scholarly journals Raman spectroscopy on blood serum samples of patients with end-stage liver disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0256045
Author(s):  
René Staritzbichler ◽  
Pascal Hunold ◽  
Irina Estrela-Lopis ◽  
Peter Werner Hildebrand ◽  
Berend Isermann ◽  
...  

Raman spectroscopy has shown to be a promising method for the examination of biomedical samples. However, until now, its efficacy has not been established in clinical diagnostics. In this study, Raman spectroscopy’s potential application in medical laboratories is evaluated for a large variety (38) of biomarkers. Given 234 serum samples from a cohort of patients with different stages of liver disease, we performed Raman spectroscopy at 780nm excitation wavelength. The Raman spectra were analyzed in combination with the results of routine diagnostics using specifically developed complex mathematical algorithms, including fluorescence filtering, frequency subset selection and several overfitting circumventing strategies, such as independent validation. With the results of this cohort, which were validated in 328 independent samples, a significant proof-of-concept study was completed. This study highlights the need to prevent overfitting and to use independent data for validation. The results reveal that Raman spectroscopy has high potential for use in medical laboratory diagnostics to simultaneously quantify multiple biomarkers.

2021 ◽  
Author(s):  
Rene Staritzbichler ◽  
Pascal Hunold ◽  
Irina Estrela-Lopis ◽  
Peter Werner Hildebrand ◽  
Berend Isermann ◽  
...  

Raman spectroscopy has shown to be a promising method for the examination of biomedical samples. However, until now, its efficacy has not been established in clinical diagnostics. In this study, Raman spectroscopy's potential application in medical laboratories is evaluated for a large variety (38) of biomarkers. Given 234 serum samples from a cohort of patients with different stages of liver disease, we performed Raman spectroscopy at 780nm excitation frequency. The Raman spectra were analyzed in combination with the results of routine diagnostics using specifically developed complex mathematical algorithms, including fluorescence filtering, frequency subset selection and several overfitting circumventing strategies, such as independent validation. Given this cohort of patients, a significant proof-of-concept study was completed. The results reveal that Raman spectroscopy has high potential for use in medical laboratory diagnostics to simultaneously quantify multiple biomarkers.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254219
Author(s):  
Pascal Hunold ◽  
Thomas Berg ◽  
Daniel Seehofer ◽  
Robert Sucher ◽  
Adam Herber ◽  
...  

Background The model of end-stage liver disease (MELD) score was established for the allocation of liver transplants. The score is based on the medical laboratory parameters: bilirubin, creatinine and the international normalized ratio (INR). A verification algorithm for the laboratory MELD diagnostic was established, and the results from the first six years were analyzed. Methods We systematically investigated the validity of 7,270 MELD scores during a six-year period. The MELD score was electronically requested by the clinical physician using the laboratory system and calculated and specifically validated by the laboratory physician in the context of previous and additional diagnostics. Results In 2.7% (193 of 7,270) of the cases, MELD diagnostics did not fulfill the specified quality criteria. After consultation with the sender, 2.0% (145) of the MELD scores remained invalid for different reasons and could not be reported to the transplant organization. No cases of deliberate misreporting were identified. In 34 cases the dialysis status had to be corrected and there were 24 cases of oral anticoagulation with impact on MELD diagnostics. Conclusion Our verification algorithm for MELD diagnostics effectively prevented invalid MELD results and could be adopted by transplant centers to prevent diagnostic errors with possible adverse effects on organ allocation.


2018 ◽  
Vol 27 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Alina M Suciu ◽  
Dana A Crisan ◽  
Bogdan D Procopet ◽  
Corina I Radu ◽  
Carmen Socaciu ◽  
...  

Background & Aims: Current management of alcoholic liver disease (ALD), especially for alcoholic hepatitis (AH) is still driven by liver biopsy. Therefore, the identification of novel and accurate noninvasive biomarkers for the diagnosis and assessment of severity is important. Metabolomics, because it unravels changes closest to the phenotype, may represent the key for novel biomarkers. The aim of this study was to identify and characterize potential metabolomic biomarkers for diagnosis, staging and severity assessment of ALD.Methods: 30 consecutive ALD patients and 10 healthy controls were included in this proof-of-concept crosssectional study. Baseline assessment consisted in evaluation of Maddrey’s Discriminant Function, Model for End-Stage Liver Disease (MELD) and ABIC scores as well as ASH-Test (Fibromax) as a surrogate for the confirmatory diagnosis of AH in suggestive clinical and biologic settings. Additionally, SOP metabolomics and lipidomics were performed from serum samples by liquid chromatography mass-spectrometry analysis.Results: From the 127 and 135 serum/urine candidate metabolites initially identified, only 11/5 metabolites were characteristic for ALD patients. None of them correlated with alcohol intake, and only 5/1 metabolites could differentiate cirrhotic from non-cirrhotic patients. Of those, N-Lauroglycine (NLG) was the best for identifying cirrhosis (100% sensitivity and 90% negative predictive value, NPV) and decatrienoic acid (DTEA) was the best for assessing disease severity (evaluated by ABIC score) with 100% sensitivity and 100% NPV.Conclusion: Due to their high NPV, NLG and DTEA could be used in conjunction in ALD patients to exclude cirrhosis or a severe disease. If further validated, they could become biomarkers for better management and risk assessment in ALD.


2010 ◽  
Vol 3 (1) ◽  
pp. 1-6
Author(s):  
D. Koutsogiannis ◽  
K. Summers ◽  
B. George ◽  
P. Adams ◽  
P. Marotta ◽  
...  

Background: Progressive fibrosis and cirrhosis, clinically presenting as end-stage liver disease are common outcomes in alcoholic hepatitis as well as non-alcoholic fatty liver disease(NAFLD). In these processes, a series of changes occurs in liver tissues leading to cell death, remodeling, fibrosis and regeneration. The aim of this study is to identify potential novel biomarkers for non-invasive diagnosis of cirrhosis due to alcoholic etiology or NAFLD. Methods: Serum from patients with biopsy proven end-stage liver disease of various etiologies, namely NAFLD(n=9), alcohol( n=5), and other end-stage liver diseases(n=6), who underwent liver transplant during the first six months of 2007 were utilized for retrospective analysis. Serum samples were also collected from a group of healthy volunteers (n=7). The samples were analysed using Luminex technology or ELISA for 27 biomarkers that are known to be involved in pathologic processes such as cell death, regeneration and fibrosis. Results: Of the 27 serum markers examined, 16 were elevated in the serum in all groups with end-stage liver diseases compared with the control group. They include adipokines, apoptosis and inflammatory mediators and growth factors. Interestingly, the serum of NAFLD patients showed significantly elevated HGF levels and trend towards increase in sFAS, TGF􀀁1, TNFR-1, TNFR-2 and leptin. The level of serum markers showed excellent correlation with each other indicating a complex interdependent pathogenetic mechanism. Conclusions: The data from this study indicate that a large number of serum markers are altered in end-stage liver diseases. A panel of such markers may potentially be useful in assessing advanced fibrosis and cirrhosis in patients with chronic end stage liver diseases.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 619
Author(s):  
Safak Gül-Klein ◽  
Deana Haxhiraj ◽  
Julian Seelig ◽  
Anika Kästner ◽  
Julian Hackler ◽  
...  

The trace element selenium (Se) is taken up from the diet and is metabolized mainly by hepatocytes. Selenoprotein P (SELENOP) constitutes the liver-derived Se transporter. Biosynthesis of extracellular glutathione peroxidase (GPx3) in kidney depends on SELENOP-mediated Se supply. We hypothesized that peri-operative Se status may serve as a useful prognostic marker for the outcome in patients undergoing liver transplantation due to hepatocellular carcinoma. Serum samples from liver cancer patients were routinely collected before and after transplantation. Concentrations of serum SELENOP and total Se as well as GPx3 activity were determined by standardized tests and related to survival, etiology of cirrhosis/carcinoma, preoperative neutrophiles, lymphocytes, thyrotropin (TSH) and Child–Pugh and Model for End-Stage Liver Disease (MELD) scores. A total of 221 serum samples from 79 transplanted patients were available for analysis. The Se and SELENOP concentrations were on average below the reference ranges of healthy subjects. Patients with ethanol toxicity-dependent etiology showed particularly low SELENOP and Se concentrations and GPx3 activity. Longitudinal analysis indicated declining Se concentrations in non-survivors. We conclude that severe liver disease necessitating organ replacement is characterized by a pronounced Se deficit before, during and after transplantation. A recovering Se status after surgery is associated with positive prognosis, and an adjuvant Se supplementation may, thus, support convalescence.


Author(s):  
Safak Gül-Klein ◽  
Deana Haxhiraj ◽  
Julian Seelig ◽  
Annika Kaestner ◽  
Julian Hackler ◽  
...  

The trace element selenium (Se) is taken up from the diet and becomes metabolized mainly by hepatocytes. Selenoprotein P (SELENOP) constitutes the liver-derived Se transporter. Biosynthesis of extracellular glutathione peroxidase (GPx3) in kidney depends on SELENOP-mediated Se supply. We hypothesized that Se status may serve as a useful prognostic marker for outcome in patients undergoing liver transplantation. Serum samples from patients were routinely collected before and after transplantation. Concentration of serum SELENOP and total Se as well as GPx3 activity were determined by standardized tests and related to survival, aetiology and pre-operative Child-Pugh and Model for End-Stage Liver Disease Scores. A total of 314 serum samples from 78 transplanted patients were available for analysis. The Se and SELENOP concentrations were on average below the reference ranges of healthy subjects. Patients with ethanol toxicity-dependent aetiology showed particularly low SELENOP and Se concentrations and GPx3 activity. Longitudinal analysis indicated declining Se concentrations in non-survivors. We conclude that severe liver disease necessitating organ replacement is characterized by a pronounced Se deficit before, during and after transplantation. A recovering Se status after surgery is associated with positive prognosis, and an adjuvant Se supplementation may thus support convalescence.


2017 ◽  
Vol 26 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Liana Gheorghe ◽  
Ioan Sporea ◽  
Speranţa Iacob ◽  
Roxana Şirli ◽  
Anca Trifan ◽  
...  

Background & Aims: Hepatitis C Virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments became available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention has been created. These items were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the first of the two parts of our Society’s recommendations for chronic HCV infection treatment. An agreement was reached regarding the diagnostic tools, the assessment of severity and the up-dated therapy schedules.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to the real-life conditions in this country.Abbreviations: DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESLD: End-stage liver disease; ESRD: End-stage renal disease; eGFR: Estimated glomerular filtration rate; EASL: European Association for the Study of the Liver; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: Fixed-dose combination; GT: Genotype; GRADE: Grading of Recommendations Assessment, Development and Evaluation; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; LLD: Lower limit of detection; MELD score: Mayo-Clinic End-Stage Liver Disease score; ANMDM: National Agency of Medicines and Medical Devices; PPIs: Proton pump inhibitors; PWID: People who inject drugs; RCT: Randomized controlled trial; RDT: Rapid diagnostic test; RAS: Resistance-associated substitution; SRGH: Romanian Society of Gastroenterology and Hepatology; SAE: serious adverse events; SPC: Summary of Product Characteristics; SVR: Sustained virologic response.


2017 ◽  
Vol 26 (3) ◽  
pp. 309-317 ◽  
Author(s):  
Liana Gheorghe ◽  
Ioan Sporea ◽  
Speranța Iacob ◽  
Roxana Șirli ◽  
Anca Trifan ◽  
...  

Background & Aims: Hepatitis C virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments have become available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention was created and these were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the second part of the Society’s recommendations for chronic HCV infection treatment. An agreement between experts was reached regarding the therapy of the special categories of patients infected with HCV, complications and monitoring of the therapy, follow-up of the patients who reached sustained virologic response and re-treatment of the patients with therapy failure.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to real-life conditions in Romania. Abbreviations: CKD: Chronic kidney disease; DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESDL: End-stage liver disease; FCH: Fibrosing cholestatic hepatitis; GT: Genotype; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; MELD score: Mayo-Clinic End-Stage Liver Disease score; PDC: Premature discontinuation; PWID: Persons who inject drugs; RASs: Resistance associated substitutions; RBV: Ribavirin; RCT: Randomized controlled trial; SAE: Serious adverse events; SRGH: Romanian Society of Gastroenterology and Hepatology; SVR: Sustained virologic response.


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