Relationship between dietary macronutrient composition and non-alcoholic fatty liver disease in lean and non-lean populations: a cross-sectional study.

OBJECTIVE: The current study aimed to customize dietary changes for lean patients with non-alcoholic fatty liver disease (NAFLD). DESIGN: The current study was done with a population-based cross-sectional design. The FFQ was used to analyse dietary macronutrient intake and ultrasonography results for NAFLD diagnosis. The study subjects were divided into the lean and non-lean groups based on their BMI (< 25 and ≥ 25). Multivariable logistic regression was used to evaluate the relationship between dietary macronutrients and NAFLD. Substitution analyses were also performed. SETTING: Amol and its suburban areas in Iran. PARTICIPANTS: Adults in the age range of 18 to < 65 with full relevant data. RESULTS: Among the total study subjects (2308), 46·7 % had fatty liver. The substitution of polysaccharides for animal protein and SFA in the lean group resulted in a significant NAFLD reduction, whereas the substitution of SFA for all types of macronutrients, except for n-6 and mono-disaccharides, led to a significant increase in NAFLD (P < 0·05). In non-lean participants, the substitution of MUFA for mono-disaccharides resulted in a significant reduction of NAFLD (P < 0·05). In this group, the substitution of SFA and mono-disaccharides for MUFA, and n-6 for all macronutrients, except vegetable protein and SFA, were significantly related to an increase in NAFLD (P < 0·05). CONCLUSIONS: Lower lean NAFLD is correlated with increasing polysaccharides in exchange for SFA and animal protein intake, whereas lower non-lean NAFLD is correlated with increasing MUFA in exchange for mono-disaccharides and reducing n-6 and SFA.

Erythrocyte membrane fatty acid profile & serum cytokine levels in patients with non-alcoholic fatty liver disease.

Background & objectives: Fatty acids may affect the expression of genes, and this process is influenced by sex hormones. Cytokines are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), so this study was aimed to assess the association of erythrocyte membrane fatty acids with three cytokines and markers of hepatic injury in NAFLD patients and to explore whether these associations were the same in both sexes. Methods: In this cross-sectional study, 62 consecutive patients (32 men and 30 women) with NAFLD during the study period. Tumour necrosis factor-α (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), aspartate aminotransferase and alanine aminotransferase were measured in a fasting serum sample, and Fibroscan was conducted for each individual. Gas chromatography was used to measure erythrocyte membrane fatty acids. Univariate and multiple linear regressions were used to analyze data. Results: In men, IL-6 had a significant (P <0.05) positive association with total ω-3 polyunsaturated fatty acids (PUFAs). In women, TNF-α had a significant positive association with total ω-3 (P <0.05) and ω-6 (P <0.01) PUFAs, IL-6 had a significant (P <0.05) positive association with total monounsaturated fatty acids and MCP-1 had a significant positive association with total trans-fatty acids (P <0.05). No significant associations were observed between erythrocyte membrane fatty acids and liver enzymes or Fibroscan report in both sexes. In this study, women were significantly older than men [51 (42.75-55) vs 35.5 (29-52), P <0.01], so the associations were adjusted for age and other confounders. Interpretation & conclusions: Erythrocyte membrane fatty acid profile was not associated with serum liver enzymes or Fibroscan reports in NAFLD patients, but it had significant associations with serum TNF-α, IL-6 and MCP-1 and these associations were probably sex dependent.

Association between Nicotinamide Phosphoribosyltransferase and de novo Lipogenesis in Nonalcoholic Fatty Liver Disease.

OBJECTIVE: This study explored the association between serum nicotinamide phosphoribosyltransferase (NAMPT) and hepatic de novo lipogenesis (DNL) in nonalcoholic fatty liver disease (NAFLD) and determined whether or not this association is sex dependent. SUBJECTS AND METHODS: In this cross-sectional study, 62 consecutive patients (32 males, 30 females) with NAFLD were recruited. Serum NAMPT (by ELISA), palmitic acid, and the DNL index of erythrocyte membranes as markers of hepatic DNL (by gas chromatography) were analyzed. The controlled attenuation parameter (CAP) and body impedance analyzer were used to assess hepatic and body fat, respectively. Univariate and multiple linear regressions (to adjust for confounders) were used to analyze the association of serum NAMPT with palmitic acid, DNL index, CAP, and body fat. RESULTS: The respective values of serum NAMPT (2.44 ± 1.03 vs. 2.45 ± 1.13 ng/mL, p = 0.98), DNL index (3.11 [2.60-3.71] vs. 3.05 [2.40-3.59], p = 0.90), and palmitic acid (20.55% [15.34-24.04] vs. 22.64% [21.15-25.95], p = 0.07) were not significantly different between men and women, but those of CAP (326 [300-340] vs. 300 [261.25-329], p = 0.002) and body fat (37.71 ± 3.80 vs. 26.60 ± 5.70, p < 0.001) were significantly higher in women. In women, serum NAMPT had a significant negative association with the DNL index (ß = -0.56, p = 0.01). The DNL index also had a significant negative association with body fat (ß = -0.46, p = 0.02). In men, the only significant association was the positive association between serum NAMPT and CAP (ß = 0.35, p = 0.035). CONCLUSION: Higher serum NAMPT in women was associated with a lower hepatic DNL index, while in men it was associated with higher hepatic fat and had no association with the DNL index. Therefore, the serum NAMPT level interpretation for NAFLD prognosis is probably sex dependent.

A population-based prospective study on obesity-related non-communicable diseases in northern Iran: rationale, study design, and baseline analysis.

Background: Iran is facing an epidemiological transition with the increasing burden of non-communicable diseases, such as obesity-related disorders and cardiovascular diseases (CVDs). We conducted a population-based prospective study to assess the prevalence and incidence rates of CVDs and obesity-related metabolic disorders and to evaluate the predictive ability of various CVD risk assessment tools in an Iranian population. Method: We enrolled 5,799 participants in Amol, a city in northern Iran, in 2009-2010 and carried out the first repeated measurement (RM) after seven years (2016-2017). For all participants, demographic, anthropometric, laboratory, hepatobiliary imaging, and electrocardiography data have been collected in the enrollment and the RM. After enrollment, all participants have been and will be followed up annually for 20 years, both actively and passively. Results: We adopted a multidisciplinary approach to overcome barriers to participation and achieved a 7-year follow-up success rate of 93.0% with an active follow-up of 5,394 participants aged 18-90 years. In the RM, about 64.0% of men and 81.2% of women were obese or overweight. In 2017, about 16.2% and 5.2% of men had moderate or severe non-alcoholic fatty liver disease, while women had a significantly higher prevalence of metabolic syndrome (35.9%), and type 2 diabetes mellitus (20.9%) than men. Of 160 deceased participants, 69 cases (43.1%) died due to CVDs over seven years. Conclusion: The most prevalent obesity-related chronic disease in the study was metabolic syndrome. Across the enrollment and RM phases, women exhibited a higher prevalence of obesity-related metabolic disorders. Focusing on obesity-related metabolic disorders in a population not represented previously and a multidisciplinary approach for enrolling and following up were the strengths of this study. The study outcomes offer an evidence base for future research and inform policies regarding non-communicable diseases in northern Iran.

Diagnostic Accuracy of Vibration Controlled Transient Elastography as Non-invasive Assessment of Liver Fibrosis in Patients with Non-alcoholic Fatty Liver Disease.

Background: Liver biopsy remain as the gold standard for diagnosing hepatic fibrosis; however, it has some limitations, such as life-threatening complications, low acceptance by the patients, and variations in the related sample. Therefore, there is a need for the development of non-invasive investigations for diagnosing hepatic fibrosis. Vibration-controlled transient elastography (VCTE) is one of these non-invasive methods. Methods: This study included 73 patients suffering from non-alcoholic fatty liver disease (NAFLD) who were older than 18 years. The patients underwent VCTE at the Baqiatallah and Firoozgar hospitals. Then, they underwent a liver biopsy by an experienced radiologist in the same hospital. A receiver operating characteristic (ROC) curve of different fibrosis stages was used to evaluate the VCTE verification. Results: VCTE could detect any fibrosis levels (stage 1 and higher) with an area under the ROC curve (AUROC) of 0.381. Moreover, it detected stage 2-4 fibrosis with an AUROC of 0.400, stage 3-4 fibrosis with an AUROC of 0.687, and stage 4 fibrosis with an AUROC of 0.984. Conclusion: The VCTE has high clinical validity in diagnosing the advanced stages of fibrosis (stages 3, 4) and can be a suitable alternative to the invasive method of liver biopsy with high reliability.

Candidate Molecular Biomarkers for the Non- Invasive Detection of Colorectal Cancer using Gene Expression Profiling.

BACKGROUND & OBJECTIVE: olorectal Cancer (CRC) is the third most common cancer after prostate (breast in women) and lung cancer; it is also the third cause of cancer deaths reported in both men and women in 2020. Currently, the most commonly used diagnostic tools for CRC are colonoscopy, serological methods, and other imaging techniques. Despite the benefits and abilities of these methods, each of them has disadvantages that reduce its functionality and acceptance. The aim of this study was identifying specific and non-invasive genetic biomarkers to diagnose colorectal cancer. METHODS: In this study, changes in the expression of HLTF and SEPT9 genes were evaluated by Real Time PCR in blood and tissue samples of CRC patients. A total of 100 samples (50 Blood and 50 Tissue samples) were evaluated with a definite diagnosis of CRC in Firoozgar Hspital, Tehran, Iran, in 2018. The QPCR method was used to compare the expression of candidate genes between the patients group and control group in both samples. Sensitivity and specificity of the test were examined using ROC curve analysis. RESULTS: The results showed a significant down-regulation in the expression of both selected genes in tissue and peripheral blood in the various stages of the CRC. The sensitivity and specifity of both genes was about 80%. CONCLUSION: The findings showed that the two candidate genes can be suggested as specific biomarkers for diagnosis of CRC using the peripheral blood as a non-invasive method. For a definite conclusion, more research is needed.

Role of microbiota-derived short-chain fatty acids in cancer development and prevention.

Following cancer, cells in a particular tissue can no longer respond to the factors involved in controlling cell survival, differentiation, proliferation, and death. In recent years, it has been indicated that alterations in the gut microbiota components, intestinal epithelium, and host immune system are associated with cancer incidence. Also, it has been demonstrated that the short-chain fatty acids (SCFAs) generated by gut microbiota are vitally crucial in cell homeostasis as they contribute to the modulation of histone deacetylases (HDACs), resulting effected cell attachment, immune cell immigration, cytokine production, chemotaxis, and the programmed cell death. Therefore, the manipulation of SCFA levels in the intestinal tract by alterations in the microbiota structure can be potentially taken into consideration for cancer treatment/prevention. In the current study, we will explain the most recent findings on the detrimental or protective roles of SFCA (particularly butyrate, propionate, and acetate) in several cancers, including bladder, colon, breast, stomach, liver, lung, pancreas, and prostate cancers.

Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

INTRODUCTION: To evaluate the efficacy of empagliflozin compared to pioglitazone in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM). METHODS: In this prospective randomized, double-blind, placebo-controlled trial, we assigned 106 patients with NAFLD and T2DM to receive empagliflozin 10 mg (n = 35), pioglitazone 30 mg (n = 34), or placebo (n = 37) for 24 weeks. Liver fat content and liver stiffness were measured using fibroscans. Body composition assessment was performed by dual-energy x-ray absorptiometry (DEXA) scans. The primary end point was change from baseline in liver steatosis, using the controlled attenuation parameter (CAP) score. RESULTS: A borderline significant decrease in CAP score was observed with empagliflozin compared to placebo, mean difference: - 29.6 dB/m (- 39.5 to - 19.6) versus - 16.4 dB/m (- 25.0 to - 7.8), respectively; p = 0.05. Using multivariate analysis, we observed a significant reduction in the placebo-corrected change in liver stiffness measurement (LSM) with empagliflozin compared to pioglitazone: - 0.77 kPa (- 1.45, - 0.09), p = 0.02, versus 0.01 kPa (95% CI - 0.70, 0.71, p = 0.98), p for comparison = 0.03. Changes in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), HOMA2-IR, fibrosis-4 index (FIB4 index), NAFLD fibrosis score, aspartate aminotransferase to platelet ratio index (APRI), android/gynecoid ratio (A/G ratio), and skeletal muscle index (SMI) were comparable between the two treatment groups, while significant reductions of the body weight and visceral fat area were observed only in the empagliflozin group (p < 0.001 and p = 0.01, respectively) and both were increased in the placebo and pioglitazone groups. There were no serious adverse events in either group. CONCLUSION: Treatment for 24 weeks with empagliflozin, in contrast to pioglitazone, was associated with improvement of liver steatosis and fibrosis in patients with NAFLD and T2DM. In addition, body weight and abdominal fat area were decreased in the empagliflozin group. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT), IRCT20190122042450N3.

Household Food Insecurity is Associated with Health-Related Quality of Life in Rural Type 2 Diabetic Patients.

BACKGROUND: Health-related quality of life (HRQOL) is associated with household food insecurity (HFI). However, the studies examining the relationship between HFI and HRQOL in patients with type 2 diabetes are scarce. Thus, this study was designed to examine the relationship between HFI and HRQOL in rural type 2 diabetic patients. METHODS: In this cross-sectional study, we included 1847 rural patients with type 2 diabetes in Neyshabur from April to July 2012. HRQOL and HFI were measured with 36-item HRQOL (SF-36) and 6-item version of Household Food Security questionnaires, respectively. HRQOL was divided into eight dimensions and two summary components. We categorized households as high food secure (HFS), low food secure (LFS), and very low food secure (VLFS). Multiple linear regression model was applied to assess the independent effect of food insecurity on HRQOL. RESULTS: The mean age of participants was 59.65 ± 12.3 years (range: 30-97) with 69.8% women. The overall prevalence of HFI was 46.1%, and the total mean score of HRQOL was 51.11. Multiple linear regression model showed that HFI was significantly associated with the total mean score of HRQOL and its eight dimensions. One-way ANOVA test also showed that HRQOL (in all dimensions) was significantly different between 3 groups of household food security status (HFS, LFS, and VLFS) (P < 0.05). CONCLUSIONS: The results of this study showed that HFI was associated with all dimensions of HRQOL and it is one of the strongest variables, in association with HRQOL among rural patients with type 2 diabetes.

Hirschsprung Disease Diagnosis: Calretinin Marker Role in Determining the Presence or Absence of Ganglion Cells.

BACKGROUND: Hirschsprung disease is a complex genetic disorder of the enteric nervous system (ENS), often called congenital aganglionic megacolon and characterized by the absence of enteric neurons along a variable length of the intestine. The definitive diagnosis of Hirschsprung disease relies on histologic and/or histochemical staining of sections from suction rectal biopsies. Calretinin immunohistochemistry (IHC) may be a useful in its diagnosis. This study aimed to proof the usefulness of immunohistochemical staining for calretinin in rule out of Hirschsprung disease. METHODS: Paraffin blocks and slides were retrieved from the pathology archives of Ali Asghar Hospital, Tehran, Iran from 2007 to 2011 with pathology report based on the presence (14 patients) or absence (70 patients) of ganglion cells and transitional zone anatomical region (10 patients). Slides were stained with hematoxylin and eosin method to confirm the initial diagnosis was verification again. After preparing the slides, they were stained by IHC for calretinin. Then, the results were analyzed using SPSS software. RESULTS: In most patients, IHC for calretinin provided highly compatible results with hematoxylin-eosin findings in diagnosis of Hirschsprung disease. The values of specificity and accuracy between calretinin and standard histology (H&E) compared by the Fisher exact test declared calretinin presented significantly higher specificity and accuracy values than H&E staining (P <0.0001). CONCLUSION: Calretinin IHC overcomes most of the difficulties encountered using the histology hematoxylin-eosin. Then, IHC for calretinin is a good ancillary method used by pathologists in diagnosis of Hirschsprung disease.