Dataset Information

Metabolic dysfunction associated fatty liver disease: The new nomenclature and its impact.

ABSTRACT:

Background

In 2020, an international expert panel proposed a new definition of fatty liver: Metabolic dysfunction-associated fatty liver disease (MAFLD). The MAFLD added the criteria for defining metabolic dysfunctions, which are high-risk factors for liver-related and cardiovascular events. Contrary to the non-alcoholic fatty liver disease (NAFLD) definition, it allows the coexistence of MAFLD and significant alcohol use in the same patient.

Aim

To review the existing data that evaluate the clinical profile and long-term outcome difference between the patients identified as MAFLD and NAFLD.

Methods

Databases MEDLINE via PubMed and EMBASE were searched and relevant publications up to June 28, 2022 were assessed. Studies were included if they involved human participants diagnosed with MAFLD.

Results

A total of 2324 records were reviewed, of which 1575 duplicate citations were removed. Of the 2324 records screened, 207 articles were excluded, and 542 articles were assessed for their eligibility, for which 511 were excluded. The remaining 31 articles were selected for review. MAFLD diagnostic criteria were able to identify more individuals with fatty liver. Studies have shown that patients included using the MAFLD criteria were associated with higher risks of hepatic fibrosis when compared to NAFLD. All-cause mortality, cardiovascular disease-related, and cancer-related mortality were shown to be higher in MAFLD patients. MAFLD patients also had higher baseline metabolic derangement, and risks of developing obesity, diabetes, and cardiovascular events. Of the 3 subtypes, diabetes mellitus has the strongest association with negative outcomes, followed by metabolic dysfunction and elevated body mass index. Within the subtypes of MAFLD, patients with more metabolic conditions at the time of diagnosis had worse hepatic and liver injury compared to those with a single metabolic condition.

Conclusion

MAFLD is a new definition of fatty liver disease that is gaining increasing acceptance. It is based on empirical clinical practice on positive inclusion of metabolic risk factors and recent evidence suggests that it helps to identify patients with higher risk for liver-related as well as cardiovascular events.

SUBMITTER: Tang SY

PROVIDER: S-EPMC9850940 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Metabolic dysfunction associated fatty liver disease: The new nomenclature and its impact.

Tang Si-Ying SY Tan Jian Shiun JS Pang Xian-Zheng XZ Lee Guan-Huei GH

World journal of gastroenterology 20230101 3

<h4>Background</h4>In 2020, an international expert panel proposed a new definition of fatty liver: Metabolic dysfunction-associated fatty liver disease (MAFLD). The MAFLD added the criteria for defining metabolic dysfunctions, which are high-risk factors for liver-related and cardiovascular events. Contrary to the non-alcoholic fatty liver disease (NAFLD) definition, it allows the coexistence of MAFLD and significant alcohol use in the same patient.<h4>Aim</h4>To review the existing data that e ...[more]

PMID: 36688021

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Project description:BackgroundTo better understand the patient's heterogeneity in fatty liver disease (FLD), metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed by international experts as a new nomenclature for nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the cardiovascular risk, assessed through coronary artery calcium (CAC) and epicardial adipose tissue (EAT), of patients without FLD and patients with FLD and its different subtypes.MethodsCross sectional study of 370 patients. Patients with FLD were divided into 4 groups: FLD without metabolic dysfunction (non-MD FLD), MAFLD and the presence of overweight/obesity (MAFLD-OW), MAFLD and the presence of two metabolic abnormalities (MAFLD-MD) and MAFLD and the presence of T2D (MAFLD-T2D). MAFLD-OW included two subgroups: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). The patients without FLD were divided into 2 groups: patients without FLD and without MD (non-FLD nor MD; reference group) and patients without FLD but with MD (non-FLD with MD). EAT and CAC (measured through the Agatston Score) were determined by computed tomography.ResultsCompared with the reference group (non-FLD nor MD), regarding EAT, patients with MAFLD-T2D and MAFLD-MUHO had the highest risk for CVD (OR 15.87, 95% CI 4.26-59.12 and OR 17.60, 95% CI 6.71-46.20, respectively), patients with MAFLD-MHO were also at risk for CVD (OR 3.62, 95% CI 1.83-7.16), and patients with non-MD FLD did not have a significantly increased risk (OR 1.77; 95% CI 0.67-4.73). Regarding CAC, patients with MAFLD-T2D had an increased risk for CVD (OR 6.56, 95% CI 2.18-19.76). Patients with MAFLD-MUHO, MAFLD-MHO and non-MD FLD did not have a significantly increased risk compared with the reference group (OR 2.54, 95% CI 0.90-7.13; OR 1.84, 95% CI 0.67-5.00 and OR 2.11, 95% CI 0.46-9.74, respectively).ConclusionMAFLD-T2D and MAFLD-OW phenotypes had a significant risk for CVD. MAFLD new criteria reinforced the importance of identifying metabolic phenotypes in populations as it may help to identify patients with higher CVD risk and offer a personalized therapeutic management in a primary prevention setting.

Project description:Recently, an expert panel proposed diagnostic criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) in the pediatric population. The aim of this study was to evaluate the prevalence of MAFLD among US adolescents and to investigate whether the new MAFLD definition is able to identify individuals with more advanced liver disease. We analyzed data from participants 12-18 years old included in the 2017-2020 cycles of the National Health and Nutrition Examination Survey, a large survey aimed at including individuals representative of the non-institutionalized general US population. Participants with a complete vibration-controlled transient elastography exam were included. Steatosis was evaluated through the median controlled attenuation parameter (CAP) and fibrosis through median liver stiffness measurement (LSM). Recently proposed criteria for the diagnosis of MAFLD were applied. Multivariable logistic regression analysis was performed to evaluate the impact of the new MAFLD definition on the odds of significant liver fibrosis. We included a total of 1446 adolescents (mean age: 14.9 years; 52.0% male; 47.3% overweight or obese). No participant reported a previous history of viral hepatitis. Steatosis (CAP ≥ 248 dB/m) was present in 25.9% (95% confidence interval [CI] 23.3-28.9) of individuals, and among these, 87.7% met the MAFLD criteria. Only 22.9% of patients with steatosis had elevated alanine aminotransferase levels. Among participants with steatosis, prevalence of significant liver fibrosis (LSM ≥ 7.4 kPa) did not differ significantly according to whether they met MAFLD criteria (9.7% vs. 15.2%, p = 0.276). In the multivariable model, odds of significant fibrosis did not differ significantly between these two groups. MAFLD criteria are met by most US adolescents with elastographic evidence of steatosis. Nonetheless, these criteria do not appear to improve detection of subjects with more advanced liver disease. Further longitudinal studies are needed to evaluate whether metabolic dysfunction is associated with faster progression toward inflammation, fibrosis, and liver-related events.

Project description:Background & aimsOxidative stress triggers metabolic-associated fatty liver disease (MAFLD) and fibrosis. Previous animal studies demonstrated that the transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2), the master regulator of antioxidant response, protects against MAFLD and fibrosis. S217879, a next generation NRF2 activator has been recently shown to trigger diet-induced steatohepatitis resolution and to reduce established fibrosis in rodents. Our aim was to evaluate the therapeutic potential of S217879 in human MAFLD and its underlying mechanisms using the relevant experimental 3D model of patient-derived precision cut liver slices (PCLS).MethodsWe treated PCLS from 12 patients with varying stages of MAFLD with S217879 or elafibranor (peroxisome proliferator-activated receptor [PPAR]α/δ agonist used as a referent molecule) for 2 days. Safety and efficacy profiles, steatosis, liver injury, inflammation, and fibrosis were assessed as well as mechanisms involved in MAFLD pathophysiology, namely antioxidant response, autophagy, and endoplasmic reticulum-stress.ResultsNeither elafibranor nor S217879 had toxic effects at the tested concentrations on human PCLS with MAFLD. PPARα/δ and NRF2 target genes (pyruvate dehydrogenase kinase 4 [PDK4], fibroblast growth factor 21 [FGF21], and NAD(P)H quinone dehydrogenase 1 [NQO1], heme oxygenase 1 [HMOX1], respectively) were strongly upregulated in PCLS in response to elafibranor and S217879, respectively. Compared with untreated PCLS, elafibranor and S217879-treated slices displayed lower triglycerides and reduced inflammation (IL-1β, IL-6, chemokine (C-C motif) ligand 2 [CCL2]). Additional inflammatory markers (chemokine (C-C motif) ligand 5 [CCL5], stimulator of interferon genes [STING], intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1]) were downregulated by S217879. S217879 but not elafibranor lowered DNA damage (phospho-Histone H2A.X [p-H2A.X], RAD51, X-ray repair cross complementing 1 [XRCC1]) and apoptosis (cleaved caspase-3), and inhibited fibrogenesis markers expression (alpha smooth muscle actin [α-SMA], collagen 1 alpha 1 [COL1A1], collagen 1 alpha 2 [COL1A2]). Such effects were mediated through an improvement of lipid metabolism, activated antioxidant response and enhanced autophagy, without effect on endoplasmic reticulum-stress.ConclusionsThis study highlights the therapeutic potential of a new NRF2 activator for MAFLD using patient-derived PCLS supporting the evaluation of NRF2 activating strategies in clinical trials.Impact and implicationsOxidative stress is a major driver of metabolic-associated fatty liver disease (MAFLD) development and progression. Nuclear factor (erythroid-derived 2)-like 2, the master regulator of the antioxidative stress response, is an attractive therapeutic target for the treatment of MAFLD. This study demonstrates that S217879, a new potent and selective nuclear factor (erythroid-derived 2)-like 2 activator, displays antisteatotic effects, lowers DNA damage, apoptosis, and inflammation and inhibits fibrogenesis in human PCLS in patients with MAFLD.

Dataset Information

Metabolic dysfunction associated fatty liver disease: The new nomenclature and its impact.

Background

Aim

Methods

Results

Conclusion

Publications

Metabolic dysfunction associated fatty liver disease: The new nomenclature and its impact.

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