Comparative Assessment and External Validation of Hepatic Steatosis Formulae in a Community-Based Setting.

Several hepatic steatosis formulae have been validated in various cohorts using ultrasonography. However, none of these studies has been validated in a community-based setting using the gold standard method. Thus, the aim of this study was to externally validate hepatic steatosis formulae in community-based settings using magnetic resonance imaging (MRI). A total of 1301 community-based health checkup subjects who underwent liver fat quantification with MRI were enrolled in this study. Diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUROC). Non-alcoholic fatty liver disease (NAFLD) liver fat score showed the highest diagnostic performance with an AUROC of 0.72, followed by Framingham steatosis index (0.70), hepatic steatosis index (HSI, 0.69), ZJU index (0.69), and fatty liver index (FLI, 0.68). There were considerable gray zones in three fatty liver prediction models using two cutoffs (FLI, 28.9%; HSI, 48.9%; and ZJU index, 53.6%). The diagnostic performance of NAFLD liver fat score for detecting steatosis was comparable to that of ultrasonography. The diagnostic agreement was 72.7% between NAFLD liver fat score and 70.9% between ultrasound and MRI. In conclusion, the NAFLD liver fat score showed the best diagnostic performance for detecting hepatic steatosis. Its diagnostic performance was comparable to that of ultrasonography in a community-based setting.

Prevalence of significant hepatic fibrosis using magnetic resonance elastography in a health check-up clinic population.

BACKGROUND: Significant hepatic fibrosis is associated with higher mortality. However, data on the estimated prevalence of liver fibrosis in the general population are scarce. AIM: To use magnetic resonance elastography (MRE) to investigate the prevalence of hepatic fibrosis in a Korean health check-up clinic cohort. METHODS: We enrolled 2170 participants at our health check-up clinic between January 2015 and May 2018, all of whom had MR with chemical shift technique and MRE. The primary objective was to estimate the prevalence of liver fibrosis. For generalisation, sex- and age-standardised prevalence was calculated based on the Korean Statistical Information Service (KOSIS) during the period 2015-2018. RESULTS: The prevalence of F2 (≥3.0 kPa) and F3 (≥3.6 kPa) in the overall cohort was 5.1% and 1.3% respectively (sex- and age-adjusted prevalence of 3.8% and 1.3%). Non-alcoholic fatty liver disease (NAFLD) prevalence (>5% fat fraction) was 27.7% in the average risk population (after excluding alcohol use and viral hepatitis), and the prevalence of significant and advanced fibrosis in NAFLD participants was 8.0% and 1.5% respectively. In participants with diabetes, 12.5% had ≥F2 and 4.3% ≥F3. In participants with NAFLD plus diabetes, 24.1% had ≥F2 and 6.0% ≥F3. On multivariate analysis, only age, insulin, diabetes and fatty liver on MR were independently associated with significant fibrosis. CONCLUSIONS: In a Korean health check-up clinic setting, the prevalence of significant and advanced liver fibrosis was 5.1% and 1.3% (sex- and age-adjusted prevalence of 3.8% and 1.3%). The prevalence of advanced liver fibrosis was five times higher for diabetic participants with NAFLD.

Near real-time immuno-optical sensor for diagnosing single point mutation: a model system: sensor for factor V Leiden diagnosis.

Factor V leiden (FVL) is an abnormality of factor V (FV), a blood coagulation factor. It is a hereditary blood coagulation disorder with a high frequency (3-7% of general population). The most common type of FVL is caused by a single amino acid mutation and, therefore, its diagnosis is currently done only by DNA analysis, which takes a long time and is expensive. We have developed a rapid, accurate, and cost-effective, sandwich immuno-optical sensing method. To produce monoclonal antibodies against FV or FVL, having minimal cross-reactivity with the other molecule, a 20 amino acid sequence (20-mer) of FV or FVL at around the mutation site was utilized. The antibodies were screened first with the 20-mers and then the ones showing no cross-affinity were reacted with native FV or FVL molecules and they showed some cross-reactivity. Using two antibodies having strongest affinity to either FV or FVL molecule, a FV and a FVL preferred sensors, were produced. After verifying that the levels of the antibody affinity to the two different molecules remained constant with changes in analyte concentration, a two-sensor system is developed to quantify FV and FVL in plasma samples. The system quantified the levels of FV and FVL at the maximum error of 0.5 microg/ml-plasma, in their physiological concentration range of 0-12 microg/ml-plasma. The levels of both molecules may provide us whether the patient has FVL or not but also the seriousness level of the disease (homozygous and different level of heterozygous).

Biosensor for diagnosing Factor V Leiden, a single amino acid mutated abnormality of Factor V.

Factor V Leiden (FVL) is an abnormality with a single amino acid mutation of Factor V (FV) and is the most common, hereditary blood coagulation disorder. FVL is currently diagnosed by DNA analysis, which takes a long assay time, high cost, and a specially trained person. We are developing a rapid, accurate, and cost-effective biosensing system to quantify both FV and FVL in blood plasma, to diagnose FVL and also to evaluate the seriousness of the disease status. This system is based on a sandwich immuno-reaction on an optical fiber. To produce the monoclonal antibody against only FV or only FVL without cross-reacting with the other molecule and with a higher probability, a 20 amino acid sequence (20-mer) of FV or FVL around the mutation region was injected into mice and then hybridoma cell lines specific to each 20-mer were selected. When these antibodies were tested with native FV or FVL molecules, they were found to be cross-reacting with the other molecules, but some with higher affinity to FV (FV preferred) and some to FVL (FVL preferred). Using these antibodies, two different sensors were developed: FV preferred and FVL preferred sensors. These two sensors allowed us to quantify FV and FVL in plasma with a maximum error of 4%. The plasma levels of both molecules provide us not only FVL diagnosis but also the level of the seriousness. The same principles may be used for developing diagnostic tools for other diseases with a single point mutation.