Background & Aims Diagnostic criteria for metabolic associated fatty liver disease (MAFLD) have been proposed, but not validated. We aimed to compare the diagnostic accuracy of the MAFLD definition vs the existing NAFLD criteria to identify patients with significant fibrosis and to characterize the impact of mild alcohol intake. Methods We enrolled 765 Japanese patients with fatty liver (median age 54 years). MAFLD and NAFLD were diagnosed in 79.6% and 70.7% of patients respectively. Significant fibrosis was defined by FIB‐4 index ≥1.3 and liver stiffness ≥6.6 kPa using shear wave elastography. Mild alcohol intake was defined as <20 g/day. Factors associated with significant fibrosis were analysed by logistic regression and decision‐tree analyses. Results Liver stiffness was higher in MAFLD compared to NAFLD (7.7 vs 6.8 kPa, P = .0010). In logistic regression, MAFLD (OR 4.401; 95% CI 2.144‐10.629; P < .0001), alcohol intake (OR 1.761; 95% CI 1.081‐2.853; P = .0234), and NAFLD (OR 1.721; 95%CI 1.009‐2.951; P = .0463) were independently associated with significant fibrosis. By decision‐tree analysis, MAFLD, but not NAFLD or alcohol consumption was the initial classifier for significant fibrosis. The sensitivity for detecting significant fibrosis was higher for MAFLD than NAFLD (93.9% vs 73.0%). In patients with MAFLD, even mild alcohol intake was associated with an increase in the prevalence of significant fibrosis (25.0% vs 15.5%; P = .0181). Conclusions The MAFLD definition better identifies a group with fatty liver and significant fibrosis evaluated by non‐invasive tests. Moreover, in patients with MAFLD, even mild alcohol consumption is associated with worsening of hepatic fibrosis measures.

Aim: Metabolic associated fatty liver disease (MAFLD) partly overlaps with nonalcoholic 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

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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.

We conducted a meta-analysis to investigate the effects of the Mediterranean Diet (Med-Diet) on hepatic steatosis and insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). Six randomized controlled trials were selected for the meta-analysis (sample size: 250 participants). In the meta-analysis, there was no significant difference in body mass index and waist circumference between the Med-Diet and control groups. Med-Diet significantly reduced fatty liver index (FLI) compared with the control diet (standard mean difference [SMD]: –1.06; 95% CI: –1.95 to –0.17; p = 0.02). Med-Diet significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR) compared with the control diet (SMD: –0.34; 95% CI: –0.65 to –0.03; p = 0.03). Similarly, a meta-regression analysis using age showed that Med-Diet significantly reduced FLI and HOMA-IR (95% CI: –0.956 to –0.237, p = 0.001 and 95% CI: –0.713 to –0.003, p = 0.048, respectively). This meta-analysis demonstrated that Med-Diet improved hepatic steatosis and insulin resistance in patients with NAFLD. Thus, Med-Diet is a beneficial pharmaconutritional therapy in patients with NAFLD.

Non‐alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and one of the leading causes of hepatocellular carcinoma and liver transplantation. Moreover, patients with NAFLD frequently complain of non‐specific symptoms including fatigue, abdominal discomfort, as well as anxiety, and NAFLD is reported to affect patient‐reported outcomes (PROs). Thus, for clarifying the total burden of NAFLD, it is crucial to assess all associated outcomes, including not only clinical and economic outcomes but also PROs. PROs are thought to reflect what is happening in one's daily life and is an important way patients and health‐care professionals communicate. There are various instruments for the assessment of PROs. Recently, a NAFLD/non‐alcoholic steatohepatitis (NASH)‐specific instrument called “Chronic Liver Disease Questionnaire (CLDQ)‐NAFLD/NASH” has been developed. CLDQ‐NAFLD/NASH comprises six domains: (i) abdominal symptoms, (ii) activity/energy, (iii) emotional health, (iv) fatigue, (v) systemic symptoms, and (vi) worry. CLDQ‐NAFLD/NASH has demonstrated excellent internal consistency, face validity, content validity, and test–retest reliability. It has been sufficiently validated in two international phase 3 clinical trials. In this review, we summarize features of various instruments for assessing PROs by focusing on CLDQ‐NAFLD/NASH. We also examine the validity of CLDQ‐NAFLD/NASH in Japanese patients and alterations in CLDQ‐NAFLD/NASH score in Japanese patients with significant hepatic fibrosis. Moreover, we discuss the utility of CLDQ‐NAFLD/NASH in phase 3 clinical trials and in a real‐world clinical setting.

The outcome of patients with hepatocellular carcinoma (HCC) is still poor. Decorin is a small leucine-rich proteoglycan, which exerts antiproliferative and antiangiogenic properties in vitro. We aimed to investigate the associations of decorin with physical function and prognosis in patients with HCC. We enrolled 65 patients with HCC treated with transcatheter arterial chemoembolization (median age, 75 years; female/male, 25/40). Serum decorin levels were measured using enzyme-linked immunosorbent assays; patients were classified into the High or Low decorin groups by median levels. Associations of decorin with physical function and prognosis were evaluated by multivariate correlation and Cox regression analyses, respectively. Age and skeletal muscle indices were not significantly different between the High and Low decorin groups. In the High decorin group, the 6-min walking distance was significantly longer than the Low decorin group and was significantly correlated with serum decorin levels (r = 0.2927, p = 0.0353). In multivariate analysis, the High decorin group was independently associated with overall survival (hazard ratio 2.808, 95% confidence interval 1.016–8.018, p = 0.0498). In the High decorin group, overall survival rate was significantly higher than in the Low decorin group (median 732 days vs. 463 days, p = 0.010). In conclusion, decorin may be associated with physical function and prognosis in patients with HCC.

Reduction in activity links to the development and progression of non-alcoholic fatty liver disease (NAFLD). Brain-derived neurotrophic factor (BDNF) is known to regulate an activity. We aimed to investigate the association between reduction in activity and BDNF in patients with NAFLD using data-mining analysis. We enrolled 48 NAFLD patients. Patients were classified into reduced (n = 21) or normal activity groups (n = 27) based on the activity score of the Chronic Liver Disease Questionnaire-NAFLD/non-alcoholic steatohepatitis. Circulating BDNF levels were measured using an enzyme-linked immunoassay. Factors associated with reduced activity were analyzed using decision-tree and random forest analyses. A reduction in activity was seen in 43.8% of patients. Hemoglobin A1c and BDNF were identified as negative independent factors for reduced activity (hemoglobin A1c, OR 0.012, p = 0.012; BDNF, OR 0.041, p = 0.039). Decision-tree analysis showed that “BDNF levels ≥ 19.1 ng/mL” was the most important classifier for reduced activity. In random forest analysis, serum BDNF level was the highest-ranked variable for distinguishing between the reduced and normal activity groups (158 valuable importance). Reduced activity was commonly seen in patients with NAFLD. Data-mining analyses revealed that BNDF was the most important independent factor corresponding with the reduction in activity. BDNF may be an important target for the prevention and treatment of NAFLD.