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A distinct serum metabonomic pattern has been previously revealed to be associated with various forms of liver disease. Here, we aimed to apply mass spectrometry to obtain serum metabolomic profiles from individuals with cholangiocarcinoma and benign hepatobiliary diseases to gain an insight into pathogenesis and search for potential early-disease biomarkers. Serum samples were profiled using a hydrophilic interaction liquid chromatography platform, coupled to a mass spectrometer. A total of 47 serum specimens from 8 cholangiocarcinoma cases, 20 healthy controls, 8 benign disease controls (bile duct strictures) and 11 patients with hepatocellular carcinoma (as malignant disease controls) were included. Data analysis was performed using univariate and multivariate statistics. The serum metabolome disparities between the metabolite profiles from healthy controls and patients with hepatobiliary disease were predominantly related to changes in lipid and lipid-derived compounds (phospholipids, bile acids and steroids) and amino acid metabolites (phenylalanine). A metabolic pattern indicative of inflammatory response due to cirrhosis and cholestasis was associated with the disease groups. The abundance of phospholipid metabolites was altered in individuals with liver disease, particularly cholangiocarcinoma, but no significant difference was seen between profiles from patients with benign biliary strictures and cholangiocarcinoma. The serum metabolome in cholangiocarcinoma exhibited changes in metabolites related to inflammation, altered energy production and phospholipid metabolism. This study serves to highlight future avenues for biomarker research in large-scale studies. [ABSTRACT FROM AUTHOR]

Background/Aims Previous studies have observed disturbances in the 1 H nuclear magnetic resonance (NMR) blood spectral profiles in malignancy. No study has metabotyped serum or plasma of hepatocellular carcinoma (HCC) patients from two diverse populations. We aimed to delineate the HCC patient metabotype from Nigeria (mostly hepatitis B virus infected) and Egypt (mostly hepatitis C virus infected) to explore lipid and energy metabolite alterations that may be independent of disease aetiology, diet and environment. Methods Patients with HCC (53) and cirrhosis (26) and healthy volunteers (19) were recruited from Nigeria and Egypt. Participants provided serum or plasma samples, which were analysed using 600 MHz 1 H NMR spectroscopy with nuclear Overhauser enhancement spectroscopy pulse sequences. Median group spectra comparison and multivariate analysis were performed to identify regions of difference. Results Significant differences between HCC patients and healthy volunteers were detected in levels of low density lipoprotein ( P = 0.002), very low density lipoprotein ( P < 0.001) and lactate ( P = 0.03). N -acetylglycoproteins levels in HCC patients were significantly different from both healthy controls and cirrhosis patients ( P < 0.001 and 0.001). Conclusion Metabotype differences were present, pointing to disturbed lipid metabolism and a switch from glycolysis to alternative energy metabolites with malignancy, which supports the Warburg hypothesis of tumour metabolism. [ABSTRACT FROM AUTHOR]

Background Discriminatory metabolic profiles have been described in urinary 1 H nuclear magnetic resonance (NMR) spectroscopy studies of African patients with hepatocellular carcinoma (HCC). This study aimed to assess similarities in a UK cohort, where there is a greater etiological diversity. Methods Urine from cirrhosis and HCC patients was analyzed using a 600 MHz 1 H NMR system. Multivariate analysis and median group MR spectra comparison identified metabolite alterations between groups. Metabolite identification was achieved through literature reference and statistical total correlation spectroscopy. Diagnostic accuracy was compared to serum alpha-fetoprotein (AFP). Results Of the 52 patients recruited, 13 samples from HCC and 25 from cirrhosis patients were selected. At 200 IU mL −1 , diagnostic sensitivity of AFP was 27%. Multivariate analysis of urinary spectra generated diagnostic models with a sensitivity/specificity of 53.6%/96%. p-Cresol sulfate ( P = 0.04), creatinine ( P = 0.03), citrate ( P = 0.21) and hippurate ( P = 0.52) were reduced in the HCC patients. Carnitine ( P = 0.31) and formate ( P = 0.44) were elevated. Conclusion Diagnostic sensitivity was lower than previous African studies, but still outperformed serum AFP. Reduced creatinine, citrate and hippurate and elevated carnitine are comparable with the African studies. p-Cresol sulfate alteration is a novel finding and may indicate an altered sulfonation capacity of the liver in patients with HCC. [ABSTRACT FROM AUTHOR]

Magnetic resonance spectroscopy (MRS) provides a non-invasive ‘window’ on biochemical processes within the body. Its use is no longer restricted to the field of research, with applications in clinical practice increasingly common. MRS can be conducted at high magnetic field strengths (typically 11–14 T) on body fluids, cell extracts and tissue samples, with new developments in whole-body magnetic resonance imaging (MRI) allowing clinical MRS at the end of a standard MRI examination, obtaining functional information in addition to anatomical information. We discuss the background physics the busy clinician needs to know before considering using the technique as an investigative tool. Some potential applications of hepatic and cerebral MRS in chronic liver disease are also discussed. [ABSTRACT FROM AUTHOR]

The development of magnetic resonance imaging (MRI) for use in medical investigation has provided a huge forward leap in the field of diagnosis, particularly with avoidance of exposure to potentially dangerous ionizing radiation. With decreasing costs and better availability, the use of MRI is becoming ever more pervasive throughout clinical practice. Understanding the principles underlying this imaging modality and its multiple applications can be used to appreciate the benefits and limitations of its use, further informing clinical decision-making. In this article, the principles of MRI are reviewed, with further discussion of specific clinical applications such as parallel, diffusion-weighted, and magnetization transfer imaging. MR spectroscopy is also considered, with an overview of key metabolites and how they may be interpreted. Finally, a brief view on how the use of MRI will change over the coming years is presented. [ABSTRACT FROM AUTHOR]

Objectives: Cholangiocarcinoma (CCA) has a poor prognosis and its aetiology is inadequately understood. Magnetic resonance spectroscopy (MRS) of bile may provide insights into the pathogenesis of CCA and help identify novel diagnostic biomarkers. The aim of this study was to compare the chemical composition of bile from patients with CCA with that of bile from patients with benign biliary disease. Methods: Magnetic resonance spectra were acquired from the bile of five CCA patients and compared with MRS of control bile from patients with benign biliary disease (seven with gallstones, eight with sphincter of Oddi dysfunction [SOD], five with primary sclerosing cholangitis [PSC]). Metabolic profiles were compared using both univariate and multivariate pattern-recognition analysis. Results: Univariate analysis showed that levels of glycine-conjugated bile acids were significantly increased in patients with CCA, compared with the benign disease groups (P = 0.002). 7b primary bile acids were significantly increased (P = 0.030) and biliary phosphatidylcholine (PtC) levels were reduced (P = 0.010) in bile from patients with CCA compared with bile from gallstone patients. These compounds were also of primary importance in the multivariate analysis: the cohorts were differentiated by partial least squares discriminant analysis (PLS-DA). Conclusions: These preliminary data suggest that altered bile acid and PtC metabolism play an important role in CCA aetiopathogenesis and that specific metabolites may have potential as future biomarkers. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatic steatosis is an important factor in pathogenesis, progression and response to treatment in hepatitis C. We aimed to investigate differences in hepatic lipid composition in liver biopsies from patients with chronic hepatitis C using proton magnetic resonance spectroscopy (1H MRS) and to translate these findings to the in vivo clinical setting. Methods: Two cohorts of patients with histologically defined chronic hepatitis C were studied. High-resolution MR spectra were obtained from 47 liver biopsy samples. These data were used to derive biologically relevant prior knowledge for the assignment and interpretation of lower-resolution in vivo hepatic MRS data acquired at 1.5T from a second cohort of 59 patients. MRS data were obtained both in vitro and in vivo from a subset of 11 patients. Results: Multivariate factor analysis demonstrated characteristic MR spectral differences by fibrosis stage and genotype. Total lipid increased with fibrosis stage (r =0.43, p= 0.003) and was higher in genotype 3 compared to genotype 1 (p= 0.03), while lipid polyunsaturation decreased with increasing fibrosis stage (r =−0.55, p <0.0005) and, independently, with increasing steatosis. Non-invasive assessment using in vivo hepatic 1H MRS corroborated in vitro findings, but the signal-to-noise ratio was insufficient for reliable assessment of lipid polyunsaturation in vivo. Conclusions: Hepatic lipid composition was analysed using MRS in patients with chronic hepatitis C in vitro and in vivo, demonstrating significant differences in indices by disease severity. High-resolution data informed the analysis and interpretation of in vivo spectra, but further improvements in spectral quality in vivo are required. [Copyright &y& Elsevier]