Background & Aims
The applicability of the novel metabolic dysfunction associated fatty liver disease (MAFLD) definition has been studied in numerous cohorts and compared to non‐alcoholic fatty liver ...disease (NAFLD). No consensus has been reached on which definition is preferred. Therefore, this meta‐analysis aims to compare the epidemiological and clinical features of NAFLD and MAFLD in the general and non‐general population.
Methods
We searched Medline, Embase and Web of Science for studies comparing MAFLD to NAFLD. Based on MAFLD and NAFLD status, the following subgroups were investigated for liver health: overlap fatty liver disease (FLD), NAFLD‐only and MAFLD‐only. Data were pooled using random‐effects models.
Results
We included 17 studies comprising 9 808 677 individuals. In the general population, MAFLD was present in 33.0% (95% CI 29.7%‐36.5%) and NAFLD in 29.1% (95% CI 27.1%‐31.1%). Among those with FLD, 4.0% (95% CI 2.4%‐6.4%) did not meet the MAFLD criteria but had NAFLD (NAFLD‐only) and 15.1% (95% CI 11.5%‐19.5%) was exclusively captured by the novel MAFLD definition (MAFLD‐only). Notably, this MAFLD‐only group was at significantly increased risk for fibrosis (RR 4.2; 95% CI 1.3‐12.9) and had higher alanine aminotransferase (mean difference: 8.0 U/L, 95% CI 2.6‐13.5) and aspartate aminotransferase (mean difference: 6.4 U/L, 95% CI 3.0‐9.7), compared to NAFLD‐only. Similar results were obtained among the non‐general population.
Conclusions
Metabolic dysfunction associated fatty liver disease and NAFLD are highly prevalent in the general population, with considerable overlap between them. However, compared to NAFLD, significantly more individuals were additionally identified by MAFLD than were missed. Importantly, by using the MAFLD criteria, more individuals with liver damage were identified. Therefore, the novel MAFLD definition is superior to NAFLD on a population level.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background and Aims
Recently metabolic dysfunction–associated fatty liver disease (MAFLD) has been introduced and was defined as hepatic steatosis with either overweight, diabetes, and/or a ...combination of other metabolic risk factors. We investigated the application of the MAFLD criteria as compared with NAFLD.
Approach and Results
We performed a cross‐sectional analysis within the Rotterdam Study, a large prospective population‐based cohort. Participants who attended the liver ultrasound and transient elastography program between 2009 and 2014 were eligible for inclusion. Subsequently, individuals with viral hepatitis, alcohol intake >60 g/day, missing alcohol data, and/or missing body mass index were excluded. According to their NAFLD and MAFLD status based on metadata and ultrasound, participants were allocated in overlap fatty liver disease (FLD), NAFLD‐only, MAFLD‐only, or no FLD. Fibrosis was defined as liver stiffness ≥8.0 kPa. In our analysis, 5445 participants were included: 1866 (34.3%) had MAFLD and 1604 (29.5%) Correction added on December 27, 2021 after first online publication: The preceding fragment was changed from “1623 (29.8%)” had NAFLD. This resulted in 1547 (28.4%) Correction added on December 27, 2021 after first online publication: The preceding fragment was changed from “1566 (28.8%)” individuals with overlap FLD, 319 (5.9%) Correction added on December 27, 2021 after first online publication: The preceding fragment was changed from “300 (5.5%)” with MAFLD‐only, 57 (1.0%) with NAFLD‐only, and 3522 (64.7%) with no FLD. The MAFLD‐only group was strongly associated with fibrosis (adjusted OR 5.30 Correction added on December 27, 2021 after first online publication: The preceding fragment was changed from "OR 5.27", p < 0.001) and log‐transformed liver stiffness (adjusted beta 0.116, p < 0.001), as opposed to the NAFLD‐only group, in which no cases of fibrosis were identified and no association with liver stiffness (adjusted beta 0.006, p = 0.90) was found.
Conclusions
FLD is highly prevalent in the general population. However, not the NAFLD‐only, but the MAFLD‐only group was associated with fibrosis and higher liver stiffness—independent of demographic and lifestyle factors. We believe that using the MAFLD criteria will help improve the identification and treatment of patients with FLD at risk for fibrosis.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Nonalcoholic fatty liver disease (NAFLD) might affect brain health via the so-called liver-brain axis. Whether this results in an increased risk for dementia remains unclear. Therefore, we ...investigated the association of NAFLD and fibrosis with incident dementia and cognition among the elderly.
We performed longitudinal and cross-sectional analyses within the Rotterdam Study, an ongoing prospective cohort. Participants visiting between 1997 and 2002 with available fatty liver index (FLI) (set 1) or participants visiting between 2009 and 2014 with abdominal ultrasound (set 2) and liver stiffness (set 3) were included. Exclusion criteria were secondary causes for steatosis, prevalent dementia, and missing alcohol data. NAFLD was defined as FLI ≥60 or steatosis on ultrasound and fibrosis as liver stiffness ≥8.0 kPa. Dementia was defined according to the
. Associations between NAFLD, fibrosis, or liver stiffness and incident dementia were quantified using Cox regression. Finally, the association between NAFLD and cognitive function was assessed cross-sectionally.
Set 1 included 3,975 participants (age 70 years, follow-up 15.5 years), set 2 4,577 participants (age 69.9 years, follow-up 5.7 years), and set 3 3,300 participants (age 67.6 years, follow-up 5.6 years). NAFLD and fibrosis were consistently not associated with an increased risk for dementia (NAFLD based on ultrasound, hazard rate HR 0.84, 95% CI 0.61-1.16; NAFLD based on FLI, HR 0.92, 95% CI 0.69-1.22; fibrosis, HR 1.07, 95% CI 0.58-1.99) in fully adjusted models. Of interest, NAFLD was associated with a significantly decreased risk for incident dementia until 5 years after FLI assessment (HR 0.48; 95% CI 0.24-0.94). Moreover, NAFLD was not associated with worse cognitive function, covering several domains.
NAFLD and fibrosis were not associated with an increased risk for incident dementia, nor was NAFLD associated with impaired cognitive function. In contrast, NAFLD was even protective in the first 5 years of follow-up, hinting toward NAFLD regression before dementia onset.
Clinical Trial Number: NTR6831.
Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non‐alcoholic fatty liver disease ...and alcohol‐related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at‐risk populations. Thus far, a limited number of population‐based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate −18% to 27%‐in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new terminology updated from non-alcoholic fatty liver disease (NAFLD). In this study, we aim to estimate the global prevalence of ...MAFLD specifically in overweight and obese adults from the general population by performing a systematic review and meta-analysis through mining the existing epidemiological data on fatty liver disease.
We searched Medline, Embase, Web of Science, Cochrane and google scholar database from inception to November, 2020. DerSimonian-Laird random-effects model with Logit transformation was performed for data analysis. Sensitivity analysis and meta-regression were used to explore predictors of MAFLD prevalence in pooled statistics with high heterogeneity.
We identified 116 relevant studies comprised of 2,667,052 participants in general population with an estimated global MAFLD prevalence as 50.7% (95% CI 46.9-54.4) among overweight/obese adults regardless of diagnostic techniques. Ultrasound was the most commonly used diagnostic technique generating prevalence rate of 51.3% (95% CI, 49.1-53.4). Male (59.0%; 95% CI, 52.0-65.6) had a significantly higher MAFLD prevalence than female (47.5%; 95% CI, 40.7-54.5). Interestingly, MAFLD prevalence rates are comparable based on classical NAFLD and non-NAFLD studies in general population. The pooled estimate prevalence of comorbidities such as type 2 diabetes and metabolic syndrome was 19.7% (95% CI, 12.8-29.0) and 57.5% (95% CI, 49.9-64.8), respectively.
MAFLD has an astonishingly high prevalence rate in overweight and obese adults. This calls for attention and dedicated action from primary care physicians, specialists, health policy makers and the general public alike.
Display omitted
MAFLD often cooccurs with excessive alcohol consumption, while its prognostic value in this group remains unclear. We aimed to study the mortality risk of MAFLD in relation to excessive alcohol ...consumption and its potential interactions.
We analyzed persons 25-74 years old enrolled in the National Health and Nutrition Examination Survey III cohort with available steatosis and alcohol data. Participants with viral hepatitis, body mass index < 18.5, and missing data on age or follow-up were excluded, leaving 12,656 participants for analysis with a median follow-up of 22.9 20.9-24.8 years. MAFLD was defined as steatosis on ultrasound in the presence of metabolic dysfunction. Daily alcohol intake of ≥10 g in females and ≥20 g in males was considered excessive alcohol consumption. We quantified mortality risk with multivariate Cox regression for MAFLD and excessive alcohol consumption. Models were adjusted for age, age squared, sex, race, marital status, education, and smoking. MAFLD was present in 31% and excessive alcohol consumption in 13% and were both independently and simultaneously associated with increased mortality risk in fully adjusted models (adjusted HR aHR, 1.21; 95% CI, 1.13-1.30 and aHR, 1.14; 95% CI, 1.04-1.26, respectively). Similarly, MAFLD was associated with increased mortality risk in participants with and without excessive alcohol consumption. Participants with both MAFLD and excessive alcohol consumption (4.0%) expressed the highest mortality risk (aHR, 1.47; 95% CI, 1.28-1.71). Results were consistent using the initial 10 years of follow-up, a stringent definition of excessive alcohol, and propensity score weighting.
MAFLD increases mortality risk independent of excessive alcohol consumption. This underscores the importance of MAFLD, even in patients with excessive alcohol consumption.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, OILJ, SBCE, SBMB, UL, UPUK
The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the city of Rotterdam, The Netherlands. The study aims to unravel etiology, preclinical course, natural history and ...potential targets for intervention for chronic diseases in mid-life and late-life. The study focuses on cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016, the cohort is being expanded by persons aged 40 years and over. The findings of the Rotterdam Study have been presented in over 1700 research articles and reports. This article provides an update on the rationale and design of the study. It also presents a summary of the major findings from the preceding 3 years and outlines developments for the coming period.
Background and Aims
Previous small studies have appraised the gut microbiome (GM) in steatosis, but large‐scale studies are lacking. We studied the association of the GM diversity and composition, ...plasma metabolites, predicted functional metagenomics, and steatosis.
Approach and Results
This is a cross‐sectional analysis of the prospective population‐based Rotterdam Study. We used 16S ribosomal RNA gene sequencing and determined taxonomy using the SILVA reference database. Alpha diversity and beta diversity were calculated using the Shannon diversity index and Bray–Curtis dissimilarities. Differences were tested across steatosis using permutational multivariate analysis of variance. Hepatic steatosis was diagnosed by ultrasonography. We subsequently selected genera using regularized regression. The functional metagenome was predicted based on the GM using Kyoto Encyclopedia of Genes and Genomes pathways. Serum metabolomics were assessed using high‐throughput proton nuclear magnetic resonance. All analyses were adjusted for age, sex, body mass index, alcohol, diet, and proton‐pump inhibitors. We included 1,355 participants, of whom 472 had steatosis. Alpha diversity was lower in steatosis (P = 1.1∙10−9), and beta diversity varied across steatosis strata (P = 0.001). Lasso selected 37 genera of which three remained significantly associated after adjustment (Coprococcus3: β = −65; Ruminococcus Gauvreauiigroup: β = 62; and Ruminococcus Gnavusgroup: β = 45, Q‐value = 0.037). Predicted metagenome analyses revealed that pathways of secondary bile‐acid synthesis and biotin metabolism were present, and D‐alanine metabolism was absent in steatosis. Metabolic profiles showed positive associations for aromatic and branched chain amino acids and glycoprotein acetyls with steatosis and R. Gnavusgroup, whereas these metabolites were inversely associated with alpha diversity and Coprococcus3.
Conclusions
We confirmed, on a large‐scale, the lower microbial diversity and association of Coprococcus and Ruminococcus Gnavus with steatosis. We additionally showed that steatosis and alpha diversity share opposite metabolic profiles.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, OILJ, SBCE, SBMB, UL, UPUK
PDF
