Bevin Gangadharan obtained his D.Phil. under the supervision of Prof. Nicole Zitzmann at the University of Oxford where he carried out the first ever gel-based proteomics study to discover novel biomarkers for liver fibrosis. He has more than a decade of experience in proteomics and biomarker discovery and first started in this field in 2000 at Smithkline Beecham looking at depletion of albumin in plasma, an important approach in biomarker discovery. He has published in several peer-reviewed journals and has two patents on novel biomarkers for liver fibrosis. He is on the editorial board for Biomarker Research and gives proteomics lectures to students in the Department of Biochemistry at the University of Oxford.
Liver biopsy is the reference standard for assessing liver fibrosis and no reliable non-invasive diagnostic approach is available to discriminate between the intermediate stages of fibrosis. Therefore suitable serological biomarkers of liver fibrosis are urgently needed. We used proteomics to identify novel fibrosis biomarkers in hepatitis C patients with different degrees of liver fibrosis. Proteins in plasma samples from healthy control individuals and patients with hepatitis C virus (HCV) induced cirrhosis were analysed using a proteomics technique: two dimensional gel electrophoresis (2-DE). This technique separated the proteins in plasma samples of control and cirrhotic patients and by visualizing the separated proteins we were able to identify proteins which were increasing or decreasing in hepatic cirrhosis. Identified markers were validated across all Ishak fibrosis stages and compared to the markers used in FibroTest, Enhanced Liver Fibrosis (ELF) test, Hepascore and FIBROSpect by Western blotting. Forty four candidate biomarkers for hepatic fibrosis were identified of which 20 were novel biomarkers of liver fibrosis. Western blot validation of all candidate markers using plasma samples from patients across all Ishak fibrosis scores showed that the markers which changed with increasing fibrosis most consistently included lipid transfer inhibitor protein, complement C3d, corticosteroid-binding globulin, apolipoprotein J and apolipoprotein L1. These five novel fibrosis markers which are secreted in blood showed a promising consistent change with increasing fibrosis stage when compared to the markers used for the FibroTest, ELF test, Hepascore and FIBROSpect. These markers are currently being further validated using a large clinical cohort. This study identifies 20 novel fibrosis biomarker candidates. The proteins identified may help to assess hepatic fibrosis and eliminate the need for invasive liver biopsies.
Stephen Mortlock is the Global Infectious Diseases and Microbiology Liaison at the Quest Diagnostics Laboratory in Heston UK. Prior to joining Quest Diagnostics, Stephen was the Chief Microbiologist at the Shaukat Khanum Memorial Cancer Hospital and Research Centre in Lahore, Pakistan and was awarded a DSc for his work setting up an antenatal screening programme for the local population. Stephen and colleagues have published over 40 papers on an eclectic mix of subjects from enteric pathogens, food science and the use of saliva for screening for HIV and cotinine. Stephen has also worked for the Health Protection Agency in the UK and spent time in both Africa and the Middle East.
Background: Many people consult their GP for upper gastrointestinal (GI) symptoms, which are often associated with pain or burning and discomfort in the abdomen and range from heartburn and acid regurgitation to nausea and vomiting. Historically, all of these symptoms have been grouped together under the single term ‘dyspepsia’, defined as having one or more symptoms of epigastric pain, burning, postprandial fullness, or early satiation. While gastric or oesophageal cancer is an unusual finding in patients with dyspepsia, excluding malignancy is a common reason for performing endoscopy.
Methods: Quest Diagnostics has been offering the GastroPanel assays for those patients who have been referred to the walk-in clinic complaining of ‘dyspepsia’. This is a set of three assays (Pepsinogen I, Gastrin 17 and Helicobacter pylori) and the results use an algorithm which can provide information about the stomach health and about the function of the stomach mucosa.
Results: Of all the samples tested nearly 70% showed no abnormalities and were reported as ‘normal function of gastric mucosa’. These patients would be classed as having functional dyspepsia. Thirty-six samples were positive for Helicobacter pylori and the remaining samples had a variety of abnormal results.
Conclusion: Dyspepsia is a common problem seen both by primary care physicians and gastroenterologists. Using the results from the serological analysis of the patients’ serum the clinician can delineate between gastric atrophy and a normal health stomach usually without the need to refer the patient for endoscopy.