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.

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.

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.
目的： 分析慢性乙型肝炎（CHB）合并代谢相关脂肪性肝病（MAFLD）患者的临床及病理组织学特征。 方法： 收集2015年1月至2021年10月郑州大学第一附属医院有肝穿刺活组织检查的529例患者的临床资料，其中CHB患者290例，CHB合并MAFLD患者155例，MAFLD患者84例。对3组患者的临床资料包括一般资料、生物化学指标、FibroScan指标、病毒载量及病理组织学进行分析。采用二元logistic回归分析探讨CHB患者发生MAFLD的影响因素。 结果： （1） CHB合并MAFLD组年龄、男性、高血压及糖尿病的比例、人体质量指数、空腹血糖、γ-谷氨酰转移酶、低密度脂蛋白、胆固醇、甘油三酯、尿酸、肌酐、肝脏脂肪变受控衰减指数均高于CHB患者，而高密度脂蛋白、HBeAg阳性率、病毒载量水平、肝脏纤维化等级（S分期）均低于CHB患者，差异均有统计学意义（P < 0.05）。（2） CHB合并MAFLD组的丙氨酸转氨酶、天冬氨酸转氨酶、γ-谷氨酰转移酶、甘油三酯、尿酸、肌酐、肝脏脂肪变受控衰减指数均低于MAFLD患者，而高密度脂蛋白高于MAFLD患者，差异具有统计学意义（P < 0.05）；两组的肝脏炎症和纤维化等级（GS分期）差异无统计学意义（P > 0.05）。二元多因素logistic回归分析结果显示，超重/肥胖、甘油三酯、低密度脂蛋白、肝脏脂肪变受控衰减指数、HBeAg阳性是CHB患者发生MAFLD的独立影响因素。 结论： CHB患者合并代谢紊乱易发生MAFLD，HBV病毒因素、肝脏纤维化程度与肝脏组织脂肪变性之间有一定相关性。.

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.
代谢相关脂肪性肝病(MAFLD)已成为影响全世界公众健康最常见的慢性肝病，发病率呈逐年上升趋势。其发病的分子机制尚不完全清楚，且临床缺乏有效的防治手段。研究发现丁酸钠在体内能够参与基因调控、免疫调节、肠道屏障功能调节、氧化应激等多种生理活动，可预防和缓解MAFLD，其在MAFLD的发生、发展过程中起着重要作用。现就丁酸钠对MAFLD的基因表达调控、改善脂肪代谢、调节肠道菌群及改善脂肪性肝炎等相关研究进行综述。.

UNASSIGNED: Oral health is closely related to extra-oral disease status, as may be represented by the manifestations of gastrointestinal and liver diseases.
UNASSIGNED: 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.
UNASSIGNED: 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.