Relationship between Dietary Fatty Acid Intake with Nonalcoholic Fatty Liver Disease and Liver Fibrosis in People with HIV

We aimed to evaluate the relationship between food intake of lipids with nonalcoholic fatty liver disease (NAFLD) and/or liver fibrosis in people living with HIV/AIDS (PLWHA). In this cross-sectional study, transient elastography was used to detect the presence of NAFLD and/or liver fibrosis. The dietary intake of fats and fatty acids (FA) were assessed by two 24 h dietary recalls (24-HDR) (n = 451). Multivariate logistic regression models were performed. Participants with higher intake of total fat were associated with higher odds for NAFLD compared to those with lower consumption [adjusted odds ratio (aOR) = 1.91 (95% confidence interval (95% CI) 1.06–3.44)]. Furthermore, participants with intermediate intake of n6-PUFA (n6-poly-unsaturated FA) and lauric FA had lower odds for NAFLD, respectively aOR = 0.54 (95% CI 0.3–0.98) and aOR = 0.42 (95% CI 0.22–0.78). Additionally, a higher intake of myristoleic FA (fourth quartile) was a significant protective factor for NAFLD [aOR = 0.56 (95% CI 0.32–0.99)]. Participants with higher intake of lauric FA [0.38 (95% CI 0.18–0.80)], myristic FA [0.38 (0.17–0.89)], palmitoleic FA [0.40 (0.19–0.82)] and oleic FA [0.35 (0.16–0.79)] had positively less odds of having liver fibrosis. On the other hand, higher intake of n-6 PUFA was significantly associated with fibrosis [aOR = 2.45 (95% CI 1.12–5.32)]. Dietary assessment of total fat and FA should be incorporated into HIV care as a tool for preventing NAFLD and fibrosis in PLWHA.     

Association between Fasting Ketonuria and Advanced Liver Fibrosis in Non-Alcoholic Fatty Liver Disease Patients without Prediabetes and Diabetes Mellitus

Ketone body production, an alternative fuel upon low glucose availability, reduces hepatic fat accumulation. However, its clinical implications have not been established in patients with nonalcoholic fatty liver disease (NAFLD). We investigated the association between spontaneous fasting ketonuria and liver fibrosis in patients with NAFLD without prediabetes and diabetes mellitus (DM). A total of 6202 patients with ultrasound confirmed NAFLD without prediabetes and DM were enrolled in the study. Using low cut off values of NAFLD fibrosis score (NFS) and fibrosis-4, liver fibrosis was defined as an intermediate–high probability of advanced liver fibrosis. Of the 6202 NAFLD patients, 360 (5.8%) had ketonuria. Compared to the patients without ketonuria, patients with ketonuria were younger (41.1 vs. 44.6 years, p < 0.001), had lower levels of glucose (87.2 vs. 91.0 mg/dL, p < 0.001), and homeostatic model assessment for insulin resistance (1.0 vs. 1.5, p < 0.001). The presence of ketonuria had an inverse association with liver fibrosis, assessed using both NFS (final adjusted odds ratio [aOR], 0.67; 95% confidence interval [CI], 0.45–1.01) and fibrosis-4 (aOR, 0.58; 95% CI, 0.40–0.84). The presence of ketonuria in NAFLD patients without prediabetes and DM may have favorable metabolic effects compared to the absence of ketonuria, independent of traditional metabolic factors.     

Coffee Consumption and Risk of Gastric Cancer: A Large Updated Meta-Analysis of Prospective Studies

The potential role of coffee consumption in the development of various types of cancer has been extensively investigated in epidemiologic studies. How coffee consumption may modulate risk of gastric cancer, however, remains a subject open for investigation. To better quantify this relation, we quantitatively summarized evidence from prospective studies. Eligible studies were identified on PubMed databases. The summary risk estimates were obtained using the random-effects model. Subgroup, sensitivity and dose-response analyses were conducted. The present meta-analysis included 12 prospective cohort studies. A pooled analysis of these studies suggested that coffee consumption (highest vs. lowest consumption) was not associated with risk of gastric cancer (RR = 1.12, 95% CI = 0.93–1.36). In the subgroup analysis, significant increased risk was detected in the U.S. studies (RR = 1.36, 95% CI = 1.06–1.74) and in the studies with <10 years of follow-up (RR = 1.24, 95% CI = 1.00–1.54), and the greatest increase in risk was observed in those studies without adjustment for smoking (RR = 1.48, 95% CI = 1.13–1.93). There was some evidence of publication bias (P for Egger’s test = 0.03). Cumulative evidence from prospective studies suggests that coffee consumption is not associated with risk of gastric cancer. The observed positive results may be confounded by smoking and need further investigation.     

Effects of Coffee Consumption on Insulin Resistance and Sensitivity: A Meta-Analysis

Coffee is widely consumed worldwide and impacts glucose metabolism. After a previous meta-analysis that evaluated the effects of coffee consumption on insulin resistance and sensitivity, additional randomized controlled trials (RCTs) were conducted. This meta-analysis aimed to evaluate the effects of coffee consumption on insulin resistance or sensitivity. We selected RCTs that evaluated the effects of coffee consumption for seven days or more on insulin sensitivity or resistance using surrogate indices (homeostasis model assessment for insulin resistance (HOMA-IR) and Matsuda index). The fixed-effects or random-effects model was used according to heterogeneity. Four studies with 268 participants were analyzed in this meta-analysis. Coffee consumption significantly decreased HOMA-IR compared to control (mean difference (MD) = −0.13; 95% CI = −0.24–−0.03; p-value = 0.01). However, the significance was not maintained in the sensitivity analysis (MD = −0.04; 95% CI = −0.18–0.10; p-value = 0.55) after excluding data from the healthy, young, normal-weight group. Matsuda index was not significantly different between coffee and control groups (standardized mean difference (SMD) = −0.33; 95% CI = −0.70–0.03; p-value = 0.08). In conclusion, long-term coffee consumption has a nonsignificant effect on insulin resistance and sensitivity. More studies evaluating the effects of coffee consumption in the healthy, young, and normal-weight individuals are needed.     

Milk Intake in Early Life and Later Cancer Risk: A Meta-Analysis

Dairy consumption in adulthood has been demonstrated to influence cancer risk. Although childhood and adolescence represent critical periods of rapid growth, the relationship between milk intake in early life and later cancer risk is unclear. Thus, we examined this relationship by conducting a meta-analysis of the observational studies. PubMed and Embase were searched for relevant articles that were published throughout December 2021. The summary relative risk (RR) and 95% confidence interval (CI) were estimated using the DerSimonian-Laird random-effects model. The summary RR for the highest vs. lowest milk intake was 0.83 (95% CI = 0.69–1.00; p = 0.05; I² = 60%; seven studies) for breast cancer, 0.98 (95% CI = 0.72–1.32; p = 0.88; I² = 51%; four studies) for prostate cancer, and 0.90 (95% CI = 0.42–1.93; p = 0.78; I² = 83%; three studies) for colorectal cancer. No evidence of an association emerged in subgroup analyses of menopausal status, cancer stage, fat content of milk, life stage of milk intake, or study design. Consistent results were observed in the meta-analyses using total dairy intake. In conclusion, milk intake during childhood and adolescence might not be associated with risks of breast, prostate, and colorectal cancer later in life. Given the small number of studies that were included in our meta-analysis, and the high heterogeneity, more studies are warranted for a definitive conclusion.     

Japanese-Style Diet and Cardiovascular Disease Mortality: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

This systematic review and meta-analysis elucidate the effects of the Japanese-style diet and characteristic Japanese foods on the mortality risk of cardiovascular disease (CVD), cerebrovascular disease (stroke), and heart disease (HD). This review article followed the PRISMA guidelines. A systematic search in PubMed, The Cochrane Library, JDreamIII, and ICHUSHI Web identified prospective cohort studies on Japanese people published till July 2020. The meta-analysis used a random-effects model, and heterogeneity and publication bias were evaluated with I² statistic and Egger’s test, respectively. Based on inclusion criteria, we extracted 58 articles, including 9 on the Japanese-style diet (n = 469,190) and 49 (n = 2,668,238) on characteristic Japanese foods. With higher adherence to the Japanese-style diet, the pooled risk ratios (RRs) for CVD, stroke, heart disease/ischemic heart disease combined (HD/IHD) mortality were 0.83 (95% CI, 0.77–0.89, I² = 58%, Egger’s test: p = 0.625, n = 9 studies), 0.80 (95% CI, 0.69–0.93, I² = 66%, Egger’s test: p = 0.602, n = 6 studies), and 0.81 (95% CI, 0.75–0.88, I² = 0%, Egger’s test: p = 0.544, n = 6 studies), respectively. Increased consumption of vegetables, fruits, fish, green tea, and milk and dairy products decreased the RR for CVD, stroke, or HD mortality. Increased salt consumption elevated the RR for CVD and stroke mortality. Increased consumption of dietary fiber and plant-derived protein decreased the RR for CVD, stroke, and HD/IHD mortality. The Japanese-style diet and characteristic Japanese foods may reduce CVD mortality. Most studies conducted diet surveys between 1980 and the 1990s. This meta-analysis used articles that evaluated the same cohort study by a different method. A new large-scale cohort study matching the current Japanese dietary habits is needed to confirm these findings.     

Dietary Patterns Modulate the Risk of Non-Alcoholic Fatty Liver Disease in Chinese Adults

Although previous studies reported the associations between the intakes of individual foods or nutrients and the risk of non-alcoholic fatty liver disease (NAFLD), the relationship between dietary patterns and NAFLD in the Chinese population has been rarely studied to date. This study aimed to investigate the associations between dietary patterns and the risk of NAFLD in a middle-aged Chinese population. The Study subjects were 999 Chinese adults aged 45–60 years in the Anhui province who participated in the Hefei Nutrition and Health Study. Dietary intake was collected by a semi-quantitative food frequency questionnaire. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by B-ultrasonic examination); the absence of excessive alcohol use (>20 g day⁻¹ in men and 10 g day⁻¹ in women); no use of steatogenic medications within the past six months; no exposure to hepatotoxins; and no history of bariatric surgery. Log-binomial regression analysis was used to examine the association between dietary patterns and NAFLD with adjustment of potential confounding variables. Out of 999 participants, 345 (34.5%) were classified as having NAFLD. Four major dietary patterns were identified: “Traditional Chinese”, “Animal food”, “Grains-vegetables” and “High-salt” dietary patterns. After adjusting for potential confounders, subjects in the highest quartile of the “Animal food” pattern scores had greater prevalence ratio for NAFLD (prevalence ratio (PR) = 1.354; 95% confidence interval (CI): 1.063–1.724; p < 0.05) than did those in the lowest quartile. After adjustment for body mass index (BMI), compared with the lowest quartile of the “Grains-vegetables” pattern, the highest quartile had a lower prevalence ratio for NAFLD (PR = 0.777; 95% CI: 0.618–0.977, p < 0.05). However, the “traditional Chinese” and “high-salt” dietary patterns showed no association with the risk of NAFLD. Our findings indicated that the “Animal food” dietary pattern was associated with an increased risk of NAFLD.     

Efficacy of Vitamin D Supplements in Prevention of Acute Respiratory Infection: A Meta-Analysis for Randomized Controlled Trials

Background: Previous systematic reviews and meta-analyses of randomized controlled trials (RCTs) have reported inconsistent results regarding the efficacy of vitamin D supplements in the prevention of acute respiratory infections (ARIs). Methods: We investigated these efficacy results by using a meta-analysis of RCTs. We searched PubMed, EMBASE, and the Cochrane Library in June 2021. Results: Out of 390 trials searched from the database, a total of 30 RCTs involving 30,263 participants were included in the final analysis. In the meta-analysis of all the trials, vitamin D supplementation showed no significant effect in the prevention of ARIs (relative risk (RR) 0.96, 95% confidence interval (CI) 0.91–1.01, I² = 59.0%, n = 30). In the subgroup meta-analysis, vitamin D supplementation was effective in daily supplementation (RR 0.83, 95% CI, 0.73–0.95, I² = 69.1%, n = 15) and short-term supplementation (RR 0.83, 95% CI, 0.71–0.97, I² = 66.8%, n = 13). However, such beneficial effects disappeared in the subgroup meta-analysis of high-quality studies (RR 0.89, 95% CI, 0.78–1.02, I² = 67.0%, n = 10 assessed by the Jadad scale; RR 0.87, 95% CI, 0.66–1.15, I² = 51.0%, n = 4 assessed by the Cochrane’s risk of bias tool). Additionally, publication bias was observed. Conclusions: The current meta-analysis found that vitamin D supplementation has no clinical effect in the prevention of ARIs.     

Sugar- and Artificially Sweetened Beverages Consumption Linked to Type 2 Diabetes,Cardiovascular Diseases,and All-Cause Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies

Although studies have examined the association between habitual consumption of sugar- (SSBs) and artificially sweetened beverages (ASBs) and health outcomes, the results are inconclusive. Here, we conducted a dose-response meta-analysis of prospective cohort studies in order to summarize the relationship between SSBs and ASBs consumption and risk of type 2 diabetes (T2D), cardiovascular diseases (CVDs), and all-cause mortality. All relevant articles were systematically searched in PubMed, Embase, and Ovid databases until 20 June 2020. Thirty-four studies met the inclusion criteria and were eligible for analysis. Summary relative risks (RRs) and 95% confidence intervals (95% CI) were estimated using random effects or fixed-effects model for highest versus lowest intake categories, as well as for linear and non-linear relationships. With each additional SSB and ASB serving per day, the risk increased by 27% (RR: 1.27, 95%CI: 1.15–1.41, I² = 80.8%) and 13% (95%CI: 1.03–1.25, I² = 78.7%) for T2D, 9% (RR: 1.09, 95%CI: 1.07–1.12, I² = 42.7%) and 8% (RR: 1.08, 95%CI: 1.04–1.11, I² = 45.5%) for CVDs, and 10% (RR: 1.10, 95%CI: 0.97–1.26, I² = 86.3%) and 7% (RR: 1.07, 95%CI: 0.91–1.25, I² = 76.9%) for all-cause mortality. Linear relationships were found for SSBs with T2D and CVDs. Non-linear relationships were found for ASBs with T2D, CVDs, and all-cause mortality and for SSBs with all-cause mortality. The findings from the current meta-analysis indicate that increased consumption of SSBs and ASBs is associated with the risk of T2D, CVDs, and all-cause mortality.     

Independent Dose–Response Associations between Fetuin-A and Lean Nonalcoholic Fatty Liver Disease

Patients with lean NAFLD make up an increasing subset of liver disease patients. The association between lean NAFLD and feutin-A, which serves as a hepatokine and adipokine, has never been examined. Our study aimed to explore the association of serum fetuin-A among lean and non-lean patients. The study comprised 606 adults from the community, stratified into lean or non-lean (BMI </≥ 24 kg/m²) and NAFLD or non-NAFLD (scoring of ultrasonographic fatty liver indicator, US-FLI ≥ 2/< 2). Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD among the tertiles of fetuin-A after adjustment. The least square means were computed by general linear models to estimate marginal means of the serum fetuin-A concentrations in relation to the NAFLD groups. The odds ratio (OR) of having NAFLD for the highest versus the lowest tertile of fetuin-A was 2.62 (95% CI: 1.72–3.98; p for trend < 0.001). Stratifying by BMI, the OR of having lean NAFLD for the highest versus the lowest tertile of fetuin-A was 2.09 (95% CI: 1.09–3.98; p for trend 0.026), while non-lean NAFLD had no significant association with the fetuin-A gradient after adjustments. Fetuin-A was positively associated with lean NAFLD after adjusting for central obesity and insulin resistance.     

Ultra-Processed Food Consumption and Adult Mortality Risk: A Systematic Review and Dose–Response Meta-Analysis of 207,291 Participants

We performed a systematic review and dose–response meta-analysis of observational studies assessing the association between UPF consumption and adult mortality risk. A systematic search was conducted using ISI Web of Science, PubMed/MEDLINE, and Scopus electronic databases from inception to August 2021. Data were extracted from seven cohort studies (totaling 207,291 adults from four countries). Using a random-effects model, hazard ratios (HR) of pooled outcomes were estimated. Our results showed that UPF consumption was related to an enhanced risk of all-cause mortality (HR = 1.21; 95% CI: 1.13, 1.30; I² = 21.9%; p < 0.001), cardiovascular diseases (CVDs)-cause mortality (HR = 1.50; 95% CI: 1.37, 1.63; I² = 0.0%; p < 0.001), and heart-cause mortality (HR = 1.66; 95% CI: 1.50, 1.85; I² = 0.0%; p = 0.022), but not cancer-cause mortality. Furthermore, our findings revealed that each 10% increase in UPF consumption in daily calorie intake was associated with a 15% higher risk of all-cause mortality (OR = 1.15; 95% CI: 1.09, 1.21; I² = 0.0%; p < 0.001). The dose–response analysis revealed a positive linear association between UPF consumption and all-cause mortality (P_nonlinearity = 0.879, P_{dose–response} = p < 0.001), CVDs-cause mortality (P_nonlinearity = 0.868, P_{dose–response} = p < 0.001), and heart-cause mortality (P_nonlinearity = 0.774, P_{dose–response} = p < 0.001). It seems that higher consumption of UPF is significantly associated with an enhanced risk of adult mortality. Despite this, further experimental studies are necessary to draw a more definite conclusion.     

Coffee Drinking and the Risk of Endometrial Cancer: An Updated Meta-Analysis of Observational Studies

Background: Several compounds contained in coffee have been found to suppress carcinogenesis in experimental studies. We conducted a dose–response meta-analysis to assess the impact of coffee consumption on the risk of endometrial cancer. Materials and methods: We searched MEDLINE and EMBASE databases for studies published up to August 2016. Using random effects models, we estimated summary relative risks (RR) for cohort studies and odds ratios (OR) for case-control studies with 95% confidence intervals (CI). Dose–response analyses were conducted by using generalized least square trend estimation. Results: We identified 12 cohort studies and 8 case-control studies eligible for inclusion, contributing with 11,663 and 2,746 endometrial cancer cases, respectively. The summary RR for highest compared with lowest coffee intake was 0.74 (95% CI: 0.68–0.81; p_{heterogeneity} = 0.09, I² = 32%). The corresponding summary RR among cohort studies was 0.78 (95% CI: 0.71–0.85; p_{heterogeneity} = 0.14, I² = 31.9%) and 0.63 (95% CI: 0.53–0.76; p_{heterogeneity} = 0.57, I² = 0%) for case-control studies. One-cup increment per day was associated with 3% risk reduction (95% CI: 2–4%) in cohort studies and 12% (95% CI: 5–18%) in case-control studies. After pooling the results from 5 cohort studies, the association remained significant only in women with body mass index over 30 (RR = 0.71, 95% CI: 0.61–0.81). Conclusion: The results from our meta-analysis strengthen the evidence of a protective effect of coffee consumption on the risk of EC and further suggest that increased coffee intake might be particularly beneficial for women with obesity.     

Dietary Composition and Its Association with Newly Diagnosed Nonalcoholic Fatty Liver Disease and Insulin Resistance

Dietary modification is essential for treating nonalcoholic fatty liver disease (NAFLD); however, the dietary components are less well defined. We enrolled 252 adults with no history of liver disease and excessive alcohol use to evaluate the relationship between macronutrients and NAFLD and insulin resistance. Participants took photographs of their meals and documented their food intake in a food diary for seven consecutive days. A dietitian estimated the type and portion size of food items and analyzed nutrients with INMUCAL-Nutrients software. Later, participants underwent transient elastography to diagnose NAFLD and blood tests to measure insulin resistance using the homeostasis model. Total energy intake and the proportion of carbohydrate, fat, and protein consumption did not differ between participants with NAFLD (n = 41) and those without NAFLD (n = 211). Using multiple logistic regression analysis, daily intake of protein < 1.0 g/kg (OR: 3.66, 95% CI: 1.41–9.52) and full-fat dairy product ≥ 50 g (OR: 0.42, 95% CI: 0.18–0.99) were associated with NAFLD. Insulin resistance was associated with a daily intake of protein < 1.0 g/kg (OR: 3.09, 95% CI: 1.59–6.05), full-fat dairy product ≥ 50 g (OR: 0.46, 95% CI: 0.25–0.82), and dietary fiber ≥ 8 g (OR: 0.41, 95% CI: 0.22–0.74). Our data show that a low protein intake increases the odds for NAFLD and insulin resistance. Contrarily, a high intake of full-fat dairy products and dietary fiber has been associated with a potential protective effect against NAFLD and insulin resistance.     

Ultra-Processed Food Consumption and Adult Diabetes Risk: A Systematic Review and Dose-Response Meta-Analysis

(1) Background: Recent individual studies have demonstrated that consumption of ultra-processed food (UPF) may be related to type two diabetes mellitus (T2DM). We aimed to synthesize the results from these individual studies by conducting an updated systematic review and meta-analysis of observational studies evaluating the association between UPF consumption and the risk of T2DM. (2) Methods: A systematic search was conducted using ISI Web of Science, PubMed/MEDLINE and Scopus electronic databases from inception up to August 2021. Data were extracted from five studies (one cross-sectional study and four cohort studies, totaling 230,526 adults from four different countries). Risk ratios (RR) of pooled results were estimated using a random-effects model. (3) Results: Our results revealed that higher UPF consumption was significantly associated with an increased risk of T2DM (RR = 1.74; 95% CI: 1.36, 2.22; I² = 68.9%; p < 0.001; n = 5). Linear dose-response analysis indicated that each 10% increase in UPF consumption (kcal/d) was associated with a 15% higher risk of T2DM (RR = 1.15; 95% CI: 1.06, 1.26; I² = 86.0%; p < 0.001; n = 5) among adults. Non-linear dose-response analysis demonstrated a positive linear association between UPF consumption and T2DM (p_nonlinearity = 0.13, p_{dose-response} < 0.001; n = 5) among adults. (4) Conclusions: A higher intake of UPF was significantly associated with an increased risk of T2DM. However, underlying mechanisms remain unknown and future experimental studies are warranted.     

Selenium Status in Patients with Chronic Liver Disease: A Systematic Review and Meta-Analysis

Background: The potential role of selenium in preventing chronic liver diseases remains controversial. This meta-analysis aimed to summarize the available evidence from observational studies and intervention trials that had evaluated the associations between body selenium status and chronic liver diseases. Methods: We comprehensively searched MEDLINE, Embase, Web of Science, and Cochrane Library from inception to April 2021. The study protocol was registered at PROSPERO (CRD42020210144). Relative risks (RR) for the highest versus the lowest level of selenium and standard mean differences (SMD) with 95% confidence intervals (CI) were pooled using random-effects models. Heterogeneity and publication bias were evaluated using the I² statistic and Egger’s regression test, respectively. Results: There were 50 studies with 9875 cases and 12975 population controls in the final analysis. Patients with hepatitis (SMD = −1.78, 95% CI: −2.22 to −1.34), liver cirrhosis (SMD = −2.06, 95% CI: −2.48 to −1.63), and liver cancer (SMD = −2.71, 95% CI: −3.31 to −2.11) had significantly lower selenium levels than controls, whereas there was no significant difference in patients with fatty liver diseases (SMD = 1.06, 95% CI: −1.78 to 3.89). Moreover, the meta-analysis showed that a higher selenium level was significantly associated with a 41% decrease in the incidence of significant advanced chronic liver diseases (RR = 0.59, 95% CI: 0.49 to 0.72). Conclusion: Our meta-analysis suggested that both body selenium status and selenium intake were negatively associated with hepatitis, cirrhosis, and liver cancer. However, the associations for fatty liver diseases were conflicting and need to be established in prospective trials.     

The Relationship between Prebiotic Supplementation and Anthropometric and Biochemical Parameters in Patients with NAFLD—A Systematic Review and Meta-Analysis of Randomized Controlled Trials

We aim to systematically review the efficacy of prebiotics in reducing anthropometric and biochemical parameters in individuals with non-alcoholic fatty liver disease (NAFLD). A systematic search using PubMed/MEDLINE, Embase, clinicaltrials.gov, Cinahl, and Web of Science of articles published up to 20 March 2020 was performed for randomized controlled trials enrolling >20 adult patients. Random-effect meta-analysis for metabolic outcomes in NAFLD patients was performed for anthropometric data in addition to liver enzyme, carbohydrate, and lipid parameters. We found six trials (comprising a total of 242 patients) with NAFLD, with subjects aged 38–52 years. The mean time of fiber administration varied between 10 and 12 weeks. The main fiber types were psyllium (seeds or powder), Ocimum basilicum (seeds), and high-performance inulin and oligofructose powder at doses of either 10 or 16 g per day. The control group received either maltodextrin (powder or capsules) or crushed wheat (powder). Patients on the diet with added fiber had improvements in body mass index (BMI) (standardized mean difference (SMD) = −0.494, 95% confidence interval (CI): −0.864 to −0.125, p = 0.009); alanine aminotransferase (ALT) (SMD = −0.667, 95% CI: −1.046 to −0.288, p = 0.001); aspartate aminotransferase (AST) (SMD = −0.466, 95% CI: −0.840 to −0.091, p = 0.015); fasting insulin (SMD = −0.705, 95% CI: −1.115 to −0.295, p = 0.001); and homeostasis model assessment for insulin resistance (HOMA-IR) (SMD = −0.619, 95% CI: −1.026 to −0.211, p = 0.003). Hence, the results show that fiber supplements result in favorable changes as reflected in the measurement of anthropometric, metabolic, and liver-related biomarkers, i.e., body mass index (BMI), homeostasis model assessment for insulin resistance (HOMA-IR), insulin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). These effects suggest the potential benefits of fiber consumption for NAFLD populations. More prospective, controlled studies should be conducted to reveal specific details regarding the fiber type, dosage, and duration for optimal intervention.     

The Effect of Probiotics (MCP® BCMC® Strains) on Hepatic Steatosis,Small Intestinal Mucosal Immune Function,and Intestinal Barrier in Patients with Non-Alcoholic Fatty Liver Disease

Treatment for non-alcoholic fatty liver disease (NAFLD) currently consists of lifestyle modifications such as a low-fat diet, weight loss, and exercise. The gut microbiota forms part of the gut–liver axis and serves as a potential target for NAFLD treatment. We investigated the effect of probiotics on hepatic steatosis, fibrosis, and biochemical blood tests in patients with NAFLD. At the small intestinal mucosal level, we examined the effect of probiotics on the expression of CD4+ and CD8+ T lymphocytes, as well as the tight junction protein zona occluden-1 (ZO-1). This was a randomized, double-blind, placebo-controlled trial involving ultrasound-diagnosed NAFLD patients (n = 39) who were supplemented with either a probiotics sachet (MCP^® BCMC^® strains) or a placebo for a total of 6 months. Multi-strain probiotics (MCP^® BCMC^® strains) containing six different Lactobacillus and Bifidobacterium species at a concentration of 30 billion CFU were used. There were no significant changes at the end of the study in terms of hepatic steatosis (probiotics: −21.70 ± 42.6 dB/m, p = 0.052 vs. placebo: −10.72 ± 46.6 dB/m, p = 0.29) and fibrosis levels (probiotics: −0.25 ± 1.77 kPa, p = 0.55 vs. placebo: −0.62 ± 2.37 kPa, p = 0.23) as measured by transient elastography. Likewise, no significant changes were found for both groups for the following parameters: LiverFAST analysis (steatosis, fibrosis and inflammation scores), alanine aminotransferase, total cholesterol, triglycerides, and fasting glucose. In the immunohistochemistry (IHC) analysis, no significant expression changes were seen for CD4+ T lymphocytes in either group (probiotics: −0.33 ± 1.67, p = 0.35 vs. placebo: 0.35 ± 3.25, p = 0.63). However, significant reductions in the expression of CD8+ T lymphocytes (−7.0 ± 13.73, p = 0.04) and ZO-1 (Z-score = −2.86, p = 0.04) were found in the placebo group, but no significant changes in the probiotics group. In this pilot study, the use of probiotics did not result in any significant clinical improvement in NAFLD patients. However, at the microenvironment level (i.e., the small intestinal mucosa), probiotics seemed to be able to stabilize the mucosal immune function and to protect NAFLD patients against increased intestinal permeability. Therefore, probiotics might have a complementary role in treating NAFLD. Further studies with larger sample sizes, a longer duration, and different probiotic strains are needed to evaluate the real benefit of probiotics in NAFLD.     

High Compliance to Mediterranean Diet Associates with Lower Platelet Activation and Liver Collagen Deposition in Patients with Nonalcoholic Fatty Liver Disease

The Mediterranean diet (Med-Diet) is considered the most effective dietary patterns to obtain weight loss in NAFLD patients. Previous evidence suggested that Med-Diet adherence could reduce cardiovascular risk and have a beneficial effect on NAFLD severity. Aim of the study was to investigate the relationship between Med-Diet adherence, platelet activation (PA), and liver collagen deposition. The study was performed in 655 consecutive NAFLD outpatients from the PLINIO study, a prospective observational cohort study aimed to identify non-conventional predictors of liver fibrosis progression in NAFLD. PA was measured by the serum thromboxane B₂ (TxB₂), and liver collagen deposition by N-terminal propeptide of type III collagen (Pro-C3). Adherence to the Med-diet was investigated by a short nine-item validated dietary questionnaire. Patients with high Med-Diet adherence were older and had less metabolic syndrome and lower serum triglycerides, GGT, TxB₂, and Pro-C3. At multivariate regression analyses, in the linear model, the Med-Diet score negatively correlated with both TxB₂ (Beta = −0.106; p = 0.009) and Pro-C3 (Beta = −0.121; p = 0.002) and in the logistic model high adherence inversely correlated with higher TxB₂ tertiles (II tertile: OR = 0.576, p = 0.044; III tertile: OR = 0.556, p = 0.026) and Pro-C3 tertile (III tertile: OR = 0.488, p = 0.013). Low consumption of red meat inversely correlated with higher TxB₂ tertile (II tertile: OR = 0.448, p < 0.001, III tertile: OR = 0.567, p = 0.004). In conclusion, NAFLD patients with high adherence to the Med-Diet show lower PA and liver collagen deposition, suggesting a protective role of the Med-Diet against NAFLD progression and cardiovascular risk. In addition, the correlation between TxB₂ and Pro-C3 suggests a link between NAFLD severity and cardiovascular risk.     

Association between Physical Activity and Non-Alcoholic Fatty Liver Disease in Adults with Metabolic Syndrome: The FLIPAN Study

Background: A lifestyle with regular PA (physical activity) and Mediterranean diet has benefits on NAFLD (non-alcoholic fatty liver disease) and MetS (metabolic syndrome). Objectives: To assess the association between physical activity and NAFLD in adults with MetS. Design: Cross-sectional study in 155 participants (40–60 years old) from Balearic Islands and Navarra (Spain) with diagnosis of NAFLD and MetS, and BMI (body mass index) between 27 and 40 Kg/m². Methods: PA level was categorized into two groups according to weekly METs (metabolic equivalents of tasks). PA was assessed using a validated Minnesota questionnaire and accelerometers. MetS parameters were assessed by blood collection analysis and NAFLD by abdominal MRI (magnetic resonance imaging). Results: Participants with high PA showed more energy expenditure and expended more calories than ingested (−143.9 Kcal/day; p < 0.001). PA was a risk factor for AST (aspartate aminotransferase) (adjusted OR: 7.26; 95% CI: 1.79–29.40) and a protective factor for ALT (alanine aminotransferase) (adjusted OR: 0.24; 95% CI: 0.12–0.48), GGT (gamma-glutamyl transferase) (adjusted OR: 0.52; 95% CI: 0.29–0.94) and IFC-NMR (intrahepatic fat content by nuclear magnetic resonance) (adjusted OR: 0.26; 95% CI: 0.12–0.56) when sociodemographic confounders were considered. Conclusions: NAFLD patients with high PA showed more positive relationship on MetS parameters and liver profile (ALT, GGT, IFC-NMR) than subjects with low PA, but not for AST. Difference between calories ingested and expended influenced this relationship.     

Association Between Low Muscle Mass and Non-alcoholic Fatty Liver Disease Diagnosed Using Ultrasonography,Magnetic Resonance Imaging Derived Proton Density Fat Fraction,and Comprehensive NAFLD Score in Korea

ObjectivesNon-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent metabolic disease. Muscle is known to influence NAFLD development. Therefore, this study aimed to determine the relationships among low muscle mass, NAFLD, and hepatic fibrosis using various definitions of low muscle mass and NAFLD diagnostic methods, including magnetic resonance imaging-based proton density fat fraction (MRI-PDFF).MethodsThis cross-sectional study included 320 participants (107 males, 213 females) from the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population cohort. Muscle mass was assessed using whole-body dual-energy X-ray absorptiometry and adjusted for the height squared, body weight, and body mass index (BMI). NAFLD was diagnosed using ultrasonography (US), MRI-PDFF, and the comprehensive NAFLD score (CNS). Hepatic fibrosis was assessed using magnetic resonance elastography. Multivariable logistic and linear regression analyses were performed to determine the aforementioned associations.ResultsAccording to US, 183 participants (57.2%) had NAFLD. Muscle mass adjusted for body weight was associated with NAFLD diagnosed using US (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.70 to 5.31), MRI-PDFF (OR, 2.00; 95% CI, 1.13 to 3.53), and CNS (OR, 3.39; 95% CI, 1.73 to 6.65) and hepatic fibrosis (males: β=-0.070, p<0.01; females: β=-0.037, p<0.04). Muscle mass adjusted for BMI was associated with NAFLD diagnosed by US (OR, 1.71; 95% CI, 1.02 to 2.86) and CNS (OR, 1.95; 95% CI, 1.04 to 3.65), whereas muscle mass adjusted for height was not associated with NAFLD.ConclusionsLow muscle mass was associated with NAFLD and liver fibrosis; therefore, maintaining sufficient muscle mass is important to prevent NAFLD. A prospective study and additional consideration of muscle quality are needed to strengthen the findings regarding this association.