Recently, international expert panels have proposed a new definition of fatty liver: metabolic dysfunction‐associated fatty liver disease (MAFLD). MAFLD is not just a simple renaming of non‐alcoholic ...fatty liver disease (NAFLD). The unique feature of MAFLD is the inclusion of metabolic dysfunctions, which are high‐risk factors for events. In addition, MAFLD is independent of alcohol intake and the co‐existing causes of liver disease. This new concept of MAFLD may have a widespread impact on patients, medical doctors, medical staff, and various stakeholders regarding fatty liver. Thus, MAFLD may renovate clinical practice and disease awareness of fatty liver. In this review, we introduce the definition of and rationale for MAFLD. We further describe representative cases showing how the diagnostic processes differ between MAFLD and NAFLD. We also summarize recent studies comparing MAFLD with NAFLD and discuss the impact of MAFLD on clinical trials, Japanese populations, and disease awareness.
Aim
Metabolic associated fatty liver disease (MAFLD) partly overlaps with non‐alcoholic fatty liver disease (NAFLD). Thus, using a generalized estimating equation (GEE) approach, we aimed to ...investigate the difference in worsening of atherosclerotic cardiovascular disease (ASCVD) risk between patients with MAFLD and NAFLD. We also investigated factors related to the difference between the two groups.
Methods
We enrolled 2306 subjects with fatty liver (MAFLD 80.7%, NAFLD 63.4%). Subjects with MAFLD/NAFLD were sub‐classified into three groups: NAFLD with no metabolic dysfunction (non‐Met NAFLD), overlapping, and MAFLD with moderate alcohol consumption (mod‐Alc MAFLD). ASCVD risk was estimated by non‐invasive tests, including the Suita score. An event was defined as worsening of these scores from the low‐risk to the high‐risk group. Independent factors for the event were analyzed by Cox regression analysis with the GEE.
Results
In Cox regression analysis, MAFLD (HR 1.08, 95% CI 1.02–1.15, p = 0.014) and alcohol consumption (20–39 g/day; HR 1.73, 95% CI 1.26–2.36, p = 0.001) were independently associated with worsening of the Suita score. In a subanalysis, the incidence of the event was significantly lower in non‐Met NAFLD than in the overlapping group (HR 0.70, 95% CI 0.50–0.98, p = 0.042). However, no significant difference was observed in the incidence between the overlapping and mod‐Alc MAFLD group (HR 1.19, 95% CI 0.89–1.58, p = 0.235).
Conclusions
The GEE approach demonstrates that MAFLD better identifies patients with worsening of ASCVD risk than NAFLD. Moreover, the superiority of MAFLD over NAFLD was due to the presence of metabolic dysfunction rather than moderate alcohol consumption.
Fatty liver is now a major cause of liver disease in the Asia-Pacific region. Liver diseases in this region have distinctive characteristics. First, fatty liver is frequently observed in ...lean/normal-weight individuals. However, there is no standard definition of this unique phenotype. Second, fatty liver is often observed in patients with concomitant viral hepatitis. The exclusion of viral hepatitis from non-alcoholic fatty liver disease limits its value and detracts from the investigation and holistic management of coexisting fatty liver in patients with viral hepatitis. Third, fatty liver-associated hepatocellular carcinoma (HCC) is generally categorized as non-B non-C HCC. Fourth, the population is aging rapidly, and it is imperative to develop a practicable, low-intensity exercise program for elderly patients. Fifth, most patients and nonspecialized healthcare professionals still lack an awareness of the significance of fatty liver both in terms of intrahepatic and extrahepatic disease and cancer. Recently, an international expert panel proposed a new definition of fatty liver: metabolic dysfunction-associated fatty liver disease (MAFLD). One feature of MAFLD is that metabolic dysfunction is a prerequisite for diagnosis. Pertinent to regional issues, MAFLD also provides its diagnostic criteria in lean/normal-weight individuals. Furthermore, MAFLD is independent of any concomitant liver disease, including viral hepatitis. Therefore, MAFLD may be a more suitable definition for fatty liver in the Asia-Pacific region. In this review, we introduce the regional characteristics of fatty liver and discuss the advantages of MAFLD for improving clinical practice for liver disease in the region.
Metabolic reprograming is crucial in the proliferation of hepatocellular carcinoma (HCC). Canagliflozin (CANA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, affects various metabolisms. We ...investigated the effects of CANA on proliferation and metabolic reprograming of HCC cell lines using multi-omics analysis of metabolomics and absolute quantification proteomics (iMPAQT).
The cells were counted 72 hours after treatment with CANA (10 μM; n = 5) or dimethyl sulfoxide (control CON; n = 5) in Hep3B and Huh7 cells. In Hep3B cells, metabolomics and iMPAQT were used to evaluate the levels of metabolites and metabolic enzymes in the CANA and CON groups (each n = 5) 48 hours after treatment.
Seventy-two hours after treatment, the number of cells in the CANA group was significantly decreased compared to that in the CON group in Hep3B and Huh7 cells. On multi-omics analysis, there was a significant difference in the levels of 85 metabolites and 68 metabolic enzymes between the CANA and CON groups. For instance, CANA significantly downregulated ATP synthase F1 subunit alpha, a mitochondrial electron transport system protein (CON 297.28±20.63 vs. CANA 251.83±22.83 fmol/10 μg protein; P = 0.0183). CANA also significantly upregulated 3-hydroxybutyrate, a beta-oxidation metabolite (CON 530±14 vs. CANA 854±68 arbitrary units; P<0.001). Moreover, CANA significantly downregulated nucleoside diphosphate kinase 1 (CON 110.30±11.37 vs. CANA 89.14±8.39 fmol/10 μg protein; P = 0.0172).
We found that CANA suppressed the proliferation of HCC cells through alterations in mitochondrial oxidative phosphorylation metabolism, fatty acid metabolism, and purine and pyrimidine metabolism. Thus, CANA may suppress the proliferation of HCC by regulating metabolic reprograming.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim
Reflux esophagitis is associated with metabolic dysfunction. Recently, fatty liver has been redefined as metabolic dysfunction‐associated fatty liver disease (MAFLD). We investigated the impact ...of MAFLD and its subtypes on the incidence of reflux esophagitis.
Methods
This multicenter, observational cohort study enrolled 9100 consecutive health‐check examinees who underwent esophagogastroduodenoscopy and ultrasonography. All patients were classified into the MAFLD or non‐MAFLD group. Based on the Asian cut‐off value for body mass index (BMI), the MAFLD group was further classified into the lean/normal‐weight (BMI <23 kg/m2) and overweight/obese (BMI ≥23 kg/m2) subgroups. The impact of MAFLD and its subtypes on the cumulative incidence of reflux esophagitis was evaluated using multivariable Cox proportional hazards regression analysis.
Results
MAFLD was diagnosed in 26.5% (2416/9100) of patients. Multivariable Cox proportional hazards regression analysis indicated that MAFLD (hazard ratio HR 1.2183; 95% confidence interval CI 1.0954–1.3550; p = 0.0003), hiatal hernia, and aging were independent risk factors for reflux esophagitis. Stratification analysis indicated that cumulative incidence of reflux esophagitis among patients with MAFLD was significantly higher in the lean/normal‐weight than in the overweight/obese group (HR 1.3274; 95% CI 1.0043–1.7547; p = 0.0466). Among various metabolic factors, visceral adiposity was the only independent metabolic risk factor for reflux esophagitis (HR 2.8331; 95% CI 1.0201–7.8691; p = 0.0457) in the lean/normal‐weight MAFLD group.
Conclusions
MAFLD, in particular lean/normal‐weight MAFLD, is independent risk factor for reflux esophagitis. Furthermore, visceral adiposity was identified as the most strong metabolic risk factor for reflux esophagitis in lean/normal‐weight patients with MAFLD.
Aim
Advanced hepatic fibrosis is seen in individuals with potential hepatocellular carcinoma and cardiovascular disease. Hepatic fibrosis can be assessed using a combination of the FIB‐4 index and ...imaging modalities, including shear wave elastography. We aimed to investigate the prevalence of advanced fibrosis in the general population and the profiles associated with advanced fibrosis using a data‐mining analysis.
Methods
We enrolled 1155 health checkup examinees (median age 53 years, 685 women, 470 male). Advanced fibrosis was defined by FIB‐4 index ≥1.3 and liver stiffness ≥8.07 kPa using shear wave elastography. Participants were classified as normal‐mild fibrosis (n = 1035) or advanced fibrosis (n = 120). Factors associated with advanced fibrosis were analyzed by logistic regression and decision‐tree analyses.
Results
Advanced fibrosis was observed in 10.4% of participants (120/1155). In the logistic regression analysis, independent factors for advanced fibrosis were age (≥75 years; OR 2.12, 95% CI 1.021–4.415; P = 0.0419) and the presence of metabolic syndrome (OR 2.51, 95% CI 1.416–4.462; P = 0.0017). The decision‐tree analysis showed two profiles associated with advanced fibrosis: profile 1 – individuals aged ≥65 years with metabolic syndrome and mild‐to‐moderate alcohol consumption (prevalence of advanced fibrosis 73.3%); and profile 2 – individuals without metabolic syndrome, aged ≥75 years, with no exercise habit (prevalence of advanced fibrosis 56.3%).
Conclusions
Advanced fibrosis was observed in 10.4% of health checkup examinees. Furthermore, we showed that aging, metabolic syndrome with mild‐to‐moderate alcohol consumption, and physical inactivity were associated with advanced fibrosis. Thus, prevention of metabolic syndrome and alcohol withdrawal, as well as exercise habits, might inhibit the progression of hepatic fibrosis.
Aim
Hepatic fibrosis is associated with various factors, including metabolic dysfunction‐associated fatty liver disease (MAFLD), insulin resistance, and alcohol intake in patients with morbid ...obesity. We investigated factors directly associated with hepatic fibrosis in patients with morbid obesity using a graphical model.
Methods
We enrolled 134 consecutive patients with morbid obesity who underwent liver biopsy during sleeve gastrectomy (median age 43.5 years; MAFLD 78.4%; homeostasis model assessment of insulin resistance HOMA‐IR 5.97; >20 g/day alcohol intake 14.2%). Patients were classified into none/mild (F0/1; n = 77) or significant/advanced fibrosis (F2/3; n = 57) groups, based on histology. Factors associated with F2/3 were analyzed using logistic regression analysis and a graphical model.
Results
F2/3 was observed in 42.5% of the enrolled patients. The prevalence of MAFLD and HOMA‐IR values were significantly higher in the F2/3 group than in the F0/1 group; however, no significant difference in alcohol intake was observed between the two groups. On logistic regression analysis, MAFLD, but not HOMA‐IR or alcohol intake, was the only independent factor associated with F2/3 (odds ratio 7.555; 95% confidence interval 2.235–25.544; p = 0.0011). The graphical model revealed that F2/3 directly interacted with MAFLD, diabetes mellitus, HOMA‐IR, and low‐density lipoprotein cholesterol. Among these factors, MAFLD showed the strongest interaction with F2/3.
Conclusions
We determined that MAFLD was more directly associated with significant/advanced fibrosis than insulin resistance or hyperlipidemia, and alcohol intake was not directly associated with hepatic fibrosis. Metabolic dysfunction‐associated fatty liver disease could be the most important factor for hepatic fibrosis in patients with morbid obesity.
Colorectal adenoma is linked to metabolic dysfunction. Metabolic dysfunction-associated fatty liver disease (MAFLD) has a precise definition and three subtypes, including non-obese MAFLD. We aimed to ...investigate the impact of MAFLD on the prevalence of colorectal adenoma by comparing it to non-alcoholic fatty liver disease (NAFLD) in health check-up examinees. This is a multicenter retrospective study. We enrolled 124 consecutive health check-up examinees who underwent colonoscopy. NAFLD and MAFLD were present in 58 and 63 examinees, respectively. Colorectal adenoma was diagnosed by biopsy. The impact of the MAFLD definition on the prevalence of colorectal adenoma was investigated by logistic regression, decision-tree, and random forest analyses. In logistic regression analysis, MAFLD was identified as the only independent factor associated with the presence of colorectal adenoma (OR 3.191; 95% CI 1.494–7.070; p = 0.003). MAFLD was also identified as the most important classifier for the presence of colorectal adenoma in decision-tree and random forest analyses (29 variable importance value). Among the three subtypes of MAFLD, non-obese MAFLD was the sole independent factor associated with the presence of colorectal adenoma (OR 3.351; 95% CI 1.589–7.262; p ≤ 0.001). Non-obese MAFLD was also the most important classifier for the presence of colorectal adenoma in decision-tree and random forest analyses (31 variable importance value). MAFLD, particularly non-obese MAFLD, is the most important factor associated with the presence of colorectal adenoma rather than NAFLD. Colonoscopy examination should be considered in patients with MAFLD, especially those who are non-obese.
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