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      Economic evaluation of a community-based diagnostic pathway to stratify adults for non-alcoholic fatty liver disease: a Markov model informed by a feasibility study

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          Abstract

          Objectives

          To assess the long-term cost-effectiveness of a risk stratification pathway, compared with standard care, for detecting non-alcoholic fatty liver disease (NAFLD) in primary care.

          Setting

          Primary care general practices in England.

          Participants

          Adults who have been identified in primary care to have a risk factor for developing NAFLD, that is, type 2 diabetes without a history of excessive alcohol use.

          Intervention

          A community-based pathway, which uses transient elastography and hepatologists to stratify patients at risk of NAFLD, has been implemented and demonstrated to be feasible (NCT02037867). Earlier identification could mean earlier treatments, referral to specialist and enrolment into surveillance programmes.

          Design

          The impact of earlier detection and treatment with the risk stratification pathway on progression to later stages of liver disease was examined using decision modelling with Markov chains to estimate lifetime health and economic effects of the two comparators.

          Data sources

          Data from a prospective cross-sectional feasibility study indicating risk stratification pathway and standard care diagnostic accuracies were combined with a Markov model that comprised the following states: no/mild liver disease, significant liver disease, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplant and death. The model data were chosen from up-to-date UK sources, published literature and an expert panel.

          Outcome measure

          An incremental cost-effectiveness ratio (ICER) indicating cost per quality-adjusted life year (QALY) of the risk stratification pathway compared with standard care was estimated.

          Results

          The risk stratification pathway was more effective than standard care and costs £2138 per QALY gained. The ICER was most sensitive to estimates of the rate of fibrosis progression and the effect of treatment on reducing this, and ranged from −£1895 to £7032/QALY. The risk stratification pathway demonstrated an 85% probability of cost-effectiveness at the UK willingness-to-pay threshold of £20 000/QALY.

          Conclusions

          Implementation of a community-based risk stratification pathway is likely to be cost-effective.

          Trial registration number

          NCT02037867, ClinicalTrials.gov.

          Related collections

          Most cited references22

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          Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma.

          An association between diabetes and chronic liver disease has been reported. However, the temporal relationship between these conditions remains unknown. We identified all patients with a hospital discharge diagnosis of diabetes between 1985 and 1990 using the computerized records of the Department of Veterans Affairs. We randomly assigned 3 patients without diabetes for every patient with diabetes. We excluded patients with concomitant liver disease. The remaining cohort was followed through 2000 for the occurrence of chronic nonalcoholic liver disease (CNLD) and hepatocellular carcinoma (HCC). Hazard rate ratios (HRR) were determined in Cox proportional hazard survival analysis. The study cohort comprised 173,643 patients with diabetes and 650,620 patients without diabetes. Most were men (98%). Patients with diabetes were older (62 vs. 54 years) than patients without diabetes. The incidence of chronic nonalcoholic liver disease was significantly higher among patients with diabetes (incidence rate: 18.13 vs. 9.55 per 10,000 person-years, respectively, P < 0.0001). Similar results were obtained for HCC (incidence rate: 2.39 vs. 0.87 per 10,000 person-years, respectively, P < 0.0001). Diabetes was associated with an HRR of 1.98 (95% CI: 1.88 to 2.09, P < 0.0001) of CNLD and an HRR of 2.16 (1.86 to 2.52, P < 0.0001) of hepatocellular carcinoma. Diabetes carried the highest risk among patients with longer than 10 years of follow-up. Among men with diabetes, the risk of CNLD and HCC is doubled. This increase in risk is independent of alcoholic liver disease, viral hepatitis, or demographic features.
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            Pioglitazone for diabetes prevention in impaired glucose tolerance.

            Impaired glucose tolerance is associated with increased rates of cardiovascular disease and conversion to type 2 diabetes mellitus. Interventions that may prevent or delay such occurrences are of great clinical importance. We conducted a randomized, double-blind, placebo-controlled study to examine whether pioglitazone can reduce the risk of type 2 diabetes mellitus in adults with impaired glucose tolerance. A total of 602 patients were randomly assigned to receive pioglitazone or placebo. The median follow-up period was 2.4 years. Fasting glucose was measured quarterly, and oral glucose tolerance tests were performed annually. Conversion to diabetes was confirmed on the basis of the results of repeat testing. Annual incidence rates for type 2 diabetes mellitus were 2.1% in the pioglitazone group and 7.6% in the placebo group, and the hazard ratio for conversion to diabetes in the pioglitazone group was 0.28 (95% confidence interval, 0.16 to 0.49; P<0.001). Conversion to normal glucose tolerance occurred in 48% of the patients in the pioglitazone group and 28% of those in the placebo group (P<0.001). Treatment with pioglitazone as compared with placebo was associated with significantly reduced levels of fasting glucose (a decrease of 11.7 mg per deciliter vs. 8.1 mg per deciliter [0.7 mmol per liter vs. 0.5 mmol per liter], P<0.001), 2-hour glucose (a decrease of 30.5 mg per deciliter vs. 15.6 mg per deciliter [1.6 mmol per liter vs. 0.9 mmol per liter], P<0.001), and HbA(1c) (a decrease of 0.04 percentage points vs. an increase of 0.20 percentage points, P<0.001). Pioglitazone therapy was also associated with a decrease in diastolic blood pressure (by 2.0 mm Hg vs. 0.0 mm Hg, P=0.03), a reduced rate of carotid intima-media thickening (31.5%, P=0.047), and a greater increase in the level of high-density lipoprotein cholesterol (by 7.35 mg per deciliter vs. 4.5 mg per deciliter [0.4 mmol per liter vs. 0.3 mmol per liter], P=0.008). Weight gain was greater with pioglitazone than with placebo (3.9 kg vs. 0.77 kg, P<0.001), and edema was more frequent (12.9% vs. 6.4%, P=0.007). As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain and edema. (Funded by Takeda Pharmaceuticals and others; ClinicalTrials.gov number, NCT00220961.).
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              Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease.

              NAFLD is highly prevalent but only a small subset of patients develop advanced liver fibrosis with impaired liver-related prognosis. We aimed to compare blood fibrosis tests and liver stiffness measurement (LSM) by FibroScan for the diagnosis of liver fibrosis and the evaluation of prognosis in NAFLD.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Open (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2017
                5 July 2017
                : 7
                : 6
                : e015659
                Affiliations
                [1 ] departmentDivision of Pharmacy Practice and Policy , School of Pharmacy, University of Nottingham , Nottingham, UK
                [2 ] departmentNottingham Digestive Diseases Centre, NIHR Nottingham Biomedical Research Centre , Nottingham University Hospitals NHS Trust and University of Nottingham. , Nottingham, United Kingdom
                [3 ] departmentNIHR Nottingham Digestive Diseases Biomedical Research Centre , Nottingham University Hospitals NHS Trust and University of Nottingham , Nottingham, UK
                [4 ] departmentPragmatic Clinical Trials Unit , Queen Mary University of London , London, UK
                [5 ] departmentManchester Centre for Health Economics , School of Health Sciences, University of Manchester , Manchester, UK
                Author notes
                [Correspondence to ] Prof. Rachel A Elliott; rachel.a.elliott@ 123456manchester.ac.uk
                Author information
                http://orcid.org/0000-0002-3650-0168
                Article
                bmjopen-2016-015659
                10.1136/bmjopen-2016-015659
                5734564
                28679676
                c13a89d1-cfad-4998-a35b-231af0d90232
                © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                : 21 December 2016
                : 25 April 2017
                : 02 May 2017
                Funding
                Funded by: East Midlands Academic Health Science Network and the University of Nottingham;
                Categories
                Gastroenterology and Hepatology
                Research
                1506
                1695
                Custom metadata
                unlocked

                Medicine
                cost effectiveness analysis,screening,transient elastography,fibrosis,quality-adjusted life-years

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