Enhanced liver fibrosis (ELF) score predicts hepatic decompensation and mortality

BACKGROUND &amp; AIMS: In community pathways for detection of liver disease the most common reason for referral is fibrosis assessment. We investigated the impact of adding the Enhanced Liver Fibrosis (ELF) score as a second-line test (subsequent to an indeterminate or high Fibrosis-4 index [FIB-4] and/or non-alcoholic fatty liver disease fibrosis score) to guide referral and prognostication in our multi-aetiology pathway.METHODS: Patients with ELF results from the intelligent Liver Function Testing (iLFT) pathway were recruited. Case note review was undertaken to compare ELF with endpoints of cirrhosis, hepatic decompensation, and mortality (liver-related and all-cause death).RESULTS: In total, 1,327 individuals were included with a median follow-up of 859 days and median ELF score of 10.2. Overall sensitivity for cirrhosis at the 9.8 threshold was 94% (100% for metabolic-associated steatotic liver disease, 89% for alcohol-related liver disease). Determination of the ELF score as a second-line test reduced the referral rate by 34%. ELF scores predicted hepatic outcomes; each unit change was associated with increased decompensation (adjusted Hazard Ratio [aHR] 2.215, 95% CI: 1.934-2.537) and liver-related mortality (aHR 2.024, 95% CI: 1.674-2.446). ELF outperformed FIB-4 for risk of liver-related mortality, particularly in the short-term (area under the curve [AUC] 94.3% vs. 82.8% at six months). Where FIB-4 was indeterminate, ELF had higher AUC for all outcomes within at least 2 years. ELF ≥13 was associated with particularly high rates of decompensation (26% within 90 days) and all-cause mortality (38% at 1 year). CONCLUSIONS: The addition of ELF reduced the number of individuals referred for fibrosis assessment following iLFT pathway testing and provided useful prognostic information. Individuals with ELF scores ≥13 were considered at high-risk of negative outcomes warranting urgent clinical assessment.IMPACT AND IMPLICATIONS: Primary care pathways for suspected liver disease are increasingly common and often lead to increased specialist hepatology referrals for fibrosis assessment. This study, using clinical follow-up for liver-related outcomes, provides further evidence supporting ELF testing to safely reduce referrals in a two-step approach when combined with other simple fibrosis markers. Additionally, ELF scores predict liver-related morbidity and mortality, with ELF scores ≥13 indicating particularly high-risk patients. This study may help inform the implementation of diagnostic pathways for early detection of liver disease and highlights the need for urgent review of individuals with very high ELF scores.</p

Rough Cilicia Archaeological Survey Project: Report of the 2002 Season

The Rough Cilicia Archaeological Project conducted archaeological and geoarchaeological research in the Gazipaşa area from July 20 through 1 September 2001. Several goals were met this season. Under the direction of Michael Hoff and Rhys Townsend, detailed plans were completed of monumental structures at the sites of Asar Tepe, Lamos, and Selinus. At Lamos, in particular, the team made a number of finds, including the discovery of an inscribed statue base of large size in a small podium complex on a hill above the so-called stadium

Induction of a chemoattractant transcriptional response by a Campylobacter jejuni boiled cell extract in colonocytes

<p>Abstract</p> <p>Background</p> <p><it>Campylobacter jejuni</it>, the commonest cause of bacterial diarrhoea worldwide, can also induce colonic inflammation. To understand how a previously identified heat stable component contributes to pro-inflammatory responses we used microarray and real-time quantitative PCR to investigate the transcriptional response to a boiled cell extract of <it>Campylobacter jejuni </it>NCTC 11168.</p> <p>Results</p> <p>RNA was extracted from the human colonocyte line HCA-7 (clone 29) after incubation for 6 hours with <it>Campylobacter jejuni </it>boiled cell extract and was used to probe the Affymetrix Human Genome U133A array. Genes differentially affected by <it>Campylobacter jejuni </it>boiled cell extract were identified using the Significance Score algorithm of the Bioconductor software suite and further analyzed using the Ingenuity Pathway Analysis program. The chemokines CCL20, CXCL3, CXCL2, Interleukin 8, CXCL1 and CXCL6 comprised 6 of the 10 most highly up-regulated genes, all with Significance Scores ≥ 10. Members of the Tumor Necrosis Factor α/Nuclear Factor-κB super-family were also significantly up-regulated and involved in the most significantly regulated signalling pathways (Death receptor, Interleukin 6, Interleukin 10, Toll like receptor, Peroxisome Proliferator Activated Receptor-γ and apoptosis). Ingenuity Pathway Analysis also identified the most affected functional gene networks such as cell movement, gene expression and cell death. In contrast, down-regulated genes were predominantly concerned with structural and metabolic functions.</p> <p>Conclusion</p> <p>A boiled cell extract of <it>Campylobacter jejuni </it>has components that can directly switch the phenotype of colonic epithelial cells from one of resting metabolism to a pro-inflammatory one, particularly characterized by increased expression of genes for leukocyte chemoattractant molecules.</p

Rough Cilicia Archaeological Survey Project: Report of the 2002 Season

The Rough Cilicia Archaeological Project conducted archaeological and geoarchaeological research in the Gazipaşa area from July 20 through 1 September 2001. Several goals were met this season. Under the direction of Michael Hoff and Rhys Townsend, detailed plans were completed of monumental structures at the sites of Asar Tepe, Lamos, and Selinus. At Lamos, in particular, the team made a number of finds, including the discovery of an inscribed statue base of large size in a small podium complex on a hill above the so-called stadium