Human thrombin for the treatment of gastric and ectopic varices

AIM: To evaluate the efficacy of human thrombin in the treatment of bleeding gastric and ectopic varices. METHODS: Retrospective observational study in a Tertiary Referral Centre. Between January 1999-October 2005, we identified 37 patients who were endoscopically treated with human thrombin injection therapy for bleeding gastric and ectopic varices. Patient details including age, gender and aetiology of liver disease/segmental portal hypertension were documented. The thrombin was obtained from the Scottish National Blood Transfusion Service and prepared to give a solution of 250 IU/mL which was injected via a standard injection needle. All patient case notes were reviewed and the total dose of thrombin given along with the number of endoscopy sessions was recorded. Initial haemostasis rates, rebleeding rates and mortality were catalogued along with the incidence of any immediate complications which could be attributable to the thrombin therapy. The duration of follow up was also listed. The study was conducted according to the United Kingdom research ethics guidelines. RESULTS: Thirty-seven patients were included. 33 patients (89%) had thrombin (250 U/mL) for gastric varices, 2 (5.4%) for duodenal varices, 1 for rectal varices and 1 for gastric and rectal varices. (1) Gastric varices, an average of 15.2 mL of thrombin was used per patient. Re-bleeding occurred in 4 patients (10.8%), managed in 2 by a transjugular intrahepatic portosystemic shunt (TIPSS) (one unsuccessfully who died) and in other 2 by a distal splenorenal shunt; (2) Duodenal varices (or type 2 isolated gastric varices), an average of 12.5 mL was used per patient over 2-3 endoscopy sessions. Re-bleeding occurred in one patient, which was treated by TIPSS; and (3) Rectal varices, an average of 18.3 mL was used per patient over 3 endoscopy sessions. No re-bleeding occurred in this group. CONCLUSION: Human thrombin is a safe, easy to use and effective therapeutic option to control haemorrhage from gastric and ectopic varices

Update of endoscopy in liver disease:More than just treating varices

The management of complications in liver disease is often complex and challenging. Endoscopy has undergone a period of rapid expansion with numerous novel and specialized endoscopic modalities that are of increasing value in the investigation and management of the patient with liver disease. In this review, relevant literature search and expert opinions have been used to provide a brief overview and update of the current endoscopic management of patients with liver disease and portal hypertension. The main areas covered are safety of endoscopy in patients with liver disease, the use of standard endoscopy for the treatment of varices and the role of new endoscopic modalities such as endoscopic ultrasound, esophageal capsule, argon plasma coagulation, spyglass and endomicroscopy in the investigation and treatment of liver-related gastrointestinal and biliary pathology. It is clear that the role of the endoscopy in liver disease is well beyond that of just treating varices. As the technology in endoscopy expands, so does the role of the endoscopist in liver disease

Insulin-like growth factor binding protein-5 as a biomarker for detection of early liver disease

Study identifying an Insulin-like growth factor binding protein-5 as a biomarker for detection of early liver disease presented at the annual congress of the british toxicology societ

Use of small bowel capsule endoscopy in patients with chronic kidney disease:Experience from a university referral center

Abstract Background There are only few reports on the diagnostic yield (DY) of small bowel capsule endoscopy (SBCE) in patients with chronic kidney disease (CKD). We aim to report our SBCE experience in patients with CKD. Methods Retrospective study; case notes of patients with low estimated glomerular filtration rate (eGFR) who underwent SBCE (March 2005-August 2012) for anemia and/or obscure gastrointestinal bleeding (OGIB) were retrieved and abstracted. Severity of CKD was defined according to Renal Association recommendations as: stage 3 (eGFR: 30-59); stage 4 (eGFR: 15-29); and stage 5 (eGFR <15 or on dialysis). Results In the aforementioned period, 69 patients with CKD [stage 3: 65/69 (92.8%), stage 4 or 5:4/69 (7.2%)] had SBCE. 51/65 (78.5%) patients with stage 3 CKD had SBCE due to unexplained anemia and/or OGIB [43 (66.1%) and 8 (12.3%), respectively]. In 25/51 (49%), the SBCE was normal and in 17/51 (33.3%) showed small-bowel angiectasias. Other findings were active bleeding (n=2), fold edema (n=2), ileal erosions (n=1), adenocarcinoma (n=1), and inconclusive/videos not available (n=3). All patients (n=4) with CKD grade 4 or 5 were referred due to unexplained anemia; 3/4 (75%) had angiectasias and 1 normal SBCE. Fecal calprotectin (FC) was measured in 12 patients with CKD stage 3 and unexplained anemia prior to their SBCE; no significant small-bowel inflammation was found in this subgroup. Conclusion SBCE has limited DY in CKD patients referred for unexplained anemia. Sinister SB pathology is rare, while the most common finding is angiectasias. Furthermore, FC measurement prior to SBCE-in this cohort of patients- is not associated with increased DY

Application of Impedance-Based Techniques in Hepatology Research

There are a variety of end-point assays and techniques available to monitor hepatic cell cultures and study toxicity within in vitro models. These commonly focus on one aspect of cell metabolism and are often destructive to cells. Impedance-based cellular assays (IBCAs) assess biological functions of cell populations in real-time by measuring electrical impedance, which is the resistance to alternating current caused by the dielectric properties of proliferating of cells. While the uses of IBCA have been widely reported for a number of tissues, specific uses in the study of hepatic cell cultures have not been reported to date. IBCA monitors cellular behaviour throughout experimentation non-invasively without labelling or damage to cell cultures. The data extrapolated from IBCA can be correlated to biological events happening within the cell and therefore may inform drug toxicity studies or other applications within hepatic research. Because tight junctions comprise the blood/biliary barrier in hepatocytes, there are major consequences when these junctions are disrupted, as many pathologies centre around the bile canaliculi and flow of bile out of the liver. The application of IBCA in hepatology provides a unique opportunity to assess cellular polarity and patency of tight junctions, vital to maintaining normal hepatic function. Here, we describe how IBCAs have been applied to measuring the effect of viral infection, drug toxicity/IC50, cholangiopathies, cancer metastasis and monitoring of the gut-liver axis. We also highlight key areas of research where IBCAs could be used in future applications within the field of hepatology

Validation of Reference Genes for Gene Expression Studies by RT-qPCR in HepaRG Cells during Toxicity Testing and Disease Modelling

Gene expression analysis by quantitative real-time polymerase chain reaction (RT-qPCR) is routinely used in biomedical studies. The reproducibility and reliability of the data fundamentally depends on experimental design and data interpretation. Despite the wide application of this assay, there is significant variation in the validation process of gene expression data from research laboratories. Since the validity of results depends on appropriate normalisation, it is crucial to select appropriate reference gene(s), where transcription of the selected gene is unaffected by experimental setting. In this study we have applied geNorm technology to investigate the transcription of 12 ‘housekeeping’ genes for use in the normalisation of RT-qPCR data acquired using a widely accepted HepaRG hepatic cell line in studies examining models of pre-clinical drug testing. geNorm data identified a number of genes unaffected by specific drug treatments and showed that different genes remained invariant in response to different drug treatments, whereas the transcription of ‘classical’ reference genes such as GAPDH (glyceralde- hyde-3-phosphate dehydrogenase) was altered by drug treatment. Comparing data normalised using the reference genes identified by geNorm with normalisation using classical housekeeping genes demonstrated substantial differences in the final results. In light of cell therapy application, RT-qPCR analyses has to be carefully evaluated to accurately interpret data obtained from dynamic cellular models undergoing sequential stages of phenotypic change