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Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set = 1.60 × 10–15 and 4.84 × 10–10; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10–4, and 7.15 × 10–4, odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set = 2.08 × 10–8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351–1.700), 1.43 × 10–12 and MD-MAFLD: 1.300 (1.191–1.416), 2.90 × 10–9]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21 × 10–8 and 1.225 (1.122, 1.340), 7.06 × 10–6, respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD. [ABSTRACT FROM AUTHOR]

Abstract Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set = 1.60 × 10–15 and 4.84 × 10–10; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10–4, and 7.15 × 10–4, odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set = 2.08 × 10–8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351–1.700), 1.43 × 10–12 and MD-MAFLD: 1.300 (1.191–1.416), 2.90 × 10–9]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21 × 10–8 and 1.225 (1.122, 1.340), 7.06 × 10–6, respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD.

Objective To investigate the influence of metabolic associated fatty liver disease (MAFLD) on carotid stenosis. Methods This study was conducted among the patients who underwent abdominal ultrasound and cervical vascular ultrasound at the same time during hospitalization in Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, from January 1, 2014 to June 30, 2020, and baseline data and clinical diagnosis were collected. According to medical history, clinical tests, and imaging indicators, they were divided into MAFLD group with 469 patients and non-MAFLD group with 365 patients. Carotid artery were assessed as normal carotid artery, carotid stenosis ＜50%, and carotid stenosis ≥50% according to the degree of stenosis. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed quantitative data between two groups; the chi-square test was used for comparison of qualitative data between two groups. The univariate and multivariate logistic regression analyses were used to investigate the influencing factors carotid stenosis. Results Compared with the non-MAFLD group, the MAFLD group had a significantly higher proportion of patients with carotid stenosis ≥50% (10.66% vs 5.21%, χ~2=8.050, P=0.005). The univariate logistic regression analysis showed that there were significant differences between the two groups in the proportion of male patients, smoking, MAFLD, body mass index (BMI), total cholesterol, high-density lipoprotein (HDL), administration of lipid-lowering drugs, systolic pressure, hypertension or medication, type 2 diabetes, insulin resistance, and aspartate aminotransferase (AST). After adjustment for sex, smoking, HDL, BMI, history of hypertension or medication, type 2 diabetes, and AST, the multivariate logistic regression analysis showed that MAFLD was a risk factor for carotid stenosis (≥50%) (odds ratio=1.979, 95% confidence interval: 1.055-3.713, P=0.033). Conclusion MAFLD is an independent risk factor for carotid stenosis (≥50%). [ABSTRACT FROM AUTHOR]

Oxidative stress is one of the pillars crucial in the development of a non-alcoholic fatty liver disease (NAFLD) and may cause DNA damage. Since the main pathway responsible for the repair of oxidative DNA damage is the base-excision repair (BER) pathway, we examined the relationship between the presence of different genetic variants of BER-associated genes and the risk of NAFLD. The study evaluates seven single nucleotide polymorphisms (SNPs) within five genes, hOGG1, APEX1, NEIL1, LIG3, LIG1, in 150 NAFLD patients and 340 healthy controls. The genotyping was performed using TaqMan probes and the results were presented as odds ratio with its corresponding 95% confidence interval. The following SNPs were assessed in the study: hOGG1 (rs1052133), APEX1 (rs176094 and rs1130409), NEIL1 (rs4462560), LIG3 (rs1052536), LIG3 (rs4796030), and LIG1 (rs20579). Four of the investigated SNPs, i.e., rs176094, rs1130409, rs4462560 and rs4796030, were found to be associated with NAFLD risk. Furthermore, the occurrence of insulin resistance in patients with steatosis depended on various LIG3 genetic variants. The findings imply the impact of genes involved in BER on NAFLD and fatty liver-related insulin sensitivity. [ABSTRACT FROM AUTHOR]

Oxidative stress is one of the pillars crucial in the development of a non-alcoholic fatty liver disease (NAFLD) and may cause DNA damage. Since the main pathway responsible for the repair of oxidative DNA damage is the base-excision repair (BER) pathway, we examined the relationship between the presence of different genetic variants of BER-associated genes and the risk of NAFLD. The study evaluates seven single nucleotide polymorphisms (SNPs) within five genes, hOGG1, APEX1, NEIL1, LIG3, LIG1, in 150 NAFLD patients and 340 healthy controls. The genotyping was performed using TaqMan probes and the results were presented as odds ratio with its corresponding 95% confidence interval. The following SNPs were assessed in the study: hOGG1 (rs1052133), APEX1 (rs176094 and rs1130409), NEIL1 (rs4462560), LIG3 (rs1052536), LIG3 (rs4796030), and LIG1 (rs20579). Four of the investigated SNPs, i.e., rs176094, rs1130409, rs4462560 and rs4796030, were found to be associated with NAFLD risk. Furthermore, the occurrence of insulin resistance in patients with steatosis depended on various LIG3 genetic variants. The findings imply the impact of genes involved in BER on NAFLD and fatty liver-related insulin sensitivity.

Oral health is closely related to extra-oral disease status, as may be represented by the manifestations of gastrointestinal and liver diseases. This review focuses on the roles that the oral–gut or the oral–gut–liver axis play in the pathogenesis of inflammatory bowel disease, colorectal cancer, metabolic fatty liver disease, and nonalcoholic steatohepatitis. The discussion will begin with clinical data, including data from preclinical animal models, to elucidate mechanisms. We will also discuss ways to target oral dysbiosis and oral inflammation to treat gastrointestinal and liver diseases. Several studies have demonstrated that oral pathobionts can translocate to the gastrointestinal tract where they contribute to inflammation and tumorigenesis. Furthermore, oral bacteria that migrate to the gastrointestinal tract can disseminate to the liver and cause hepatic disease. Thus, oral bacteria that ectopically colonize the intestine may serve as biomarkers for gastrointestinal and liver diseases. Also, understanding the characteristics of the oral–gut and oral–gut–liver microbial and immune axes will provide new insights into the pathogenesis of these diseases. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease( NAFLD) has become the most important chronic liver disease in the world, but there is still no approved drug for clinical practice. Due to the heterogeneity of NAFLD itself, although drug therapy is being developed, the response rate seems to remain low. In order to meet the needs of clinical trial design and provide accurate information for drug developers, relevant scholars have proposed to change the name of NAFLD to metabolic associated fatty liver disease This article summarizes the origin of NAFLD heterogeneity and the background of NAFLD renaming, so as to provide new ideas for accelerating the development of new therapies. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical and histopathological features of patients with chronic hepatitis B (CHB) combined with metabolic-associated fatty liver disease (MAFLD). Methods: Clinical data of 529 cases who had liver biopsies at the First Affiliated Hospital of Zhengzhou University between January 2015 and October 2021 were collected. Among them were 290 cases with CHB, 155 cases with CHB combined with MAFLD, and 84 cases with MAFLD. Three groups of patients clinical data, including general information, biochemical indicators, FibroScan indicators, viral load, and histopathology, were analyzed. A binary logistic regression analysis was used to explore the factors influencing MAFLD in patients with CHB. Results: (1) Age, male status, proportion of hypertension and diabetes, body mass index, fasting blood glucose, γ-glutamyl transpeptidase, low-density lipoprotein, cholesterol, triglycerides, uric acid, creatinine, and the controlled attenuation parameter for hepatic steatosis were higher in CHB combined with MAFLD than in CHB patient groups. In contrast, the high-density lipoprotein, HBeAg positivity rate, viral load level, and liver fibrosis grade (S stage) were lower in CHB patients, and the differences were statistically significant ( P < 0.05). (2) Alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, triglycerides, uric acid, creatinine, and the controlled attenuation parameter for hepatic steatosis in CHB combined with the MAFLD were lower than those in MAFLD patient groups, while high-density lipoprotein was higher than that of MAFLD patients, and the difference was statistically significant ( P < 0.05). There was no statistically significant difference in the grade of liver inflammation and fibrosis (GS stage) between the two groups ( P > 0.05). Binary multivariate logistic regression analysis showed that overweight/obesity, triglycerides, low-density lipoprotein, the controlled attenuation parameter for hepatic steatosis, and HBeAg positivity were independent influencing factors for MAFLD in CHB patients. Conclusion: Patients with CHB combined with metabolic disorders are prone to developing MAFLD, and there is a certain correlation between HBV viral factors, the degree of liver fibrosis, and the fatty degeneration of hepatocytes.

Metabolic-associated fatty liver disease (MAFLD) has become the most common chronic liver disease affecting global public health, and its incidence rate is increasing year by year. The molecular mechanism of its pathogenesis is not yet fully understood, and there is a shortage of effective clinical prevention and treatment methods. Studies have found that sodium butyrate can participate in gene regulation, immune regulation, intestinal barrier function regulation, oxidative stress and other in-vivo physiological activities. Furthermore, it also plays an important role in preventing and alleviating the MAFLD occurrence and development. This article reviews the related studies of sodium butyrate on gene expression regulation, fat metabolism improvement, intestinal flora regulation, and steatohepatitis improvement with MAFLD.