OBJECTIVES: To systematically evaluate the prevalence and risk factors of non-alcoholic fatty liver disease (NAFLD) in overweight and obese children and adolescents in China. METHODS: Databases including China National Knowledge Infrastructure, Wanfang Data, VIP Database, China Biomedical Literature Database, PubMed, Embase, Web of Science, and Cochrane Library were searched, from database inception to October 2024. Two researchers independently screened the literature, extracted data, and assessed the quality of the studies according to inclusion and exclusion criteria. A Meta analysis was conducted using Stata 16.0 software. RESULTS: A total of 42 studies involving 16 481 overweight and obese children and adolescents were included. The Meta analysis results showed that the prevalence of NAFLD among overweight and obese children in China was 43% (95%CI: 37%-48%). Factors associated with NAFLD included being male (OR=1.61, 95%CI: 1.17-2.04), increased weight (MD=10.33, 95%CI: 9.08-11.57), increased waist circumference (MD=5.49, 95%CI: 3.36-7.62), longer duration of obesity (MD=0.31, 95%CI: 0.02-0.61), higher body mass index (MD=3.11, 95%CI: 2.07-4.16), elevated fasting blood glucose levels (MD=0.17, 95%CI: 0.06-0.29), higher triglyceride levels (MD=0.32, 95%CI: 0.17-0.47), elevated total cholesterol levels (MD=0.15, 95%CI: 0.10-0.21), higher low-density lipoprotein cholesterol levels (MD=0.14, 95%CI: 0.04-0.23), increased alanine aminotransferase levels (MD=24.39, 95%CI: 18.57-30.20), increased aspartate aminotransferase levels (MD=12.49, 95%CI: 9.67-15.32), elevated serum insulin levels (MD=4.47, 95%CI: 2.57-6.36), higher homeostasis model assessment-insulin resistance (MD=0.45, 95%CI: 0.30-0.59), and elevated uric acid levels (MD=55.91, 95%CI: 35.49-76.32) (P<0.05). CONCLUSIONS The prevalence of NAFLD among overweight and obese children and adolescents in China is high. Male gender, increased weight, increased waist circumference, prolonged obesity duration, higher body mass index, dyslipidemia, and elevated levels of fasting blood glucose, liver enzymes, serum insulin, homeostasis model assessment-insulin resistance, and uric acid are potential risk factors for NAFLD in this population.
Humans ; Non-alcoholic Fatty Liver Disease/etiology* ; Risk Factors ; Adolescent ; Child ; Overweight/complications* ; Prevalence ; China/epidemiology* ; Obesity/complications* ; Male ; Female

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) and hypertension are common metabolic disorders, both closely associated with insulin resistance (IR), suggesting potential shared pathological mechanisms. This study aims to investigate the mediating role of IR in the relationship between hypertension and NAFLD, and to evaluate the applicability and modeling value of various IR surrogate indices in predicting NAFLD risk. METHODS: A total of 280 976 individuals who underwent health examinations at the Health Management Center of the Third Xiangya Hospital of Central South University between August 2017 and December 2021 were included. NAFLD was diagnosed based on abdominal ultrasound findings, and hypertension was defined according to the criteria of the Chinese Guidelines for the Management of Hypertension. Demographic information, anthropometric indices, and biochemical parameters were collected, and multiple IR surrogate indices were constructed, including the triglyceride-glucose index (TyG) and its derivatives, as well as the metabolic score for insulin resistance (METS-IR). Group comparisons were performed between hypertensive and non-hypertensive participants, as well as between NAFLD and non-NAFLD participants. Pearson correlation analysis was applied to assess the associations of metabolic parameters and IR indices with NAFLD. Furthermore, mediation models were constructed to explore the mediating role of IR in the "hypertension-NAFLD" relationship. Finally, parametric models and machine learning algorithms were compared to evaluate their predictive performance and value in assessing NAFLD risk in this population. RESULTS: The prevalence of NAFLD was significantly higher in hypertensive individuals than in non-hypertensive participants (63.61% vs 33.79%, P<0.001), accompanied by elevated IR levels and adverse metabolic features. Correlation analysis and variable importance rankings across multiple models consistently identified TyG-waist circumference (TyG-WC) and METS-IR as the IR indices most strongly associated with NAFLD. In mediation analysis, the TyG-WC pathway explained 32.03% of the total effect, and the METS-IR pathway explained 17.02%. Interaction analysis showed that hypertension status may attenuate the mediating effect of IR (all interaction estimates were negative). In prediction model comparisons, the simplified model incorporating sex, age, WC, TyG-WC, and METS-IR demonstrated good performance in the test set. Logistic regression and its regularized form (LASSO regression) achieved an accuracy of 0.83, receiver operating characteristic (ROC)-area under the curve (AUC) of 0.91, and a Brier score of 0.12, comparable to ensemble models (random forest and XGBoost), with consistently stable performance across different algorithms. CONCLUSIONS IR plays a significant mediating role in the association between hypertension and NAFLD, with TyG-WC identified as a key indicator showing strong mechanistic relevance and predictive value. Risk prediction models based on IR surrogate indices demonstrate advantages in simplicity and interpretability, providing empirical support for the early screening and individualized prevention of NAFLD in the general population.
Humans ; Non-alcoholic Fatty Liver Disease/complications* ; Insulin Resistance ; Hypertension/epidemiology* ; Male ; Female ; Middle Aged ; Risk Factors ; Adult ; Machine Learning ; Triglycerides/blood*

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China

Objective: To compare the clinical and pathological features of children with chronic viral hepatitis B combined with metabolic-associated fatty liver disease (CHB-MAFLD) and chronic viral hepatitis B alone (CHB alone), and to further explore the effect of MAFLD on the progression of hepatic fibrosis in CHB. Methods: 701 initially treated CHB children confirmed by liver biopsy admitted to the Fifth Medical Center of the PLA General Hospital from January 2010 to December 2021 were collected continuously. They were divided into CHB-MAFLD and CHB-alone groups according to whether they were combined with MAFLD. A retrospective case-control study was conducted. CHB-MAFLD was used as the case group, and 1:2 propensity score matching was performed with the CHB alone group according to age and gender, including 56 cases in the CHB-MAFLD group and 112 cases in the CHB alone group. The body mass index (BMI), metabolic complications, laboratory indicators, and pathological characteristics of liver tissue were compared between the two groups. The related factors affecting liver disease progression in CHB were analyzed by a binary logistic regression model. The measurement data between groups were compared using the t-test and rank sum test. The χ (2) test was used for the comparison of categorical data between groups. Results: Alanine aminotransferase (ALT, P = 0.032) and aspartate aminotransferase (AST, P = 0.003) levels were lower in the CHB-MAFLD group than those in the CHB alone group, while BMI (P < 0.001), triglyceride (TG, P < 0.001), total cholesterol (P = 0.016) and the incidence of metabolic syndrome (P < 0.001) were higher in the CHB alone group. There were no statistically significant differences in HBsAg quantification or HBV DNA load between the two groups (P > 0.05). Histologically, the proportion of significant liver fibrosis (S2-S4) was higher in the CHB-MAFLD group than that in the CHB alone group (67.9% vs. 49.1%, χ (2) = 5.311, P = 0.021). Multivariate regression results showed that BMI (OR = 1.258, 95% CI: 1.145 ~ 1.381, P = 0.001) and TG (OR = 12.334, 95% CI: 3.973 ~ 38.286, P < 0.001) were the risk factors for hepatic steatosis occurrence in children with CHB. MAFLD (OR = 4.104, 95% CI: 1.703 ~ 9.889, P = 0.002), liver inflammation (OR = 3.557, 95% CI: 1.553 ~ 8.144, P = 0.003), and γ-glutamyl transferase (OR = 1.019, 95% CI: 1.001 to 1.038, P = 0.038) were independent risk factors for significant hepatic fibrosis in children with CH. Conclusion: MAFLD occurrence is related to metabolic factors in children with CHB. Additionally, the combination of MAFLD may promote liver fibrosis progression in CHB patients.
Humans ; Child ; Hepatitis B, Chronic/pathology* ; Retrospective Studies ; Case-Control Studies ; Hepatitis B virus/genetics* ; Liver Cirrhosis/pathology* ; Non-alcoholic Fatty Liver Disease/complications* ; Risk Factors

Objective: To investigate the clinical characteristics and maternal and fetal prognosis of pregnant women with acute fatty liver of pregnancy (AFLP). Methods: The clinical data of 86 AFLP pregnant women admitted to the Third Affiliated Hospital of Guangzhou Medical University from September 2017 to August 2022 were collected, and their general data, clinical characteristics, laboratory tests and maternal and fetal outcomes were retrospectively analyzed. Results: (1) General information: the age of the 86 pregnant women with AFLP was (30.8±5.4) years, and the body mass index was (21.0±2.5) kg/m². There were 50 primiparas (58.1%, 50/86) and 36 multiparas (41.9%, 36/86). There were 64 singleton pregnancies (74.4%, 64/86) and 22 twin pregnancies (25.6%, 22/86). (2) Clinical characteristics: the main complaints of AFLP pregnant women were gastrointestinal symptoms, including epigastric pain (68.6%, 59/86), nausea (47.7%, 41/86), anorexia (46.5%, 40/86), vomiting (39.5%, 34/86). The main non-gastrointestinal symptoms were jaundice of skin and/or scleral (54.7%, 47/86), edema (38.4%, 33/86), fatigue (19.8%, 17/86), bleeding tendency (16.3%, 14/86), polydipsia or polyuria (14.0%, 12/86), skin itching (8.1%, 7/86), and 17.4% (15/86) AFLP pregnant women had no obvious symptoms. (3) Laboratory tests: the incidence of liver and kidney dysfunction and abnormal coagulation function in AFLP pregnant women was high, and the levels of blood ammonia, lactate dehydrogenase and lactic acid were increased, and the levels of hemoglobin, platelet and albumin decreased. However, only 24 cases (27.9%, 24/86) of AFLP pregnant women showed fatty liver by imageology examination. (4) Pregnancy outcomes: ① AFLP pregnant women had a high incidence of pregnancy complications, mainly including renal insufficiency (95.3%, 82/86), preterm birth (46.5%, 40/86), hypertensive disorders in pregnancy (30.2%, 26/86), gestational diabetes mellitus (36.0%, 31/86), fetal distress (24.4%, 21/86), pulmonary infection (23.3%, 20/86), disseminated intravascular coagulation (16.3%, 14/86), multiple organ dysfunction syndrome (16.3%, 14/86), hepatic encephalopathy (9.3%, 8/86), and intrauterine fetal death (2.3%, 2/86). ② Treatment and outcome of AFLP pregnant women: the intensive care unit transfer rate of AFLP pregnant women was 66.3% (57/86). 82 cases were improved and discharged after treatment, 2 cases were transferred to other hospitals for follow-up treatment, and 2 cases (2.3%, 2/86) died. ③ Neonatal outcomes: except for 2 cases of intrauterine death, a total of 106 neonates were delivered, including 39 cases (36.8%, 39/106) of neonatal asphyxia, 63 cases (59.4%, 63/106) of neonatal intensive care unit admission, and 3 cases (2.8%, 3/106) of neonatal death. Conclusions: AFLP is a severe obstetric complication, which is harmful to mother and fetus. In the process of clinical diagnosis and treatment, attention should be paid to the clinical manifestations and laboratory tests of pregnant women, early diagnosis and active treatment, so as to improve maternal and fetal outcomes.
Pregnancy ; Infant, Newborn ; Female ; Humans ; Adult ; Retrospective Studies ; Premature Birth/epidemiology* ; Pregnancy Complications/diagnosis* ; Fatty Liver/diagnosis* ; Fetal Death ; Stillbirth

Nonalcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury that is closely associated with insulin resistance and genetic susceptibility. The continuum of liver injury in NAFLD can range from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and even lead to cirrhosis and liver cancer. The pathogenesis of NAFLD is complicated. Pro-inflammatory cytokines, lipotoxicity, and gut bacterial metabolites play a key role in activating liver-resident macrophages (Kupffer cells, KCs) and recruiting circulating monocyte-derived macrophages (MoDMacs) to deposit fat in the liver. With the application of single-cell RNA-sequencing, significant heterogeneity in hepatic macrophages has been revealed, suggesting that KCs and MoDMacs located in the liver exert distinct functions in regulating liver inflammation and NASH progression. This study focuses on the role of macrophage heterogeneity in the development and occurrence of NAFLD and NASH, in view of the fact that innate immunity plays a key role in the development of NAFLD.
Humans ; Non-alcoholic Fatty Liver Disease/pathology* ; Liver/pathology* ; Macrophages/metabolism* ; Liver Cirrhosis/complications* ; Disease Progression

BACKGROUND: There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension. METHODS: The study cohort comprised 25,433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD. RESULTS: During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10-1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10-1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07-1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03-1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association. CONCLUSIONS NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.
Humans ; Non-alcoholic Fatty Liver Disease/complications* ; Prehypertension/diagnosis* ; Risk Factors ; Hypertension ; Incidence

Humans ; Non-alcoholic Fatty Liver Disease/complications* ; Cardiovascular Diseases/complications* ; Risk Factors ; Liver

Adult ; Humans ; Non-alcoholic Fatty Liver Disease/complications* ; Cross-Sectional Studies ; Folic Acid/therapeutic use* ; Risk Factors

Non-alcoholic fatty liver disease (NAFLD) is a metabolic-related disorder induced by multiple factors and mainly characterized by excessive fat buildup in hepatocytes. With the consumption of a Western-style diet and obesity prevalence in recent years, the incidence of NAFLD has gradually increased, becoming an increasingly serious public health problem. Bilirubin is a heme metabolite and a potent antioxidant. Studies have demonstrated that bilirubin levels have an inverse correlation with the incidence rate of NAFLD; however, which form of bilirubin plays the main protective role is still controversial. It is considered that the main protective mechanisms for NAFLD are bilirubin antioxidant properties, insulin resistance reduction, and mitochondrial function. This article summarizes the correlation, protective mechanism, and possible clinical application of NAFLD and bilirubin.
Humans ; Non-alcoholic Fatty Liver Disease/metabolism* ; Bilirubin ; Antioxidants ; Obesity/complications* ; Hepatocytes/metabolism* ; Liver/metabolism*