Validation of fatty liver index as a predictor of hepatic steatosis in Asian populations: Impact of alcohol consumption and sex

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Abstract

Aim

This study was undertaken to investigate the utility of the fatty liver index (FLI) as a noninvasive tool for predicting hepatic steatosis based on alcohol consumption and sex in a large Asian population.

Methods

We carried out a single-center observational cohort study at the HITO Medical Center in Japan and enrolled 1976 Asian subjects. The subjects were categorized into nondrinkers and light drinkers (0–19 g/day) and moderate drinkers (20–59 g/day) based on their self-reported alcohol intake. We used physical examinations, laboratory tests, and a questionnaire to collect information on various factors related to the FLI, including body mass index, waist circumference, and levels of γ-glutamyl transferase and triglycerides.

Results

The diagnostic accuracy of the FLI was assessed by calculating the area under the receiver operating characteristic curve (AUROC), and optimal cut-off values were determined using Youden's index. The FLI had an acceptable performance index of >0.7 both overall and in all subgroups, with an overall AUROC of 0.844. The AUROCs were higher in women and moderate drinkers of both sexes. We also compared the cut-off values obtained in the present study with the previously reported values of 30 and 60. Optimal cut-off values for the FLI were calculated for the total population and subgroups and were found to differ from the previously established values in other countries.

Conclusions

Our study suggests that the FLI is a useful noninvasive marker for predicting hepatic steatosis in a large Asian population, irrespective of alcohol consumption and sex.

Agile 3+ and Agile 4, noninvasive tests for liver fibrosis, are excellent formulae to predict liver‐related events in nonalcoholic fatty liver disease

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Agile 3+ and Agile 4, noninvasive tests for liver fibrosis, are excellent formulae to predict liver-related events in nonalcoholic fatty liver disease

Patients with nonalcoholic fatty liver disease in high-risk groups (F3–4 of fibrosis stage, rule-in [IN] of Agile 3+, and IN of Agile 4) showed a stepwise increase of liver-related events. Hazard ratios of the high-risk groups were much higher in Agile 3+ and Agile 4 than fibrosis, compared to their counterparts.


Abstract

Aim

The noninvasive tests (NITs) Agile 3+ and Agile 4 effectively identify patients with nonalcoholic fatty liver disease (NAFLD) complicated with advanced fibrosis (F3–4) and cirrhosis (F4), respectively. Little information is available on associations between Agile scores and intra-/extrahepatic events. The aim of this study was to determine the predictive performance of Agile scores for intra-/extrahepatic events in Asian patients with biopsy-proven NAFLD.

Methods

We undertook a retrospective multicenter cohort study to investigate associations between intra-/extrahepatic events and two Agile scores, Agile 3+ and Agile 4. The scores were obtained by combining clinical parameters and liver stiffness measurement using transient elastography.

Results

Among 403 enrolled patients, 11 had liver-related events (LREs), including seven with hepatocellular carcinoma (HCC). The incidence of LREs and HCC showed a stepwise increase in the advanced fibrosis group (F3–4), Agile 3+ rule-in (F3–4, highly suspected), and Agile 4 rule-in (F4, highly suspected) groups, compared to their counterparts. Hazard ratios for LREs in the advanced fibrosis group, Agile 3+ rule-in, and Agile 4 rule-in groups were 4.05 (p = 0.03), 23.5 (p = 0.003), and 45.5 (p < 0.001), respectively. The predictive performance results for Agile 3+ and Agile 4 were 0.780 and 0.866, respectively, which were higher than for fibrosis (0.595). Unlike for LREs, Agile scores failed to identify patients with extrahepatic events, including cardiovascular events and extrahepatic cancer.

Conclusions

Agile 3+ and Agile 4 scores are excellent NITs for predicting LREs in patients with NAFLD, possibly without histological assessment.

Report of the 23rd nationwide follow‐up survey of primary liver cancer in Japan (2014–2015)

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Abstract

For the 23rd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 20 889 newly registered patients and 42 274 previously registered follow-up patients were compiled from 516 institutions over a 2-year period from January 1, 2014 to December 31, 2015. Basic statistics compiled for patients newly registered in the 23rd survey were cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 22nd survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2004 and 2015 whose final outcome was survival or death. The median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, Child–Pugh grade, or albumin-bilirubin grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2015 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer in the world.

miR‐34a/SIRT1/HIF‐1α axis is involved in cardiac angiogenesis of type 2 diabetic rats: The protective effect of sodium butyrate combined with treadmill exercise

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miR-34a/SIRT1/HIF-1α axis is involved in cardiac angiogenesis of type 2 diabetic rats: The protective effect of sodium butyrate combined with treadmill exercise

Sodium butyrate and treadmill exercise, alone or together, significantly reduced the blood glucose levels in type 2 diabetic rats. Combination of sodium butyrate and treadmill exercise, improved oral glucose tolerance test in type 2 diabetic rats. Diabetes increased miR-34a expression and FOXO1 levels, and decreased SIRT1 and HIF-1α levels that were measured by real-time PCR and ELISA method. A combination of sodium butyrate and treadmill exercise significantly decreased miR-34a expression and FOXO1 levels, and improved SIRT1 and HIF-1α levels in the heart tissue of diabetic rats. Sodium butyrate and treadmill exercises, alone or together, increased angiogenesis in the heart tissue of diabetic rats. So, those may be useful in the treatment of diabetes through the mir-34a/SIRT1/FOXO1-HIF-1α pathway.


Abstract

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders worldwide. Recent research has indicated that sodium butyrate (NaB) affects glucose metabolism and exercise has an anti-hyperglycemic effect in diabetes. This study aimed to evaluate the effects of NaB and treadmill exercise on heart angiogenesis through the miR-34a/SIRT1/FOXO1-HIF-1α pathway. Diabetic animals received NaB (400 mg/kg daily, orally) and treadmill exercise for 6 weeks. The effect of NaB and treadmill exercise, alone or combined, on miR-34a expression, SIRT1, FOXO1, HIF-1α levels, and angiogenesis in diabetic heart tissue was measured. Diabetes caused increased miR-34a (p < 0.01) and FOXO1 (p < 0.001) expression levels. Also, SIRT1 (p < 0.001) and HIF-1α (not significant) expression levels were reduced in diabetic rats. NaB and treadmill exercise decreased miR-34a (respectively p < 0.05 and not significant) and FOXO1 (both p < 0.001) expression levels and improved SIRT1 (both not significant) and HIF-1α (respectively p < 0.01 and p < 0.001) levels. Also, NaB combined with treadmill exercise decreased miR-34a (p < 0.001) and FOXO1 (p < 0.001) expression levels, and elevated SIRT1 (p < 0.05) and HIF-1α (p < 0.001) levels in comparison with the diabetic group. NaB and treadmill exercises modulate the expression of miR-34a and the levels of SIRT1, FOXO1, and HIF-1α proteins, thus increasing angiogenesis in the heart tissue of diabetic rats. It can be concluded that NaB and treadmill exercise, alone or combined, may be useful in the treatment of diabetes through the miR-34a/SIRT1/FOXO1-HIF-1α pathway.

Torpor‐responsive microRNAs in the heart of the Monito del monte, Dromiciops gliroides

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Torpor-responsive microRNAs in the heart of the Monito del monte, Dromiciops gliroides

Monito del monte (Dromiciops gliroides) undergoes metabolic rate depression to conserve energy during torpor. Differential microRNA expression plays a key role in metabolic reorganization by regulating key signaling and metabolic pathways.


Abstract

The marsupial Monito del monte (Dromiciops gliroides) utilizes both daily and seasonal bouts of torpor to preserve energy and prolong survival during periods of cold and unpredictable food availability. Torpor involves changes in cellular metabolism, including specific changes to gene expression that is coordinated in part, by the posttranscriptional gene silencing activity of microRNAs (miRNA). Previously, differential miRNA expression has been identified in D. gliroides liver and skeletal muscle; however, miRNAs in the heart of Monito del monte remained unstudied. In this study, the expression of 82 miRNAs was assessed in the hearts of active and torpid D. gliroides, finding that 14 were significantly differentially expressed during torpor. These 14 miRNAs were then used in bioinformatic analyses to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were predicted to be most affected by these differentially expressed miRNAs. Overexpressed miRNAs were predicted to primarily regulate glycosaminoglycan biosynthesis, along with various signaling pathways such as Phosphoinositide-3-kinase/protein kinase B and transforming growth factor-β. Similarly, signaling pathways including phosphatidylinositol and Hippo were predicted to be regulated by the underexpression of miRNAs during torpor. Together, these results suggest potential molecular adaptations that protect against irreversible tissue damage and enable continued cardiac and vascular function despite hypothermia and limited organ perfusion during torpor.

Platelet‐activating factor as an endogenous cofactor of food anaphylaxis

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Platelet-activating factor as an endogenous cofactor of food anaphylaxis

PAF is an endogenous factor of food anaphylaxis.


Abstract

Anaphylaxis is a severe, acute, life-threatening generalized or systemic hypersensitivity reaction. The incidence of anaphylaxis is increasing worldwide, with medications and food contributing to most cases. Physical exercise, acute infections, drugs, alcohol, and menstruation are the external cofactors associated with more severe systemic reaction. The aim of this review is to show that platelet-activating factor contributes to the development of severe anaphylactic reaction, and even to anaphylactic shock.

Therapeutic potential of phytochemicals for cystic fibrosis

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Therapeutic potential of phytochemicals for cystic fibrosis

The aim of this review was to review and discuss various phytochemicals that exhibit beneficial effects on mutated membrane channels, and hence, improve transmembrane conductance. Four databases were searched using keywords. In conclusion, while curcumin, genistein, and resveratrol have demonstrated effectiveness in this regard, it should be emphasized that coumarins, quercetin, and other herbal medicines also have beneficial effects on transporter function, transmembrane conductivity, and overall channel activity.


Abstract

The aim of this review was to review and discuss various phytochemicals that exhibit beneficial effects on mutated membrane channels, and hence, improve transmembrane conductance. These therapeutic phytochemicals may have the potential to decrease mortality and morbidity of CF patients. Four databases were searched using keywords. Relevant studies were identified, and related articles were separated. Google Scholar, as well as gray literature (i.e., information that is not produced by commercial publishers), were also checked for related articles to locate/identify additional studies. The relevant databases were searched a second time to ensure that recent studies were included. In conclusion, while curcumin, genistein, and resveratrol have demonstrated effectiveness in this regard, it should be emphasized that coumarins, quercetin, and other herbal medicines also have beneficial effects on transporter function, transmembrane conductivity, and overall channel activity. Additional in vitro and in vivo studies should be conducted on mutant CFTR to unequivocally define the mechanism by which phytochemicals alter transmembrane channel function/activity, since the results of the studies evaluated in this review have a high degree of heterogenicity and discrepancy. Finally, continued research be undertaken to clearly define the mechanism(s) of action and the therapeutic effects that therapeutic phytochemicals have on the symptoms observed in CF patients in an effort to reduce mortality and morbidity.