Highlights
- •Optimal liver stiffness thresholds for community-based screening of at-risk patients are 9.1–9.5 kPa for fibrosis (stages ≥F2).
- •Transient elastography is a cost-effective intervention for identifying patients with liver fibrosis in primary care.
- •Between 2,500 to 6,500 PPP-adjusted euros are needed to gain an extra year of life, adjusted for quality of life.
- •The survival effect of screening is most pronounced for the identification of significant (≥F2) fibrosis.
Background & Aims
Non-alcoholic fatty liver disease and alcohol-related liver disease pose an important
challenge to current clinical healthcare pathways because of the large number of at-risk
patients. Therefore, we aimed to explore the cost-effectiveness of transient elastography
(TE) as a screening method to detect liver fibrosis in a primary care pathway.
Methods
Cost-effectiveness analysis was performed using real-life individual patient data
from 6 independent prospective cohorts (5 from Europe and 1 from Asia). A diagnostic
algorithm with conditional inference trees was developed to explore the relationships
between liver stiffness, socio-demographics, comorbidities, and hepatic fibrosis,
the latter assessed by fibrosis scores (FIB-4, NFS) and liver biopsies in a subset
of 352 patients. We compared the incremental cost-effectiveness of a screening strategy
against standard of care alongside the numbers needed to screen to diagnose a patient
with fibrosis stage ≥F2.
Results
The data set encompassed 6,295 participants (mean age 55 ± 12 years, BMI 27 ± 5 kg/m2, liver stiffness 5.6 ± 5.0 kPa). A 9.1 kPa TE cut-off provided the best accuracy
for the diagnosis of significant fibrosis (≥F2) in general population settings, whereas
a threshold of 9.5 kPa was optimal for populations at-risk of alcohol-related liver
disease. TE with the proposed cut-offs outperformed fibrosis scores in terms of accuracy.
Screening with TE was cost-effective with mean incremental cost-effectiveness ratios
ranging from 2,570 €/QALY (95% CI 2,456–2,683) for a population at-risk of alcohol-related
liver disease (age ≥45 years) to 6,217 €/QALY (95% CI 5,832–6,601) in the general
population. Overall, there was a 12% chance of TE screening being cost saving across
countries and populations.
Conclusions
Screening for liver fibrosis with TE in primary care is a cost-effective intervention
for European and Asian populations and may even be cost saving.
Lay summary
The lack of optimized public health screening strategies for the detection of liver
fibrosis in adults without known liver disease presents a major healthcare challenge.
Analyses from 6 independent international cohorts, with transient elastography measurements,
show that a community-based risk-stratification strategy for alcohol-related and non-alcoholic
fatty liver diseases is cost-effective and potentially cost saving for our healthcare
systems, as it leads to earlier identification of patients.
Graphical abstract
Graphical Abstract
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of HepatologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
Author names in bold designate shared co-first authorship
- The global NAFLD epidemic.Nat Rev Gastroenterol Hepatol. 2013; 10: 686-690https://doi.org/10.1038/nrgastro.2013.171
- Disease burden and costs from excess alcohol consumption, obesity, and viral hepatitis: fourth report of the Lancet Standing Commission on Liver Disease in the UK.Lancet (London, England). 2018; 391: 1097-1107https://doi.org/10.1016/S0140-6736(17)32866-0
- Alcoholic liver disease.Clin Liver Dis. 2016; 20: xiii-xivhttps://doi.org/10.1016/j.cld.2016.05.001
- Alcoholic liver disease: mechanisms of injury and targeted treatment.Nat Rev Gastroenterol Hepatol. 2015; 12: 231-242https://doi.org/10.1038/nrgastro.2015.35
- EASL Clinical Practice Guidelines: Management of alcohol-related liver disease.J Hepatol. 2018; 69: 154-181https://doi.org/10.1016/j.jhep.2018.03.018
- Clinical course of alcoholic liver cirrhosis: a Danish population-based cohort study.Hepatology. 2010; 51: 1675-1682https://doi.org/10.1002/hep.23500
- Screening for liver fibrosis in the general population: a call for action.Lancet Gastroenterol Hepatol. 2016; 1: 256-260https://doi.org/10.1016/S2468-1253(16)30081-4
- Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD.J Hepatol. 2017; 67: 1265-1273https://doi.org/10.1016/j.jhep.2017.07.027
- Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease.Gastroenterology. 2015; 149 (389–97.e10)https://doi.org/10.1053/j.gastro.2015.04.043
- Non-alcoholic fatty liver disease and the interface between primary and secondary care.Lancet Gastroenterol Hepatol. 2018; 3: 509-517https://doi.org/10.1016/S2468-1253(18)30077-3
- Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease.Hepatology. 2010; 51: 454-462https://doi.org/10.1002/hep.23312
- Non-invasive evaluation of liver fibrosis using transient elastography.J Hepatol. 2008; 48: 835-847https://doi.org/10.1016/j.jhep.2008.02.008
- Magnetic resonance elastography vs transient elastography in detection of fibrosis and noninvasive measurement of steatosis in patients with biopsy-proven nonalcoholic fatty liver disease.Gastroenterology. 2017; 152 (598–607.e2)https://doi.org/10.1053/j.gastro.2016.10.026
- Magnetic resonance imaging more accurately classifies steatosis and fibrosis in patients with nonalcoholic fatty liver disease than transient elastography.Gastroenterology. 2016; 150 (626–637e7)https://doi.org/10.1053/j.gastro.2015.11.048
- Magnetic resonance elastography for the noninvasive staging of liver fibrosis.Gastroenterology. 2008; 135: 32-40https://doi.org/10.1053/j.gastro.2008.03.076
- Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease.Gastroenterology. 2019; 156 (1264–1281.e4)https://doi.org/10.1053/j.gastro.2018.12.036
- Prevalence of clinically significant liver disease within the general population, as defined by non-invasive markers of liver fibrosis: a systematic review.Lancet Gastroenterol Hepatol. 2017; 2: 288-297https://doi.org/10.1016/S2468-1253(16)30205-9
- A stepwise algorithm using an at-a-glance first-line test for the non-invasive diagnosis of advanced liver fibrosis and cirrhosis.J Hepatol. 2017; 66: 1158-1165https://doi.org/10.1016/j.jhep.2017.01.003
- Liver fibrosis in non-alcoholic fatty liver disease-diagnostic challenge with prognostic significance.World J Gastroenterol. 2015; 21: 11077-11087https://doi.org/10.3748/wjg.v21.i39.11077
- Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease.J Hepatol. 2016; 65: 570-578https://doi.org/10.1016/j.jhep.2016.04.023
- Liver stiffness in nonalcoholic fatty liver disease: a comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy.Hepatology. 2016; 63: 1817-1827https://doi.org/10.1002/hep.28394
- Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis.J Hepatol. 2017; 66: 1022-1030https://doi.org/10.1016/j.jhep.2016.12.022
- Transient elastography as a screening tool for liver fibrosis and cirrhosis in a community-based population aged over 45 years.Gut. 2011; 60: 977-984https://doi.org/10.1136/gut.2010.221382
- High prevalence of liver fibrosis among European adults with unknown liver disease: a population-based study.Clin Gastroenterol Hepatol. 2018; https://doi.org/10.1016/j.cgh.2017.12.048
- Prevalence of hepatic steatosis as assessed by controlled attenuation parameter (CAP) in subjects with metabolic risk factors in primary care. A population-based study.PLoS One. 2018; 13: e0200656https://doi.org/10.1371/journal.pone.0200656
- Transient and 2-dimensional shear-wave elastography provide comparable assessment of alcoholic liver fibrosis and cirrhosis.Gastroenterology. 2016; 150: 123-133https://doi.org/10.1053/j.gastro.2015.09.040
- Direct targeting of risk factors significantly increases the detection of liver cirrhosis in primary care: a cross-sectional diagnostic study utilising transient elastography.BMJ Open. 2015; 5
- Nichtinvasive Früherkennung von Lebererkrankungen im Rahmen der betrieblichen Gesundheitsförderung.Zentralblatt Für Arbeitsmedizin, Arbeitsschutz Und Ergonomie. 2017; 67: 201-210https://doi.org/10.1007/s40664-017-0187-z
- Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography.Gut. 2012; 61: 409-415https://doi.org/10.1136/gutjnl-2011-300342
- Design and validation of a histological scoring system for nonalcoholic fatty liver disease.Hepatology. 2005; 41: 1313-1321https://doi.org/10.1002/hep.20701
- Noninvasive evaluation of NAFLD.Nat Rev Gastroenterol Hepatol. 2013; 10: 666https://doi.org/10.1038/nrgastro.2013.175
- Unbiased recursive partitioning: a conditional inference framework.J Comput Graph Stat. 2006; 15: 651-674https://doi.org/10.1198/106186006X133933
Holmes G, Pfahringer B, Kirkby R. Multiclass Alternating Decision Trees. Proc 13th Eur Conf Mach Learn (ECML ’02) 2002;2430:161–72. doi:10.1007/3-540-36755-1_14.
- SMOTE: Synthetic minority over-sampling technique.J Artif Intell Res. 2002; https://doi.org/10.1613/jair.953
- Best-subset selection procedure.Proc Winter Simul Conf. 2011; : 4310-4318https://doi.org/10.1109/WSC.2011.6148118
R Core Team R Foundation for Statistical Computing, Vienna A. R: A language and environment for statistical computing, 2016. n.d.
- 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.BMJ Open. 2017; 7
- Thresholds for the cost-effectiveness of interventions: alternative approaches.Bull World Health Organ. 2015; 93: 118-124https://doi.org/10.2471/BLT.14.138206
- Reduced mortality rates following elective percutaneous liver biopsies.Gastroenterology. 2010; 139: 1230-1237https://doi.org/10.1053/j.gastro.2010.06.015
- Incremental Cost-Effectiveness Ratio (ICER).York Heal Econ Consort. 2017; https://doi.org/10.1111/j.1524-4733.2004.75003.x/full
- Natural history of liver fibrosis progression in patients with chronic hepatitis C.The Lancet. 1997; 349: 825-832https://doi.org/10.1016/S0140-6736(96)07642-8
- Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study.Lancet (London, England). 2013; 381: 468-475https://doi.org/10.1016/S0140-6736(12)61425-1
- Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C.Gastroenterology. 2002; 122: 1303-1313https://doi.org/10.1053/gast.2002.33023
- Noninvasive biomarkers in NAFLD and NASH – current progress and future promise.Nat Rev Gastroenterol Hepatol. 2018; 15: 461-478https://doi.org/10.1038/s41575-018-0014-9
- Critical comparison of elastography methods to assess chronic liver disease.Nat Rev Gastroenterol Hepatol. 2016; 13: 402
- Cost-effectiveness of organized versus opportunistic cervical cytology screening in Hong Kong.J Public Health (Bangkok). 2004; 26: 130-137https://doi.org/10.1093/pubmed/fdh138
- Cost-effectiveness of CT screening in the national lung screening trial.N Engl J Med. 2014; 371: 1793-1802https://doi.org/10.1056/NEJMoa1312547
- Cancer screening and aging: research barriers and opportunities.Cancer. 2008; 113: 3493-3504https://doi.org/10.1002/cncr.23938
- What implementation interventions increase cancer screening rates? A systematic review.Implement Sci. 2011; 6: 111https://doi.org/10.1186/1748-5908-6-111
- Multilevel barriers to the successful implementation of lung cancer screening: why does it have to be so hard?.Ann Am Thorac Soc. 2017; 14: 1261-1265https://doi.org/10.1513/AnnalsATS.201703-204PS
- Implementation of and barriers to routine HIV screening for adolescents.Pediatrics. 2009; 124: 1076-1084https://doi.org/10.1542/peds.2009-0237
- Implementation of colon cancer screening: techniques, costs, and barriers.Gastroenterol Clin North Am. 2008; 37: 83-95https://doi.org/10.1016/j.gtc.2007.12.015
- Cost-effectiveness analysis of population-based screening of hepatocellular carcinoma: Comparing ultrasonography with two-stage screening.World J Gastroenterol. 2016; 22: 3460-3470https://doi.org/10.3748/wjg.v22.i12.3460
Article info
Publication history
Published online: August 27, 2019
Accepted:
August 17,
2019
Received in revised form:
August 4,
2019
Received:
October 26,
2018
Identification
Copyright
© 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
