Cost Effectiveness of Different Strategies for Detecting Cirrhosis in Patients With Nonalcoholic Fatty Liver Disease Based on United States Health Care System

doi:10.1016/j.cgh.2020.04.017

Clinical Gastroenterology and Hepatology

Volume 18, Issue 10, September 2020, Pages 2305-2314.e12

https://doi.org/10.1016/j.cgh.2020.04.017 Get rights and content

Background & Aims

Several strategies are available for detecting cirrhosis in patients with nonalcoholic fatty liver disease (NAFLD), but their cost effectiveness is not clear. We developed a decision model to quantify the accuracy and costs of 9 single or combination strategies, including 3 noninvasive tests (fibrosis-4 [FIB-4], vibration-controlled transient elastography [VCTE], and magnetic resonance elastography [MRE]) and liver biopsy, for the detection of cirrhosis in patients with NAFLD.

Methods

Data on the diagnostic accuracy, costs, adverse events, and cirrhosis outcomes over a 5-year period were obtained from publications. The diagnostic accuracy, per-patient cost per correct diagnosis of cirrhosis, and incremental cost-effectiveness ratios (ICERs) were calculated for each strategy for base cirrhosis prevalence values of 0.27%, 2%, and 4%.

Results

The combination of the FIB-4 and VCTE identified patients with cirrhosis in NAFLD populations with a 0.27%, 2%, and 4% prevalence of cirrhosis with the lowest cost per person ($401, $690, and $1024, respectively) and highest diagnostic accuracy (89.3%, 88.5%, and 87.5% respectively). The combination of FIB-4 and MRE ranked second in cost per person ($491, $781, and $1114, respectively) and diagnostic accuracy (92.4%, 91.6%, 90.6%, respectively). Compared with the combination of FIB-4 and VCTE (least costly), the ICERs were lower for the combination of FIB-4 and MRE ($2864, $2918, and $2921) than the combination of FIB-4 and liver biopsy ($4454, $5156, and $5956) at the cirrhosis prevalence values tested. When the goal was to avoid liver biopsy, FIB-4 + VCTE and FIB-4 + MRE had similar diagnostic accuracies, ranging from 87.5% to 89.3% and 90.6% to 92.4% for a cirrhosis diagnosis, respectively, although FIB-4 + MRE had a slightly higher cost.

Conclusions

In our cost-effectiveness analysis based on the US health care system, we found that results from FIB-4, followed by either VCTE, MRE, or liver biopsy, detect cirrhosis in patients with NAFLD with a high level of accuracy and low cost. Compared with FIB-4 + VCTE, which was the least costly strategy, FIB-4 + MRE had a lower ICER than FIB-4 + LB.

Section snippets

Study Population

Our study population consisted of a hypothetical cohort of middle-aged patients with NAFLD seen in 3 different settings: (1) in a specialty clinic setting in which the prevalence of cirrhosis in NAFLD is estimated to be 2%,¹¹ (2) in a general population-based setting in which the prevalence of cirrhosis is estimated to be 0.27%,¹² and (3) a tertiary referral center setting in which cirrhosis prevalence is reported to be approximately 4%.⁵^,⁷^,⁸

Model Structures

We constructed a decision model to compare the

Low prevalence of cirrhosis (0.27%)

Fib-4 alone correctly classified the lowest percentage of persons (57%), whereas Fib-4 + LB correctly classified 97.7%, the highest percentage (Table 2). Figure 2A shows diagnostic accuracy by cost per person for each strategy. The solid line connecting the blue dots represents the efficiency frontier, which identifies strategies with the lowest cost and highest accuracy, and includes the following: Fib-4 + VCTE (89.3%; $401), Fib-4 + MRE (92.4%; $491), and Fib-4 + LB (97.7%; $729). Relative to

Discussion

Because cirrhosis is the major determinant of long-term morbidity and mortality in patients with NAFLD, there is a critical need to detect cirrhosis before complications occur, which are associated with high mortality and increased health care utilization. The sequential combination of 2 NITs or a NIT test plus LB may detect cirrhosis more accurately,⁹^,¹⁰ however, whether these approaches are cost effective is unknown. This study suggests that the use of Fib-4 followed by VCTE is likely the

Acknowledgments

The authors thank Ms Carolina Vivas-Valencia from the Purdue Weldon School of Biomedical Engineering for her participation in initial meetings on decision tree construction and conceptualization of the microsimulation; Mr Robert W. Klein from Medical Decision Modeling, Inc, for his thoughtful review and suggestions; Drs Samer Gawrieh and Niharika Samala for their comments regarding study design and results; and Julianne Nanzer for her editorial assistance.

CRediT Authorship Contributions

Eduardo Vilar-Gomez, M.D., Ph.D.

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Cited by (37)

AGA Clinical Practice Update on the Role of Noninvasive Biomarkers in the Evaluation and Management of Nonalcoholic Fatty Liver Disease: Expert Review
2023, Gastroenterology
The purpose of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review is to provide clinicians with guidance on the use of noninvasive tests (NITs) in the evaluation and management of patients with nonalcoholic fatty liver disease (NAFLD). NAFLD affects nearly 30% of the global population and is a growing cause of end-stage liver disease and liver-related health care resource utilization. However, only a minority of all patients with NAFLD experience a liver-related outcome. It is therefore critically important for clinicians to assess prognosis and identify those with increased risk of disease progression and negative clinical outcomes at the time of initial assessment. It is equally important to assess disease trajectory over time, particularly in response to currently available therapeutic approaches. The reference standard for assessment of prognosis and disease monitoring is histologic examination of liver biopsy specimens. There are, however, many limitations of liver biopsies and their reading that have limited their use in routine practice. The utilization of NITs facilitates risk stratification of patients and longitudinal assessment of disease progression for patients with NAFLD. This clinical update provides best practice advice based on a review of the literature on the utilization of NITs in the management of NAFLD for clinicians. Accordingly, a combination of available evidence and consensus-based expert opinion, without formal rating of the strength and quality of the evidence, was used to develop these best practice advice statements.
This Expert Review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. These best practice advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these best practice advice statements do not carry formal ratings of the quality of evidence or strength of the presented considerations.
Best Practice Advice Statements
NITs can be used for risk stratification in the diagnostic evaluation of patients with NAFLD.
A Fibrosis 4 Index score <1.3 is associated with strong negative predictive value for advanced hepatic fibrosis and may be useful for exclusion of advanced hepatic fibrosis in patients with NAFLD.
A combination of 2 or more NITs combining serum biomarkers and/or imaging-based biomarkers is preferred for staging and risk stratification of patients with NAFLD whose Fibrosis 4 Index score is >1.3.
Use of NITs in accordance with manufacturer’s specifications (eg, not in patients with ascites or pacemakers) can minimize risk of discordant results and adverse events.
NITs should be interpreted with context and consideration of pertinent clinical data (eg, physical examination, biochemical, radiographic, and endoscopic) to optimize positive predictive value in the identification of patients with advanced fibrosis.
Liver biopsy should be considered for patients with NIT results that are indeterminate or discordant; conflict with other clinical, laboratory, or radiologic findings; or when alternative etiologies for liver disease are suspected.
Serial longitudinal monitoring using NITs for assessment of disease progression or regression may inform clinical management (ie, response to lifestyle modification or therapeutic intervention).
Patients with NAFLD and NITs results suggestive of advanced fibrosis (F3) or cirrhosis (F4) should be considered for surveillance of liver complications (eg, hepatocellular carcinoma screening and variceal screening per Baveno criteria). Patients with NAFLD and NITs suggestive of advanced hepatic fibrosis (F3) or (F4), should be monitored with serial liver stiffness measurement; vibration controlled transient elastography; or magnetic resonance elastography, given its correlation with clinically significant portal hypertension and clinical decompensation.
A global research priority agenda to advance public health responses to fatty liver disease
2023, Journal of Hepatology
An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community.
Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy.
The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of ‘agree’ responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement (‘agree’ + ‘somewhat agree’); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% ‘agree’), 13 priorities had <80% ‘agree’, with greater reliance on ‘somewhat agree’ to achieve >90% combined agreement.
Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community’s efforts to advance and accelerate responses to this widespread and fast-growing public health threat.
An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat.
Healthcare and socioeconomic costs of NAFLD: A global framework to navigate the uncertainties
2023, Journal of Hepatology
Left unaddressed, non-alcoholic fatty liver disease (NAFLD) will continue to have substantial health, economic and social implications. To address the challenge, a paradigm shift is needed in the way NAFLD is conceptualised. Concerted, collaborative action across medical specialities, industry sectors and governments will be vital in tackling this public health threat. To drive this change, in this review, we present data on the current global healthcare and socioeconomic costs of NAFLD and highlight priority actions. The estimated healthcare costs of patients with NAFLD are nearly twice as high as their age-matched counterparts without the disease and are highest in those with advanced fibrosis and end-stage liver disease. NAFLD is accountable for the highest increase in DALYs (disability-adjusted life years) among all liver diseases globally. NAFLD and non-alcoholic steatohepatitis (NASH)-specific drug therapies are not yet available and there is considerable uncertainty regarding cost, optimal length of treatment, and their impact on liver-related outcomes and mortality. Among the currently available bariatric procedures, sleeve gastrectomy is reported to be the most cost-effective for NASH resolution. Gastric bypass remains very expensive, while data on bariatric endoscopy are limited. Lastly, we propose a global NAFLD/NASH investment framework to guide the development of achievable yet ambitious country-specific targets and strategic actions to optimise resource allocation and reduce the prevalence of NAFLD and NASH. Its focus on high-level inputs will be critical to enabling a political and financial environment that supports clinical-level implementation of NAFLD prevention, treatment and care efforts, across all settings.
Roles of Radiological Tests in Clinical Trials and the Clinical Management of Nonalcoholic Fatty Liver Disease
2023, Clinics in Liver Disease
AEEH «Consensus about detection and referral of hidden prevalent liver diseases»
2023, Gastroenterologia y Hepatologia
Noninvasive Fibrosis Testing in Chronic Liver Disease Including Caveats
2023, Clinics in Liver Disease
Citation Excerpt :
For example, FibroSure and Fibrospect II have reported average costs of $215 and $350, respectively.34 Excluding equipment costs and focusing on billed costs, a VCTE (FibroScan) costs approximately $140, whereas MRE is $481.35 The cost of ARFI and 2D-SWE likely approximates that of VCTE at approximately $150.36

View all citing articles on Scopus

: Conflicts of interest This author discloses the following: Naga Chalasani has consulted for NuSirt, AbbVie, Afimmune (DS Biopharma), Allergan (Tobira), Madrigal, Coherus, Siemens, La Jolla, Foresite Labs, and Genentech; has received research grant support from Exact Sciences, Intercept, and Galectin Therapeutics; and has served as a paid consultant to more than 35 pharmaceutical companies. The remaining authors disclose no conflicts.

^a: Authors share co-first authorship.

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Original ArticlePancreas, Biliary Tract, and LiverCost Effectiveness of Different Strategies for Detecting Cirrhosis in Patients With Nonalcoholic Fatty Liver Disease Based on United States Health Care System

Background & Aims

Methods

Results

Conclusions

Section snippets

Study Population

Model Structures

Low prevalence of cirrhosis (0.27%)

Discussion

Acknowledgments

CRediT Authorship Contributions

Gastroenterology

Gastroenterology

J Hepatol

J Hepatol

Hepatology

Hepatology

Gastroenterology

Clin Gastroenterol Hepatol

The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases

Hepatology

Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection

Hepatology

Performance characteristics of vibration-controlled transient elastography for evaluation of nonalcoholic fatty liver disease

Hepatology

Novel 3D magnetic resonance elastography for the noninvasive diagnosis of advanced fibrosis in NAFLD: a prospective study

Am J Gastroenterol

Magnetic resonance elastography predicts advanced fibrosis in patients with nonalcoholic fatty liver disease: a prospective study

Hepatology

Comparison of FIB-4 index, NAFLD fibrosis score and BARD score for prediction of advanced fibrosis in adult patients with non-alcoholic fatty liver disease: a meta-analysis study

Hepatol Res

Original Article
Pancreas, Biliary Tract, and Liver
Cost Effectiveness of Different Strategies for Detecting Cirrhosis in Patients With Nonalcoholic Fatty Liver Disease Based on United States Health Care System