AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease

Hepatology, Journal Year: 2023, Volume and Issue: 77(5), P. 1797 - 1835

Published: Feb. 2, 2023

PREAMBLE The study of NAFLD has intensified significantly, with more than 1400 publications since 2018, when the last American Association for Study Liver Diseases (AASLD) Guidance document was published.1 This new AASLD reflects many advances in field pertinent to any practitioner caring patients and emphasizes noninvasive risk stratification therapeutics. A separate guideline focused on management context diabetes been written jointly by Clinical Endocrinology AASLD.2 Given significant growth pediatric NAFLD, it will not be covered here allow a robust discussion diagnosis upcoming Pediatric Guidance. "Guidance" differs from "Guideline" that is bound Grading Recommendations, Assessment Development Evaluation system. Thus, actionable statements rather formal recommendations are provided herein. highest available level evidence used develop these statements, and, where high-level available, expert opinion guidance inform clinical practice. Key points highlight important concepts relevant understanding disease its management. most profound practice biomarkers Biomarkers tests (NITs) can clinically either exclude advanced diseases or identify those high probability cirrhosis.3,4 NIT "cut points" vary populations studied, underlying severity, setting. Those proposed this meant aid decision-making clinic interpreted isolation. Identifying "at-risk" NASH (biopsy-proven stage 2 higher fibrosis) recent area interest. Although definitive staging remain linked histology, tools now assess likelihood fibrosis, predict progression decompensation, make decisions, some degree, response treatment. There an ongoing debate over nomenclature fatty liver disease, which had finalized at time published. At culmination rigorous consensus process, intended change advance without negative impact awareness, trial endpoints, drug development/approval process. Furthermore, should emergence newly recognized subtypes address heterogeneity, including role alcohol, therapy. Input central all stages process ensure minimization nomenclature-related stigma. DEFINITIONS overarching term includes grades refers population ≥5% hepatocytes display macrovesicular steatosis absence readily identified alternative cause (eg, medications, starvation, monogenic disorders) individuals who drink little no alcohol (defined as < 20 g/d women <30 men). spectrum NAFL, characterized hepatic may accompanied mild inflammation, NASH, additionally presence inflammation cellular injury (ballooning), finally cirrhosis, bands fibrous septa leading formation cirrhotic nodules, earlier features longer fully appreciated biopsy. UPDATE ON EPIDEMIOLOGY AND NATURAL HISTORY prevalence rising worldwide parallel increases obesity metabolic comorbid (insulin resistance, dyslipidemia, obesity, hypertension).5,6 adults estimated 25%–30% general population7–9 varies setting, race/ethnicity, geographic region studied but often remains undiagnosed.10–14 associated economic burden attributable substantial.15–17 challenging determine certainty; however, 14% asymptomatic undergoing colon cancer screening.14 also highlights publication prior prospective study,18 fibrosis (stage increased >2-fold. supported projected rise 2030, defined bridging (F3) compensated cirrhosis (F4), increase disproportionately, mirroring doubling NASH.5,19 As such, incidence HCC, death related likewise expected 2- 3-fold 2030.5 further, NASH-related already indication transplantation >65 years age par overall.20–22 Natural history Data meta-analyses pooled studies demonstrate steatohepatitis primary predictors progression.23–25 collinearity between induces makes independent contribution adverse outcomes multivariable analyses.26,27 determinant outcomes, liver-related morbidity mortality nonhepatic malignancy observed even initial biopsy.25 Nevertheless, least (F2), referred have demonstrably mortality.24,28 Fibrosis influenced factors such severity genomic profile, environmental factors. meta-analysis placebo-treated 35 trials found minimal progression, suggesting nonpharmacologic (frequent visits/monitoring, dietary lifestyle counseling, changes) reduce progression.29 An cohorts longitudinal paired biopsies30 demonstrated rate one per 7 versus 14 NAFL.30 determined biopsy noninvasively, because changes require biannual screening HCC well varices monitoring signs symptoms decompensation.31,32 Among decompensation ranges 3% 20% year.12,33–35 common causes overall cardiovascular (CVD) malignancy, followed disease. amount histologically strongly development death.24,26,36,37 Bridging exponentially greater fibrosis.23,24,35 In 1773 patients, all-cause 0–2 0.32 100 person-years, compared 0.89 person-years 1.76 cirrhosis. After correcting multiple factors, (HR, 6.8; 95% CI, 2.2–21.3).35 Cirrhosis regression 6-fold reduction events trials.38Key points: Patients F2–4 considered NASH. rates depending baseline genetic, individual environmental, determinants. CVD malignancies fibrosis; predominates fibrosis. MOLECULAR CELLULAR PATHOGENESIS NAFL substantially govern supply disposition acids, diacylglycerols, ceramides, cholesterol, phospholipids, other intrahepatic lipids. Energy oversupply limited adipose tissue expansion contribute insulin resistance disease.39 When energy intake exceeds needs disposal capacity, carbohydrates, form sugars fructose, sucrose, glucose), drive accumulation fat de novo lipogenesis (DNL).40,41 substantial interindividual heterogeneity DNL among NAFLD.42,43 addition, type consumed plays saturated unsaturated consumption (Figure 1).44–46FIGURE 1: Pathogenic drivers therapeutic targets. Overview major mechanisms lead phenotype consequences, leveraged therapeutically. Not shown areas genetic polymorphisms play modifying types fats [saturated vs. polyunsaturated acid (PUFA)], gut microbiome, uric acid, periodic hypoxia (sleep apnea) influence pathways. driver adipocytes their ability store triglyceride inducing cell stress exceeded, activates inflammatory pathways resistance. Understanding facilitates rational therapies Specific sites intervention might prevent resolve include interventions modulate food portion sizes, bariatric surgery, satiety regulators), exercise, thermogenesis), improve adipocyte sensitivity [eg, peroxisome proliferator-activated receptor (PPAR)γ ligands], impair acetyl-coenzyme carboxylase synthase inhibitors), oxidative metabolism (PPARα ligands thyroid hormone beta agonists), attenuate death, fibrogenesis. Therapeutic agents affecting throughout body potential beneficial effects peptide analogs fibroblast factor-19, factor-21, glucagon-like peptide-1, gastric inhibitory peptide, glucagon) nuclear drugs target PPARα, PPARδ, PPARγ, β, farnesoid X receptor. Abbreviations: ER, endoplasmic reticulum; CVD, disease.Insulin nearly universal present liver, tissue, muscle.47 Adipose release free acids (lipolysis) fasting state48 worsens NASH.39,47,49 Important frequency intensity activation brown energy-consuming thermogenic phenotype, counterregulatory diminish reductions calorie intake.39,50 desire engage regular exercise personal, community, corporate, societal, legislative thus roles contributing pathophysiology impeded diagnostic therapeutics.51 driven substrate overload heavily impacting hepatocyte lipid handling.43 Genetic I148M polymorphism PNPLA3 impairs lipolysis droplets,52 proteins transmembrane 6 superfamily member (TM6SF2), cholesterol metabolism,53 MBOAT7, influences phospholipid metabolism.54 Recently, loss-of-function variants HSD17B13, gene encodes enzyme localizes droplets hepatocytes, protection against progressive HCC.55 Rare mutations CIDEB, protein needed DNL,56 protective.57 host additional review beyond scope guidance, activity progression.49,58–63 Additional production, exposure products derived perhaps low magnesium levels, phenotype.64–69 Transcriptomic profiling large further our progression.70,71 lipotoxic recruitment resident macrophages, contributes hepatocellular stellate part complex interplay types.60,72,73 markers consistent finding pathogenesis humans uncertain.74Key Fundamental elements imbalance nutrient delivery utilization coupled dysfunction. Interindividual differences dietary, behavioral, course. Systemic particularly stemming dysfunctional progression. Insulin promotes COMORBID CONDITIONS ASSOCIATED WITH closely precedes abnormalities hypertension).47,61,75–77 Having several confers histological mortality.8,47,78–81 association comorbidities reflect bidirectional interactions endocrine organs pancreas, muscle) through secretion hepatokines regulate metabolism, action, glucose metabolism,82–88 adipokines, myokines.39,89,90 Obesity progression.91–93 Body distribution contributory (Table 1). Android distribution, truncal subcutaneous visceral irrespective mass index (BMI).94–99 contrast, gynoid predominantly hips buttocks, appears protective NAFLD.39,100 Visceral fat, metabolically active mediates majority risk.101–105 becomes stressed, dysfunctional, inflamed, signaling progressively impaired, promoting inappropriate inflammation.47,106,107 TABLE 1 - Initial evaluation patient History Weight history; medical comorbidities; current medications; family T2DM, cirrhosis; OSA; use, amount, pattern duration Physical examination android gynoid, lipodystrophic), dorsal-cervical pad, acanthosis nigricans), firm splenomegaly, prominent abdominal veins, ascites, gynecomastia, spider angiomata, palmar erythema) Laboratory Hepatic panel, CBC platelets, plasma glycated hemoglobin (A1c), creatinine urine microalbumin ratio, hepatitis C if previously screened. Consider appropriate steatosis/steatohepatitis (). elevated chemistries present: autoimmune serologies, transferrin saturation, ceruloplasmin, alpha-1 antitrypsin genotype, CBC, complete blood count; OSA, obstructive sleep apnea; mellitus. Type mellitus (T2DM) T2DM impactful factor HCC.108–111 pathogenic both surprising (ranging 30% 75%)10,112,113 developing fibrosis.93,114–117 T2DM. there length biases, underscore strong relationship NAFLD. epidemiological studies. Early course, sensitivity,47 overt diabetes. 5-fold incident diabetes,75,118–121 therefore, screened progresses, so does failure, making manage.107 glycemic control NAFLD/NASH controversial, small showing poor fibrosis,68,122 whereas corroborated finding.116,117,123 described diabetes, much lower coexistent BMI).124,125 Hypertension commonly hypertension across spectrum, 6.5 early 14.5 cirrhosis.35 clearly additive respect NASH126,127 progression.30 Whether mechanistically inverse, manifestations drivers, established.128,129 Dyslipidemia twice likely exhibit NAFLD,120 serum subfractions atherogenic NAFLD.130,131 resolution improved HDL levels favorably lipoprotein subfractions, although unclear what extent mechanism intervention.132–134 progress they continue coronary artery disease135 despite normalization lipids lipoproteins due synthetic failure.130,136 Management dyslipidemia use moderate-intensity high-intensity statins first-line therapy based atherosclerotic scores. Combination hypolipemic agents, ezetimibe, PCSK-9 inhibitors, inclisiran, bempedoic fibrates, omega 3 icosapent ethyl, monotherapy statin achieve goals. Statins safe demonstrable mortality.137–140 However, practice, underused extensive data demonstrating safety, cirrhosis.141–144 future risk, confirmatory needed.138 safely decompensated statin-induced population,144 caution warranted. transplantation, careful monitoring.136 severely triglycerides >500 mg/dL), combination fibrates prescription grade omega-3 pancreatitis. Fibrates concentrations ≥200 mg/dL HDL-C <40 mg/dL. high-risk individuals, ethyl indicated adjunct risk. Pioglitazone optimization concomitant benefits profile. Caution taken myopathy. Obstructive apnea (OSA) OSA NAFLD,145 suggest histology.146–151 Intermittent hypoxia, critical consequence mitochondrial dysfunction,145 dysregulation metabolism,152,153 worse resistance,154–156 DNL.157 overweight obese polysomnography NAFLD158; independently drives unclear. exists heart arrhythmias, atrial fibrillation.159–167 Perturbed endothelial function, higher-risk nature lesions, impaired ischemic compensatory support link CVD.130,168–170 prospectively observational cohort, cardiac same stages; number relatively low.35 Optimizing goal reducing improving NAFLD.36,171,172 Aggressively treating conditions hypertension, hyperglycemia smoking cessation recommended decrease risk.173 Chronic kidney (CKD) cross-sectional (n=28,000 individuals) 2-fold CKD.174 overall, specifically, microvascular diabetic complications, especially CKD.175,176 Recently published CRN CKD stages.35 determined.Guidance statements: 1. 2. Limited exist safety efficacy could 3. Hypertriglyceridemia managed supplementation fibrates. 4. 5. Prevalence Death thus, adherence age-appropriate survival. INITIAL EVALUATION OF PATIENT incidentally noted imaging chemistries. It note normal values laboratories true alanine aminotransferase (ALT) 29 33 U/L men 19 25 women.177 comorbidities, assessment intake, exclusion physical profile atypical comorbidities) additional/alternate etiologies, less excluded 2). fibrosing isolation explain exaggerated specific contexts 2).178 Several exacerbate during 3). gene-based currently familial aggregation supports gene-environment fibrosis.209,210 consider testing Condition scenario Diagnostic test Treatment Hypobetalipoproteinemia Low LDL, triglycerides, malabsorption ApoB level, (MTTP, PCSK-9) Low-fat diet, fat-soluble vitamin LAL deficiency Markedly LDL-C HDL-C, xanthelasma, hypersplenism, young age, predominately microvesicular Enzyme assay, replacement Nutrient carnitine, choline) Anorexia, short bowel, bypass surgeries Supplementation Wilson Younger neuropsychiatric symptoms, alkaline phosphatase, ceruloplasmin 24-h copper; quantitative copper Chelation Celiac Iron deficiency, pain, bloating, D bone loss, diarrhea, dermatitis herpetiformis Tissue transglutaminase IgA, duodenal Gluten-free diet ApoB, apolipoprotein B; high-density cholesterol; immunoglobulin A; LAL, lysosomal lipase; LDL-C, LDL cholesterol. Drugs mechanistic links Drug Mechanism Histological References Amiodarone Promotion DNL, impairment β-oxidation steatohepatitis, phospholipidosis, 179–184 5-FU Accumulation catabolites capacity metabolize 185–188 Irinotecan Induces dysfunction, autophagy Steatohepatitis 189–194 Tamoxifen Estrogen modulator, promotion β-oxidation. *May Steatosis 195–203 Methotrexate Mitochondrial (inhibits electron transport chain), canals Hering Steatosis, 204–206 Corticosteroids Exacerbation

Language: Английский

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EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD)

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 81(3), P. 492 - 542

Published: June 7, 2024

Language: Английский

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Impact of non-invasive biomarkers on hepatology practice: Past, present and future

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 76(6), P. 1362 - 1378

Published: May 16, 2022

Language: Английский

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Breakthroughs in therapies for NASH and remaining challenges

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 76(6), P. 1263 - 1278

Published: May 16, 2022

Language: Английский

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

Gastroenterology, Journal Year: 2023, Volume and Issue: 165(4), P. 1080 - 1088

Published: Aug. 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

Language: Английский

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Non-alcoholic fatty liver disease: pathophysiological concepts and treatment options

Cardiovascular Research, Journal Year: 2023, Volume and Issue: 119(9), P. 1787 - 1798

Published: June 26, 2023

Abstract The prevalence of non-alcoholic fatty liver disease (NAFLD) is continually increasing due to the global obesity epidemic. NAFLD comprises a systemic metabolic accompanied frequently by insulin resistance and hepatic inflammation. Whereas simple steatosis most common manifestation, more progressive course characterized fibrosis inflammation (i.e. steatohepatitis) present in 10–20% affected individuals. furthermore progresses substantial number patients towards cirrhosis hepatocellular carcinoma. this now affects almost 25% world’s population mainly observed type 2 diabetes, also lean Pathophysiology involves lipotoxicity, immune disturbances resistance, gut dysbiosis, commonly defining disorder prototypic disorder. Not surprisingly many have other manifestations, indeed cardiovascular disease, chronic kidney extrahepatic malignancies are all contributing substantially patient outcome. Weight loss lifestyle change reflect cornerstone treatment, several medical treatment options currently under investigation. promising strategies include glucagon-like peptide 1 receptor antagonists, sodium–glucose transporter inhibitors, Fibroblast Growth Factor analogues, Farnesoid X agonists, peroxisome proliferator–activated agonists. Here, we review epidemiology, pathophysiology, therapeutic for NAFLD.

Language: Английский

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Noninvasive Assessment of Liver Fibrosis in NAFLD

Clinical Gastroenterology and Hepatology, Journal Year: 2023, Volume and Issue: 21(8), P. 2026 - 2039

Published: April 14, 2023

Language: Английский

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Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease

JAMA, Journal Year: 2024, Volume and Issue: 331(15), P. 1287 - 1287

Published: March 21, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic worldwide. It important to develop noninvasive tests assess severity and prognosis.

Language: Английский

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EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Obesity Facts, Journal Year: 2024, Volume and Issue: 17(4), P. 374 - 444

Published: Jan. 1, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty (NAFLD), is defined as (SLD) in the presence of one or more cardiometabolic risk factor(s) and absence harmful alcohol intake. The spectrum MASLD includes steatosis, metabolic steatohepatitis (MASH, NASH), fibrosis, cirrhosis MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis treatment for MASLD. Case-finding strategies with using non-invasive tests, should be applied individuals factors, abnormal enzymes, and/or radiological signs hepatic particularly type 2 diabetes (T2D) obesity additional factor(s). A stepwise approach blood-based scores (such FIB-4) and, sequentially, imaging techniques transient elastography) suitable to rule-out/in advanced which predictive liver-related outcomes. In adults MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise discouraging consumption well optimal management comorbidities use incretin-based therapies (e.g. semaglutide, tirzepatide) T2D obesity, if indicated advised. Bariatric surgery also option obesity. If locally approved dependent label, non-cirrhotic MASH significant fibrosis (stage ≥2) considered a MASH-targeted resmetirom, demonstrated histological effectiveness acceptable safety tolerability profile. No pharmacotherapy can currently recommended cirrhotic stage. Management adaptations drugs, nutritional counselling, surveillance portal hypertension HCC, transplantation decompensated cirrhosis.

Language: Английский

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Liver disease is a significant risk factor for cardiovascular outcomes – A UK Biobank study

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 79(5), P. 1085 - 1095

Published: June 20, 2023

•Liver disease on cT1 MRI is associated with a high risk of CVD events, CVD-related hospitalization, and all-cause mortality.•The association between liver independent function tests, fibrosis metabolic risk.•Risk events increased even in the early stages chronic disease. Background & AimsChronic (CLD) cardiovascular (CVD) risk. We investigated whether signs (measured by iron-corrected T1-mapping [cT1]) were an major events.MethodsLiver activity (cT1) fat (proton density fraction [PDFF]) measured using LiverMultiScan® January 2016 February 2020 UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations (MRI) primary (coronary artery disease, atrial fibrillation [AF], embolism/vascular heart failure [HF] stroke), hospitalisation mortality. Liver blood biomarkers, general metabolism demographics also included. Subgroup analysis was conducted those without syndrome (defined as at least three of: large waist, triglycerides, low high-density lipoprotein cholesterol, systolic pressure, or elevated haemoglobin A1c).ResultsA total 33,616 participants (mean age 65 years, mean BMI 26 kg/m2, A1c 35 mmol/mol) had complete data linked clinical outcomes (median time to event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 1.1-5.2]). (cT1), but not (PDFF), higher any (hazard ratio 1.14; 95% CI 1.03–1.26; p = 0.008), AF (1.30; 1.12–1.51; <0.001); HF 1.09–1.56; 0.004); (1.27; 1.18-1.37; <0.001) mortality (1.19; 1.02–1.38; 0.026). FIB-4 index (1.06; 1.01–1.10; 0.007). Risk independently individuals (1.26; 1.13-1.4; <0.001).ConclusionLiver activity, cT1, incident mortality, pre-existing syndrome, fat.Impact implicationsChronic twofold greater incidence Our work shows that T1 mapping (14%), (27%) (19%). These findings highlight prognostic relevance comprehensive evaluation health populations and/or CLD, absence manifestations when there opportunity modify/address factors prevent progression. As such, they are relevant patients, carers, clinicians, policymakers. Chronic events. A1c). A <0.001). fat.

Language: Английский

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