Imperial College London

Dr I. Jane Cox

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Honorary Senior Lecturer
 
 
 
//

Contact

 

j.cox Website

 
 
//

Location

 

Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

//

Summary

 

Publications

Publication Type
Year
to

156 results found

Alsaleh M, Sithithaworn P, Khuntikeo N, Loilome W, Yongvanit P, Hughes T, O'Connor T, Andrews R, Wadsworth C, Williams R, Koomson L, Cox IJ, Holmes E, Taylor-Robinson SDet al., 2023, Urinary metabolic profiling of liver fluke-induced cholangiocarcinoma—a follow-up study, Journal of Clinical and Experimental Hepatology, Vol: 13, Pages: 203-217, ISSN: 0973-6883

Background/Aims:Global liquid chromatography mass spectrometry (LC-MS) profiling in a Thai population has previously identified a urinary metabolic signature in Opisthorchis viverrini-induced cholangiocarcinoma (CCA), primarily characterised by disturbance in acylcarnitine, bile acid, steroid, and purine metabolism. However, the detection of thousands of analytes by LC-MS in a biological sample in a single experiment potentially introduces false discovery errors. To verify these observed metabolic perturbations, a second validation dataset from the same population was profiled in a similar fashion.Methods:Reverse-phase ultra-performance liquid-chromatography mass spectrometry was utilised to acquire the global spectral profile of 98 spot urine samples (from 46 healthy volunteers and 52 CCA patients) recruited from Khon Kaen, northeast Thailand (the highest incidence of CCA globally).Results:Metabolites were differentially expressed in the urinary profiles from CCA patients. High urinary elimination of bile acids was affected by the presence of obstructive jaundice. The urine metabolome associated with non-jaundiced CCA patients showed a distinctive pattern, similar but not identical to published studies. A panel of 10 metabolites achieved a diagnostic accuracy of 93.4% and area under the curve value of 98.8% (CI = 96.3%–100%) for the presence of CCA.Conclusions:Global characterisation of the CCA urinary metabolome identified several metabolites of biological interest in this validation study. Analyses of the diagnostic utility of the discriminant metabolites showed excellent diagnostic potential. Further larger scale studies are required to confirm these findings internationally, particularly in comparison to sporadic CCA, not associated with liver fluke infestation.

Journal article

Cox IJ, Idiliman R, Fagan A, Turan D, Ajayi L, Le Guennec AD, Taylor-Robinson SD, Karakaya F, Gavis E, Andrew Atkinson R, Williams R, Sikaroodi M, Nizam S, Gillevet PM, Bajaj JSet al., 2020, Metabolomics and microbial composition increase insight into the impact of dietary differences in cirrhosis., Liver International, Vol: 40, Pages: 416-427, ISSN: 1478-3223

BACKGROUND & AIMS: Dietary changes can modulate gut microbiota and interact with cirrhosis. Our prior study demonstrated that microbial diversity was higher in Turkish versus USA cirrhotics, which was associated with lower risk of 90-day hospitalizations. We aimed to define gut microbial functional and metabolomic changes to increase insight into benefits of the Mediterranean compared to Western diets. METHODS: 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied. Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake while Americans consumed a Western diet. Predicted gut microbial functionalities and plasma metabolomics were compared between/within countries. Correlation network differences between microbiota and metabolites in cirrhotics from Turkey versus USA were evaluated. RESULTS: Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in Turkey compared to USA cirrhotics. Plasma metabolomics demonstrated higher relative lactate levels in Turkey versus USA. The metabolite changes in decompensated cirrhosis, compared to controls, showed similar trends in Turkey and USA, with reduced lipids and phosphocholines. Phosphocholines were significantly lower in patients hospitalized in 90 days (p=0.03). Correlation networks in cirrhotics demonstrated linkage differences between beneficial taxa, Blautia and Oscillispira, and lactate and unsaturated lipids, in Turkey compared to American patients. CONCLUSIONS: A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis. These altered diet-microbial interactions could potentially affect the 90-day hospitalization risk.

Journal article

Bajaj JS, Salzman N, Acharya C, Takei H, Kakiyama G, Fagan A, White MB, Gavis EA, Holtz ML, Hayward M, Nittono H, Hylemon PB, Cox IJ, Williams R, Taylor-Robinson SD, Sterling RK, Matherly SC, Fuchs M, Lee H, Puri P, Stravitz RT, Sanyal AJ, Ajayi L, Le Guennec A, Atkinson RA, Siddiqui MS, Luketic V, Pandak WM, Sikaroodi M, Gillevet PMet al., 2019, Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis, JCI insight, Vol: 4, Pages: 1-11, ISSN: 2379-3708

BACKGROUND. Hepatic encephalopathy (HE) is associated with poor outcomes. A prior randomized, pilot trial demonstrated safety after oral capsular fecal microbial transplant (FMT) in HE, with favorable changes in microbial composition and cognition. However, microbial functional changes are unclear. The aim of this study was to determine the effect of FMT on the gut-brain axis compared with placebo, using microbial function based on bile acids (BAs), inflammation (serum IL-6, LPS-binding protein [LBP]), and their association with EncephalApp.METHODS. Twenty cirrhotic patients were randomized 1:1 into groups that received 1-time FMT capsules from a donor enriched in Lachnospiraceae and Ruminococcaceae or placebo capsules, with 5-month follow-up for safety outcomes. Stool microbiota and BA; serum IL-6, BA, and LBP; and EncephalApp were analyzed at baseline and 4 weeks after FMT/placebo. Correlation networks among microbiota, BAs, EncephalApp, IL-6, and LBP were performed before/after FMT.RESULTS. FMT-assigned participants had 1 HE recurrence and 2 unrelated infections. Six placebo-assigned participants developed negative outcomes. FMT, but not placebo, was associated with reduced serum IL-6 and LBP and improved EncephalApp. FMT-assigned participants demonstrated higher deconjugation and secondary BA formation in feces and serum compared with baseline. No change was seen in placebo. Correlation networks showed greater complexity after FMT compared with baseline. Beneficial taxa, such as Ruminococcaceae, Verrucomicrobiaceae, and Lachnospiraceae, were correlated with cognitive improvement and decrease in inflammation after FMT. Fecal/serum secondary/primary ratios and PiCRUST secondary BA pathways did not increase in participants who developed poor outcomes.CONCLUSION. Gut microbial function in cirrhosis is beneficially affected by capsular FMT, with improved inflammation and cognition. Lower secondary BAs in FMT recipients could select for participants who develop negati

Journal article

Bryant DJ, Cox IJ, Taylor-Robinson S, 2019, The Hammersmith Spin on Metabolism Using Clinical MR Spectroscopy, MRIS History UK, Editors: Bydder, Young, Paley, Publisher: https://mrishistory.org.uk

Book chapter

Cox IJ, Idilman R, Fagan A, Turan D, Ajayi L, Karakaya F, Williams R, Gavis E, Atkinson A, Le Guennec A, Taylor-Robinson S, Sikaroodi M, Gillevet P, Bajaj JSet al., 2019, Plasma metabolomic changes modulate the impact of Middle Eastern versus Western Diet in an international cirrhosis cohort, International Liver Congress / 54th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL), Publisher: ELSEVIER, Pages: E52-E53, ISSN: 0168-8278

Conference paper

Bajaj JS, Kakiyama G, Cox IJ, Nittono H, Takei H, White M, Fagan A, Gavis EA, Heuman DM, Gilles H-C, Hylemon P, Taylor-Robinson SD, Williams R, Sikaroodi M, Pandak WM, Gillevet PMet al., 2017, Gut microbial functional changes after liver transplant can modulate infection risk and increase atherogenic metabolites, The 68th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2017, Publisher: Wiley, Pages: 52A-53A, ISSN: 0270-9139

Conference paper

Bajaj JS, Kassam Z, Cox IJ, Gurry T, Williams R, Alm E, John B, Smith M, Taylor-Robinson SD, Gillevet PMet al., 2017, Fecal Microbiota Transplant From a Rational Stool Donor Improves Hepatic Encephalopathy: A Randomized Clinical Trial REPLY, HEPATOLOGY, Vol: 66, Pages: 1355-1356, ISSN: 0270-9139

Journal article

Karanjia RN, Crossey MME, Cox IJ, Fye HKS, Njie R, Goldin RD, Taylor-Robinson SDet al., 2016, Hepatic steatosis and fibrosis: Non-invasive assessment, World Journal of Gastroenterology, Vol: 22, Pages: 9880-9897, ISSN: 1007-9327

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and noninvasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy.

Journal article

McPhail MJW, Montagnese S, Villaneuva M, El Hadi H, Amodio P, Crossey M, Williams R, Cox IJ, Taylor-Robinson SDet al., 2016, Urinary metabolic profiling by 1H NMR spectroscopy in patients with cirrhosis may discriminate overt but not covert hepatic encephalopathy, Metabolic Brain Disease, Vol: 32, Pages: 331-341, ISSN: 1573-7365

To date urinary metabolic profiling has been applied to define a specific metabolic fingerprintof hepatocellular carcinoma on a background of cirrhosis. Its utility for the stratification of othercomplications of cirrhosis, such as hepatic encephalopathy (HE), remains to be established. Urinaryproton nuclear magnetic resonance (1H-NMR) spectra were acquired and NMR data from 52 patientswith cirrhosis (35 male; 17 female, median (range) age [60 (18-81) years]) and 17 controls werecompared. A sub-set of 45 patients (33 male; 12 female, [60 (18-90) years, median model for end stageliver disease (MELD) score 11 (7-27)]) were fully characterised by West-Haven criteria, PsychometricHepatic Encephalopathy Score (PHES) and electroencephalogram (EEG), and defined as overt HE(OHE, n=21), covert HE (cHE, n=7) or no HE (n=17). Urinary proton nuclear magnetic resonance (1HNMR)spectra were analysed by partial-least-squares discriminant analysis (PLS-DA). The resultsshowed good discrimination between patients with cirrhosis (n=52) and healthy controls (n=17)(R2X=0.66, R2Y=0.47, Q2Y=0.31, sensitivity-60%, specificity-100%) as the cirrhosis group hadhigher 1-methylnicotinamide with lower hippurate, acetate, phenylacetylglycine and N-methyl nicotinicacid levels. While patients with OHE could be discriminated from those with no HE, with higherhistidine, citrate and creatinine levels, the best models lack robust validity (R2X=0.65, R2Y=0.48,Q2Y=0.12, sensitivity-100%, specificity-64%) with the sample size used. Urinary 1H-NMR metabolicprofiling did not discriminate patients with cHE from those without HE, nor discriminate subjects onthe basis of PHES/EEG result or MELD score. In conclusion, patients with cirrhosis showed differenturinary 1H-NMR metabolic profiles compared to healthy controls and those with OHE may bedistinguished from those with no HE although larger studies are required. However, urinary 1H-NMRmetabolic profiling did not discriminate patients with differing grades of

Journal article

Grover VP, McPhail M, Wylezinska M, Crossey MM, Fitzpatrick J, Southern L, Saxby B, Cook NA, Cox IJ, Waldman A, Dhanjal N, Bak-Bol A, Williams R, Morgan MY, Taylor-Robinson SDet al., 2016, A longitudinal study of patients with cirrhosis treated with L-ornithine L-aspartate, examined with magnetization transfer, diffusion-weighted imaging and magnetic resonance spectroscopy, Metabolic Brain Disease, Vol: 32, Pages: 77-86, ISSN: 1573-7365

The presence of overt hepatic encephalopathy (HE) is associated with structural, metabolic and functional changes in the brain discernible by use of a variety of magnetic resonance (MR) techniques. The changes in patients with minimal HE are less well documented. Twenty-two patients with well-compensated cirrhosis, seven of whom had minimal HE, were examined with cerebral 3 Tesla MR techniques, including T1- and T2-weighted, magnetization transfer and diffusion-weighted imaging and proton magnetic resonance spectroscopy sequences. Studies were repeated after a 4-week course of oral L-ornithine L-aspartate (LOLA). Results were compared with data obtained from 22 aged-matched healthy controls. There was no difference in mean total brain volume between patients and controls at baseline. Mean cerebral magnetization transfer ratios were significantly reduced in the globus pallidus and thalamus in the patients with cirrhosis irrespective of neuropsychiatric status; the mean ratio was significantly reduced in the frontal white matter in patients with minimal HE compared with healthy controls but not when compared with their unimpaired counterparts. There were no significant differences in either the median apparent diffusion coefficients or the mean fractional anisotropy, calculated from the diffusion-weighted imaging, or in the mean basal ganglia metabolite ratios between patients and controls. Psychometric performance improved in 50% of patients with minimal HE following LOLA, but no significant changes were observed in brain volumes, cerebral magnetization transfer ratios, the diffusion weighted imaging variables or the cerebral metabolite ratios. MR variables, as applied in this study, do not identify patients with minimal HE, nor do they reflect changes in psychometric performance following LOLA.

Journal article

Cox IJ, Aliev AE, Crossey MM, Dawood M, Al-Mahtab M, Akbar SM, Rahman S, Riva A, Williams R, Taylor-Robinson SDet al., 2016, Urinary nuclear magnetic resonance spectroscopy of a Bangladeshi cohort with hepatitis-B hepatocellular carcinoma: a biomarker corroboration study, World Journal of Gastroenterology, Vol: 22, Pages: 4191-4200, ISSN: 1007-9327

AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma (HCC) patients compared to cirrhosis patients and controls. METHODS: Urine samples from 42 Bangladeshi patients with HCC (39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance (NMR) spectroscopy. A full dietary and medication history was recorded for each subject. The urinary NMR data were analyzed using principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLS-DA were compared between subject groups using an independent samples Kruskal-Wallis one-way analysis of variance (ANOVA) test with all pairwise multiple comparisons. Within the patient subgroups, the Mann-Whitney U test was used to compare metabolite levels depending on hepatitis B e-antigen (HBeAg) status and treatment with anti-viral therapy. A Benjamini-Hochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P < 0.05. RESULTS: There were significant differences in age (P < 0.001), weight (P < 0.001), and body mass index (P < 0.001) across the four clinical subgroups. Serum alanine aminotransferase (ALT) was significantly higher in the HCC group compared to controls (P < 0.001); serum α-fetoprotein was generally markedly elevated in HCC compared to controls; and serum creatinine levels were significantly reduced in the HCC group compared to the cirrhosis group (P = 0.004). A three-factor PCA scores plot showed clustering of the urinary NMR spectra from the four subgroups. Metabolites that contributed to the discrimination between the subgroups included acetate, cr

Journal article

Shariff MIF, Kim JU, Ladep NG, Crossey MME, Koomson LK, Zabron A, Reeves H, Cramp M, Ryder S, Greer S, Cox IJ, Williams R, Holmes E, Nash K, Taylor-Robinson SDet al., 2016, Urinary Metabotyping of Hepatocellular Carcinoma in a UK Cohort Using Proton Nuclear Magnetic Resonance Spectroscopy, Journal of Clinical and Experimental Hepatology, Vol: 6, Pages: 186-194, ISSN: 2213-3453

Background: Discriminatory metabolic profiles have been described in urinary 1H 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 600MHz 1H 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 200IUmL-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.

Journal article

Kim JU, Shariff MI, Crossey MM, Gomez-Romero M, Holmes E, Cox IJ, Fye HK, Njie R, Taylor-Robinson SDet al., 2016, Hepatocellular carcinoma: Review of disease and tumor biomarkers., World Journal of Hepatology, Vol: 8, Pages: 471-484, ISSN: 1948-5182

Hepatocellular carcinoma (HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial. International guidelines advise regular surveillance of high-risk populations but the current tools lack sufficient sensitivity for early stage tumors on the background of a cirrhotic nodular liver. A number of novel biomarkers have now been suggested in the literature, which may reinforce the current surveillance methods. In addition, recent metabonomic and proteomic discoveries have established specific metabolite expressions in HCC, according to Warburg's phenomenon of altered energy metabolism. With clinical validation, a simple and non-invasive test from the serum or urine may be performed to diagnose HCC, particularly benefiting low resource regions where the burden of HCC is highest.

Journal article

Tognarelli JM, Dawood M, Shariff MIF, Grover VPB, Crossey MME, Cox IJ, Taylor-Robinson SD, McPhail MJWet al., 2015, Magnetic Resonance Spectroscopy: Principles and Techniques: Lessons for Clinicians, JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY, Vol: 5, Pages: 320-328, ISSN: 0973-6883

Journal article

Grover VPB, Tognarelli JM, Crossey MME, Cox IJ, Taylor-Robinson SD, McPhail MJWet al., 2015, Magnetic Resonance Imaging: Principles and Techniques: Lessons for Clinicians, JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY, Vol: 5, Pages: 246-255, ISSN: 0973-6883

Journal article

Cox IJ, Podrini C, Markwick LJ, Williams R, Al-Mahtab M, Akbar F, Rahman S, Islam A, Montagnese S, Crossey M, McPhail M, Taylor-Robinson SDet al., 2015, Urinary 1h nuclear magnetic resonance spectroscopy profiling in hepatoecellular carninoma in a Bangladeshi cohort corroborates a urinary metabolic fingerprint for liver cancer, 2nd Digestive-Disorders-Federation Conference, Publisher: BMJ Publishing Group, Pages: A257-A257, ISSN: 1468-3288

Conference paper

Bajaj JS, Cox IJ, Betrapally NS, Heuman DM, Schubert ML, Ratneswaran M, Hylemon PB, White MB, Daita K, Noble NA, Sikaroodi M, Williams R, Crossey MME, Taylor-Robinson SD, Gillevet PMet al., 2014, Systems biology analysis of omeprazole therapy in cirrhosis demonstrates significant shifts in gut microbiota composition and function, AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, Vol: 307, Pages: G951-G957, ISSN: 0193-1857

Journal article

Possamai LA, McPhail MJW, Khamri W, Wu B, Concas D, Harrison M, Williams R, Cox RD, Cox IJ, Anstee QM, Thursz MRet al., 2014, The role of intestinal microbiota in murine models of acetaminophen-induced hepatotoxicity, Liver International, Vol: 35, Pages: 764-773, ISSN: 1478-3231

Background & AimsVariations in intestinal microbiota may influence acetaminophen metabolism. This study aimed to determine whether intestinal microbiota are a source of differential susceptibility to acetaminophen-induced hepatotoxicity.MethodsConventionally housed C3H/HeH (CH) and C3H/HeH germ-free (GF) mice were administered a 200 mg/kg IP dose of acetaminophen. The severity of hepatotoxicity at 8 h was assessed by histology and biochemical indices. A urinary metabolic profile was obtained using 1H-NMR. Baseline hepatic glutathione content and CYP2E1 expression were quantified. An additional group of C3H/HeJ (LPS-r) mice were assessed to determine the contribution of LPS/TLR4 signalling.ResultsBaseline glutathione levels were significantly reduced (P = 0.03) in GF mice. CYP2E1 mRNA expression and protein levels were not altered. Interindividual variability did not differ between GF and CH groups. No significant differences in the extent of hepatocellular injury (ALT or percentage necrosis) were demonstrated. However, a milder acute liver failure (ALF) phenotype was shown in GF compared with CH mice, with reduced plasma bilirubin and creatinine and increased blood glucose. Differential acetaminophen metabolism was demonstrated. GF mice displayed a higher urinary acetaminophen-sulphate:glucuronide ratio compared with CH (P = 0.01). Urinary analysis showed metabolic differentiation of GF and CH groups at baseline and 8 h (cross-validated anova P = 1 × 10-22). Interruption of TLR4 signalling in LPS-r mice had additional protective effects.ConclusionVariations in intestinal microbiota do not fully explain differential susceptibility to acetaminophen-induced hepatotoxicity. GF mice experienced some protection from secondary complications following acetaminophen overdose and this may be mediated through reduced TLR4/LPS signalling.

Journal article

McPhail MJ, Villa M, Cox IJ, Williams R, Amodio P, Montagnese S, Taylor-Robinson SDet al., 2014, URINARY METABOLIC PROFILING BY <SUP>1</SUP>H NMR SPECTROSCOPY IN PATIENTS WITH CIRRHOSIS DISCRIMINATES OVERT BUT NOT MINIMAL HEPATIC ENCEPHALOPATHY, 49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver, Publisher: ELSEVIER SCIENCE BV, Pages: S232-S233, ISSN: 0168-8278

Conference paper

Bajaj JS, Cox IJ, Betrapally N, Heuman DM, Schubert ML, Williams R, White M, Noble N, Sikaroodi M, Taylor-Robinson SD, Gillevet PMet al., 2014, Systems Biology Analysis of Omeprazole Therapy in Cirrhosis Demonstrates Significant Shifts in Gut Microbiota Composition and Function, 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases, Publisher: WILEY-BLACKWELL, Pages: 1181A-1181A, ISSN: 0270-9139

Conference paper

Williams HRT, Willsmore JD, Cox IJ, Walker DG, Cobbold JFL, Taylor-Robinson SD, Orchard TRet al., 2012, Serum Metabolic Profiling in Inflammatory Bowel Disease, DIGESTIVE DISEASES AND SCIENCES, Vol: 57, Pages: 2157-2165, ISSN: 0163-2116

Journal article

Cobbold JFL, Cox IJ, Brown AS, Williams HRT, Goldin RD, Thomas HC, Thursz MR, Taylor-Robinson SDet al., 2012, Lipid profiling of pre-treatment liver biopsy tissue predicts sustained virological response in patients with chronic hepatitis C, Hepatology Research, Vol: 42, Pages: 714-720, ISSN: 1386-6346

Aim: Hepatic lipid is important in the pathogenesis and progression of hepatitis C-related liver disease. Polyunsaturated fatty acids have been shown to reduce viral replication in cell culture. Proton magic angle spinning magnetic resonance spectroscopy (1H MAS MRS) enables metabolic analysis of intact tissue. The aim was to examine the relationship between hepatic lipid composition by metabolic profiling of liver tissue at baseline and treatment response to pegylated-Interferon alfa2 and Ribavirin.Methods: Baseline liver biopsy samples from 31 patients with chronic hepatitis C were analyzed histologically and by 1H MAS MRS. Indices of lipid composition were derived and partial least squares discriminant analysis with cross-validation was used to predict treatment outcome.Results: Of 31 patients, 14 achieved sustained virological response (SVR). Lipid polyunsaturation (median (IQR)) was higher in SVR (3.41% (2.31)) than in treatment failure (TF) (2.15% (1.51)), P = 0.02. Lipid saturation was lower in SVR (85.9% (3.39)) than TF (86.7% (2.17)), P = 0.04. The total lipid content was lower in SVR (1.54% (0.81)) than TF (2.72% (3.47)), P = 0.004. Total choline to lipid ratio was higher in SVR (11.51% (9.99)) than TF (7.5% (6.82)), P = 0.007. Cross-validation correctly predicted the SVR group in 13 of 14 samples with 1 sample misclassified, and the TF group in all 17 samples.Conclusions: Lipid polyunsaturation was greater and total lipid lower in those with SVR, compared with TF. Metabolic profiling of intact liver biopsy samples predicted SVR with high accuracy. Hepatic lipid composition may impact on treatment success.

Journal article

Possamai LA, Harrison M, Cox RD, Williams R, Anstee QM, Thursz MR, Cox IJet al., 2012, <SUP>1</SUP>H-NMR METABOLIC PROFILING IN GERM-FREE AND CONVENTIONALLY HOUSED MOUSE MODELS OF ACETAMINOPHEN-INDUCED HEPATOTOXICITY, 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL), Publisher: ELSEVIER SCIENCE BV, Pages: S529-S529, ISSN: 0168-8278

Conference paper

Solanky BS, Sanchez-Canon GJ, Cobbold JFL, Taylor-Robinson SD, Bell JD, Scudamore CL, Ross E, Holder JC, So P-W, Cox IJet al., 2012, Metabolic Profiling of the Rat Liver After Chronic Ingestion of Alpha-Naphthylisothiocyanate Using <i>In Vivo</i> and <i>Ex Vivo</i> Magnetic Resonance Spectroscopy, TOXICOLOGICAL SCIENCES, Vol: 126, Pages: 306-316, ISSN: 1096-6080

Journal article

Solanky BS, Sanchez-Canon GJ, Cobbold JFL, Taylor-Robinson SD, Bell JD, Scudamore CL, Holder JC, So P-W, Cox IJet al., 2011, METABOLIC PROFILING OF THE RAT LIVER AFTER CHRONIC INGESTION OF α-NAPHTHYLISOTHIOCYANATE USING IN VIVO AND EX VIVO MAGNETIC RESONANCE SPECTROSCOPY, GUT, Vol: 60, Pages: A48-A48, ISSN: 0017-5749

Journal article

Shariff MIF, Gomaa AI, Cox IJ, Patel M, Williams HRT, Crossey MME, Thillainayagam AV, Thomas HC, Waked I, Khan SA, Taylor-Robinson SDet al., 2011, Urinary Metabolic Biomarkers of Hepatocellular Carcinoma in an Egyptian Population: A Validation Study, JOURNAL OF PROTEOME RESEARCH, Vol: 10, Pages: 1828-1836, ISSN: 1535-3893

Journal article

Wylezinska M, Cobbold JFL, Fitzpatrick J, McPhail MJW, Crossey MME, Thomas HC, Hajnal JV, Vennart W, Cox IJ, Taylor-Robinson SDet al., 2011, A comparison of single-voxel clinical <i>in vivo</i> hepatic <SUP>31</SUP>P MR spectra acquired at 1.5 and 3.0 Tesla in health and diseased states, NMR IN BIOMEDICINE, Vol: 24, Pages: 231-237, ISSN: 0952-3480

Journal article

Milona A, Owen BM, Cobbold JFL, Willemsen ECL, Cox IJ, Boudjelal M, Cairns W, Schoonjans K, Taylor-Robinson SD, Klomp LWJ, Parker MG, White R, van Mil SWC, Williamson Cet al., 2010, Raised Hepatic: Bile Acid Concentrations During Pregnancy in Mice Are Associated with Reduced Farnesoid X Receptor Function, HEPATOLOGY, Vol: 52, Pages: 1341-1349, ISSN: 0270-9139

Journal article

Williams HRT, Cox IJ, Walker DG, Cobbold JFL, Taylor-Robinson SD, Marshall SE, Orchard TRet al., 2010, Differences in gut microbial metabolism are responsible for reduced hippurate synthesis in Crohn's disease, BMC GASTROENTEROLOGY, Vol: 10, ISSN: 1471-230X

Journal article

Cobbold JFL, Crossey MME, Colman P, Goldin RD, Murphy PS, Patel N, Fitzpatrick J, Vennart W, Thomas HC, Cox IJ, Taylor-Robinson SDet al., 2010, Optimal combinations of ultrasound-based and serum markers of disease severity in patients with chronic hepatitis C, JOURNAL OF VIRAL HEPATITIS, Vol: 17, Pages: 537-545, ISSN: 1352-0504

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00162783&limit=30&person=true