The roles and potential mechanisms of plant polysaccharides in liver diseases: a review.

Plant polysaccharides (PP) demonstrate a diverse array of biological and pharmacological properties. This comprehensive review aims to compile and present the multifaceted roles and underlying mechanisms of plant polysaccharides in various liver diseases. These diseases include non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), fibrosis, drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC). This study aims to elucidate the intricate mechanisms and therapeutic potential of plant polysaccharides, shedding light on their significance and potential applications in the management and potential prevention of these liver conditions. An exhaustive literature search was conducted for this study, utilizing prominent databases such as PubMed, Web of Science, and CNKI. The search criteria focused on the formula "(plant polysaccharides liver disease) NOT (review)" was employed to ensure the inclusion of original research articles up to the year 2023. Relevant literature was extracted and analyzed from these databases. Plant polysaccharides exhibit promising pharmacological properties, particularly in the regulation of glucose and lipid metabolism and their anti-inflammatory and immunomodulatory effects. The ongoing progress of studies on the molecular mechanisms associated with polysaccharides will offer novel therapeutic strategies for the treatment of chronic liver diseases (CLDs).

The effect of probiotic consumption on lipid profile, glycemic index, inflammatory markers, and liver function in NAFLD patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND-AIM: Non-alcoholic fatty liver disease (NAFLD1) is the most frequent chronic liver disorder worldwide. Currently, no pharmacological treatment has been approved for NAFLD. Probiotics have been suggested as a potential therapy for NAFLD. The aim of this systematic review and meta-analysis was to assess the impact of probiotic intake on liver tests, lipids, glycemic parameters and inflammatory markers in NAFLD patients. METHODS: We searched electronic databases using related terms. Meta-analysis was performed using random-effects models. Clinical outcomes were presented as standard mean difference (SMD2) with a 95 % confidence interval (CI3). Publication bias and heterogeneity were evaluated in eligible studies. RESULTS: Fifteen randomized clinical trials comprising 899 participants were included in our meta-analysis. Probiotic supplementation improved alanine transaminase [SMD -0.796; 95 % CI (-1.419, -0.172); p = 0.012], Homeostatic Model Assessment for Insulin Resistance (HOMA-IR4) [SMD -0.596; 95 % CI (-1.071, -0.121); p = 0.01] and insulin levels [SMD -1.10; 95 % CI (-2.121, -0.087); p = 0.03]. No significant effects were observed on fasting glucose, hemoglobin A1c, aspartate transaminase, lipid profile, interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: Probiotic intake may improve insulin sensitivity and alanine transaminase in NAFLD patients.

Methane Gas in Breath Test is Associated with Non-Alcoholic Fatty Liver Disease.

Although the association between Body Mass Index (BMI) level and metabolic diseases as well as the association between the breath test results and BMI level have been studied, their relationship between breath hydrogen/methane level and metabolic diseases need to be further clarified. This study aimed to investigate how the composition of exhaled breath gases relates to metabolic disorders and their key risk factors. An elevated BMI level significantly increases the risk of developing metabolic disease; it was included in this study to find their association. Diabetes mellitus, dyslipidemia, hypertension, and non-alcoholic fatty liver disease (NAFLD) are metabolic diseases included in this study. An analysis was performed on the medical records including the lactulose breath test (LBT) data of patients who visited the Ajou University Medical Center, Suwon, Republic of Korea, between January 2016 and December 2021. Subjects were grouped according to four different criteria of the LBT hydrogen and methane level: 1) Normal (N) (Hydrogen < 20 ppm and Methane < 3 ppm); 2) Hydrogen only (H+) (Hydrogen ≥ 20 ppm and Methane < 3 ppm); 3) Methane positive (M+) (Hydrogen < 20 ppm and Methane ≥ 3 ppm); and 4) Methane and hydrogen positive (M+/H+) (Hydrogen ≥ 20 ppm and Methane ≥ 3 ppm). Of 441 subjects, 325 (72.1%) had positive results for methane only (M+). BMI and prevalence of NAFLD were higher in subjects with M+ than in subjects with hydrogen and methane positivity (H+/M+). According to multivariate analysis, the odds ratio (OR) of M+ was 2.002 (with 95% CI: 1.244-3.221, P = 0.004) for NAFLD. Our results demonstrate that breath methane positivity is related to NAFLD and suggest that increased methane gas in breath tests has the potential to be an easily measurable biomarker for the diagnosis of NAFLD. .

Evaluation of the ability of insulin resistance and lipid-related indices to predict the presence of NAFLD in obese adolescents.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become an important health issue in adolescents. Although several parameters and indices have been investigated for the evaluation of NAFLD in adults, these indices are limited in adolescents. In this study, body mass index, waist circumference, triponderal mass index, HbA1c, homeostatic model assessment insulin resistance (HOMA-IR), triglyceride/high-density lipoprotein (Tg/HDL), the lipid accumulation product (LAP) index, the triglyceride-glucose (TyG) index and the aminotransferase (AT) index were examined together, and their diagnostic values in the clinical treatment of NAFLD were compared. MATERIALS AND METHODS: Seventynine adolescents (10-19 years old) with obesity who were admitted to a pediatric clinic between January and August 2022 and who were diagnosed with exogenous obesity without any comorbidities were included in the study. The presence of NAFLD was evaluated by liver magnetic resonance imaging. The laboratory findings were obtained retrospectively from system records. Parameters were compared between the NAFLD (+) and NAFLD (-) groups. Logistic regression analysis was used to determine the most effective factors for NAFLD treatment. Receiver operating characteristic (ROC) analysis was performed with significant indices. Sex, HOMA-IR, TyG and AT indices were evaluated together with multivariate analysis to design a diagnostic scale. RESULTS: HbA1c, HOMA-IR, AT indices and TyG indices were greater in the NAFLD (+) group (P = 0.012; P = 0.001; P = 0.012; P = 0.002, respectively). There was a positive correlation between liver fat percentage and HOMA-IR, the TyG index, the AT index, and Tg/HDL. According to the regression analysis, male sex and elevated HOMA-IR were determined to be significant risk factors for the presence of NAFLD. A probability scale with 4 parameters [sex, HOMA-IR, the TyG index, and alanine aminotransferase (ALT)] was designed with 82.5% specificity and 80% sensitivity. CONCLUSION: Evaluation of the HOMA-IR and TyG indices, especially in high-risk patients, will support the diagnosis of NAFLD via ultrasonography. A probability scale with ALT, HOMA-IR, TyG, and sex data with a diagnostic accuracy of 80% may aid in the diagnosis of NAFLD in adolescents with obesity.

Recurrence and tumor-related death after resection of hepatocellular carcinoma in patients with metabolic syndrome.

Background & Aims: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. Methods: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. Results: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p = 0.002). Conclusions: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. Impact and implications: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

Research advances in serum chitinase-3-like protein 1 in liver fibrosis.

While liver fibrosis remains a serious, progressive, chronic liver disease, and factors causing damage persist, liver fibrosis may develop into cirrhosis and liver cancer. However, short-term liver fibrosis is reversible. Therefore, an early diagnosis of liver fibrosis in the reversible transition phase is important for effective treatment of liver diseases. Chitinase-3-like protein 1 (CHI3L1), an inflammatory response factor that participates in various biological processes and is abundant in liver tissue, holds promise as a potential biomarker for liver diseases. Here, we aimed to review research developments regarding serum CHI3L1 in relation to the pathophysiology and diagnosis of liver fibrosis of various etiologies, providing a reference for the diagnosis, treatment, and prognosis of liver diseases.

[Interpretation of the 2024 American Diabetes Association guidelines for the comprehensive management of non-alcoholic fatty liver disease combined with diabetes mellitus].

Non-alcoholic fatty liver disease (NAFLD) is a common concomitant disease in adults with type 2 diabetes mellitus (T2DM) and prediabetes. Therefore, T2DM/NAFLD patient populations are at high risk for cardiovascular disease. The occurrence and progression of non-alcoholic fatty liver disease-related liver fibrosis and cardiovascular disease have a severe impact on the patient's prognosis and mortality rate. The American Diabetes Association's 2024 "Guidelines for the Standardized Management of Diabetes" put forward recommendations relevant to the screening, evaluation, treatment, and management of NAFLD in T2DM and prediabetic populations, as well as liver fibrosis. The important measures for decelerating liver inflammation and fibrosis progression and the risk of cardiovascular disease are based on improvements in lifestyle methods, weight loss, and blood sugar control.

Unique metabolomics characteristics for distinguishing cirrhosis related to different liver diseases: A systematic review and meta-analysis.

BACKGROUND AND AIM: Clinical evidence for early identification and diagnosis of liver cirrhosis (LC) caused by different types of liver disease is limited. We investigated this topic through a meta-analysis of quantitative metabolomics. METHODS: Four databases were searched until October 31, 2022 for studies comparing metabolite levels between patients with different types of liver disease and control individuals. A random-effects model was applied for the meta-analysis. RESULTS: This study included 55 studies with 8266 clinical participants, covering 348 metabolites. In LC related to drug-induced liver injury (DILI), hepatitis B virus (HBV) infection, and non-alcoholic fatty liver disease (NAFLD), the primary bile acid biosynthesis (taurocholic acid: SMD, 1.08[0.81, 1.35]; P < 0.00001; glycocholic acid: SMD, 1.35[1.07, 1.62]; P < 0.00001; taurochenodeoxycholic acid: SMD, 1.36[0.94, 1.78]; P < 0.00001; glycochenodeoxycholic acid: SMD, 1.49[0.93, 2.06]; P < 0.00001), proline and arginine (l-proline: SMD, 1.06[0.53, 1.58]; P < 0.0001; hydroxyproline: SMD, 0.81[0.30, 1.33]; P = 0.002), and fatty acid biosynthesis (palmitic acid: SMD, 0.44[0.21, 0.67]; P = 0.0002; oleic acid: SMD, 0.46[0.19, 0.73]; P = 0.0008; stearic acid: SMD, 0.37[0.07, 0.68]; P = 0.02) metabolic pathways were significantly altered. CONCLUSION: We identified key biomarkers and metabolic characteristics for distinguishing and identifying LC related to different types of liver disease, providing a new perspective for early diagnosis, disease monitoring, and precise treatment.

Berberine alleviates high-energy and low-protein diet-induced fatty liver hemorrhagic syndrome in laying hens: insights from microbiome and metabolomics.

Berberine (BBR), a well-known quaternary ammonium alkaloid, is recognized for its ability to prevent and alleviate metabolic disorders because of its anti-oxidative and anti-inflammatory properties. However, the underlying mechanisms of BBR to mitigate fatty liver hemorrhagic syndrome (FLHS) through the modulation of gut microbiota and their metabolism remained unclear. The results revealed that BBR ameliorates lipid metabolism disorder in high-energy and low-protein (HELP) diet-induced FLHS laying hens, as evidenced by improved liver function and lipid deposition of the liver, reduced blood lipids, and the expression of liver lipid synthesis-related factors. Moreover, BBR alleviated HELP diet-induced barrier dysfunction, increased microbial population, and dysregulated lipid metabolism in the ileum. BBR reshaped the HELP-perturbed gut microbiota, particularly declining the abundance of Desulfovibrio_piger and elevating the abundance of Bacteroides_salanitronis_DSM_18170. Meanwhile, metabolomic profiling analysis revealed that BBR reshaped microbial metabolism and function, particularly by reducing the levels of hydrocinnamic acid, dehydroanonaine, and leucinic acid. Furthermore, fecal microbiota transplantation (FMT) experiments revealed that BBR-enriched gut microbiota alleviated hepatic lipid deposition and intestinal inflammation compared with those chicks that received a gut microbiota by HELP. Collectively, our study provided evidence that BBR effectively alleviated FLHS induced by HELP by reshaping the microbial and metabolic homeostasis within the liver-gut axis.

Remnant cholesterol is associated with the progression and regression of metabolic dysfunction-associated steatotic liver disease in Chinese adults.

BACKGROUND: The aim of this study was to explore the associations of serum remnant cholesterol (RC) levels with the progression and regression of metabolic dysfunction-associated steatotic liver disease (MASLD) in Chinese adults. METHODS: We conducted a cross-sectional study in 13,903 individuals who underwent transient elastography tests (cohort 1) and a longitudinal study in 17,752 individuals who underwent at least two health check-up exams with abdominal ultrasound (cohort 2). Anthropometric and biochemical parameters were collected. Serum RC levels were calculated. Noninvasive fibrosis indices such as FIB-4 were evaluated in cohort 2. RESULTS: In cohort 1, serum RC levels were positively and independently associated with the severity of hepatic steatosis and liver fibrosis according to logistic regression analysis. In cohort 2, baseline serum RC levels were increased in participants with the incidence of MASLD and decreased in participants with the regression of MASLD during the follow-up period. Baseline serum RC levels were independently associated with an increased risk of development and a decreased likelihood of regression of MASLD: the fully adjusted hazard ratios (HR) were 2.785 (95 % CI 2.332-3.236, P < 0.001) and 2.925 (95 % CI 2.361-3.623, P < 0.001), respectively. In addition, when we used FIB-4 to evaluate liver fibrosis, baseline serum RC levels were positively correlated with the incidence of high-intermediate probability of advanced fibrosis. However, we did not find an association between serum RC levels and the regression of liver fibrosis. CONCLUSION: Serum RC levels are independently correlated with the progression and regression of MASLD in Chinese adults, suggesting that RC may participate in the pathophysiological process of MASLD.

Effect of Bariatric Surgery on the Sonographic Grade of Metabolic-Associated Fatty Liver Disease at 12-Month Follow-Up.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is the most prevalent liver disease across the globe. One of the most effective treatments for this disease is weight loss. This study aimed to determine how metabolic and bariatric surgery (MBS) affects MAFLD sonographic grades. METHODS: In 2021, a pre-post study was conducted on 73 patients who underwent MBS. The study collected demographic information and ultrasound grades of MAFLD before and after MBS. RESULTS: A total of 73 patients underwent MBS, with 58 females and 15 males. The patients had a mean age of 39.8 ± 8.88 years and a mean BMI of 42.12 ± 5.98 kg/m2. Of these patients, 53 (72.6%) underwent SG, while 20 (27.4%) underwent RYGB. The preoperative BMI for females and males decreased significantly at the 12-month follow-up (P = 0.0001). However, males experienced more prominent weight changes (P = 0.009), but there was no statistically significant difference in fatty liver grade changes after MBS between males and females (P = 0.056), which suggests that the effect of MBS on fatty liver grades is not gender-specific. There was a significant reduction in BMI and fatty liver grade for patients under and over 40 years old after surgery (P = 0.0001). However, there was no statistically significant difference in fatty liver grade and BMI changes after MBS between the two age groups. RYGB was found to be more effective than SG in reducing fatty liver grade, BMI, and %TWL (P < 0.05). CONCLUSION: Bariatric surgery can play a vital role in reducing the weight and severity of metabolic-associated fatty liver disease.

Lactococcus lactis KF140 Ameliorates Nonalcoholic Fatty Liver Disease Induced by Nε-Carboxymethyl-Lysine and High-Fat Diet.

SCOPE: Long-term consumption of excessive dietary advanced glycation end-products such as Nε-carboxymethyl-lysine (CML), which are produced by the Maillard reaction during food thermal processing, leads to nonalcoholic fatty liver disease (NAFLD) along with high fat consumption. The study previously finds that administration of Lactococcus lactis KF140 (LL-KF140) detoxifies CML by decreasing CML absorption both in a rat model and clinical trial. METHODS AND RESULTS: The present study evaluates the ameliorative effect of LL-KF140 on NAFLD and fatty liver-related biomarkers in a mouse model induced by CML and high fat. LL-KF140 is orally administered to mice at a concentration of 1 × 107 or 1 × 108 colony-forming unit (CFU) per mouse for 8 weeks. LL-KF140 administration ameliorates the NAFLD-related symptoms by reducing body weight and fat mass gain along with levels of serum aspartate transaminase, alanine transferase, and lipids as well as glucose intolerance and insulin resistance in CML-treated mice. In addition, histological analysis including staining and western blotting shows that LL-KF140 suppresses the lipogenesis pathway and CML absorption, thereby suppressing CML-induced NAFLD. CONCLUSION: These findings suggest that LL-KF140 attenuates dietary CML-induced NAFLD by suppressing the de novo lipogenesis pathway, and it may be used as a probiotic strain.

The fatty liver index and risk of incident venous thromboembolism: the Tromsø Study.

Background: For the relationship between obesity and venous thromboembolism (VTE), nonalcoholic fatty liver disease (recently termed metabolic dysfunction-associated steatotic liver disease) is of interest given the hepatic role in hemostasis. Objectives: We aimed to assess the association between the fatty liver index (FLI), as a proxy for nonalcoholic fatty liver disease, and VTE risk in a population-based cohort. Methods: Data from the Tromsø 4 (1994-1995) and 6 (2007-2008) surveys were used to calculate the FLI in 9870 participants. All VTEs were recorded up to December 31, 2020. We used Cox regression to estimate hazard ratios for VTE with 95% CIs by FLI groups defined according to clinical cut-offs (<30, 30-59, and ≥60). Because waist circumference and body mass index (BMI) are main determinants for FLI calculation, we assessed the potential contribution of FLI to VTE risk beyond these body fat measures. Results: During a median follow-up of 13.1 years, 507 incident VTEs occurred. Compared with the reference group (FLI < 30), the hazard ratios for VTE were 1.5 (95% CI, 1.1-1.9) and 1.8 (95% CI, 1.4-2.3) for the FLI 30-59 and ≥60 groups, respectively, in models adjusted for age, sex, alcohol intake, educational level, and physical activity. The association of FLI with VTE was no longer observed, with risk estimates close to unity, when participants were stratified by clinical categories of waist circumference and BMI. Conclusion: Higher values of the FLI were associated with a higher VTE risk. This association was explained by waist circumference and BMI, which reflect excessive body fat deposition and are determinants of the FLI.

Disinfection Byproducts of Haloacetaldehydes Disrupt Hepatic Lipid Metabolism and Induce Lipotoxicity in High-Fat Culture Conditions.

Unhealthy lifestyles, obesity, and environmental pollutants are strongly correlated with the development of nonalcoholic fatty liver disease (NAFLD). Haloacetaldehyde-associated disinfection byproducts (HAL-DBPs) at various multiples of concentrations found in finished drinking water together with high-fat (HF) were examined to gauge their mixed effects on hepatic lipid metabolism. Using new alternative methods (NAMs), studying effects in human cells in vitro for risk assessment, we investigated the combined effects of HF and HAL-DBPs on hepatic lipid metabolism and lipotoxicity in immortalized LO-2 human hepatocytes. Coexposure of HAL-DBPs at various multiples of environmental exposure levels with HF increased the levels of triglycerides, interfered with de novo lipogenesis, enhanced fatty acid oxidation, and inhibited the secretion of very low-density lipoproteins. Lipid accumulation caused by the coexposure of HAL-DBPs and HF also resulted in more severe lipotoxicity in these cells. Our results using an in vitro NAM-based method provide novel insights into metabolic reprogramming in hepatocytes due to coexposure of HF and HAL-DBPs and strongly suggest that the risk of NAFLD in sensitive populations due to HAL-DBPs and poor lifestyle deserves further investigation both with laboratory and epidemiological tools. We also discuss how results from our studies could be used in health risk assessments for HAL-DBPs.

Pharmacotherapeutic options for metabolic dysfunction-associated steatotic liver disease: where are we today?

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by hepatic steatosis and cardiometabolic risk factors like obesity, type 2 diabetes, and dyslipidemia. Persistent metabolic injury may promote inflammatory processes resulting in metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. Mechanistic insights helped to identify potential drug targets, thereby supporting the development of novel compounds modulating disease drivers. AREAS COVERED: The U.S. Food and Drug Administration has recently approved the thyroid hormone receptor ß-selective thyromimetic resmetirom as the first compound to treat MASH and liver fibrosis. This review provides a comprehensive overview of current and potential future pharmacotherapeutic options and their modes of action. Lessons learned from terminated clinical trials are discussed together with the first results of trials investigating novel combinational therapeutic approaches. EXPERT OPINION: Approval of resmetirom as the first anti-MASH agent may revolutionize the therapeutic landscape. However, long-term efficacy and safety data for resmetirom are currently lacking. In addition, heterogeneity of MASLD reflects a major challenge to define effective agents. Several lead compounds demonstrated efficacy in reducing obesity and hepatic steatosis, while anti-inflammatory and antifibrotic effects of monotherapy appear less robust. Better mechanistic understanding, exploration of combination therapies, and patient stratification hold great promise for MASLD therapy.

Correlation between Serum 25 (OH) D Levels with Insulin Resistance and Metabolic Associated Fatty Liver Disease - A Retrospective Study based on Chinese Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

AIMS: The objective of this study was to investigate the correlation between serum 25 hydroxyvitamin D [25(OH)D] levels and insulin resistance, as well as metabolic associated fatty liver disease (MAFLD) in newly diagnosed with type 2 diabetes mellitus(T2DM) patients. METHOD: A retrospective analysis was conducted on 491 T2DM patients who were newly diagnosed between January 2017 and August 2022 at Peking University International Hospital. These patients were categorized into three groups based on their 25(OH)D levels. RESULTS: The prevalence of MAFLD was significantly elevated in both the Vitamin D(VD) deficiency group and the VD insufficiency group compared to the VD sufficiency group (χ2 = 6.51, p<0.05). The patients in the VD sufficiency group had lower levels of insulin resistance，as assessed by the homeostasis model assessment when compared to the VD deficiency group and the VD insufficiency group (F = 8.61，p < 0.05). Additionally, the VD sufficiency group demonstrated higher levels of ß cell function in comparison to the other two groups(p<0.05， respectively). (2) A significant negative correlation was observed between 25(OH)D levels and insulin resistance, as assessed by the homeostasis model assessment in T2DM patients(r=-0.33，p<0.05 for females; r=-0.32，p<0.05 for males). (3) In male patients, 25(OH)D was identified as a protective factor against MAFLD(OR = 0.42;95%CI:0.19-0.95;p<0.05). Meanwhile，in female patients, 25(OH)D was also associated with a reduced risk of MAFLD(OR = 0.35;95%CI 0.17-0.89;p<0.05). Additionally, the study determined that the threshold values for 25(OH)D were 15.06 ng/ml in female patients and 18.79 ng/ml in male patients for predicting MAFLD. CONCLUSION: In newly diagnosed with T2DM patients, the level of 25(OH)D may be related to insulin resistance and ß cell secretion function independently and VD deficiency is an independent risk factor for MAFLD in patients with newly diagnosed T2DM.

Impairments of insulin and glucagon sensitivity in Chinese women with gestational diabetes mellitus.

AIM: To evaluate insulin and glucagon sensitivity in Han Chinese women with and without gestational diabetes mellitus (GDM). METHODS: In total, 81 women with GDM and 81 age-matched healthy controls were evaluated with a 75 g oral glucose tolerance test (OGTT) at gestational weeks 24-28. Plasma glucose concentrations were measured at fasting and 1 h and 2 h post-OGTT. Fasting plasma insulin, glucagon and amino acids were also measured. Insulin and glucagon sensitivity were assessed by the homeostatic model assessment of insulin resistance (HOMA-IR) and glucagon-alanine index, respectively. RESULTS: As expected, plasma glucose concentrations were higher at fasting and 1 h and 2 h post-OGTT in GDM participants (p < .001 each). Both the HOMA-IR and the glucagon-alanine index were higher in GDM participants. There was a weak positive correlation between HOMA-IR and glucagon-alanine index (r = 0.24, p = .0024). Combining the HOMA-IR and the glucagon-alanine index yielded better capacity (area under the curve = 0.878) than either alone (area under the curve = 0.828 for HOMA-IR and 0.751 for glucagon-alanine index, respectively) in differentiating GDM from healthy participants. While the majority of GDM participants (64%) exhibited both reduced insulin and glucagon sensitivity, a third of them presented either reduced insulin (20%) or glucagon (14%) sensitivity alone. HOMA-IR and glucagon-alanine index correlated differentially with fasting glucose, triglycerides, low-density lipoprotein cholesterol, sum of amino acids and hepatic steatosis index. CONCLUSIONS: Impairments of both insulin and glucagon sensitivity occur frequently in Chinese women with GDM, which may, individually or together, drive metabolic derangements in GDM. These observations provide new insights into the pathophysiology of GDM and support the need to target insulin or glucagon resistance, or both, in the management of GDM.

Gut microbiota dysbiosis links chronic apical periodontitis to liver fibrosis in nonalcoholic fatty liver disease: Insights from a mouse model.

AIM: In this study, we investigated the systemic implications of chronic apical periodontitis (CAP). CAP may contribute to the nonalcoholic fatty liver disease (NAFLD) progression through the gut microbiota and its metabolites, which are related to the degree of fibrosis. METHODOLOGY: Sixteen 7-week-old male apolipoprotein E knockout (apoE-/-) mice were randomly divided into two groups: the CAP and Con groups. A CAP model was established by sealing the first- and second-maxillary molars with bacterium-containing cotton balls. Apical lesions were evaluated by micro-CT. Histological evaluations of NAFLD were performed using second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) assays. Additionally, we comprehensively analyzed the gut microbiota using 16S rRNA gene sequencing and explored metabolic profiles by liquid chromatography-mass spectrometry (LC-MS). Immunofluorescence analysis was used to examine the impact of CAP on tight junction proteins and mucin expression. Transcriptome assays have elucidated gene expression alterations in liver tissues. RESULTS: Micro-CT scans revealed an evident periapical bone loss in the CAP group, and the total collagen percentage was increased (Con, 0.0361 ± 0.00510%, CAP, 0.0589 ± 0.00731%, p < .05). 16S rRNA sequencing revealed reduced diversity and distinct taxonomic enrichment in the CAP group. Metabolomic assessments revealed that differentially enriched metabolites, including D-galactosamine, were enriched and that 16-hydroxyhexadecanoic acid and 3-methylindole were depleted in the CAP group. Immunofluorescence analyses revealed disruptions in tight junction proteins and mucin production, indicating intestinal barrier integrity disruption. Liver transcriptome analysis revealed upregulation of Lpin-1 expression in the CAP group. CONCLUSION: This study provides comprehensive evidence of the systemic effects of CAP on liver fibrosis in NAFLD patients by elucidating alterations in the gut microbiota composition and metabolism.

Fruit and vegetable intake and the risk of non-alcoholic fatty liver disease: a meta-analysis of observational studies.

Purpose: This systematic review and meta-analysis of clinical observational studies aims to clarify the correlation between the intake levels of fruits and vegetables and non-alcoholic fatty liver disease (NAFLD). Materials and methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies on the association between vegetable or fruit intake with the risk of NAFLD from the foundation of each database up until September 2023. The relative risk (OR) and the 95% confidence interval (CI) were pooled for both the highest and lowest consumption levels of vegetables and fruits to explore their association with the incidence of NAFLD. Results: The meta-analysis encompassed 11 studies with a total of 493,682 patients. A higher consumption of vegetables (OR = 0.78, 95% CI = 0.67-0.91) and fruits (OR = 0.88, 95% CI = 0.83-0.93) was found to have a negative correlation with the risk of NAFLD, denoting an inverse association. This correlation, however, varied among different ethnic groups and gender. Conclusions: Our results indicate that increased consumption of vegetables and fruits is associated with a reduced likelihood of developing NAFLD. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier: CRD42023460430.