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

Hepatology, Journal Year: 2017, Volume and Issue: 67(1), P. 328 - 357

Published: July 17, 2017

Potential conflict of interest: Dr. Chalasani consults for and received grants from Eli Lilly. He NuSirt, AbbVie, Afimmune, Tobira, Madrigal, Shire, Cempra, Ardelyx, Axovant, Amarin. Intercept, Gilead, Galectin, Cumberland. Younossi Bristol‐Myers Squibb, Allergan, GlaxoSmithKline. advises Vertex Janssen. Brunt Gilead. Charlton NGM Bio, Genfit, Novartis. Conatus. Cusi Novo Nordisk. Tobira. Cirius, Novartis, Janssen, Zydus, Nordic, Rinella Nusirt. She Fibrogen, Immuron, Enanta, AbbVie. Harrison Echosens, Prometheus, Perspectum, HistoIndex. Garland, Pfizer. is on the speakers' bureau Alexion. Sanyal Salix, Conatus, malinckrodt, Echosens‐Sandhill, Sequana. employed by Bio. owns stock in GenFit, Hemoshear, Durect, Indalo. Pfizer, Boehringer Ingleheim, Nimbus, Nitto Denko, Lilly, Nordisk, Fractyl, Chemomab, Affimmune, Teva, Ardelyx. Squibb Merck. royalties UptoDate. Exhalenz, Arkana, NewCo LLC. The funding development this Practice Guidance was provided American Association Study Liver Diseases. This practice guidance approved Diseases June 15, 2017. Preamble provides a data‐supported approach to diagnostic, therapeutic, preventive aspects nonalcoholic fatty liver disease (NAFLD) care. A "Guidance" document different "Guideline." Guidelines are developed multidisciplinary panel experts rate quality (level) evidence strength each recommendation using Grading Recommendations, Assessment Development, Evaluation system. topic, statements, not recommendations, put forward help clinicians understand implement most recent evidence. commissioned (AASLD) an update Guideline published 2012 conjunction with Gastroenterology College (ACG).1 Sections where there have been no notable newer publications modified, so some paragraphs remain unchanged. narrative review statements based following: (1) formal analysis recently world literature topic (Medline search up August 2016); (2) Physicians' Manual Assessing Health Practices Designing Guidelines2; (3) guideline policies AASLD; (4) experience authors independent reviewers regard NAFLD. intended use physicians other health professionals. As clinically appropriate, should be tailored individual patients. Specific whenever possible, and, when such available or inconsistent, made consensus opinion authors.3 rather than article, interested readers can refer several comprehensive reviews.4 Because lengthy, make it easier reader, list all recommendations tabular form as Supporting Table S1. Definitions For defining NAFLD, must hepatic steatosis (HS), either imaging histology, lack secondary causes fat accumulation significant alcohol consumption, long‐term steatogenic medication, monogenic hereditary disorders (Table 1). In majority patients, NAFLD commonly associated metabolic comorbidities obesity, diabetes mellitus, dyslipidemia. categorized histologically into (NAFL) steatohepatitis (NASH; 2). NAFL defined presence ≥5% HS without hepatocellular injury hepatocyte ballooning. NASH inflammation (e.g., ballooning), any fibrosis. "advanced" fibrosis, will referring specifically stages 3 4, that is, bridging fibrosis cirrhosis. 1 - Common Causes Secondary Macrovesicular ‐ Excessive consumption Hepatitis C (genotype 3) WD Lipodystrophy Starvation Parenteral nutrition Abetalipoproteinemia Medications mipomersen, lomitapide, amiodarone, methotrexate, tamoxifen, corticosteroids) Microvesicular Reye's syndrome (valproate, antiretroviral medicines) Acute pregnancy HELLP Inborn errors metabolism lecithin‐cholesterol acyltransferase deficiency, cholesterol ester storage disease, Wolman's disease) 2 Related Encompasses entire spectrum FLD individuals ranging SH cirrhosis Presence ballooning hepatocytes risk progression failure considered minimal. (ballooning) progress cirrhosis, failure, rarely cancer. current previous histological Cryptogenic obvious etiology. Patients cryptogenic heavily enriched factors obesity MetS. NAS An unweighted composite steatosis, lobular inflammation, scores. useful tool measure changes histology patients clinical trials. Fibrosis scored separately.126 SAF score semiquantitative consisting amount, activity (lobular plus fibrosis.130 Incidence Prevalence General Population INCIDENCE OF There paucity data regarding incidence general population. few studies reported Asian countries, which briefly summarized below: study followed 11,448 subjects 5 years, documented ultrasound 12% (n = 1,418).10 635 Nagasaki atomic bomb survivors who were 11.6 19.9 per 1,000 person‐years.11 565 subjects, at 3‐5 diagnosed magnetic resonance (MR) (MRI) transient elastography (TE), estimated 13.5% (34 person‐years).12 cohort study, 77,425 free baseline average 4.5 years. During 348,193.5 person‐years follow‐up, 10,340 participants ultrasound, translating 29.7 person‐years.13 rates population Western countries even less reported: England International Classification Diseases, Tenth Revision (ICD‐10) codes 29 100,000 person‐years. Given inaccuracy administrative coding ICD‐10, likely underestimates true NAFLD.14 Israel 28 person‐years.15 meta‐analysis pooled regional Asia 52.34 (95% confidence interval [CI], 28.31‐96.77) whereas West around CI, 19.34‐40.57).16 PREVALENCE contrast data, significantly higher number describing prevalence These epidemiology NAFLD: overall global 25.24% 22.10‐28.65).16 highest Middle East (31.79% [95% 13.48‐58.23]) South America (30.45% 22.74‐39.440]) lowest Africa (13.48% [5.69‐28.69]).16 described elsewhere, gold standard diagnosing remains biopsy. biopsy feasible population, direct assessment NASH. Nevertheless, attempts estimate indirect means.16 following paragraphs: among had "clinical indication" 59.10% 47.55‐69.73).16 specific (random living‐related donors, etc.) 6.67% 2.17‐18.73) 29.85% 22.72‐38.12).16 these estimates, one estimates ranges between 1.5% 6.45%.16 High‐Risk Groups Features (MetS) only highly prevalent but components MetS also increase developing NAFLD.16 bidirectional association has strongly established. context, established conditions (obesity, type diabetes, hypertension, dyslipidemia) emerging (sleep apnea, colorectal cancer, osteoporosis, psoriasis, endocrinopathies, polycystic ovary obesity) NAFLD.21 Obesity (excessive body mass index [BMI] visceral common well‐documented factor fact, overweight obese severely obese, (>95%) severe undergoing bariatric surgery NAFLD.23 Type mellitus (T2DM): very high T2DM. suggested third two thirds diabetic NAFLD.18 It important remember importance T2DM develop almost simultaneously patient, confounds its causal relationship require additional investigation.28 Dyslipidemia: High serum triglyceride (TG) levels low high‐density lipoprotein (HDL) dyslipidemia attending lipid clinics 50%.29 large, cross‐sectional conducted 44,767 Taiwanese attended single clinic, enrollees stratified four subgroups their total HDL‐cholesterol TG ratios. 53.76%; however, those ratios 33.41%, group 78.04%. Age, sex, ethnicity: may vary according age, ethnicity.31 both stage appear age.34 Risk Factors Associated With Conditions Established Other Hypothyroidism Obstructive sleep apnea Dyslipidemia Hypopituitarism MetSa Hypogonadism Polycystic Pancreatoduodenal resection Psoriasis aThe Adult Treatment Panel III definition requires three more features: waist circumference greater 102 cm men 88 women; level 150 mg/dL greater; HDL 40 50 systolic blood pressure 130 mm Hg diastolic 85 (5) fasting plasma glucose 110 greater.287 Although controversial, male sex Furthermore, times women.33 issues ethnicity impact evolved over initial reports compared non‐Hispanic whites, Hispanic blacks lower NAFLD.39 American‐Indian Alaskan‐Native populations seem (0.6%‐2.2%), need confirmed.31 intriguing suggest ethnic differences explained genetic variation related patatin‐like phospholipase domain‐containing protein (PNPLA‐3) gene.40 summary, varies across world, 28.01 19.34‐40.57) 28.31‐96.77). Natural History Outcomes Over past decades, natural history NAFLD.1 growing NASH, especially degree adverse outcomes liver‐related mortality.1 shown increased mortality matched control NAFLD.53 cause death cardiovascular (CVD), comorbidities. 12th leading second NAFLD.55 Cancer‐related top rate.56 meta‐analysis, liver‐specific determined 0.77 (range, 0.33‐1.77) 11.77 7.10‐19.53) 15.44 11.72‐20.34) 25.56 6.29‐103.80), respectively.16 1.94 1.28‐2.92) 1.05 0.70‐1.56), feature fibrosis; specifically, zone sinusoidal periportal (stage 2) advanced (bridging [stage 3] 4]). independently predictive mortality.44 now third‐most carcinoma (HCC) United States, attributed enormous condition.60 epidemic NAFLD‐related HCC 9% annual rate.61 older, shorter survival time, often heart die primary cancer patients.60 Around 13% Veteran Administration did Among factors, having absence confirms small cirrhosis.62 recognize what "burned out" NAFLD.63 particular disproportionately (T2DM, MetS) resemble pathological seldom features consistent cirrhosis.63 Important One surrogates documentation progressive (HF). HF showed mean 0.09 0.06‐0.12).16 Several investigated comparison hepatitis cirrhosis.9 prospective, U.S.‐based observed decompensation cirrhosis.65 However, international 247 cirrhosis) duration 85.6 ± 54.5 months 10‐year 81.5%—a cirrhosis.1 confirmed increasing numbers presenting requiring transplantation (LT). ranked second‐most LT overtake future, virus (HCV) treated curative antiviral regimens.9 noted previously, another important, outcome HCC. 0.44 0.29‐0.66) person‐years.16 HCC, 54.9% cases HCV, 16.4% alcoholic 14.1% 9.5% B virus. given extremely large within population.61 Alcohol Consumption Definition By definition, indicates ongoing amounts alcohol. precise suspected uncertain. meeting recommended that, trials candidate eligibility purposes, >21 drinks week >14 women 2‐year period preceding histology.68 According National Institute Abuse Alcoholism (NIAAA), drink contains about 14 g pure alcohol.69 Unfortunately, inconsistent.70 Statement: 1. Ongoing reasonable threshold evaluating Incidentally Discovered HEPATIC STEATOSIS (HS) Some thoracic abdominal reasons symptoms, signs, abnormal biochemistry demonstrate unsuspected HS. 11% incidentally discovered calculated (NFS).71 optimal diagnostic management strategies patient investigated. Statements: 2. detected symptoms signs attributable chemistries evaluated though they worked accordingly. 3. incidental normal biochemistries assessed alternate medications. Screening Primary Care, Diabetes, Clinics argued systematic screening least higher‐risk obesity. example, do suggests patients.72 gaps our knowledge diagnosis, history, treatment recent, cost‐effective Markov model present, because disutility treatment.75 sufficiently sensitive serve tests, TE potentially sensitive, utility tools unproven. called "vigilance" chronic (CLD) routine screening.76 4. Routine high‐risk groups care, advised time uncertainties surrounding tests options, along benefits cost‐effectiveness screening. 5. suspicion diabetes. Clinical decision aids NFS fibrosis‐4 (FIB‐4) vibration controlled (VCTE) used identify cirrhosis). Family Members familial clustering NAFLD.77 retrospective Willner et al. 18% similarly affected first‐degree relative.80 aggregation children after adjusting race, BMI, heritability MR‐measured fraction 0.386, present family members elevated alanine aminotransferase (ALT) obesity.81 Data reporting variable, detectable heritability, Hungarian twin cohort, nearly universal adolescents.77 ongoing, well‐characterized community‐dwelling twins California, MRI quantify correlated monozygotic, dizygotic, pairs, multivariable adjustment, 0.52 0.31‐0.73; P < 1.1 × 10–11) 0.50 0.28‐0.72; 6.1 10–1), respectively.84 6. Systematic currently. Initial Patient Suspected diagnosis competing etiologies HS, coexisting CLD. alternative C, medications, parenteral nutrition, Wilson's (WD), malnutrition When newly exclude CLD, including hemochromatosis, autoimmune viral hepatitis, alpha‐1 antitrypsin WD, drug‐induced injury. Serological evaluation uncover laboratory abnormalities always reflect disease. Two examples ferritin antibodies. Mildly does necessarily indicate iron overload, progression. somewhat conflicting, >1.5 upper limit (ULN) 628 adults.85 If transferrin saturation hemochromatosis excluded. Mutations HFE gene occur variable frequency significance unclear.86 setting determine extent Low titers autoantibodies, particularly antismooth muscle antinuclear antibodies, generally epiphenomenon consequence, 864 Research Network (NASH CRN), elevations autoantibodies (antinuclear antibodies >1:160 >1:40) 21% atypical features.87 While diseases being excluded, carefully taken comorbidities, central dyslipidemia, insulin resistance (IR), hypothyroidism, syndrome, obstructive apnea. 7. essential 8. persistently ferritin, saturation, context homozygote heterozygote C282Y mutation, considered. 9. suggestive (>5 ULN aminotransferases, globulins, albumin ratio) prompt work‐up 10. consider IR Noninvasive Steatohepatitis Advanced fairly dichotomous—NAFL benign, currently reliable identifying (SH) acknowledged limited cost, sampling error, procedure‐related morbidity mortality. Serum computed tomography (CT), MR, reliably Therefore, interest prediction rules noninvasive biomarkers detailed discussion beyond scope guidance.47 NONINVASIVE QUANTIFICATION IN predict severity SH)88 NAFLD.89 MR imaging, spectroscopy92 proton density fraction,93 excellent modality quantifying widely trials.95 obtain continuous attenuation parameters promising ambulatory setting.74 noninvasively qua

Language: Английский

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A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement

Journal of Hepatology, Journal Year: 2020, Volume and Issue: 73(1), P. 202 - 209

Published: April 8, 2020

Language: Английский

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Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease

Hepatology, Journal Year: 2017, Volume and Issue: 67(1), P. 123 - 133

Published: Aug. 12, 2017

Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are highly prevalent in the United States, where they a growing cause of cirrhosis hepatocellular carcinoma (HCC) increasingly an indicator for transplantation. A Markov model was used to forecast NAFLD progression. Incidence based on historical projected changes adult prevalence obesity type 2 diabetes mellitus (DM). Assumptions were derived from published literature available validated using national surveillance data incidence NAFLD‐related HCC. Projected cirrhosis, advanced disease, liver‐related mortality quantified through 2030. Prevalent cases forecasted increase 21%, 83.1 million (2015) 100.9 (2030), while NASH will 63% 16.52 27.00 cases. Overall among population (aged ≥15 years) is at 33.5% 2030, median age 50 55 years during 2015‐2030. In 2015, approximately 20% classified as NASH, increasing 27% by reflection both progression aging population. decompensated 168% 105,430 HCC 137% 12,240 Liver deaths 178% estimated 78,300 During 2015‐2030, there be nearly 800,000 excess deaths. Conclusion: With continued high rates DM along with population, States. Strategies slow growth therapeutic options necessary mitigate burden. (H epatology 2018;67:123‐133).

Language: Английский

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The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis

Journal of Hepatology, Journal Year: 2019, Volume and Issue: 71(4), P. 793 - 801

Published: July 4, 2019

Language: Английский

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Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016–2030

Journal of Hepatology, Journal Year: 2018, Volume and Issue: 69(4), P. 896 - 904

Published: June 7, 2018

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis hepatocellular carcinoma globally. This burden is expected to increase as epidemics obesity, diabetes metabolic syndrome continue grow. The goal this analysis was use Markov model forecast NAFLD using currently available data.A used estimate NASH progression in eight countries based on data for adult prevalence obesity type 2 mellitus (DM). Published estimates expert consensus were build validate the projections.If DM level off future, we project modest growth total cases (0-30%), between 2016-2030, with highest China result urbanization lowest Japan shrinking population. However, at same time, will 15-56%, while mortality advanced more than double an aging/increasing population.NAFLD represent large growing public health problem efforts understand epidemic mitigate needed. If current historical rates, both increase. Since reversible, campaigns awareness diagnosis, promote diet exercise can help manage future burden.Non-alcoholic lead disease. Both conditions becoming prevalent A mathematical built how associated change over time. Results suggest increasing liver-related coming years.

Language: Английский

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Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis

Journal of Hepatology, Journal Year: 2016, Volume and Issue: 65(3), P. 589 - 600

Published: May 18, 2016

Language: Английский

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NAFLD and diabetes mellitus

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2016, Volume and Issue: 14(1), P. 32 - 42

Published: Oct. 12, 2016

Language: Английский

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Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies

The Lancet Diabetes & Endocrinology, Journal Year: 2018, Volume and Issue: 7(4), P. 313 - 324

Published: Aug. 30, 2018

Language: Английский

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Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta‐analysis

Journal of Gastroenterology and Hepatology, Journal Year: 2015, Volume and Issue: 31(5), P. 936 - 944

Published: Dec. 15, 2015

Abstract Background and Aim: The magnitude of the risk incident type 2 diabetes (T2D) metabolic syndrome (MetS) among patients with nonalcoholic fatty liver disease (NAFLD) is poorly known. We gauged developing T2D MetS in NAFLD diagnosed by either serum enzymes (aminotransferases or gamma‐glutamyltransferase [GGT]) ultrasonography. Methods: Pertinent prospective studies were identified through extensive electronic database research, fulfilling enrolment criteria included meta‐analysis. Results Overall, a pooled population 117020 (from 20 studies), who followed‐up for median period 5 years (range: 3–14.7 years), was associated an increased relative 1.97 (95% confidence interval [CI], 1.80–2.15) alanine aminotransferase, 1.58 CI, 1.43–1.74) aspartate 1.86 1.71–2.03) GGT (last vs first quartile quintile), 1.76–1.95) ultrasonography, respectively. 81411 eight studies) 4.5 3–11 1.80 1.72–1.89) aminotransferase 1.98 1.89–2.07) GGT, 3.22 3.05–3.41) Conclusions: Nonalcoholic disease, as significantly increases over 5‐year follow‐up.

Language: Английский

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Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence?

Journal of Hepatology, Journal Year: 2017, Volume and Issue: 68(2), P. 335 - 352

Published: Nov. 6, 2017

Language: Английский

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