Differences in phosphatidylcholine and bile acids in bile from Egyptian and UK patients with and without cholangiocarcinoma

Hashim, Mohamed; Taylor‐Robinson, Simon D.; Sharif, Amar; Williams, Horace R T; Crossey, Mary M.E.; Badra, Gamal; Thillainayagam, Andrew V.; Bansi, Devinder S.; Thomas, Howard; Waked, Imam; Khan, Shahid A.

doi:10.1111/j.1477-2574.2011.00296.x

Cited by 26 publications

(23 citation statements)

References 22 publications

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“…Despite the complex nature of bile, including variations due to diet, medication, and environmental factors, in vitro MRS of bile has been successful in differentiating various HPB disorders. Among the major bile metabolites, alterations in the levels of chol‐PLs, cholesterol, taurine‐conjugated bile acids (TCBAs), and glycine‐conjugated bile acids (GCBAs) have been observed in HPB disorders . In our laboratory, ex vivo 1 H MRS‐based analysis of bile obtained from patients with hyper‐bilirubinemia showed alteration in the ratio of GCBAs to TCBAs .…”

Section: Introductionmentioning

confidence: 78%

“…There are a number of in vitro studies that used MRS for the detection and quantification of major bile metabolites . We extended our recent in vitro results to in vivo MRS application, and devised a method for the simultaneous quantification of major biliary lipids in gallbladder bile using a 3 T scanner and a custom‐built receive array coil .…”

Section: Discussionmentioning

confidence: 99%

“…MRS has shown potential as an investigational technique to achieve a better understanding of HPB disorders . MRS (both in vitro and in vivo) has been utilized in unraveling metabolic changes in different liver and pancreatic diseases including malignancies, hepatitis, cirrhosis, PSC, and alcoholic liver disease . In vivo MRS of abdominal organs is particularly challenging due to problems associated with breathing motion.…”

Section: Discussionmentioning

confidence: 99%

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In vivo ¹H MRS of human gallbladder bile in understanding the pathophysiology of primary sclerosing cholangitis (PSC): Immune‐mediated disease versus bile acid‐induced injury

et al. 2019

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Primary sclerosing cholangitis (PSC) has been considered to be either an "autoimmune disease" or a "bile acid-induced injury." In vitro MRS studies on PSC patients have limitations due to the contamination of bile with contrast agent (commonly administered during endoscopic retrograde cholangiopancreatography) and/or the use of patient cohorts with other diseases as controls. The objective of this study was to quantify biliary metabolites using in vivo 1 H MRS and gain insight into the pathogenesis of PSC. Biliary metabolites in 10 PSC patients and 14 healthy controls were quantified in vivo using 1 H MRS on a 3 T MR scanner. The concentrations of total bile acids plus cholesterol, glycine-conjugated bile acids, taurine-conjugated bile acids, and cholinecontaining phospholipids (chol-PLs) were compared between the two groups. There were statistically significant decreases in the levels of the above mentioned biliary metabolites in the PSC patients compared with controls. The reduction in bile acid secretion in bile of PSC patients indicates accumulation of bile acids in hepatocytes.Moreover, reduction in the levels of chol-PLs in bile may increase the toxic effects of bile acids. Our findings suggest that the bile duct injury in PSC patients is most likely due to "bile acid-induced injury." KEYWORDS choline-containing phospholipids, glycine-conjugated bile acids, human bile, in vivo 1 H MRS, L-COSY, pathogenesis, primary sclerosing cholangitis, taurine-conjugated bile acids

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Section: Introductionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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In vivo ¹H MRS of human gallbladder bile in understanding the pathophysiology of primary sclerosing cholangitis (PSC): Immune‐mediated disease versus bile acid‐induced injury

et al. 2019

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“…It has also been proposed that genetically impaired biliary excretion of phospholipids underlies CCA [94, 95]. Metabolomic investigations support this view, with lower phosphatidylcholine and elevated glycine- and taurine-conjugated bile acids reported in the bile of CCA patients [96, 97]. …”

Section: The Metabolomic Window Into Other Hepatobiliary Diseasesmentioning

confidence: 99%

The metabolomic window into hepatobiliary disease

Beyoğlu¹,

Idle²

2013

Journal of Hepatology

205

198

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Summary The emergent discipline of metabolomics has attracted considerable research effort in hepatology. Here we review the metabolomic data for nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), cirrhosis, hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), alcoholic liver disease (ALD), hepatitis B and C, cholecystitis, cholestasis, liver transplantation and acute hepatotoxicity in animal models. A metabolomic window has permitted a view into the changing biochemistry occurring in the transitional phases between a healthy liver and hepatocellular carcinoma or cholangiocarcinoma. Whether provoked by obesity and diabetes, alcohol use or oncogenic viruses, the liver develops a core metabolomic phenotype (CMP) that involves dysregulation of bile acid and phospholipid homeostasis. The CMP commences at the transition between the healthy liver (Phase 0) and NAFLD/NASH, ALD or viral hepatitis (Phase 1). This CMP is maintained in the presence or absence of cirrhosis (Phase 2) and whether or not either HCC or CCA (Phase 3) develop. Inflammatory signalling in the liver triggers the appearance of the CMP. Many other metabolomic markers distinguish between Phases 0, 1, 2 and 3. A metabolic remodelling in HCC has been described but metabolomic data from all four Phases demonstrate that the Warburg shift from mitochondrial respiration to cytosolic glycolysis foreshadows HCC and may occur as early as Phase 1. The metabolic remodelling also involves an upregulation of fatty acid β-oxidation, also beginning in Phase 1. The storage of triglycerides in fatty liver provides high energy-yielding substrates for Phases 2 and 3 of liver pathology. The metabolomic window into hepatobiliary disease sheds new light on the systems pathology of the liver.

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“…There have been several recent advances in this area by analysing various types of samples and using several techniques. Metabolomic analysis of bile by nuclear magnetic resonance (NMR) has identified differences in lipids and bile salts in CCA patients (Hashim Abdalla et al, 2011). Proteomic urinary capillary electrophoresis recently demonstrated abundant interstitial collagen fragments in CCA compared with PSC, with a 42-peptide panel giving an area under the curve (AUC) of 0.87, indicating good sensitivity and specificity (Metzger et al, 2012).…”

Section: Currently Available Modelsmentioning

confidence: 99%

The challenge of cholangiocarcinoma: dissecting the molecular mechanisms of an insidious cancer

Zabron

Edwards

Khan

2013

Disease Models &Amp; Mechanisms

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Cholangiocarcinoma is a fatal cancer of the biliary epithelium and has an incidence that is increasing worldwide. Survival beyond a year of diagnosis is less than 5%, and therapeutic options are few. Known risk factors include biliary diseases such as primary sclerosing cholangitis and parasitic infestation of the biliary tree, but most cases are not associated with any of these underlying diseases. Numerous in vitro and in vivo models, as well as novel analytical techniques for human samples, are helping to delineate the many pathways implicated in this disease, albeit at a frustratingly slow pace. As yet, however, none of these studies has been translated into improved patient outcome and, overall, the pathophysiology of cholangiocarcinoma is still poorly understood. There remains an urgent need for new approaches and models to improve management of this insidious and devastating disease. In this review, we take a bedside-to-bench approach to discussing cholangiocarcinoma and outline research opportunities for the future in this field.

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Differences in phosphatidylcholine and bile acids in bile from Egyptian and UK patients with and without cholangiocarcinoma

Abstract: Biliary PtC levels potentially differentiate CC from benign biliary disease. Reduced biliary PtC in Egyptian compared with UK patients may reflect underlying carcinogenic mechanisms.

Cited by 26 publications

References 22 publications

In vivo ¹H MRS of human gallbladder bile in understanding the pathophysiology of primary sclerosing cholangitis (PSC): Immune‐mediated disease versus bile acid‐induced injury

In vivo ¹H MRS of human gallbladder bile in understanding the pathophysiology of primary sclerosing cholangitis (PSC): Immune‐mediated disease versus bile acid‐induced injury

The metabolomic window into hepatobiliary disease

The challenge of cholangiocarcinoma: dissecting the molecular mechanisms of an insidious cancer

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Differences in phosphatidylcholine and bile acids in bile from Egyptian and UK patients with and without cholangiocarcinoma

Abstract: Biliary PtC levels potentially differentiate CC from benign biliary disease. Reduced biliary PtC in Egyptian compared with UK patients may reflect underlying carcinogenic mechanisms.

Cited by 26 publications

References 22 publications

In vivo 1H MRS of human gallbladder bile in understanding the pathophysiology of primary sclerosing cholangitis (PSC): Immune‐mediated disease versus bile acid‐induced injury

In vivo 1H MRS of human gallbladder bile in understanding the pathophysiology of primary sclerosing cholangitis (PSC): Immune‐mediated disease versus bile acid‐induced injury

The metabolomic window into hepatobiliary disease

The challenge of cholangiocarcinoma: dissecting the molecular mechanisms of an insidious cancer

Contact Info

Product

Resources

About

In vivo ¹H MRS of human gallbladder bile in understanding the pathophysiology of primary sclerosing cholangitis (PSC): Immune‐mediated disease versus bile acid‐induced injury

In vivo ¹H MRS of human gallbladder bile in understanding the pathophysiology of primary sclerosing cholangitis (PSC): Immune‐mediated disease versus bile acid‐induced injury