AGA Clinical Practice Update on the Role of Noninvasive Biomarkers in the Evaluation and Management of Nonalcoholic Fatty Liver Disease: Expert Review

Gastroenterology, Год журнала: 2023, Номер 165(4), С. 1080 - 1088

Опубликована: Авг. 4, 2023

DescriptionThe purpose of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review is to provide clinicians with guidance on the use noninvasive tests (NITs) in evaluation and management patients nonalcoholic fatty liver disease (NAFLD). NAFLD affects nearly 30% global population a growing cause end-stage liver-related health care resource utilization. However, only minority all experience outcome. It therefore critically important for assess prognosis identify those increased risk progression negative clinical outcomes at time initial assessment. equally trajectory over time, particularly response currently available therapeutic approaches. The reference standard assessment monitoring histologic examination biopsy specimens. There are, however, many limitations biopsies their reading that have limited routine practice. utilization NITs facilitates stratification longitudinal NAFLD. This update provides best practice advice based review literature clinicians. Accordingly, combination evidence consensus-based expert opinion, without formal rating strength quality evidence, was used develop these statements.MethodsThis commissioned approved by AGA Institute Updates Committee Governing Board timely topic high importance membership underwent internal peer external through procedures Gastroenterology. These statements were drawn from published opinion. Because systematic reviews not performed, do carry ratings or presented considerations.Best Advice StatementsBest 1NITs can be diagnostic NAFLD.Best 2A Fibrosis 4 Index score <1.3 associated strong predictive value advanced hepatic fibrosis may useful exclusion 3A 2 more combining serum biomarkers and/or imaging-based preferred staging whose >1.3.Best 4Use accordance manufacturer's specifications (eg, ascites pacemakers) minimize discordant results adverse events.Best 5NITs should interpreted context consideration pertinent data physical examination, biochemical, radiographic, endoscopic) optimize positive identification fibrosis.Best 6Liver considered NIT are indeterminate discordant; conflict other clinical, laboratory, radiologic findings; when alternative etiologies suspected.Best 7Serial using regression inform (ie, lifestyle modification intervention).Best 8Patients suggestive (F3) cirrhosis (F4) surveillance complications hepatocellular carcinoma screening variceal per Baveno criteria). Patients (F4), monitored serial stiffness measurement; vibration controlled transient elastography; magnetic resonance elastography, given its correlation clinically significant portal hypertension decompensation. statements. considerations. Best Statements A >1.3. Use events. fibrosis. Liver suspected. Serial intervention). Nonalcoholic (NAFLD) an emerging public crisis. approximately worldwide population.1Younossi Z.M. Golabi P. Paik J.M. et al.The epidemiology steatohepatitis (NASH): review.Hepatology. 2023; 77: 1335-1347Crossref PubMed Scopus (230) Google Scholar As metabolic representing manifestation systemic disorder, morbidity mortality, as well substantial utilization.2Allen A.M. Lazarus J.V. Younossi Healthcare socioeconomic costs NAFLD: framework navigate uncertainties.J Hepatol. 79: 209-217Abstract Full Text PDF (20) Scholar,3Younossi Non-alcoholic - perspective.J 2019; 70: 531-544Abstract (1252) traditional approach defining severity has been perform grading necroinflammation fibrosis—2 key features severity. Disease activity refers biological processes leading injury inflammation, whereas stage amount scarring thus proximity cirrhosis. strongest predictor future greatest prognostic information. Natural history studies found fibrosis, specifically cirrhosis, serves meaningful surrogate outcomes, such (HCC), decompensation hemorrhage, ascites, encephalopathy), transplantation, death.3Younossi Scholar,4Angulo Kleiner D.E. Dam-Larsen S. al.Liver but no features, long-term disease.Gastroenterology. 2015; 149: 389-397.e10Abstract (2012) biopsies, invasive; variable sampling5Ratziu V. Charlotte F. Heurtier A. al.Sampling variability 2005; 128: 1898-1906Abstract (1630) Scholar; subject intra- interobserver variability; and, rarely, severe fatal procedural complications. impractical biopsy-based prevalent chronic Noninvasive emerged validated tools address problem early Guidance limited. We reviewed (AF) predict guide responses therapies. subcategorized into serum-based biomarkers. Multiple models biochemical measurements proposed detect focus will readily available, point-of-care, cost-effective testing strategies stratify AF. designed (BPA) several issues pertaining NITs. developed BPA 8 issues. journal represent current studied populations. undertaken upon confirmation diagnosis NAFLD, competing diagnoses, presenting signs symptoms good Furthermore, final patient must take unique having discussed "pros cons" Among (NASH) progression. Most experts believe development NASH fibrosis). Within gastroenterology practice, implemented knowledge presence patient's access engagement system, ability follow recommendations, effective extrahepatic also improve AF, defined 3 (bridging fibrosis) (cirrhosis) biopsy.6Sanyal A.J. Van Natta M.L. Clark J. al.Prospective study adults disease.N Engl J Med. 2021; 385: 1559-1569Crossref (347) synchronized across liver, stages 3–4 continuum Initial applied viral hepatitis,7Sterling R.K. Lissen E. Clumeck N. al.Development simple index HIV/HCV coinfection.Hepatology. 2006; 43: 1317-1325Crossref (3120) subsequently diseases, NAFLD.8McPherson Stewart S.F. Henderson al.Simple non-invasive scoring systems reliably exclude non-alcoholic disease.Gut. 2010; 59: 1265-1269Crossref (660) Several [FIB-4] score, [NAFLD-FS], aspartate aminotransferase platelet ratio [APRI]; FIB-4 most validated. calculated algorithm age, alanine aminotransferase, count7Sterling outperforms calculations low probability High values all-cause population-based studies.9Unalp-Arida Ruhl C.E. scores mortality United States population.Hepatology. 2017; 66: 84-95Crossref (145) Although does outperform proprietary FibroTest/FibroSure [eviCore Healthcare], FIBROSpect [Prometheus Laboratories], Hepamet Score, Pro-C3 [ADAPT], FibroMeter [ARUP Hepascore), recommended first-line practitioners simplicity cost.10Kanwal Shubrook J.H. Adams L.A. al.Clinical pathway 161: 1657-1669Abstract (186) Scholar, 11Cusi K. Isaacs Barb D. al.American Endocrinology Guideline Diagnosis Management Fatty Primary Care Settings: Co-Sponsored Study Diseases (AASLD).Endocr Pract. 2022; 28: 528-562Abstract (247) 12Rinella M.E. Neuschwander-Tetri B.A. Siddiqui M.S. al.AASLD disease.Hepatology. 1797-1835Crossref (238) Enhanced (ELF; Siemens Healthineers USA) test, blood test consisting elements involved matrix turnover, NIS2+™ (property GENFIT; Loos, France), optimization NIS4® France) technology, blood-based detection "at-risk" F2 higher, respectively. An ELF ≥9.8 identifies events.13Miele L. De Michele T. Marrone G. al.Enhanced reliable tool assessing setting.Int Biol Markers. 32: e397-e402Crossref (26) Scholar,14Guha I.N. Parkes Roderick al.Noninvasive markers disease: validating European Panel exploring markers.Hepatology. 2008; 47: 455-460Crossref (621) Such options secondary assessments elastography available. Imaging-based biomarkers, (VCTE), shear wave (SWE), (MRE), frequently Ultrasound-based 3-dimensional (Velacur) iron-corrected T1 imaging, although less frequently, technologies. Currently, there minimum cutoff established accuracy AF Using histology standard, meta-analysis 10 evaluated performance imaging NAFLD.15Xiao Zhu Xiao X. al.Comparison laboratory tests, ultrasound, meta-analysis.Hepatology. 1486-1501Crossref (569) absence 1.24–1.45 range 2759 demonstrated mean sensitivity 77.8% (range, 63.0%–90.0%), specificity 71.2% 55.5%–88.0%), (PPV) 40.3% 24.0%–50.6%), (NPV) 92.7% 88.0%–98.0%). threshold otherwise adapted being ideal NAFLD-FS –1.455 3057 had 72.9% 22.7%–96.0%), 73.8% 42.9%–100%), PPV 50.4% 24.0%–100%), NPV 91.8% 81.3%–98.1%).15Xiao APRI 1.00 1101 43.2% 27.0%–67.0%), 86.1% 81.0%–89.0%), 33.5% 26.0%–40.0%), 89.8% 84.0%–95.0%). FIB-4, NAFLD-FS, APRI), Performance improved NPV. 1.92–2.48 439 76.4% 72.7%–80.0%), 82.4% 76.0%–88.7%), 39.0% 37.5%–40.4%), 96.2% 95.5%–96.9%). –0.014 197 80%, 80.8%, 42.8%, 95.7%. For 0.54–2.00 790 patients, 56.2% 20.5%–77.3%), 83.6% 56.3%–100%), 37.8% 16.7%–100%), 91.7% 83.0%–96.7%). Despite some profile consistent concordance reassurance stratification16Morling J.R. Fallowfield J.A. Guha al.Using people type diabetes mellitus: Edinburgh study.J 2014; 60: 384-391Abstract (58) (Table 1).Table 1Noninvasive Tests Accuracy Advanced (F3–4) DiseaseNoninvasive testRecommended rule fibrosisAF biopsy, AUROC (95% CI)Serum score>2.670.83 (0.79–0.86) NAFLD-FS>0.6760.75 (0.71–0.79) APRI>0.840.76 (0.74–0.79) ELF>9.80.81 (0.77–0.85)Imaging VCTE, kPa>12.00.93 (0.89–0.96) SWE, kPa>8.00.89 (0.80–0.98) MRE, kPa>3.60.93 (0.90–0.96)AUROC, area under receiver operating curve. Open table new tab AUROC, Evaluation VCTE M-probe within same 1540 9 7.6–8 kPa 88.9% 65.0%–100.0%), 77.2% 65.9%–90.2%), 43.4% 27.0%–52.0%), 95.5% 86.0%–100%). XL-probe 5.7–9.3 579 75.3% 57.0%–91.0%), 74.0% 54.0%–90.0%), 58.7% 45.0%–71.0%), 88.7% 84.0%–93.0%). In similarly improved; 10.3–11.3 1362 87.7% 78.0%–100%), 86.3% 82.0%–90.0%), 46.8% 33.0%–75.0%), 98.0% 94.0%–100%). XL-probe, broader 7.2–16 654 87.8% (71.0%–100%), 82.0% (70.0%–91.0%), 39.8% 31.0%–53.0%), 97.8% 95.0%–100%). SWE MRE excellent cutoffs 3.02–10.6 among 429 89.9% 88.2%–91.5%), 90.0%–94.0%), 88.2% 83.3%–93.1%), 93.4% 92.6%–94.2%). 3.36 181 100%, 85.6%, 55.2%, 100%. 3.62–4.8 628 85.7% 74.5%–92.2%), 90.8% 86.9%–93.3%), 71.0% 67.9%–74.5%), 81.0%–98.1%). measurement (LSM) 4.15–6.7 384 86.6% 80.0%–90.9%), 91.4%–94.5%), 53.4% 44.4%–58.8%), 98.8% 98.1%–99.2%).15Xiao NAFLD,10Kanwal it if uncertainty exists, need concomitant cross-sectional techniques unavailable. goal algorithms establish confidence. Indeterminate require additional testing. NITs, reported curve, sensitivity, specificity. utility dependent prevalence target population. populations, endocrinology clinics, practices likely differ Shah al17Shah A.G. Lydecker Murray disease.Clin Gastroenterol 2009; 7: 1104-1112Abstract (999) compared 7 national database predominantly Caucasian subjects histologically confirmed Statistically differences between groups included female gender nondiabetic status earlier (F1–2) vs cohorts. <1.30 74% 71%, More importantly, 90% When predictively 96% 10% dropped 73% 50% prevalence. comparison follows, remember than functions prevalence, hence, specialty clinics general distinction. One notable limitation proportion populations.18Sun W. Cui H. Li index, BARD prediction adult study.Hepatol Res. 2016; 46: 862-870Crossref (160) this, 30%, reasonable choose augment individuals AF.f influenced age performs poorly younger 35 years older 65 years. alone, poor adults.19Mosca Della Volpe Alisi al.Non-invasive adolescents disease.Front Pediatr. 10885576Crossref (5) Scholar,20van Kleef Sonneveld M.J. de Man R.A. al.Poor elderly implications EASL guideline.J 76: 245-246Abstract (9) Given heterogeneity diverse overreliance 1 reduce identifying both primary specialist contexts. second biomarker, ELF, considered.12Rinella referral Kingdom determination comprehensive revealed benefit sequential testing.21Srivastava Gailer R. Tanwar disease.J 71: 371-378Abstract (271) Of 1452 years, 1022 (71.3%) F

Язык: Английский

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A global research priority agenda to advance public health responses to fatty liver disease

Journal of Hepatology, Год журнала: 2023, Номер 79(3), С. 618 - 634

Опубликована: Июнь 20, 2023

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 this are profound. This study aimed develop an aligned, prioritised research agenda for global community.

Язык: Английский

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Epidemiology of Metabolic Dysfunction Associated Steatotic Liver Disease

Clinical and Molecular Hepatology, Год журнала: 2024, Номер unknown

Опубликована: Авг. 19, 2024

As the rates of obesity and type 2 diabetes (T2D) continue to increase globally, so does prevalence metabolic dysfunction associated steatotic liver disease (MASLD). Currently, 38% all adults 7-14% children adolescents have MASLD. By 2040, MASLD rate for is projected over 55%. Although many with will not develop progressive disease, given vast number patients MASLD, it has now become top indication transplant in United States those hepatocellular carcinoma (HCC) women. However, most common cause mortality among remains death cardiovascular diseases. In addition outcomes (cirrhosis HCC), increased risk developing de-novo T2D, chronic kidney sarcopenia extrahepatic cancers. Furthermore, decreased health related quality life, work productivity, fatigue healthcare resource utilization substantial economic burden. Similar other lifestyle interventions heathy diet physical activity remain cornerstone managing these patients. a T2D drugs are available treat co-morbid Resmetirom only MASH-targeted medication that was recently approved by Federal Drug Administration use stage 2-3 fibrosis. The following review provides an overview epidemiology, its factors demonstrates without further global initiatives, may increase.

Язык: Английский

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Steatotic liver disease

The Lancet, Год журнала: 2024, Номер 404(10464), С. 1761 - 1778

Опубликована: Ноя. 1, 2024

Язык: Английский

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Disparities in metabolic dysfunction-associated steatotic liver disease and cardiometabolic conditions in low and lower middle-income countries: a systematic analysis from the global burden of disease study 2019

Metabolism, Год журнала: 2024, Номер 158, С. 155958 - 155958

Опубликована: Июнь 26, 2024

Язык: Английский

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The pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 10, 2024

Abstract Lanifibranor, a pan-PPAR agonist, improves liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH), who have poor cardiometabolic health (CMH) and cardiovascular events as major mortality cause. NATIVE trial secondary exploratory outcomes (ClinicalTrials.gov NCT03008070) were analyzed for the effect of lanifibranor on IR, lipid glucose metabolism, systemic inflammation, blood pressure (BP), hepatic steatosis (imaging histological grading) all original analysis. With lanifibranor, triglycerides, HDL-C, apolipoproteins, insulin, HOMA-IR, HbA1c, fasting (FG), hs-CRP, ferritin, diastolic BP improved significantly, independent diabetes status: most prediabetes returned to normal FG levels. Significant adiponectin increases correlated CMH marker improvement; had an average weight gain 2.5 kg, 49% gaining ≥2.5% weight. Therapeutic benefits similar regardless change. Here, we show that effects MASH are accompanied improvement, indicative potential clinical benefits.

Язык: Английский

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Metabolic dysfunction-associated steatotic liver disease in adults

Nature Reviews Disease Primers, Год журнала: 2025, Номер 11(1)

Опубликована: Март 6, 2025

Язык: Английский

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Modeling the Health and Economic Impact of Pharmacologic Therapies for MASLD in the United States

Journal of Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Steatotic Liver Disease: Metabolic Dysfunction, Alcohol, or Both?

Biomedicines, Год журнала: 2023, Номер 11(8), С. 2108 - 2108

Опубликована: Июль 26, 2023

Non-alcoholic fatty liver disease (NAFLD) and alcohol-related (ALD), both of them accounting for (FLD), are among the most common chronic diseases globally, contributing to substantial public health burden. Both NAFLD ALD share a similar picture clinical presentation yet may have differences in prognosis treatment, which renders early accurate diagnosis difficult but necessary. While is fastest increasing disease, prevalence has seemingly remained stable recent years. Lately, term steatotic (SLD) been introduced, replacing FLD reduce stigma. SLD represents an overarching primarily comprise metabolic dysfunction-associated (MASLD), formerly known as non-alcoholic (NAFLD), well MetALD, defined continuum across contribution MASLD varies. The present review discusses current knowledge on denominators NAFLD/MASLD order highlight research needs improve our understanding SLD.

Язык: Английский

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A global action agenda for turning the tide on fatty liver disease

Hepatology, Год журнала: 2023, Номер 79(2), С. 502 - 523

Опубликована: Авг. 4, 2023

Background and Aims: Fatty liver disease is a major public health threat due to its very high prevalence related morbidity mortality. Focused dedicated interventions are urgently needed target prevention, treatment, care. Approach Results: We developed an aligned, prioritized action agenda for the global fatty community of practice. Following Delphi methodology over 2 rounds, large panel (R1 n = 344, R2 288) reviewed priorities using Qualtrics XM, indicating agreement 4-point Likert-scale providing written feedback. Priorities were revised between in R2, panelists also ranked within 6 domains: epidemiology, treatment care, models education awareness, patient perspectives, leadership policy. The consensus encompasses 29 priorities. In mean percentage “agree” responses was 82.4%, with all individual having at least super-majority (> 66.7% “agree”). highest-ranked included collaboration specialists primary care doctors on early diagnosis, address needs people living multiple morbidities, incorporation into relevant non-communicable strategies guidance. Conclusions: This consensus-driven multidisciplinary by providers, clinical researchers, policy experts provides path reduce improve outcomes. To implement this agenda, concerted efforts will be global, regional, national levels.

Язык: Английский

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