Editorial Open Access
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 27, 2024; 16(4): 511-516
Published online Apr 27, 2024. doi: 10.4254/wjh.v16.i4.511
Metabolic dysfunction-associated steatotic liver disease: A silent pandemic
Arghya Samanta, Moinak Sen Sarma, Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
ORCID number: Arghya Samanta (0000-0002-1768-0263); Moinak Sen Sarma (0000-0003-2015-4069).
Author contributions: Samanta A did the literature review and wrote the original manuscript; Sen Sarma M reviewed and revised the manuscript, did critical analysis; All authors approved the final draft of the manuscript.
Conflict-of-interest statement: All authors declare no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Moinak Sen Sarma, MBBS, MD, Adjunct Associate Professor, Doctor, Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, India. moinaksen@yahoo.com
Received: January 23, 2024
Revised: March 5, 2024
Accepted: April 7, 2024
Published online: April 27, 2024

Abstract

The worldwide epidemiology of non-alcoholic fatty liver disease (NAFLD) is showing an upward trend, parallel to the rising trend of metabolic syndrome, owing to lifestyle changes. The pathogenesis of NAFLD has not been fully understood yet. Therefore, NAFLD has emerged as a public health concern in the field of hepatology and metabolisms worldwide. Recent changes in the nomenclature from NAFLD to metabolic dysfunction-associated steatotic liver disease have brought a positive outlook changes in the understanding of the disease process and doctor-patient communication. Lifestyle changes are the main treatment modality. Recently, clinical trial using drugs that target ‘insulin resistance’ which is the driving force behind NAFLD, have shown promising results. Further translational research is needed to better understand the underlying pathophysiological mechanism of NAFLD which may open newer avenues of therapeutic targets. The role of gut dysbiosis in etiopathogenesis and use of fecal microbiota modification in the treatment should be studied extensively. Prevention of this silent epidemic by spreading awareness and early intervention should be our priority.

Key Words: Metabolic dysfunction, Fatty liver, Obesity, Insulin resistance

Core Tip: Non-alcoholic fatty liver disease is often considered the hepatic manifestation of metabolic syndrome. The new nomenclature of “metabolic dysfunction associated steatotic liver disease” emphasizes the role of disordered metabolism in the pathogenesis. Weight reduction by lifestyle changes is the mainstay of treatment.



INTRODUCTION

Non-alcoholic fatty liver disease (NAFLD) is a broad spectrum of liver disorders related to dysmetabolic conditions. It is characterized by macrovesicular steatosis with or without hepatocellular ballooning, lobular inflammation, and hepatic fibrosis[1]. NAFLD is the leading cause of hepatic morbidity and mortality worldwide and is now the most common indication of liver transplantation (LT)[2-5]. Thus, NAFLD is associated with exorbitant healthcare costs[6,7]. It affects nearly one third of the adult population[8-11] and 9%-12% of the pediatric population[12-14]. The latest meta-analysis by Younossi et al[15], showed a global rise in NAFLD prevalence at an alarming rate- from 25.26% (21.59-29.33) in 1990-2006 to 38% (33.71-42.49) in 2016-2019 (P < 0.001)[15]. The prevalence in Asia is following a trajectory similar to that in the western countries[16-18].

THE DEBATE OVER THE NEW NOMENCLATURE: NAFLD VS MASLD

NAFLD is usually defined as the presence of steatosis in >5% hepatocytes, detected by imaging or histopathology after exclusion of secondary causes for hepatic steatosis[19]. Pathologically, it is strongly linked to metabolic syndrome, which is a constellation of obesity, hypertension, hyperlipidemia, type 2 diabetes mellitus (T2DM)[20]. Patients with NAFLD are at higher risk of liver-related complications as well as cardiovascular complications and mortality[20,21]. The most common cause of mortality in patients with NAFLD is cardiovascular complications, followed by extrahepatic malignancies and hepatic complications, highlighting the fact that NAFLD is a multisystemic disease[22,23]. Recently, an international expert group proposed to change the existing nomenclature “Non-Alcoholic Fatty Liver Disease” and adopt the acronym MASLD, or “Metabolic dysfunction-Associated Steatotic Liver Disease”, thus emphasizing the role of systemic metabolic dysfunction in the etiopathogenesis[24]. The shift in the nomenclature introduces a “positive” diagnostic criteria and highlights the cardiovascular risk profile of these individuals. The new nomenclature thus aims for a better understanding of the disease and patient-physician communication.

The diagnosis of MASLD is based on the detection of steatosis of hepatocytes (diagnosed by imaging, biomarkers, or histology) and at least one feature among the following three - overweight/obesity, type 2 diabetes mellitus and metabolic dysregulation. The criterion of metabolic dysregulation is fulfilled when atleast two features among the following are found: increased waist circumference, hypertension, hyperlipidemia, low level of high-density lipoprotein-C (HDL-C), prediabetes, insulin resistance, and subclinical inflammation. These criteria will ensure the identification of a more homogenous disease condition than NAFLD, overcoming the dilemmas and controversies in defining alcohol intake, thereby encouraging new pathophysiological developments and augmenting clinical studies (as elegantly reviewed by Vargas et al[25] in this present issue).

LEAN NAFLD

The prevalence of NAFLD showed a rising trend similar to the rising burden of obesity[26,27]. In contrast, lean patients with NAFLD were also detected. In the meta-analysis by Young et al[28], 11% and 25% of the general and NAFLD populations, were identified to be “lean NAFLD” respectively[29]. Metabolic profile was more deranged in lean NAFLD patients than healthy controls. These patients also had a higher prevalence of insulin resistance, metabolic syndrome and higher levels of pro-inflammatory mediators[30,31]. On the contrary, lean NAFLD patients have more favorable histologic features than obese NAFLD patients[31].

The ethnicity of the study population should be considered for correctly defining lean MAFLD patients. Body mass index (BMI) cutoffs depending on the ethnicity of the individual have been recommended to define “lean MAFLD”. The cutoffs for defining lean MAFLD are BMI < 25 kg/m2 for Caucasians and < 23 kg/m2 for Asians[32]. The prevalence of lean NAFLD has been found to be 5%–45% in the Asian population and 5%–20% among Europeans[33]. Further studies are needed to better characterize the newly-defined lean MAFLD patients.

T2DM AND NAFLD

Presence of concomitant T2DM accelerates the disease progression in NAFLD, as patients with concomitant T2DM and NAFLD had higher rates of advanced fibrosis and adverse outcomes compared to NAFLD without T2DM[10]. Furthermore, the concomitant NAFLD and T2DM causes increased liver-related, cardiovascular complications as well as overall mortalities[10]. Other complications of T2DM like diabetic retinopathy, nephropathy, and polyneuropathy, have been detected more frequently in diabetes patients with coexisting NAFLD[34-36]. Therefore, a novel diagnostic score has been recommended for T2DM patients with NAFLD[37]. Those with an FIB-4 score of more than 1.3 have a higher risk of developing severe disease[38]. Recent NAFLD guidelines recommend that T2DM populations be screened for NAFLD[24].

NAFLD AND METABOLIC SYNDROME

NAFLD is considered as the hepatic manifestation of metabolic syndrome[39]. In the meta-analysis by Ballestri et al[40], NAFLD was associated with incident metabolic syndrome in 5-year follow-up. On the other hand, another study by Ma et al[41] demonstrated that patients with metabolic syndrome had a higher risk of developing NAFLD. While comparing the new term ‘MASLD’ with the traditional definition of ‘NAFLD’, Lin et al[42] found higher proportions of metabolic comorbidities in patients with MASLD, emphasizing the impact of positive diagnostic criteria.

DIAGNOSTIC EVALUATION

Liver biopsy is the gold standard to assess disease activity and severity. The severity of liver fibrosis has been identified as the most important prognostic factor and is independently linked with hepatic outcomes in NAFLD patients. Sanyal et al[2], in an elegantly done prospective study of 1773 adult patients with NAFLD, found that F3, and F4 fibrosis were associated with increased risk of hepatic complications and death, after adjustment for age, sex, race and diabetes status.

Several non-invasive tests have been developed as diagnostic and prognostic tools in patients of NAFLD as liver biopsy is invasive and less preferred for disease monitoring. Imaging to detect and quantify hepatic steatosis has gained prominence with advances of computerized tomography (liver attenuation index) and magnetic resonance imaging (magnetic resonance imaging proton density fat fraction-MRI-PDFF)[43-45]. Multiparametric MRI, which consists of MR spectroscopy, MR elastography and T1 mapping, has demonstrated high diagnostic accuracy, comparable to liver histology[45,46]. Similar multiparametric CT sequences that can evaluate the hepatic attenuation, liver segmental volume ratio, splenic volume, and liver surface nodularity score, have shown encouraging results as an alternative diagnostic tool to identify advanced fibrosis in NAFLD patients[47]. MRI-PDFF response has been studied as a potential surrogate for histologic improvement after treatment of NAFLD. Several studies have shown a clear correlation between a reduction in MRI-PDFF (usually taken as a ≥ 30% relative reduction) and improvement in the NAFLD activity score, resolution of NASH, and fibrosis[48,49]. Boursier et al[50], in a large cohort of 1097 patients, compared the prognostic efficacy of fibrosis index based on 4-factors (FIB4), transient elastography (TE) and liver biopsy. The results showed that FIB4 and TE showed good accuracy for the prediction of liver-related events (LRE), with Harrell’s C-indexes > 0.80 [0.817 (0.768-0.866) vs. 0.878 (0.835-0.921), respectively, P = 0.059], as compared to liver biopsy. The authors proposed a stepwise algorithm to accurately stratify NAFLD patients based on their risk for LRE: compared to patients with “FIB4 < 1.30”, those with “FIB4 ≥ 1.30 then TE < 8.0 kPa” had a similar risk of LREs [adjusted hazard ratio (aHR) 1.3; 95%CI 0.3–6.8], whereas the risk of LREs significantly increased in patients with “FIB4 ≥ 1.30 then TE 8.0-12.0 kPa” (aHR 3.8; 95%CI 1.3–10.9), and even more for those with “FIB4 ≥ 1.30 then TE > 12.0 kPa” (aHR 12.4; 95%CI 5.1–30.2).

However, we need to keep in mind a major limitation of using these non-invasive methods to diagnose and monitor hepatic steatosis is that it provides no information on the underlying etiology or associated risk factors.

TREATMENT

As NAFLD is a systemic disease of disordered metabolism, a multi-disciplinary approach is of utmost importance for the treatment. Weight reduction by lifestyle changes and dietary interventions is the cornerstone of treatment in obese and lean NAFLD patients[19,51]. The beneficial effects of lifestyle modifications have been consistently found to be helpful in the resolution of hepatic steatosis in both lean Asian and Caucasian NAFLD patients[51-53]. Medical treatment with glucagon-like peptide receptor agonists, sodium-glucose cotransporter-2 inhibitors, and peroxisome proliferator-activated receptor-γ agonists was able to improve inflammation and fibrosis, as well as reduction in blood pressure, better glycemic control and lipid profile[54-56]. Bariatric surgery is an effective treatment for a select group of patients who are non-responsive to dietary interventions and exercise or unable to lose weight through lifestyle changes. It can improve both histological characteristics of NASH as well as mortality due to cardiovascular complications[57]. Lim et al[58] studied the usefulness of endoscopic bariatric therapies such as intragastric balloon, endoscopic sleeve gastroplasty, and duodenojejunal bypass liner in reducing weight and found better results as compared to standard medical therapy. With extensive research into the therapeutic options in the pipeline, treatment strategies for NAFLD treatment are promising[59].

FUTURE PERSPECTIVE

Further prospective studies are the need of the hour to develop more accurate diagnostic tools for advanced fibrosis in NAFLD and to explore the underlying pathophysiological mechanisms linking NAFLD with other conditions. More in-depth research on gut microbiota in the etiopathogenesis of NAFLD and its role in the therapeutics is warranted. Most randomized clinical trials of available drugs do not reflect the proper scenario, due to the limitations of therapeutic targets, drug safety, and other factors. This current review by Vargas in this issue serves as a valuable resource for researchers seeking a comprehensive understanding of NAFLD and tries to address these issues[25].

CONCLUSION

NAFLD must be evaluated as a multisystemic metabolic disorder. It may lead to liver-related complications, thus the need for multidisciplinary screening and disease management cannot be over emphasized. Routine screening for NAFLD is recommended in patients with metabolic syndrome. Lifestyle intervention remains the most important treatment modality. The global pandemic of NAFLD poses significant social and economic burden; thus it is of utmost importance to create widespread awareness in order to make early interventions and achieve better outcome.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: India

Peer-review report’s classification

Scientific Quality: Grade B

Novelty: Grade B

Creativity or Innovation: Grade A

Scientific Significance: Grade B

P-Reviewer: Nashwan AJ, Qatar S-Editor: Gong ZM L-Editor: A P-Editor: Cai YX

References
1.  Brunt EM, Kleiner DE, Carpenter DH, Rinella M, Harrison SA, Loomba R, Younossi Z, Neuschwander-Tetri BA, Sanyal AJ; American Association for the Study of Liver Diseases NASH Task Force. NAFLD: Reporting Histologic Findings in Clinical Practice. Hepatology. 2021;73:2028-2038.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 52]  [Cited by in F6Publishing: 67]  [Article Influence: 22.3]  [Reference Citation Analysis (0)]
2.  Sanyal AJ, Van Natta ML, Clark J, Neuschwander-Tetri BA, Diehl A, Dasarathy S, Loomba R, Chalasani N, Kowdley K, Hameed B, Wilson LA, Yates KP, Belt P, Lazo M, Kleiner DE, Behling C, Tonascia J; NASH Clinical Research Network (CRN). Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease. N Engl J Med. 2021;385:1559-1569.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 195]  [Cited by in F6Publishing: 387]  [Article Influence: 129.0]  [Reference Citation Analysis (0)]
3.  Horn P, Newsome PN. Nonalcoholic Fatty Liver Disease. N Engl J Med. 2022;386:294.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 1]  [Reference Citation Analysis (0)]
4.  Pais R, Barritt AS 4th, Calmus Y, Scatton O, Runge T, Lebray P, Poynard T, Ratziu V, Conti F. NAFLD and liver transplantation: Current burden and expected challenges. J Hepatol. 2016;65:1245-1257.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 307]  [Cited by in F6Publishing: 274]  [Article Influence: 34.3]  [Reference Citation Analysis (1)]
5.  Battistella S, D'Arcangelo F, Grasso M, Zanetto A, Gambato M, Germani G, Senzolo M, Russo FP, Burra P. Liver transplantation for non-alcoholic fatty liver disease: indications and post-transplant management. Clin Mol Hepatol. 2023;29:S286-S301.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 7]  [Article Influence: 7.0]  [Reference Citation Analysis (0)]
6.  Allen AM, Lazarus JV, Younossi ZM. Healthcare and socioeconomic costs of NAFLD: A global framework to navigate the uncertainties. J Hepatol. 2023;79:209-217.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 22]  [Cited by in F6Publishing: 26]  [Article Influence: 26.0]  [Reference Citation Analysis (0)]
7.  Premkumar M, Anand AC. Overview of Complications in Cirrhosis. J Clin Exp Hepatol. 2022;12:1150-1174.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 8]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
8.  Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, George J, Bugianesi E. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15:11-20.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2383]  [Cited by in F6Publishing: 3076]  [Article Influence: 512.7]  [Reference Citation Analysis (2)]
9.  Riazi K, Azhari H, Charette JH, Underwood FE, King JA, Afshar EE, Swain MG, Congly SE, Kaplan GG, Shaheen AA. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022;7:851-861.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 149]  [Cited by in F6Publishing: 497]  [Article Influence: 248.5]  [Reference Citation Analysis (0)]
10.  Younossi ZM, Golabi P, de Avila L, Paik JM, Srishord M, Fukui N, Qiu Y, Burns L, Afendy A, Nader F. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. J Hepatol. 2019;71:793-801.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 773]  [Cited by in F6Publishing: 1099]  [Article Influence: 219.8]  [Reference Citation Analysis (0)]
11.  Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73-84.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5322]  [Cited by in F6Publishing: 6343]  [Article Influence: 792.9]  [Reference Citation Analysis (0)]
12.  Quek J, Chan KE, Wong ZY, Tan C, Tan B, Lim WH, Tan DJH, Tang ASP, Tay P, Xiao J, Yong JN, Zeng RW, Chew NWS, Nah B, Kulkarni A, Siddiqui MS, Dan YY, Wong VW, Sanyal AJ, Noureddin M, Muthiah M, Ng CH. Global prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in the overweight and obese population: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2023;8:20-30.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 83]  [Reference Citation Analysis (0)]
13.  Anderson EL, Howe LD, Jones HE, Higgins JP, Lawlor DA, Fraser A. The Prevalence of Non-Alcoholic Fatty Liver Disease in Children and Adolescents: A Systematic Review and Meta-Analysis. PLoS One. 2015;10:e0140908.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 459]  [Cited by in F6Publishing: 550]  [Article Influence: 61.1]  [Reference Citation Analysis (1)]
14.  Nobili V, Alisi A, Valenti L, Miele L, Feldstein AE, Alkhouri N. NAFLD in children: new genes, new diagnostic modalities and new drugs. Nat Rev Gastroenterol Hepatol. 2019;16:517-530.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 120]  [Cited by in F6Publishing: 171]  [Article Influence: 34.2]  [Reference Citation Analysis (0)]
15.  Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77:1335-1347.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 270]  [Reference Citation Analysis (0)]
16.  Zhou J, Zhou F, Wang W, Zhang XJ, Ji YX, Zhang P, She ZG, Zhu L, Cai J, Li H. Epidemiological Features of NAFLD From 1999 to 2018 in China. Hepatology. 2020;71:1851-1864.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 183]  [Cited by in F6Publishing: 304]  [Article Influence: 76.0]  [Reference Citation Analysis (0)]
17.  Fan JG, Kim SU, Wong VW. New trends on obesity and NAFLD in Asia. J Hepatol. 2017;67:862-873.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 570]  [Cited by in F6Publishing: 671]  [Article Influence: 95.9]  [Reference Citation Analysis (0)]
18.  Li J, Zou B, Yeo YH, Feng Y, Xie X, Lee DH, Fujii H, Wu Y, Kam LY, Ji F, Li X, Chien N, Wei M, Ogawa E, Zhao C, Wu X, Stave CD, Henry L, Barnett S, Takahashi H, Furusyo N, Eguchi Y, Hsu YC, Lee TY, Ren W, Qin C, Jun DW, Toyoda H, Wong VW, Cheung R, Zhu Q, Nguyen MH. Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999-2019: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2019;4:389-398.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 325]  [Cited by in F6Publishing: 544]  [Article Influence: 108.8]  [Reference Citation Analysis (0)]
19.  Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67:328-357.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3544]  [Cited by in F6Publishing: 4089]  [Article Influence: 681.5]  [Reference Citation Analysis (7)]
20.  Ng CH, Chan KE, Chin YH, Zeng RW, Tsai PC, Lim WH, Tan DJH, Khoo CM, Goh LH, Ling ZJ, Kulkarni A, Mak LL, Huang DQ, Chan M, Chew NW, Siddiqui MS, Sanyal AJ, Muthiah M. The effect of diabetes and prediabetes on the prevalence, complications and mortality in nonalcoholic fatty liver disease. Clin Mol Hepatol. 2022;28:565-574.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 40]  [Article Influence: 20.0]  [Reference Citation Analysis (0)]
21.  Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK, Luketic VA, Shiffman ML, Clore JN. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology. 2001;120:1183-1192.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1458]  [Cited by in F6Publishing: 1436]  [Article Influence: 62.4]  [Reference Citation Analysis (0)]
22.  Mantovani A, Scorletti E, Mosca A, Alisi A, Byrne CD, Targher G. Complications, morbidity and mortality of nonalcoholic fatty liver disease. Metabolism. 2020;111S:154170.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 184]  [Cited by in F6Publishing: 252]  [Article Influence: 63.0]  [Reference Citation Analysis (0)]
23.  Muzurović E, Peng CC, Belanger MJ, Sanoudou D, Mikhailidis DP, Mantzoros CS. Nonalcoholic Fatty Liver Disease and Cardiovascular Disease: a Review of Shared Cardiometabolic Risk Factors. Hypertension. 2022;79:1319-1326.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 45]  [Article Influence: 22.5]  [Reference Citation Analysis (0)]
24.  Eslam M, Sanyal AJ, George J; International Consensus Panel. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology. 2020;158:1999-2014.e1.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1188]  [Cited by in F6Publishing: 1612]  [Article Influence: 403.0]  [Reference Citation Analysis (1)]
25.  Vargas M, Cardoso Toniasso SC, Riedel PG, Baldin CP, Dos Reis FL, Pereira RM, Brum MCB, Joveleviths D, Alvares-da-Silva MR. Metabolic disease and the liver: A review. World J Hepatol. 2024;16:33-40.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (3)]
26.  Li L, Liu DW, Yan HY, Wang ZY, Zhao SH, Wang B. Obesity is an independent risk factor for non-alcoholic fatty liver disease: evidence from a meta-analysis of 21 cohort studies. Obes Rev. 2016;17:510-519.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 196]  [Cited by in F6Publishing: 226]  [Article Influence: 28.3]  [Reference Citation Analysis (0)]
27.  Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, Farzadfar F, Riley LM, Ezzati M; Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Body Mass Index). National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants. Lancet. 2011;377:557-567.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2897]  [Cited by in F6Publishing: 2836]  [Article Influence: 218.2]  [Reference Citation Analysis (1)]
28.  Young S, Tariq R, Provenza J, Satapathy SK, Faisal K, Choudhry A, Friedman SL, Singal AK. Prevalence and Profile of Nonalcoholic Fatty Liver Disease in Lean Adults: Systematic Review and Meta-Analysis. Hepatol Commun. 2020;4:953-972.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 48]  [Cited by in F6Publishing: 82]  [Article Influence: 20.5]  [Reference Citation Analysis (0)]
29.  Kumar R, Rastogi A, Sharma MK, Bhatia V, Garg H, Bihari C, Sarin SK. Clinicopathological characteristics and metabolic profiles of non-alcoholic fatty liver disease in Indian patients with normal body mass index: Do they differ from obese or overweight non-alcoholic fatty liver disease? Indian J Endocrinol Metab. 2013;17:665-671.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 71]  [Cited by in F6Publishing: 72]  [Article Influence: 6.5]  [Reference Citation Analysis (0)]
30.  Fracanzani AL, Petta S, Lombardi R, Pisano G, Russello M, Consonni D, Di Marco V, Cammà C, Mensi L, Dongiovanni P, Valenti L, Craxì A, Fargion S. Liver and Cardiovascular Damage in Patients With Lean Nonalcoholic Fatty Liver Disease, and Association With Visceral Obesity. Clin Gastroenterol Hepatol. 2017;15:1604-1611.e1.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 105]  [Cited by in F6Publishing: 133]  [Article Influence: 19.0]  [Reference Citation Analysis (0)]
31.  Chakrabarty M, Jha AN, Sharma DJ. Clinical Characteristics and Metabolic Profiles of Non-Alcoholic Fatty Liver Disease (NAFLD) in Lean Patients and Their Comparison with Obese and Overweight NAFLD. J Assoc Physicians India. 2022;70:11-12.  [PubMed]  [DOI]  [Cited in This Article: ]
32.  Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:i-xii, 1.  [PubMed]  [DOI]  [Cited in This Article: ]
33.  Eslam M, Chen F, George J. NAFLD in Lean Asians. Clin Liver Dis (Hoboken). 2020;16:240-243.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 9]  [Cited by in F6Publishing: 14]  [Article Influence: 4.7]  [Reference Citation Analysis (0)]
34.  Mantovani A, Byrne CD, Bonora E, Targher G. Nonalcoholic Fatty Liver Disease and Risk of Incident Type 2 Diabetes: A Meta-analysis. Diabetes Care. 2018;41:372-382.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 321]  [Cited by in F6Publishing: 369]  [Article Influence: 61.5]  [Reference Citation Analysis (0)]
35.  Hazlehurst JM, Woods C, Marjot T, Cobbold JF, Tomlinson JW. Non-alcoholic fatty liver disease and diabetes. Metabolism. 2016;65:1096-1108.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 308]  [Cited by in F6Publishing: 344]  [Article Influence: 43.0]  [Reference Citation Analysis (0)]
36.  Targher G, Lonardo A, Byrne CD. Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus. Nat Rev Endocrinol. 2018;14:99-114.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 217]  [Cited by in F6Publishing: 239]  [Article Influence: 39.8]  [Reference Citation Analysis (0)]
37.  Younossi ZM, Corey KE, Alkhouri N, Noureddin M, Jacobson I, Lam B, Clement S, Basu R, Gordon SC, Ravendhra N, Puri P, Rinella M, Scudera P, Singal AK, Henry L; US Members of the Global Nash Council. Clinical assessment for high-risk patients with non-alcoholic fatty liver disease in primary care and diabetology practices. Aliment Pharmacol Ther. 2020;52:513-526.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 34]  [Cited by in F6Publishing: 56]  [Article Influence: 14.0]  [Reference Citation Analysis (0)]
38.  Yilmaz Y, Kaya E, Eren F. Letter: the use of Fibrosis-4 score in primary care and diabetology practices-Occam's razor applied to advanced fibrosis screening. Aliment Pharmacol Ther. 2020;52:1759-1760.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
39.  Kim D, Touros A, Kim WR. Nonalcoholic Fatty Liver Disease and Metabolic Syndrome. Clin Liver Dis. 2018;22:133-140.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 115]  [Cited by in F6Publishing: 133]  [Article Influence: 22.2]  [Reference Citation Analysis (0)]
40.  Ballestri S, Zona S, Targher G, Romagnoli D, Baldelli E, Nascimbeni F, Roverato A, Guaraldi G, Lonardo A. 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. J Gastroenterol Hepatol. 2016;31:936-944.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 398]  [Cited by in F6Publishing: 470]  [Article Influence: 58.8]  [Reference Citation Analysis (0)]
41.  Ma J, Hwang SJ, Pedley A, Massaro JM, Hoffmann U, Chung RT, Benjamin EJ, Levy D, Fox CS, Long MT. Bi-directional analysis between fatty liver and cardiovascular disease risk factors. J Hepatol. 2017;66:390-397.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 110]  [Cited by in F6Publishing: 129]  [Article Influence: 18.4]  [Reference Citation Analysis (0)]
42.  Lin S, Huang J, Wang M, Kumar R, Liu Y, Liu S, Wu Y, Wang X, Zhu Y. Comparison of MAFLD and NAFLD diagnostic criteria in real world. Liver Int. 2020;40:2082-2089.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 232]  [Cited by in F6Publishing: 323]  [Article Influence: 80.8]  [Reference Citation Analysis (0)]
43.  Schaapman JJ, Tushuizen ME, Coenraad MJ, Lamb HJ. Multiparametric MRI in Patients With Nonalcoholic Fatty Liver Disease. J Magn Reson Imaging. 2021;53:1623-1631.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 19]  [Cited by in F6Publishing: 20]  [Article Influence: 5.0]  [Reference Citation Analysis (0)]
44.  van Werven JR, Marsman HA, Nederveen AJ, Smits NJ, ten Kate FJ, van Gulik TM, Stoker J. Assessment of hepatic steatosis in patients undergoing liver resection: comparison of US, CT, T1-weighted dual-echo MR imaging, and point-resolved 1H MR spectroscopy. Radiology. 2010;256:159-168.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 232]  [Cited by in F6Publishing: 235]  [Article Influence: 16.8]  [Reference Citation Analysis (0)]
45.  Park CC, Nguyen P, Hernandez C, Bettencourt R, Ramirez K, Fortney L, Hooker J, Sy E, Savides MT, Alquiraish MH, Valasek MA, Rizo E, Richards L, Brenner D, Sirlin CB, Loomba R. 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.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 374]  [Cited by in F6Publishing: 449]  [Article Influence: 64.1]  [Reference Citation Analysis (0)]
46.  Bannas P, Kramer H, Hernando D, Agni R, Cunningham AM, Mandal R, Motosugi U, Sharma SD, Munoz del Rio A, Fernandez L, Reeder SB. Quantitative magnetic resonance imaging of hepatic steatosis: Validation in ex vivo human livers. Hepatology. 2015;62:1444-1455.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 102]  [Cited by in F6Publishing: 104]  [Article Influence: 11.6]  [Reference Citation Analysis (0)]
47.  Lubner MG, Graffy PM, Said A, Watson R, Zea R, Malecki KM, Pickhardt PJ. Utility of Multiparametric CT for Identification of High-Risk NAFLD. AJR Am J Roentgenol. 2021;216:659-668.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 5]  [Article Influence: 1.7]  [Reference Citation Analysis (0)]
48.  Stine JG, Munaganuru N, Barnard A, Wang JL, Kaulback K, Argo CK, Singh S, Fowler KJ, Sirlin CB, Loomba R. Change in MRI-PDFF and Histologic Response in Patients With Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol. 2021;19:2274-2283.e5.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 40]  [Cited by in F6Publishing: 86]  [Article Influence: 28.7]  [Reference Citation Analysis (0)]
49.  Tamaki N, Munaganuru N, Jung J, Yonan AQ, Loomba RR, Bettencourt R, Ajmera V, Valasek MA, Behling C, Sirlin CB, Loomba R. Clinical utility of 30% relative decline in MRI-PDFF in predicting fibrosis regression in non-alcoholic fatty liver disease. Gut. 2022;71:983-990.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 33]  [Cited by in F6Publishing: 33]  [Article Influence: 16.5]  [Reference Citation Analysis (0)]
50.  Boursier J, Hagström H, Ekstedt M, Moreau C, Bonacci M, Cure S, Ampuero J, Nasr P, Tallab L, Canivet CM, Kechagias S, Sánchez Y, Dincuff E, Lucena A, Roux M, Riou J, Trylesinski A, Romero-Gomez M. Non-invasive tests accurately stratify patients with NAFLD based on their risk of liver-related events. J Hepatol. 2022;76:1013-1020.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 19]  [Cited by in F6Publishing: 64]  [Article Influence: 32.0]  [Reference Citation Analysis (0)]
51.  Risi R, Tozzi R, Watanabe M. Beyond weight loss in nonalcoholic fatty liver disease: the role of carbohydrate restriction. Curr Opin Clin Nutr Metab Care. 2021;24:349-353.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 8]  [Article Influence: 2.7]  [Reference Citation Analysis (0)]
52.  Hamurcu Varol P, Kaya E, Alphan E, Yilmaz Y. Role of intensive dietary and lifestyle interventions in the treatment of lean nonalcoholic fatty liver disease patients. Eur J Gastroenterol Hepatol. 2020;32:1352-1357.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 20]  [Cited by in F6Publishing: 17]  [Article Influence: 4.3]  [Reference Citation Analysis (0)]
53.  Brunner KT, Henneberg CJ, Wilechansky RM, Long MT. Nonalcoholic Fatty Liver Disease and Obesity Treatment. Curr Obes Rep. 2019;8:220-228.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 58]  [Cited by in F6Publishing: 48]  [Article Influence: 9.6]  [Reference Citation Analysis (0)]
54.  Ng CH, Lin SY, Chin YH, Lee MH, Syn N, Goh XL, Koh JH, Quek J, Hao Tan DJ, Mok SF, Tan E, Dan YY, Chew N, Khoo CM, Siddiqui MS, Muthiah M. Antidiabetic Medications for Type 2 Diabetics with Nonalcoholic Fatty Liver Disease: Evidence From a Network Meta-Analysis of Randomized Controlled Trials. Endocr Pract. 2022;28:223-230.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 12]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
55.  Feng W, Gao C, Bi Y, Wu M, Li P, Shen S, Chen W, Yin T, Zhu D. Randomized trial comparing the effects of gliclazide, liraglutide, and metformin on diabetes with non-alcoholic fatty liver disease. J Diabetes. 2017;9:800-809.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 87]  [Cited by in F6Publishing: 83]  [Article Influence: 11.9]  [Reference Citation Analysis (0)]
56.  Dwinata M, Putera DD, Hasan I, Raharjo M. SGLT2 inhibitors for improving hepatic fibrosis and steatosis in non-alcoholic fatty liver disease complicated with type 2 diabetes mellitus: a systematic review. Clin Exp Hepatol. 2020;6:339-346.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 22]  [Article Influence: 7.3]  [Reference Citation Analysis (0)]
57.  Chauhan M, Singh K, Thuluvath PJ. Bariatric Surgery in NAFLD. Dig Dis Sci. 2022;67:408-422.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 16]  [Article Influence: 8.0]  [Reference Citation Analysis (0)]
58.  Lim WH, Lin SY, Ng CH, Tan DJH, Xiao J, Yong JN, Tay PWL, Syn N, Chin YH, Chan KE, Khoo CM, Chew N, Foo RSY, Shabbir A, Tan EX, Huang DQ, Noureddin M, Sanyal AJ, Siddiqui MS, Muthiah MD. Foregut bypass vs. restrictive bariatric procedures for nonalcoholic fatty liver disease: a meta-analysis of 3,355 individuals. Hepatobiliary Surg Nutr. 2023;12:658-670.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
59.  Chew NWS, Ng CH, Truong E, Noureddin M, Kowdley KV. Nonalcoholic Steatohepatitis Drug Development Pipeline: An Update. Semin Liver Dis. 2022;42:379-400.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 14]  [Article Influence: 7.0]  [Reference Citation Analysis (0)]