Prospective evaluation of a primary care referral pathway for patients with non-alcoholic fatty liver disease.

BACKGROUND & AIMS: We aimed to develop and evaluate a pathway for management of patients with non-alcoholic fatty liver disease (NAFLD) using blood tests to stratify patients in primary care to improve detection of cases of advanced fibrosis and cirrhosis, and avoid unnecessary referrals to secondary care. METHODS: This was a prospective longitudinal cohort study with before-and-after analysis and comparison to unexposed controls. We used a two-step algorithm combining the use of FIB-4 followed by the ELF test if required RESULTS: In total, 3,012 patients were analysed. Use of the pathway detected 5 times more cases of advanced fibrosis (Kleiner F3) and cirrhosis (OR=5.18; 95%CI=2.97 to 9.04; p<0.0001). Unnecessary referrals from primary care to secondary care fell by 81% (OR=0.193; 95%CI 0.111 to 0.337; p<0.0001). Three times more cases of cirrhosis were diagnosed (OR=3.14; 95%CI=1.57 to 24; p=0.00011). Although it was used for only 48% of referrals, significant benefits were observed across all referrals from the practices exposed to the pathway. Unnecessary referrals fell by 77% (OR=0.23; 95% CI=0.658 to 0.082; p=0.006) with a 4-fold improvement in detection of cases of advanced fibrosis and cirrhosis (OR=4.32; 95% CI=1.52 to 12.25; p=0.006). Compared to referrals made before introduction of the pathway, unnecessary referrals fell from 79/83 referrals (95.2%) to 107/152 (70.4%) representing an 88% reduction in unnecessary referrals when the pathway was followed (OR=0.12; 95%CI=0.042 to 0.349; p<0.0001). CONCLUSIONS: The use of non-invasive blood tests for liver fibrosis to stratify patients with NAFLD improves the detection of cases of advanced fibrosis and cirrhosis and reduces unnecessary referrals to secondary care of patients with lesser degrees of liver fibrosis. This strategy improves resource use and benefits patients. LAY SUMMARY: Non-alcoholic fatty liver disease effects up to 30% of the population but only a minority of cases develop liver disease. Our study has shown that established blood tests can be used in primary care to stratify patients with fatty liver disease to reduce unnecessary referrals by 80% and improve the detection of cases of advanced fibrosis 5 fold and cirrhosis 3 fold

Tetrathiomolybdate causes formation of hepatic copper-molybdenum clusters in an animal model of Wilson's disease

Copyright © 2003 American Chemical SocietyWilson's disease is an autosomal recessive human illness in which large quantities of copper accumulate in various organs, including the brain and the liver. If left untreated, it results in hepatitis, neurological complications, and death. Long-Evans Cinnamon (LEC) rats have a homologous mutation to Wilson's disease and thus provide an animal model. Liver lysosomes from tetrathiomolybdate-treated LEC rats were isolated and analyzed by Cu and Mo K-edge X-ray absorption spectroscopy. The lysosomes contained a Cu-Mo-S cluster in which the Mo is coordinated by four sulfurs at 2.24 A with approximately three copper neighbors at 2.70 A. Each Cu is coordinated to 3-4 sulfurs at 2.28 A with approximately one Mo neighbor at 2.70 A. These results indicate the formation of a biologically novel molybdenum-copper-sulfur cluster.Graham N. George, Ingrid J. Pickering, Hugh H. Harris, Jürgen Gailer, Dominik Klein, Josef Lichtmannegger, and Karl-Heinz Summe