Non-invasive assessment of intestinal permeability in healthy volunteers using transcutaneous fluorescence spectroscopy.

The permeability of the intestinal barrier is altered in a multitude of gastrointestinal conditions such as Crohn's and coeliac disease. However, the clinical utility of gut permeability is currently limited due to a lack of reliable diagnostic tests. To address this issue, we report a novel technique for rapid, non-invasive measurement of gut permeability based on transcutaneous ('through-the-skin') fluorescence spectroscopy. In this approach, participants drink an oral dose of a fluorescent dye (fluorescein) and a fibre-optic fluorescence spectrometer is attached to the finger to detect permeation of the dye from the gut into the blood stream in a non-invasive manner. To validate this technique, clinical trial measurements were performed in 11 healthy participants. First, after 6 h of fasting, participants ingested 500 mg of fluorescein dissolved in 100 ml of water and fluorescence measurements were recorded at the fingertip over the following 3 h. All participants were invited back for a repeat study, this time ingesting the same solution but with 60 g of sugar added (known to transiently increase intestinal permeability). Results from the two study datasets (without and with sugar respectively) were analysed and compared using a number of analysis procedures. This included both manual and automated calculation of a series of parameters designed for assessment of gut permeability. Calculated values were compared using Student's T-tests, which demonstrated significant differences between the two datasets. Thus, transcutaneous fluorescence spectroscopy shows promise in non-invasively discriminating between two differing states of gut permeability, demonstrating potential for future clinical use.

Assessment of the cobas® HBV RNA investigational assay in the setting of nucleoside analog therapy cessation.

HBV RNA is used as a marker of cccDNA transcription and is applicable in the setting of nucleos(t)ide analog (NA) treatment, which suppresses HBV DNA. Traditional assays for quantification of HBV RNA rely on labor-intensive 3'RACE assays targeting the polyA tail. In this study, the high-throughput Roche cobas®HBV RNA investigational assay was assessed on the Roche cobas® 6800 automated platform. Of 969 samples collected for a NA treatment cessation trial, and tested on the cobas assay, 249 were analyzed for sensitivity, reproducibility, sample type applicability, and results were compared to a RACE-based assay. Results of 97 paired serum and plasma samples demonstrated an excellent correlation of 0.98. However, 14.5% of plasma samples yielded detectable (below the limit of quantification) results, when the paired serum was undetectable, and plasma was shown to yield a statistically significant (p < 0.001) greater mean 0.119 log10 copies/ml. Quantification of 152 samples showed good correlation (0.91) between the cobas and RACE assays. The cobas assay demonstrated superior lower limit of quantification, 10 copies/ml, which resulted in detection of 13.2% more samples than the RACE assay. Reproducibility and linear range of the automated assay were also confirmed. The Roche cobas assay for HBV RNA is sensitive and highly recommended.

A case for improved assessment of gut permeability: a meta-analysis quantifying the lactulose:mannitol ratio in coeliac and Crohn's disease.

BACKGROUND: A widely used method in assessing small bowel permeability is the lactulose:mannitol test, where the lactulose:mannitol ratio (LMR) is measured. However, there is discrepancy in how the test is conducted and in the values of LMR obtained across studies. This meta-analysis aims to determine LMR in healthy subjects, coeliac and Crohn's disease. METHODS: A literature search was performed using PRISMA guidance to identify studies assessing LMR in coeliac or Crohn's disease. 19 studies included in the meta-analysis measured gut permeability in coeliac disease, 17 studies in Crohn's disease. Outcomes of interest were LMR values and comparisons of standard mean difference (SMD) and weighted mean difference (WMD) in healthy controls, inactive Crohn's, active Crohn's, treated coeliac and untreated coeliac. Pooled estimates of differences in LMR were calculated using the random effects model. RESULTS: Pooled LMR in healthy controls was 0.014 (95% CI: 0.006-0.022) while pooled LMRs in untreated and treated coeliac were 0.133 (95% CI: 0.089-0.178) and 0.037 (95% CI: 0.019-0.055). In active and inactive Crohn's disease, pooled LMRs were 0.093 (95% CI: 0.031-0.156) and 0.028 (95% CI: 0.015-0.041). Significant differences were observed in LMR between: (1) healthy controls and treated coeliacs (SMD = 0.409 95% CI 0.034 to 0.783, p = 0.032), (2) healthy controls and untreated coeliacs (SMD = 1.362 95% CI: 0.740 to 1.984, p < 0.001), (3) treated coeliacs and untreated coeliacs (SMD = 0.722 95% CI: 0.286 to 1.157, p = 0.001), (4) healthy controls and inactive Crohn's (SMD = 1.265 95% CI: 0.845 to 1.686, p < 0.001), (5) healthy controls and active Crohn's (SMD = 2.868 95% CI: 2.112 to 3.623, p < 0.001), and (6) active Crohn's and inactive Crohn's (SMD = 1.429 (95% CI: 0.580 to 2.278, p = 0.001). High heterogeneity was observed, which was attributed to variability in protocols used across different studies. CONCLUSION: The use of gut permeability measurements in screening and monitoring of coeliac and Crohn's disease is promising. LMR is useful in performing this function with significant limitations. More robust alternative tests with higher degrees of clinical evidence are needed if measurements of gut permeability are to find widespread clinical use.

Intestinal permeability and bacterial translocation in patients with liver disease, focusing on alcoholic aetiology: methods of assessment and therapeutic intervention.

Increased bacterial translocation (BT) across the gut barrier due to greater intestinal permeability (IP) is seen across a range of conditions, including alcohol-related liver disease (ArLD). The phenomenon of BT may contribute to both the pathogenesis and the development of complications in ArLD. There are a number of methods available to assess IP and in this review we look at their various advantages and limitations. The knowledge around BT and IP in ArLD is also reviewed, as well as the therapeutic strategies currently in use and in development.

Medical resource utilization and costs among Australian patients with genotype 1 chronic hepatitis C: results of a retrospective observational study.

OBJECTIVE: To evaluate medical resource utilization (MRU) and associated costs among Australian patients with genotype 1 chronic hepatitis C (GT1 CHC), including both untreated patients and those receiving treatment with first-generation protease inhibitor-based regimens (telaprevir, boceprevir with pegylated interferon and ribavirin). METHODS: Medical records were reviewed for a stratified random sample of GT1 CHC patients first attending two liver clinics between 2011-2013 (principal population; PP), supplemented by all GT1 CHC patients attending one transplant clinic in the same period (transplant population; TP). CHC-related MRU and associated costs are reported for the PP by treatment status (treated/not treated) stratified by baseline fibrosis grade; and for the TP for the pre-transplant, year of transplant and post-transplant periods. RESULTS: A total 1636 patients were screened and 590 patients (36.1%) were included. Comprehensive MRU data were collected for 276 PP patients (F0-1 n = 59, F2 n = 58, F3 n = 53, F4 n = 106; mean follow-up = 17.3 months). Thirty-eight (13.8%) were treatment-experienced prior to enrolment; 55 (19.9%) received triple therapy during the study. Data were collected for 112 TP patients (mean follow-up = 29.9 months), 33 (29.5%) received a transplant during the study, and 51 (45.5%) beforehand. The annual direct medical costs, excluding drug costs, were higher among treated PP vs untreated PP (AU$: $1,954 vs $1,202); and year of transplant TP vs pre-/post-transplant TP (AU$: pre-transplant $32,407, transplant $155,138, post-transplant $7,358). LIMITATIONS: To aid interpretation of results, note that only patients with GT1 CHC who are actively managed are included, and MRU data were collected specifically from liver outpatient clinics. That said, movement of patients between hospitals is rare, and any uncaptured MRU is expected to be minimal. CONCLUSIONS: CHC-related MRU increases substantially with disease severity. These real-world MRU data for GT1 CHC will be valuable in assessing the impact of new hepatitis C treatments.