MAFLD might be better in identifying subjects with sarcopenia or cardiovascular risk than NAFLD: A nationwide study.

BACKGROUND AND AIM: Clinical features of non-alcoholic fatty liver disease (NAFLD), but not fulfilling the diagnostic criteria of metabolic dysfunction-associated fatty liver disease (MAFLD), remain unclear. We investigated the risk of sarcopenia and cardiovascular disease (CVD) in MAFLD and non-metabolic risk (MR) NAFLD. METHODS: Subjects were selected from the Korean National Health and Nutrition Examination Surveys 2008-2011. Liver steatosis was assessed using fatty liver index. Significant liver fibrosis was defined using fibrosis-4 index, categorized by age cut-offs. Sarcopenia was defined as the lowest quintile sarcopenia index. Atherosclerotic CVD (ASCVD) risk score > 10% was defined as high probability. RESULTS: A total of 7248 subjects had fatty liver (137 with non-MR NAFLD, 1752 with MAFLD/non-NAFLD, and 5359 with overlapping MAFLD and NAFLD). In non-MR NAFLD group 28 (20.4%) had significant fibrosis. The risk of sarcopenia (adjusted odds ratio [aOR] = 2.71, 95% confidence index [CI] = 1.27-5.78) and high probability of ASCVD (aOR = 2.79, 95% CI = 1.23-6.35) was significantly higher in MAFLD/non-NAFLD group than in non-MR NAFLD group (all P < 0.05). The risk of sarcopenia and high probability of ASCVD was similar between subjects with and without significant fibrosis in non-MR NAFLD group (all P > 0.05). However, the risk was significantly higher in MAFLD group than in non-MR NAFLD group (aOR = 3.38 for sarcopenia and 3.73 for ASCVD; all P < 0.05). CONCLUSIONS: The risks of sarcopenia and CVD were significantly higher in MAFLD group but did not differ according to fibrotic burden in non-MR NAFLD group. The MAFLD criteria might be better for identifying high-risk fatty liver disease than the NAFLD criteria.

Evogliptin Directly Inhibits Inflammatory and Fibrotic Signaling in Isolated Liver Cells.

Chronic liver inflammation can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Kupffer cells (KC) secrete proinflammatory and fibrogenic cytokines in response to lipopolysaccharide (LPS), and so play an important role in liver inflammation, where they induce hepatocellular damage. LPS also activates hepatic stellate cells and induces extracellular matrix deposition. In this study, we used isolated primary KC, primary hepatocytes, and primary hepatic stellate cells (HSC) to investigate whether evogliptin directly inhibits inflammatory and fibrotic signaling. We found that evogliptin inhibited LPS-induced secretion of inducible nitric oxide synthase and transforming growth factor ß (TGF-ß) from KC. Moreover, evogliptin inhibited inflammatory mediator release from hepatocytes and hepatic stellate cell activation that were induced by KC-secreted cytokines. In hepatocytes, evogliptin also inhibited LPS-induced expression of proinflammatory cytokines and fibrotic TGF-ß. In addition, evogliptin inhibited TGF-ß-induced increases in connective tissue growth factor levels and HSC activation. These findings indicate that evogliptin inhibits inflammatory and fibrotic signaling in liver cells. We also showed that the inhibitory effect of evogliptin on inflammatory and fibrotic signaling is associated with the induction of autophagy.

Nonalcoholic Fatty Liver Disease and Sarcopenia Are Independently Associated With Cardiovascular Risk.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) and sarcopenia have a close association with an increased risk of atherosclerotic cardiovascular disease (ASCVD). This study investigated the influence of NAFLD and sarcopenia on ASCVD risk. METHODS: Data from the 2008-2011 Korean National Health and Nutrition Examination Surveys database were analyzed (n = 7,191). The sarcopenia index was calculated using dual-energy x-ray absorptiometry. Sarcopenia was defined as the lowest quintile sarcopenia index value (cutoffs = 0.882 for men and 0.582 for women). NAFLD was defined as a comprehensive NAFLD score ≥40. Liver fibrosis was assessed using the fibrosis-4 (FIB-4) index. ASCVD risk was evaluated using American College of Cardiology/American Heart Association guidelines. High probability of ASCVD was defined as ASCVD risk >10%. RESULTS: The prevalence rates of NAFLD and sarcopenia were 31.2% (n = 2,241) and 19.5% (n = 1,400), respectively. The quartile-stratified ASCVD risk scores were positively associated with NAFLD and sarcopenia (all P for trend < 0.001). Subjects with both NAFLD and sarcopenia had a higher risk for high probability of ASCVD (odds ratio = 1.83, P = 0.014) compared with controls without NAFLD and sarcopenia. Among subjects with NAFLD, FIB-4-defined significant liver fibrosis and sarcopenia additively raised the risk for high probability of ASCVD (odds ratio = 3.56, P < 0.001) compared with controls without FIB-4-defined significant liver fibrosis or sarcopenia. DISCUSSION: NAFLD and sarcopenia were significantly associated with an increased risk of ASCVD in the general population. In addition, NAFLD with significant liver fibrosis and sarcopenia were significantly associated with an increased risk of ASCVD in subjects with NAFLD.

TRiC subunits enhance BDNF axonal transport and rescue striatal atrophy in Huntington's disease.

Corticostriatal atrophy is a cardinal manifestation of Huntington's disease (HD). However, the mechanism(s) by which mutant huntingtin (mHTT) protein contributes to the degeneration of the corticostriatal circuit is not well understood. We recreated the corticostriatal circuit in microfluidic chambers, pairing cortical and striatal neurons from the BACHD model of HD and its WT control. There were reduced synaptic connectivity and atrophy of striatal neurons in cultures in which BACHD cortical and striatal neurons were paired. However, these changes were prevented if WT cortical neurons were paired with BACHD striatal neurons; synthesis and release of brain-derived neurotrophic factor (BDNF) from WT cortical axons were responsible. Consistent with these findings, there was a marked reduction in anterograde transport of BDNF in BACHD cortical neurons. Subunits of the cytosolic chaperonin T-complex 1 (TCP-1) ring complex (TRiC or CCT for chaperonin containing TCP-1) have been shown to reduce mHTT levels. Both CCT3 and the apical domain of CCT1 (ApiCCT1) decreased the level of mHTT in BACHD cortical neurons. In cortical axons, they normalized anterograde BDNF transport, restored retrograde BDNF transport, and normalized lysosomal transport. Importantly, treating BACHD cortical neurons with ApiCCT1 prevented BACHD striatal neuronal atrophy by enhancing release of BDNF that subsequently acts through tyrosine receptor kinase B (TrkB) receptor on striatal neurons. Our findings are evidence that TRiC reagent-mediated reductions in mHTT enhanced BDNF delivery to restore the trophic status of BACHD striatal neurons.

Effect of statin on hepatocellular carcinoma in patients with type 2 diabetes: A nationwide nested case-control study.

Relationship on new statin use and the risk of hepatocellular carcinoma (HCC) in patients with incident type 2 diabetes mellitus (T2DM), who might be at the risk of developing HCC, is uncertained. A nationwide population-based nested case-control study was conducted within the National Health Insurance Service National Sample Cohort 2002-2013 in Korea. Newly prescribed statin after newly diagnosed T2DM was defined as statin use. Controls were matched to case patients on age, sex, follow-up time, and the date of diabetes diagnosis at a five-to-one ratio. Odds ratios (ORs) for associations of statin use with HCC were calculated using conditional logistic regression. After at least a 5-year HCC-free period, there were 229 incident HCC cases and 1,145 matched controls from 47,738 patients with incident diabetes. Of these 229 incident HCC cases, 27 (11.8%) were statin users, whereas 378 (33.0%) were statin users among 1,145 controls. Statin use was associated with a reduced risk of HCC development (adjusted OR [AOR]= 0.36, 95% confidence interval [CI] 0.22-0.60) after adjustment for chronic viral hepatitis, liver cirrhosis, alcoholic liver disease, previous cancer, aspirin use, insulin use, sulfonylurea use, metformin use, thiazolidinedione use, history of chronic obstructive pulmonary disease, Charlson comorbidity score, household income level, and residential area. Risk reduction was accentuated with an increase of cumulative defined daily doses (cDDD) compared with non-users (AORs 0.53, 0.36, 0.32, and 0.26 in ≤60, 60-180, 181-365, and >365cDDD, respectively; P for trend <0.0001). The risk reduction was apparent in the presence of liver disease (AOR = 0.27, 95% CI 0.14-0.50), including heterogeneous groups of clinical diagnosis of liver disease, but not significant in the absence of liver disease (AOR = 0.64, 95% CI 0.32-1.29). Among patients with new onset T2DM, statin use before HCC diagnosis may have a beneficial inhibitory effect on HCC development in a dose-dependent manner, especially in individuals with liver disease.

Anatomic fat depots and cardiovascular risk: a focus on the leg fat using nationwide surveys (KNHANES 2008-2011).

BACKGROUND: Although central fat is a well-known risk factor for cardiovascular disease (CVD) and cardiometabolic disorders, the effect of other regional fats or muscle distribution on CVD risk has not been fully investigated. METHODS: This was a cross-sectional study using nationally representative samples of 15,686 subjects from the 2008-2011 Korea National Health and Nutrition Examination Survey. Individual CVD risk was evaluated in adults aged ≥20 without prior CVD, using atherosclerotic cardiovascular disease (ASCVD) risk equations according to the 2013 ACC/AHA guidelines. Body composition was assessed by dual X-ray absorptiometry. RESULTS: Ratio of leg fat to total fat (LF/TF ratio) was the most predictive for CVD among body fat or muscle distribution parameters (AUC = 0.748, 95% CI 0.741-0.755). ASCVD risk score was gradually increased with decreased LF/TF ratio (P < 0.001), and individuals whose LF/TF ratio in lowest tertile tended to belong to the high-risk (10-year risk >10%) group compared to those in the highest tertile (OR = 6.25, 95% CI 5.60-6.98). Subjects in the lowest tertile showed increased risk of cardiometabolic risk factor components including obesity, hypertension, diabetes, dyslipidemia, chronic kidney disease, and albuminuria (OR range 2.57-11.24, all P < 0.001). In addition, a higher LF/TF ratio was associated with decreased ASCVD risk, even in subjects with multiple CVD risk factors. Multiple logistic regression analyses also demonstrated this association (OR = 1.85, 95% CI 1.36-2.52). CONCLUSIONS: Among various body composition parameters, LF/TF ratio was superior in predicting higher CVD risk and a higher LF/TF ratio was independently associated with decreased risk of CVD and each cardiometabolic risk factor.

Association between dietary acid load and the risk of cardiovascular disease: nationwide surveys (KNHANES 2008-2011).

BACKGROUND: Acid-base imbalance has been reported to increase incidence of hypertension and diabetes. However, the association between diet-induced acid load and cardiovascular disease (CVD) risk in the general population has not been fully investigated. METHODS: This was a population-based, retrospectively registered cross-sectional study using nationally representative samples of 11,601 subjects from the Korea National Health and Nutrition Examination Survey 2008-2011. Individual CVD risk was evaluated using atherosclerotic cardiovascular disease (ASCVD) risk equations according to 2013 ACC/AHA guideline assessment in subjects aged 40-79 without prior CVD. Acid-base status was assessed with both the potential renal acid load (PRAL) and the dietary acid load (DAL) scores derived from nutrient intake. RESULTS: Individuals in the highest PRAL tertile had a significant increase in 10 year ASCVD risks (9.6 vs. 8.5 %, P < 0.01) and tended to belong to the high-risk (10 year risk >10 %) group compared to those in the lowest PRAL tertile (odds ratio [OR] 1.23, 95 % confidence interval [CI] 1.22-1.35). The association between higher PRAL score and high CVD risk was stronger in the middle-aged group. Furthermore, a multiple logistic regression analysis also demonstrated this association (OR 1.20 95 % CI 1.01-1.43). Subgroup analysis stratified obesity or exercise status; individuals in unhealthy condition with lower PRAL scores had comparable ASCVD risk to people in the higher PRAL group that were in favorable physical condition. In addition, elevated PRAL scores were associated with high ASCVD risk independent of obesity, exercise, and insulin resistance, but not sarcopenia. Similar trends were observed with DAL scores. CONCLUSION: Diet-induced acid load was associated with increased risk of CVD, independent of obesity and insulin resistance.

Purification and identification of ß-casein phosphopeptide (1-25).

The ß-casein phosphopeptide 1-25 (ßCPP) is involved in calcium binding, cellular transduction, and dental remineralization. The objective of this work was to improve upon the original protocol commonly used for isolation of this phosphopeptide from ß-casein. This method exploits the isoelectric point of ß-casein fragments to selectively precipitate ßCPP. The highest ßCPP extraction yield reported to date with this protocol is 14.4±0.5% of theoretically available ßCPP. The present work optimizes 2 steps in this procedure, namely the length of trypsin digestion and incorporation of cold acetone precipitation, to increase the yield to 32.3±5.4%. Reverse-phase HPLC indicated high purity of the isolate, whereas mass spectrometry confirmed 2 forms of the phosphopeptide: fragments 1-25 (87%) and 2-25 (13%). The adaptation of the existing protocol represents a significant improvement in extraction yield and facilitates preparation of larger amounts of high-purity ßCPP for subsequent analysis and use in functional foods and other applications.

Distalization of the mandibular dentition with a ramal plate for skeletal Class III malocclusion correction.

The retromolar fossa is an anatomically suitable skeletal anchorage site. The aim of this report was to introduce a novel appliance for the correction of skeletal Class III malocclusions with mandibular dentition distalization. The placement site and the procedure of the ramal plate are described. The resulting force vectors are parallel to the functional occlusal plane leading to efficient molar distalization. This approach is demonstrated with 2 adult patients who refused a surgical treatment option. This ramal plate may be indicated for total arch distalization for nonextraction and nonsurgical cases.

Visceral adiposity is associated with altered myocardial glucose uptake measured by (18)FDG-PET in 346 subjects with normal glucose tolerance, prediabetes, and type 2 diabetes.

BACKGROUND: The heart requires constant sources of energy mostly from free fatty acids (FFA) and glucose. The alteration in myocardial substrate metabolism occurs in the heart of diabetic patients, but its specific association with other metabolic variables remains unclear. We aimed to evaluate glucose uptake in hearts of subjects with normal glucose tolerance (NGT), prediabetes, and type 2 diabetes mellitus (T2DM) using [(18)F]-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) in association with visceral and subcutaneous adiposity, and metabolic laboratory parameters. METHODS: A total of 346 individuals (NGT, n = 76; prediabetes, n = 208; T2DM, n = 62) in a health promotion center of a tertiary hospital were enrolled. The fasting myocardial glucose uptake, and visceral and subcutaneous fat areas were evaluated using (18)FDG-PET and abdominal computed tomography, respectively. RESULTS: Myocardial glucose uptake was significantly decreased in subjects with T2DM compared to the NGT or prediabetes groups (p for trend = 0.001). Multivariate linear regression analyses revealed that visceral fat area (ß = -0.22, p = 0.018), fasting FFA (ß = -0.39, p < 0.001), and uric acid levels (ß = -0.21, p = 0.007) were independent determinants of myocardial glucose uptake. Multiple logistic analyses demonstrated that decreased myocardial glucose uptake (OR 2.32; 95% CI 1.02-5.29, p = 0.045) and visceral fat area (OR 1.02, 95% CI 1.01-1.03, p = 0.018) were associated with T2DM. CONCLUSIONS: Our findings indicate visceral adiposity is strongly associated with the alteration of myocardial glucose uptake evaluated by (18)FDG-PET, and its association further relates to T2DM.

Metal versus plastic for pancreatic pseudocyst drainage: clinical outcomes and success.

BACKGROUND: Endoscopic transmural drainage of pancreatic pseudocysts (PPs) by using double-pigtail (DP) plastic stents requires placement of multiple stents and can be restricted by inadequate drainage and leakage risk. Recently, the use of fully covered self-expanding metal stents (FCSEMSs) has been reported as an alternative to DP plastic stents. OBJECTIVE: To evaluate the clinical outcomes, success rate, and adverse events of EUS-guided drainage of PPs with DP plastic stents and FCSEMSs. DESIGN: Retrospective cohort study. SETTING: Two tertiary-care academic medical centers. PATIENTS: This study involved 230 patients (mean age, 52.6 years) with PPs who underwent EUS-guided transmural drainage including 118 that were drained by using DP plastic stents and 112 by using FCSEMSs. A transgastric approach was used in 210 patients (91%), and transduodenal drainage was performed in 20 patients (9%). INTERVENTIONS: Stent deployment under EUS guidance. MAIN OUTCOME MEASUREMENTS: Technical success, early adverse events, stent occlusion requiring reintervention, and long-term success. RESULTS: At 12-month follow-up after the initial procedure, complete resolution of PPs by using DP plastic stents was lower compared with those that underwent drainage with FCSEMSs (89% vs 98%; P = .01). Procedural adverse events were noted in 31% in the DP plastic stent group and 16% in the FCSEMS group (P = .006). On multivariable analysis, patients with plastic stents were 2.9 times more likely to experience adverse events (odds ratio 2.9; 95% confidence interval, 1.4-6.3). LIMITATIONS: Retrospective study. CONCLUSION: In patients with PPs, EUS-guided drainage by using FCSEMSs improves clinical outcomes and lowers adverse event rates compared with those drained with DP plastic stents.

Mortality in metabolic dysfunction-associated steatotic liver disease: A nationwide population-based cohort study.

BACKGROUND: A new fatty liver disease nomenclature, steatotic liver disease (SLD) has been proposed; however, there are no data on clinical outcomes. We investigated the impact of SLD with metabolic dysfunction (MD; SLD-MD) on all-cause mortality. METHODS: We evaluated nationally representative participants aged ≥19 years using data from the Korea National Health and Nutrition Examination Survey 2007-2015 and their linked death data through 2019. The presence of fatty liver disease was assessed by liver fat score, fatty liver index and significant liver fibrosis was evaluated by the Fibrosis-4 Index, and fibrosis score. SLD-MD was categorized into three groups: metabolic dysfunction-associated steatotic liver disease (MASLD); metabolic alcoholic liver disease (MetALD); and SLD with other combination etiologies. RESULTS: Among 26734 individuals (11561 men and 15173 women, mean age 48.8 years), 1833 (6.9 %) died during a mean follow-up period of 110.6 ± 33.9 months. Mortality risk was significantly higher in individuals with SLD-MD (hazard ratio [HR] = 1.35) than in those without (P < 0.001). Among the three groups, MASLD (HR = 1.32) and SLD with other combination etiologies (HR = 2.06) independently increased mortality risk (all P < 0.001). When individuals with SLD-MD had significant liver fibrosis or diabetes, mortality risk increased further (HR = 1.68 and 1.85, respectively; all P < 0.001). SLD-MD with both significant liver fibrosis and diabetes showed the highest mortality risk (HR = 2.29, P < 0.001). When applied fatty liver index and fibrosis score, similar results were observed. CONCLUSIONS: SLD-MD is associated with a higher mortality risk. When SLD-MD was combined with significant liver fibrosis or diabetes, the mortality risk became much higher. Treatment strategies to reduce fibrotic burden and improve glycemic control in individuals with MASLD are needed.

Loss of SREBP-1c ameliorates iron-induced liver fibrosis by decreasing lipocalin-2.

Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression. Wild-type and SREBP-1c knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl4), and subjected to lipocalin-2 (LCN2) overexpression. The role of LCN2 in NASH progression was assessed using mouse primary hepatocytes, Kupffer cells, and HSCs. LCN2 expression was examined in samples from normal patients and those with NASH. LCN2 gene expression and secretion increased in CCl4-induced liver fibrosis mice model, and SREBP-1c regulated LCN2 gene transcription. Moreover, treatment with holo-LCN2 stimulated intracellular iron accumulation and fibrosis-related gene expression in mouse primary HSCs, but these effects were not observed in 1cKO HSCs, indicating that SREBP-1c-induced LCN2 expression and secretion could stimulate HSCs activation through iron accumulation. Furthermore, LCN2 expression was strongly correlated with inflammation and fibrosis in patients with NASH. Our findings indicate that SREBP-1c regulates Lcn2 gene expression, contributing to diet-induced NASH. Reduced Lcn2 expression in 1cKO mice protects against NASH development. Therefore, the activation of Lcn2 by SREBP-1c establishes a new connection between iron and lipid metabolism, affecting inflammation and HSCs activation. These findings may lead to new therapeutic strategies for NASH.

Richard Schatzki: a familiar ring.

OBJECTIVE: The Schatzki ring was named for Richard Schatzki, a renowned radiologist who described the entity with his colleague, John E. Gary. The purpose of this article is to shed more light on a man who made such a significant contribution and to chronicle developments concerning this important radiologic finding. CONCLUSION: The Schatzki ring was described long ago, but its cause is poorly understood even today.

Age at Mortality in Patients with Type 2 Diabetes Who Underwent Kidney Transplantation: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018.

BACKGROUND: Although the clinical outcomes of diabetes have improved, diabetes remains the principal cause of end-stage renal disease. The aim of the study is to investigate whether mortality trends in individuals with type 2 diabetes and kidney transplantation (KT) have changed. METHODS: This study analyzed data from the National Health Insurance Service claims database linked to death records from the National Statistical Information Service in Korea. Information from a total of 2521 deaths of KT recipients was collected from 2006 to 2018. RESULTS: The age at death of KT recipients increased from 57.4 years in 2006 to 65.2 years in 2018, with a mean change of +0.65 years/year (p < 0.001). The overall age at death increased by 0.55 and 0.66 years/year in the type 2 diabetes and non-diabetes populations, respectively. The age at death was significantly higher in the type 2 diabetes group, and was maintained during the study period. The proportion of death due to malignancy and cerebrovascular and heart disease was maintained, that due to type 2 diabetes decreased and that due to pneumonia increased. Neither diabetes nor hypertension determined the age at death, and the age at KT was the most prominent factor affecting age at death in KT recipients. CONCLUSIONS: The age at death in KT recipients increased over the 12 years between 2006 and 2018, with similar trends in the type 2 diabetes and non-diabetes groups. The age at KT was higher in patients with type 2 diabetes, and was the main contributor to the age at death in KT recipients.

High Sodium Intake, as Assessed by Urinary Sodium Excretion, Is Associated with Nonalcoholic Fatty Liver Disease or Sarcopenia.

Background/Aims: We explored whether high sodium intake, assessed by urinary excretion, determines the risk of sarcopenia and nonalcoholic fatty liver disease (NAFLD). Methods: We analyzed 10,036 adult participants with normal kidney function from the Korea National Health and Nutrition Examination Survey (2008-2011). NAFLD was identified using the fatty liver index, and the muscle mass was evaluated using dual X-ray absorptiometry. The dietary sodium intake was estimated using Tanaka's equation. Results: The mean 24-hour urinary sodium excretion was 144.2±36.1 mmol/day (corresponding to 3.3 g/day Na) in the total population. The 24-hour urinary sodium excretion showed moderate accuracy in predicting NAFLD (area under the receiver operating characteristic, 0.702; 95% confidence interval [CI], 0.692 to 0.712). A cutoff value of 99.96 mmol/day (corresponding to 2.30 g/day Na) for urinary sodium excretion in predicting NAFLD showed 76.1% sensitivity and 56.1% specificity. The results of multiple adjusted models indicated that the participants with the highest urinary sodium excretion had a significantly higher risk of NAFLD (odds ratio, 1.46; 95% CI, 1.27 to 1.66; p<0.001) and sarcopenia (odds ratio, 1.49; 95% CI, 1.28 to 1.73; p<0.001) than those with the lowest urinary sodium excretion. The association between a higher 24-hour urinary sodium excretion and NAFLD was independent of sarcopenia. Conclusions: Participants with a high sodium intake, as assessed by sodium excretion, had a substantial risk of NAFLD and sarcopenia.

Lobeglitazone inhibits LPS-induced NLRP3 inflammasome activation and inflammation in the liver.

Liver inflammation is a common feature of chronic liver disease and is often associated with increased exposure of the liver to lipopolysaccharide (LPS). Kupffer cells (KCs) are macrophages in the liver and produce various cytokines. Activation of KCs through the NLRP3 inflammasome pathway leads to release of proinflammatory cytokines and induces hepatocyte injury and hepatic stellate cell (HSC) activation. Lobeglitazone is a peroxisome proliferator-activated receptor gamma ligand and a type of thiazolidinedione that elicits anti-inflammatory effects. However, there is no clear evidence that it has direct anti-inflammatory effects in the liver. This study showed that lobeglitazone reduces LPS-induced NLPR3 inflammasome activation and production of proinflammatory cytokines in primary KCs and hepatocytes. Cytokines secreted by activated KCs increased hepatocyte inflammation and HSC activation, and lobeglitazone inhibited these responses. In addition, lobeglitazone suppressed liver fibrosis by inhibiting LPS-induced transforming growth factor (TGF)-ß secretion and TGF-ß-induced CTGF expression. The inhibitory effect of lobeglitazone on inflammasome activation was associated with suppression of liver fibrosis. These results suggest that lobeglitazone may be a treatment option for inflammation and fibrosis in the liver.

Fatty Liver & Diabetes Statistics in Korea: Nationwide Data 2009 to 2017.

BACKGROUND: This study investigated the changes of fatty liver disease prevalence in general Korean population. METHODS: This study analyzed data from the Korean National Health Insurance Service from 2009 to 2017 that included individuals aged 20 years or older who had undergone a medical health examination. Fatty liver disease was assessed using the fatty liver index (FLI). The disease severity was defined by FLI cutoff, ≥30 as moderate, and ≥60 as severe fatty liver disease. RESULTS: The prevalence of Korean adults aged 20 years or over with fatty liver disease (FLI ≥60) increased from 13.3% in 2009 to 15.5% in 2017 (P for trend <0.001). The increase in fatty liver disease prevalence was prominent in men (from 20.5% to 24.2%) and the young age (20 to 39 years) group (from 12.8% to 16.4%) (P for interaction <0.001). The prevalence of fatty liver disease was the highest in type 2 diabetes mellitus (T2DM, 29.6%) population compared to that of prediabetes or normoglycemia (10.0% and 21.8%) in 2017. The prevalence of fatty liver disease had statistically increased in individuals with T2DM and prediabetes (P for trend <0.001). Its prevalence increased more steeply in the young-aged population with T2DM, from 42.2% in 2009 to 60.1% in 2017. When applying a lower FLI cutoff (≥30) similar results were observed. CONCLUSION: The prevalence of fatty liver disease in the Korean population has increased. Individuals who are young, male, and have T2DM are vulnerable to fatty liver disease.

Appendicular Skeletal Muscle Mass to Visceral Fat Area Ratio Predicts Hepatic Morbidities.

Background/Aims: : Reports on the association between sarcopenic visceral obesity and non-alcoholic fatty liver disease (NAFLD)-associated morbidities remain scarce. We investigated the association between sarcopenia and visceral obesity, and the influence of this association on hepatic and coronary comorbidities. Methods: : The appendicular skeletal muscle mass to visceral fat area ratio (SV ratio) was evaluated using bioelectric impedance analysis. NAFLD and significant liver fibrosis were assessed using transient elastography, and high atherosclerotic cardiovascular disease (ASCVD) risk was defined as a 10-year ASCVD risk score >10%. Sarcopenia was defined as appendicular skeletal muscle mass adjusted by body mass index (<0.789 for men and <0.512 for women). Results: : In total, 82.0% (n=1,205) of the entire study population had NAFLD, and 14.6% of these individuals (n=176) exhibited significant liver fibrosis. Individuals with the lowest SV ratio had a significantly increased risk of NAFLD, significant liver fibrosis, and high ASCVD risk (all p<0.05). Individuals with both the lowest SV ratio and sarcopenia had the highest risk of developing NAFLD (odds ratio [OR]=3.11), significant liver fibrosis (OR=2.03), and high ASCVD risk (OR=4.15), compared with those with a higher SV ratio and without sarcopenia (all p<0.05). Conclusions: : Low SV ratio combined with sarcopenia was significantly associated with an increased risk of NAFLD, significant liver fibrosis, and high ASCVD risk among individuals with a high risk of NAFLD.