New-onset Non-alcoholic Fatty Liver Disease Research Articles

Triglyceride glucose index as a predictor for non-alcoholic fatty liver disease: insights from a longitudinal analysis in non-obese individuals.

A substantial portion of non-obese population is afflicted with Non-alcoholic Fatty Liver Disease (NAFLD). The Triglyceride Glucose (TyG) index, a quantifier of insulin resistance magnitude, is determined by the product of fasting plasma glucose and triglyceride concentrations. The relationship between the TyG index and NAFLD within this cohort remains ambiguous. We conducted a retrospective analysis utilizing datasets acquired from the Dryad digital repository. Non-obese participants (BMI < 25 kg/m2) were enrolled at the Wenzhou Medical Center of Wenzhou People's Hospital between January 2010 and December 2014. Demographic information and biochemical parameters were systematically compiled, and the diagnosis of NAFLD was established through ultrasonographic evidence. This study cohort included 16,172 non-obese participants with a 5-year follow-up, among whom 2,322 (14.36%) developed NAFLD. The disparity between TyG index quartiles in the accumulative incidence of new-onset NAFLD was distinct, with an increasing risk of new-onset NAFLD as the TyG index increased. Participants in highest quartile exhibited the maximum risk of NAFLD. In the fully adjusted model 3, the hazard ratios for NAFLD in Q2, Q3, and Q4 were 2.15 (1.62, 2.87), 2.89 (2.20, 3.80) and 4.58 (3.48, 6.02), respectively. Meanwhile, the TyG index and NAFLD risk showed a highly significant overall correlation (p < 0.0001) and nonlinearity (p < 0.0001) according to the limited cubic splines. In subgroup analysis, a significant interaction was noted between new-onset NAFLD and SBP (<140 mmHg vs. ≥140 mmHg; P for interaction = 0.0114). The SBP < 140 mmHg subgroup demonstrated an enhanced TyG index influence on NAFLD risk (HR = 2.83, 95% CI: 2.48-3.23, p < 0.0001). The TyG index serves as a straightforward instrument for assessing NAFLD risk in non-obese individuals, enabling prompt identification and management in this population segment.

Association between TyG index trajectory and new-onset lean NAFLD: a longitudinal study.

The purpose of this manuscript is to identify longitudinal trajectories of changes in triglyceride glucose (TyG) index and investigate the association of TyG index trajectories with risk of lean nonalcoholic fatty liver disease (NAFLD). Using data from 1,109 participants in the Health Management Cohort longitudinal study, we used Latent Class Growth Modeling (LCGM) to develop TyG index trajectories. Using a Cox proportional hazard model, the relationship between TyG index trajectories and incident lean NAFLD was analyzed. Restricted cubic splines (RCS) were used to visually display the dose-response association between TyG index and lean NAFLD. We also deployed machine learning (ML) via Light Gradient Boosting Machine (LightGBM) to predict lean NAFLD, validated by receiver operating characteristic curves (ROCs). The LightGBM model was used to create an online tool for medical use. In addition, NAFLD was assessed by abdominal ultrasound after excluding other liver fat causes. The median age of the population was 46.6 years, and 440 (39.68%) of the participants were men. Three distinct TyG index trajectories were identified: "low stable" (TyG index ranged from 7.66 to 7.71, n=206, 18.5%), "moderate stable" (TyG index ranged from 8.11 to 8.15, n=542, 48.8%), and "high stable" (TyG index ranged from 8.61 to 8.67, n=363, 32.7%). Using a "low stable" trajectory as a reference, a "high stable" trajectory was associated with an increased risk of lean-NAFLD (HR: 2.668, 95% CI: 1.098-6.484). After adjusting for baseline age, WC, SBP, BMI, and ALT, HR increased slightly in "moderate stable" and "high stable" trajectories to 1.767 (95% CI:0.730-4.275) and 2.668 (95% CI:1.098-6.484), respectively. RCS analysis showed a significant nonlinear dose-response relationship between TyG index and lean NAFLD risk (χ2=11.5, P=0.003). The LightGBM model demonstrated high accuracy (Train AUC 0.870, Test AUC 0.766). An online tool based on our model was developed to assist clinicians in assessing lean NAFLD risk. The TyG index serves as a promising noninvasive marker for lean NAFLD, with significant implications for clinical practice and public health policy.

Association between the ZJU index and risk of new-onset non-alcoholic fatty liver disease in non-obese participants: a Chinese longitudinal prospective cohort study.

Non-alcoholic fatty liver disease (NAFLD) is increasingly observed in non-obese individuals. The ZJU (Zhejiang University) index has been established as a new and efficient tool for detecting NAFLD, but the relationship between the ZJU index and NAFLD within non-obese individuals still remains unclear. A post-hoc evaluation was undertaken using data from a health assessment database by the Wenzhou Medical Center. The participants were divided into four groups based on the quartile of the ZJU Index. Cox proportional hazards regression, Kaplan-Meier analysis and tests for linear trends were used to evaluate the relationship between the ZJU index and NAFLD incidence. Subgroup analysis was conducted to test the consistency of the correlation between ZJU and NAFLD in subsgroups. Receiver operative characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the ZJU index, compared with the Atherogenic index of plasma (AIP) and Remnant lipoprotein cholesterol (RLP-C) index. A total of 12,127 were included in this study, and 2,147 participants (17.7%) developed NAFLD in 5 years follow-up. Participants in higher ZJU quartiles tended to be female and have higher liver enzymes (including ALP, GGT, ALT, AST), GLU, TC, TG, LDL and higher NAFLD risk. Hazard Ratios (HR) and 95% confidence intervals (CI) for new-onset NAFLD in Q2, Q3, and Q4 were 3.67(2.43 to 5.55), 9.82(6.67 to 14.45), and 21.67(14.82 to 31.69) respectively in the fully adjusted model 3. With increased ZJU index, the cumulative new-onset NAFLD gradually increased. Significant linear associations were observed between the ZJU index and new-onset NAFLD (p for trend all<0.001). In the subgroup analysis, we noted a significant interaction in sex, with HRs of 3.27 (2.81, 3.80) in female and 2.41 (2.21, 2.63) in male (P for interaction<0.01). The ZJU index outperformed other indices with an area under the curve (AUC) of 0.823, followed by AIP (AUC=0.747) and RLP-C (AUC=0.668). The ZJU index emerges as a promising tool for predicting NAFLD risk in non-obese individuals, outperforming other existing parameters including AIP and RLP-C. This could potentially aid in early detection and intervention in this specific demographic.

U-Shaped relationship of insulin-like growth factor I and incidence of nonalcoholic fatty liver in patients with pituitary neuroendocrine tumors: a cohort study.

Although the role of insulin-like growth factor I (IGF-1) in nonalcoholic fatty liver disease (NAFLD) has garnered attention in recent years, few studies have examined both reduced and elevated levels of IGF-1. The aim of this study was to examine the potential relationship between IGF-1 levels and the risk of new-onset NAFLD in patients with pituitary neuroendocrine tumors (PitNET). We employed multivariable Cox regression models and two-piecewise regression models to assess the association between IGF-1 and new-onset NAFLD. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated to quantify this association. Furthermore, a dose-response correlation between lgIGF-1 and the development of NAFLD was plotted. Additionally, we also performed subgroup analysis and a series sensitivity analysis. A total of 3,291 PitNET patients were enrolled in the present study, and the median duration of follow-up was 65 months. Patients with either reduced or elevated levels of IGF-1 at baseline were found to be at a higher risk of NAFLD compared to PitNET patients with normal IGF-1(log-rank test, P < 0.001). In the adjusted Cox regression analysis model (model IV), compared with participants with normal IGF-1, the HRs of those with elevated and reduced IGF-1 were 2.33 (95% CI 1.75, 3.11) and 2.2 (95% CI 1.78, 2.7). Furthermore, in non-adjusted or adjusted models, our study revealed a U-shaped relationship between lgIGF-1 and the risk of NAFLD. Moreover, the results from subgroup and sensitivity analyses were consistent with the main results. There was a U-shaped trend between IGF-1 and new-onset NAFLD in patients with PitNET. Further evaluation of our discoveries is warranted.

Lifestyle factors affecting new-onset nonalcoholic fatty liver disease

Evidence for the influence of lifestyle factors on nonalcoholic fatty liver disease (NAFLD) onset is limited because the association between lifestyle factors and NAFLD has been reported mostly in cross-sectional studies. Our purpose was to elucidate which lifestyle factors are associated with NAFLD onset by performing a longitudinal study. This was a longitudinal study of 1,713 Japanese participants who underwent multiple health checkups from June 2013 to the end of March 2018 and were not diagnosed with NAFLD at the first health checkup at Watari Hospital in Fukushima, Japan. Baseline characteristics, including lifestyle factors, were compared among participants with and without NAFLD. Cox proportional hazards models were used to identify the association between lifestyle factors and NAFLD onset. Among the 1,713 participants, 420 (24.5 %) developed NAFLD during the observation period (median 47 months). There were significant differences in body mass index and hepatobiliary enzyme levels between participants with and without NAFLD. In Cox proportional hazards models, eating between meals (hazard ratio (HR): 2.08, 95 % confidence interval (CI): 1.25–3.45, p < 0.01) and eating fast (HR: 1.59, 95 % CI: 1.26–2.00, p < 0.01) were risk factors for NAFLD onset in men and women, respectively. Moreover, fast walking was a protective factor against NAFLD onset in women (HR: 0.76, 95 % CI: 0.60–0.96, p = 0.02). These findings could help to identify patients at risk and prevent future NAFLD onset.

Plant-based diets, genetic predisposition and risk of non-alcoholic fatty liver disease

BackgroundDiets rich in plant-based foods are associated with lower risks of non-alcoholic fatty liver disease (NAFLD), while the prospective evidence is limited. We aimed to examine longitudinal associations of plant-based diets and genetic susceptibility with NAFLD risk.MethodsThis longitudinal cohort study included 159,222 participants (58.0 ± 8.0 years old, 55.7% female) free of NAFLD in the UK Biobank. We calculated the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI). New-onset NAFLD was the primary outcome. The weighted polygenic risk score was calculated based on risk variants associated with NAFLD. Hazard ratios (HR) and 95% confidential intervals (CI) were estimated by Cox proportional hazards model. Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) measured liver fat content in a subsample of 20,692 participants (57.5 ± 7.4 years old, 52.6% female) was the secondary outcome. The associations between plant-based diet indices and MRI-PDFF were evaluated using generalized linear models.ResultsDuring a median follow-up of 9.5 years, 1541 new-onset NAFLD cases were documented. Compared to the lowest quintile, multivariable-adjusted hazard ratios (HRs) of NAFLD in the highest quintile were 0.78 (95% confidential intervals [CI], 0.66–0.93, p-trend =0.02), 0.74 (95% CI, 0.62–0.87, p-trend <0.0001), and 1.24 (95% CI, 1.05–1.46, p-trend = 0.02) for overall PDI, hPDI, and uPDI, respectively. For liver fat content, higher overall PDI and hPDI were associated with lower MRI-PDFF, while higher uPDI was associated with higher liver fat content. We observed a significant interaction between hPDI and PRS (p-interaction =0.03), and the NAFLD risk was lowest among participants with the highest hPDI and low genetic risk.ConclusionsHigher intake of plant-based diets especially healthful plant-based diets was associated with lower NAFLD risk and liver fat content regardless of genetic susceptibility, whereas an unhealthful plant-based diet was associated with higher NAFLD risk and intrahepatic steatosis. These results suggest that the quality of plant-based foods should be highlighted when adopting a plant-based diet.

Relationship Between Plasma Aldosterone Concentrations and Non-Alcoholic Fatty Liver Disease Diagnosis in Patients with Hypertension: A Retrospective Cohort Study.

To investigate the association between plasma aldosterone concentration (PAC) and non-alcoholic fatty liver disease (NAFLD) diagnosis in Chinese hypertensive patients. We conducted a retrospective study of all patients diagnosed with hypertension between January 1, 2010, and December 31, 2021. We included 3713 hypertensive patients based on the criteria for inclusion and exclusion. PAC measurement was performed using a radioimmunoassay. NAFLD was diagnosed using abdominal ultrasonography. Cox regression analysis was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for univariable and multivariable models. A generalized additive model was used to identify nonlinear relationships between PAC and NAFLD diagnosis. A total of 3713 participants were included in the analysis. Over a median follow-up of 30 months, 1572 hypertensive individuals developed new-onset NAFLD. When PAC was used as a continuous variable, the risk of NAFLD increased by 1.04 and 1.24-fold for each 1 ng/dL and 5 ng/dL increase in PAC, respectively. When PAC was considered a categorical variable, the HR for tertile 3 was 1.71 (95% CI, 1.47-1.98, P < 0.001) compared to tertile 1. Overall, there was a J-shaped relationship between PAC and new-onset NAFLD. By fitting a two-piecewise linear regression model and using a recursive algorithm, we identified a PAC inflection point at 13 ng/dL (log-likelihood ratio test, P = 0.005). In adjusted model 3, for PAC ≥ 13 ng/dL, a 5 ng/dL increase in PAC was associated with a 30% increase in the risk of new-onset NAFLD (95% CI, 1.25-1.35, P < 0.001). The study revealed a non-linear relationship between elevated PAC levels and the incidence of NAFLD in hypertensive patients. Notably, the risk of new-onset NAFLD was significantly increased when PAC levels were ≥13 ng/dL. Larger, prospective studies are necessary to confirm these findings.

Association Between Hypertension and New-Onset Non-Alcoholic Fatty Liver Disease in Chinese Non-Obese People: A Longitudinal Cohort Study.

Quantification of the relationship between hypertension and non-alcoholic fatty liver disease (NAFLD) risk is limited and controversial. This study aimed to investigate the relationship between hypertension and NAFLD in non-obese Chinese and to use different methods to demonstrate that hypertension is an independent risk factor for NAFLD. On 16,153 nonobese individuals, a retrospective cohort study was conducted in China to examine the impact of hypertension on incident NAFLD. We compared five methods: multivariable Cox proportional-hazards regression, propensity score-matched (PSM) analysis, propensity score adjustment method (considering the propensity score as a covariate in a multivariable Cox proportional-hazard regression), and two propensity score-based weighted methods-The first one estimated the hypertension effect in the overall study population-inverse probability of treatment weights (IPTW), the other in the hypertensive population-standardized mortality ratio (SMR) weights. We also used a genetic matching (GenMatch) algorithm to match the participants for sensitive analysis. Between 2010 and 2014, 16,153 participants met our inclusion criteria, including 2427 (15.03%) with hypertension. A total of 2321 (14.37%) participants developed NAFLD during the median follow-up of 2.98 years. The crude hazard ratio (HR) between hypertension and incident NAFLD was 2.05 (95% confidence interval (CI): 1.87, 2.25). The adjusted HR depended on the different methods, ranging from 1.09 (95% CI: 0.77, 1.23) for the PSM method to 2.24 (95% CI: 2.05, 2.44) for the SMR weighted analysis. Hypertensive participants with high propensity scores had a higher risk of developing NAFLD in the future. Excluding participants with propensity scores <8% yielded comparable hazard ratios with a narrower range, from 1.04 to 1.80. After adjusting for the confounding variables, the relationship also existed in the GenMatch cohort as a sensitivity analysis (HR=1.06, 95% CI 1.01-1.13). Hypertension is a significant cause of NAFLD in Chinese adults in non-obese Chinese adults, with the hazard ratio ranging from 1.09 to 2.24.

Ideal cardiovascular health metrics and the risk of nonalcoholic fatty liver disease in Korean adults

BackgroundThe association between cardiovascular risk factors and nonalcoholic fatty liver disease (NAFLD) is well established, but whether cardiovascular health (CVH) metrics is associated with NAFLD had not been fully studied. Thus, we examined the association between CVH metrics and NAFLD in the middle-aged Korean population.MethodsWe used data of 2,928 (851 men and 2,077 women) participants aged 30–64 years from the Cardiovascular and Metabolic Disease Etiology Research Center study. CVH metrics were measured using a modified version of Life’s Simple 7 by the American Heart Association. NAFLD diagnosis was based on the fatty liver index or liver-to-spleen ratio on computed tomography. A multiple logistic regression model was used to investigate the cross-sectional and longitudinal associations between CVH metrics and NAFLD.ResultsIn the cross-sectional analysis, the odds ratio for NAFLD was lower in participants with ideal CVH (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.08–0.18), while it was higher in individuals with poor CVH (OR, 2.87; 95% CI, 2.13–3.86). Similarly, the risk of new-onset NAFLD was lower in participants with ideal CVH (OR, 0.28; 95% CI, 0.11–0.74), and higher in individuals with poor CVH (OR, 2.20; 95% CI, 0.50–9.72) in the longitudinal analysis of a subgroup.ConclusionsIdeal CVH was associated with a lower risk of NAFLD while poor CVH was associated with a higher risk of NAFLD. These findings suggest that making efforts to encourage people to manage their CVH to the ideal level may prevent and manage NAFLD.

Assessing the longitudinal association between the GGT/HDL-C ratio and NAFLD: a cohort study in a non-obese Chinese population

BackgroundA cross-sectional association between the combination indicator of high-density lipoprotein cholesterol (HDL-C) and gamma-glutamyl transferase (GGT) and fatty liver has been described in several recent studies, and this study aims to further evaluate the longitudinal relationship between the ratio of GGT to HDL-C (GGT/HDL-C ratio) and nonalcoholic fatty liver disease (NAFLD).MethodsThis cohort study included 12,126 individuals without NAFLD at baseline, followed prospectively for 5 years, and the endpoint of interest was new-onset NAFLD. The relationship of the GGT/HDL-C ratio with new-onset NAFLD and the shape of the association was assessed by Cox regression models and restricted cubic spline (RCS) regression, respectively. Time-dependent receiver operator characteristics (ROC) curves were constructed to evaluate the predictive value of GGT, HDL-C, GGT/HDL-C ratio and BMI for the occurrence of NAFLD at different time points in the future.ResultsThe prevalence of NAFLD was 72.46/1000 person-years during the 5-year follow-up period. Results of multivariate Cox regression analysis showed a positive association of the GGT/HDL-C ratio with new-onset NAFLD after adequate adjustment of the related confounding factors, and the degree of correlation was slightly higher than that of GGT, and further subgroup analysis found that this association was more significant in the population with elevated systolic blood pressure (SBP). In addition, we also found a nonlinear relationship of the GGT/HDL-C ratio with the risk of new-onset NAFLD using the RCS regression, where the saturation threshold was about 31.79 U/mmol. Time-dependent ROC analysis results showed that the GGT/HDL-C ratio was increasingly valuable in predicting NAFLD over time, and was better than HDL-C in predicting NAFLD in the early stage (1–3 years), but was not superior to BMI and GGT.ConclusionsIn this large longitudinal cohort study based on a Chinese population, our results supported that the GGT/HDL-C ratio was positively and nonlinearly associated with the risk of new-onset NAFLD in a non-obese population. In the assessment of future NAFLD risk, the GGT/HDL-C ratio was slightly better than GGT alone; However, the GGT/HDL-C ratio did not appear to have a significant advantage over GGT and BMI alone in predicting NAFLD.

Association between the atherogenic index of plasma and new-onset non-alcoholic fatty liver disease in non-obese participants.

IntroductionNon-alcoholic fatty liver disease (NAFLD) in the non-obese population accounts for a large proportion of NAFLD. Atherogenic index of plasma (AIP, defined as the logarithm of the triglyceride/high-density lipoprotein cholesterol ratio.) can provide a stronger reflection of dyslipidemia and studies on the longitudinal association between AIP and NAFLD were limited in non-obese participants, especially in different BMI groups.MethodsWe performed a post-hoc analysis of data obtained from the Dryad data repository (Dryad is a nonprofit open database of medicine.) and explored the predictive value of AIP on the risk of NAFLD among non-obese participants.ResultsThis study included 16173 participants with AIP, of which 2322(14.4%) non-obese participants developed into individuals with NAFLD with the 5-year follow-up examination. The difference between AIP quartiles in the cumulative estimation of new-onset NAFLD was significant, and with increased AIP, the cumulative new-onset NAFLD gradually increased. Participants in higher AIP quartiles had a significantly increased risk of NAFLD. In the fully adjusted model 3, hazard ratios of the new-onset NAFLD for subjects in Q2, Q3, and Q4 of AIP were 2.00 (1.59, 2.53), 2.61 (2.09, 3.72), and 4.49 (3.62, 5.57) respectively. Meanwhile, the trend test for the association between AIP quartiles and the new-onset NAFLD presented that AIP quartile was positively and strongly associated with the new-onset NAFLD (adjusted hazard ratio (95%CI) in Model 3: 1.59 (1.51, 1.67), P<0.001). We found that AIP was also positively and strongly associated with new-onset NAFLD in different sex groups and different age groups in female patients. Moreover, the predictive ability of AIP was no significant difference in different sex groups and different age groups in female patients. In the subgroup analysis, we found that in the low BMI population, the predictive effect of AIP for new-onset NAFLD was expanded by 2-3 times for each quality increase of AIP.ConclusionThis study found that AIP was a strong independent risk factor for new-onset NAFLD among non-obese individuals especially in the low BMI participants, and screening for AIP in this population can be used to prevent future NAFLD.

Sex-specific metabolic risk factors and their trajectories towards the non-alcoholic fatty liver disease incidence.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease. This study examined sex-specific associations between NAFLD and metabolic factors and investigated the trajectory of risk factors. We retrospectively investigated 16,140 individuals from Beijing Health Management Cohort. Univariate and multivariate time-dependent Cox regression analyses were performed to identify independent risk factors for new-onset NAFLD. The trajectory of risk factors was investigated using the latent growth curve model and growth mixture model. Over a median follow-up of 3.15years, 2,450 (15.18%) participants developed NAFLD. The risk factors for NAFLD in men were increased body mass index (BMI); waist circumference (WC); triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), haemoglobin (Hb), and serum uric acid (SUA) levels; and platelet (PLT) count and decreased serum creatinine-to-body weight (sCr/bw) and high-density lipoprotein cholesterol (HDL-C) levels. In women, the risk factors were increased BMI, WC, and fasting plasma glucose (FPG), TG, LDL-C, SUA, white blood cell (WBC), and PLT and decreased sCr/bw and HDL-C levels. In addition, BMI, LDL-C, sCr/bw and PLT changing trajectories were associated with NAFLD in men; BMI, WC, TG, LDL-C, SUA and sCr/bw trends was associated with NAFLD risk in women. Development of NAFLD is associated with BMI, LDL-C, sCr/bw and PLT changing trajectories in men; BMI, WC, TG, LDL-C, SUA and sCr/bw trends are associated an increased risk of NAFLD in women. Deterioration of metabolic risk factors status can be a predictor of NAFLD many years before its occurrence.

Effects of serum branched-chain amino acids on nonalcoholic fatty liver disease and subsequent cardiovascular disease.

To reveal the role of branched-chain amino acids (BCAAs) in the development and progression of nonalcoholic fatty liver disease (NAFLD) and the effect on the incidence of subsequent cardiovascular disease. A total of 1302 subjects in the cohort study of the Huai'an Diabetes Prevention Program were divided into two groups according to whether NAFLD was present at baseline. The group without NAFLD at baseline was only followed up, and the group with NAFLD at baseline received diet and exercise interventions. Anthropometric and biochemical examinations were performed at baseline and at the end of 4years for all subjects. Serum BCAA (leucine, isoleucine, and valine) levels were measured by hydrophilic interaction chromatography-tandem mass spectrometry. The associations of baseline serum BCAA levels with the risk for NAFLD, coronary heart disease (CHD), and cardiovascular events (CVEs) after 4years were further evaluated. (1) At baseline and after the 4-year follow-up, baseline serum leucine, valine, and total BCAAs in the NAFLD group were significantly higher than those in the non-NAFLD group (p < 0.05). (2) According to whether NAFLD was present at baseline and after follow-up, all subjects were divided into four groups, including the control group, new case group, improvement group, and unchanged group. There was no significant difference in baseline BCAAs levels between the new case group and the improvement group (p > 0.05). (3) Risk factors for the occurrence and development of NAFLD were analysed by a multiple logistic regression model according to whether NAFLD existed at baseline. Serum leucine (OR = 1.058, 95% CI 1.005-1.114, p = 0.033) and total BCAAs (OR = 1.023, 95% CI 1.001-1.046, p = 0.045) were independent risk factors for new-onset NAFLD. Serum valine (OR = 1.131, 95% CI 1.043-1.226, p = 0.003), and total BCAAs (OR = 1.040, 95% CI 1.003-1.078, p = 0.035) were independent risk factors showing that NAFLD could not be reversed. (4) The cross-table Chi-square test showed that the incidence of both CHD and CVEs was significantly highest in the new case group (p < 0.05). (5) After adjusting for confounding factors, baseline isoleucine, valine, and BCAA levels were independently associated with new-onset CHD in subjects with or without NAFLD at baseline (p < 0.05). High BCAA levels exacerbate the risk of CHD and CVEs by influencing the occurrence and progression of NAFLD. However, lifestyle interventions could reverse the risk of NAFLD, CHD and CVEs associated with BCAAs.

Bidirectional Association between Hypertension and NAFLD: A Systematic Review and Meta-Analysis of Observational Studies.

An increasing body of evidence connects non-alcoholic fatty liver disease (NAFLD) to hypertension. The objective of this systematic review and meta-analysis was to estimate the nature and magnitude of the association between NAFLD and hypertension. We systematically searched PubMed, Embase, Cochrane Library, and Web of Science for observational studies published up to May 1, 2021. Cohort studies that reported data on the association between NAFLD and incident hypertension or between hypertension and incident NAFLD were included. We used random-effects models to conduct meta-analysis on the measures of association from individual studies. A total of 11 studies were eligible for inclusion, among which 4 studies including 25,260 participants reported the association between hypertension and new-onset NAFLD. The presence of hypertension was significantly associated with an increased risk of incident NAFLD (HR 1.63, 95% CI: 1.41–1.88; I2 = 37.6%). On the other hand, 9 studies with data on 46,487 participants analyzed the effects of NAFLD on incident hypertension. Pooled analysis showed that the presence of NAFLD was significantly associated with an increased incidence of hypertension (HR 1.55, 95% CI: 1.29–1.87; I2 = 80.5%). There was significant heterogeneity among the studies in this analysis (p < 0.01). Sensitivity analyses showed that the magnitude of the association was significantly different in subgroups stratified by a mean age of participants and geographical location, which explains part of the heterogeneity. In conclusion, this meta-analysis indicates the existence of a bidirectional relationship between NAFLD and hypertension independent of traditional cardiometabolic risk factors.

Dose-Response Associations of Metabolic Score for Insulin Resistance Index with Nonalcoholic Fatty Liver Disease among a Nonobese Chinese Population: Retrospective Evidence from a Population-Based Cohort Study.

Purpose This study is aimed at investigating the association between the metabolic score for insulin resistance (METS-IR) index and nonalcoholic fatty liver disease (NAFLD) in the nonobese population and its predictive value. Methods 10730 nonobese subjects were selected from longitudinal cohort research conducted from January 2010 to December 2014. Cox proportional hazards models were employed to assess the relationship between METS-IR and new-onset NAFLD. Generalized additive models were used to identify nonlinear relationships. In addition, we performed subgroup analyses and interaction tests. The time-dependent receiver operating curve (ROC) and area under the ROC (AUC) were utilized to measure the discriminatory ability of METS-IR for new-onset NAFLD. Beyond clinical risk factors, the incremental predictive value of METS-IR was appraised using integrated discrimination improvement (IDI), C-index, and net reclassification index (NRI). Results Over a median period of 804.50 days of follow-up, 1859 (17.33%) participants had a new onset of NAFLD. After adjusting for confounders, the HR for new-onset NAFLD in the Q4 group was 6.40 compared with the Q1 group. When METS-IR was considered a continuous variable, the risk of NAFLD increased by 34% for every 1 SD increase in METS-IR. The smoothing curve shows the dose-response relationship between METS-IR and the presence of new-onset NAFLD. Using a two-piecewise linear regression model, we derived a METS-IR inflection point of 36. HRs were 1.31 on the left side of the inflection point and 1.04 on the right side of the inflection point (log-likelihood ratio test, P < 0.001). Subgroup analyses and interaction tests revealed an interaction between gender and SBP in the association between METS-IR and new-onset NAFLD. In the subgroup analysis of gender and SBP, we observed a higher risk of new-onset NAFLD in men and in those with abnormal SBP levels. We evaluated the ability of METS-IR to identify new-onset NAFLD at different time points. The AUCs at 1, 2, 3, and 4 years were 0.784, 0.756, 0.758, and 0.752, respectively, which represent good discrimination of new-onset NAFLD. The addition of METS-IR greatly improved the reclassification and differentiation of clinical risk factors, with an NRI of 0.276 and an IDI of 0.068. In addition, the addition of METS-IR increased the C-index from 0.719 to 0.771. Conclusion In a nonobese Chinese population, elevated METS-IR was independently associated with an enhanced risk of NAFLD development and a dose-response relationship existed. In addition, METS-IR might be a reliable indicator for screening individuals at risk for early NAFLD, especially in nonobese populations.

Bidirectional Association Between Psoriasis and Nonalcoholic Fatty Liver Disease: Real-World Evidence From Two Longitudinal Cohort Studies.

BackgroundAssociation between nonalcoholic fatty liver disease (NAFLD) and future psoriasis has not yet been confirmed, although the two diseases partially share a common pathogenesis pathway. Studies have revealed an association between psoriasis and subsequent NAFLD; however, these studies were limited to small sample sizes and a cross-sectional study design. Hence, the main objective of this population-based longitudinal cohort study was to evaluate the bidirectional association between psoriasis and NAFLD.MethodsData were retrieved from Taiwan’s National Health Insurance Research Database. Patients with new-onset NAFLD and psoriasis were respectively enrolled in two cohorts. For each comparison cohort, propensity-score-matched controls with no record of NAFLD or psoriasis were selected. An adjusted hazard ratio (aHR) was applied to evaluate subsequent risks.ResultsThe risk of patients with new-onset NAFLD developing psoriasis was statistically significant, with an HR of 1.07 (95% CI, 1.01–1.14). For younger patients with NAFLD, the risk of developing psoriasis was 1.3-fold higher. The risk of patients with new-onset psoriasis developing NAFLD in the future was 1.28-fold higher than that of patients without psoriasis (95% CI, 1.21–1.35), and patients in younger psoriasis subgroups below the age of 40 years were at a higher risk than those in older subgroups, with an aHR of 1.55 (95% CI, 1.40–1.71).ConclusionEvidence supports a bidirectional association between NAFLD and psoriasis, especially in patients below the age of 40 years. The correlation between the two diseases and the subsequent risk of disease development should be considered when caring for patients.

LDL/HDL cholesterol ratio is associated with new-onset NAFLD in Chinese non-obese people with normal lipids: a 5-year longitudinal cohort study

BackgroundLow-density lipoprotein to high density lipoprotein (LDL/HDL) cholesterol ratio has been reported to predict the risk of many metabolic diseases. However, the association between the LDL/HDL cholesterol ratio and nonalcoholic fatty liver disease (NAFLD) has not been established.MethodsA longitudinal cohort design was adopted in this study; 9767 non-obese subjects without NAFLD were included and analyzed. The subjects were grouped according to the quintile of LDL/HDL cholesterol ratio. The cumulative incidence of NAFLD and the independent effect of the LDL/HDL cholesterol ratio on NAFLD during 5 years of follow-up were calculated using the Kaplan-Meier method and Cox proportional-hazards regression model.ResultsDuring the 5-year follow-up period, 841 subjects were diagnosed with new-onset NAFLD, and the 1-, 2-, 3-, 4-, and 5-year cumulative incidence rates of NAFLD were 1.16, 4.65, 8.33, 12.43, and 25.14%, respectively. In the multivariable-adjusted Cox proportional-hazards regression model, the LDL/HDL cholesterol ratio was significantly associated with the risk for NAFLD (HR: 1.66, 95% CI: 1.38–1.99, P trend< 0.001), especially among young people (HR: 3.96, 95% CI: 1.50–10.46, P interaction< 0.05). Additionally, receiver operating characteristic curve analysis showed that the LDL/HDL cholesterol ratio was better than HDL cholesterol and LDL cholesterol in predicting new-onset NAFLD.ConclusionsLDL/HDL cholesterol ratio is an independent predictor of NAFLD in Chinese non-obese people with normal lipids, and its predictive value is higher than that of other lipoproteins. In clinical practice, the LDL/HDL cholesterol ratio can be used to identify people at high risk of NAFLD.

Association between the alanine aminotransferase/aspartate aminotransferase ratio and new-onset non-alcoholic fatty liver disease in a nonobese Chinese population: a population-based longitudinal study

BackgroundThe alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ratio has been considered an alternative marker for hepatic steatosis. However, few studies have investigated the association of the ALT/AST ratio with non-alcoholic fatty liver disease (NAFLD) in nonobese people.MethodsA total of 12,127 nonobese participants who were free of NAFLD participated in this study. The participants were divided into quintiles of the ALT/AST ratio. Multiple Cox regression models were used to explore the association of the ALT/AST ratio with new-onset NAFLD.ResultsDuring the five-year follow-up period, 2147 individuals (17.7%) developed new-onset NAFLD.After adjusting for all non-collinear covariates, the multiple Cox regression analysis results showed that a higher ALT/AST ratio was independently associated with new-onset NAFLD in nonobese Chinese (adjusted hazard ratios [aHRs]: 2.10, 95% confidence intervals: 1.88, 2.36). The aHRs for NAFLD across increasing quintiles of the ALT/AST ratio were 1, 1.63 (1.30, 2.04), 2.07 (1.65, 2.60), 2.84 (2.33, 3.48) and 3.49 (2.78, 4.39) (P for trend< 0.001). The positive association was more significant among people with high blood pressure, high blood lipids and hyperglycaemia, as well as in men. Additionally, the regression spline showed that the saturation effect of the ALT/AST ratio on NAFLD risk was at 0.93 in this study population, which was 1.22 in males and 0.89 in females.ConclusionsIn nonobese Chinese individuals without NAFLD at baseline, the increase in the ALT/AST ratio is closely associated with the risk of new-onset NAFLD.

An inverse association of weight and the occurrence of asymptomatic gallbladder stone disease in hypercholesterolemia patients: a case-control study

BackgroundDespite the fact that the majority of gallstones formed in the gallbladder are mainly composed of cholesterol, as they are formed from cholesterol-supersaturated bile, and hypercholesterolemia is a common metabolic disorder, which is closely related to cardiac, hepatic, renal and other oxidative damage inflammation and necrosis, there is still no consensus regarding the contribution of blood serum lipids in the pathogenesis of gallbladder stone disease (GSD). This study aimed to investigate the relationship between hypercholesterolemia and the risk of new-onset asymptomatic GSD, and to determine the prevalence of factors associated with new-onset asymptomatic GSD in patients with hypercholesterolemia.MethodsIn this study, 927 Chinese patients with new-onset asymptomatic gallstone disease and 845 healthy controls were enrolled starting from August 2012. Patients were matched for age, gender, race, occupation, systolic blood pressure, diastolic blood pressure, and fasting blood glucose levels (FBG). Body mass index (BMI), nonalcoholic fatty liver disease (NAFLD) and serum lipids indexes were compared and the relationships between BMI, blood lipid and gallbladder stone hazards were examined by logistic multivariate regression models.ResultsThe result showed a significantly higher morbidity with GSD in hypercholesterolemia than non-hypercholesterolemia patients (Χ2 = 17.211, P < 0.001). Of hypercholesterolemia patients, low density lipoprotein (OR = 1.493, P = 0.029) and NAFLD (OR = 2.723, P = 0.022) were significant risk factors for GSD, while being male (OR = 0.244, P = 0.033), weight (OR = 0.961, P = 0.022), high density lipoprotein (OR = 0.305, P < 0.001), and FBG (OR = 0.687, P = 0.034) were significantly negatively correlated with GSD in univariate analysis. Multivariate logistic regression indicated weakly positive correlations with NAFLD (OR = 3.284, P = 0.054), and significant negative correlations with weight (OR = 0.930, P = 0.018), HDL-c (OR = 0.144, P < 0.001), and GSD.ConclusionHypercholesterolemia acts as an independent risk factor for new-onset asymptomatic GSD, while obesity and NAFLD are synergistic factors. Interestingly, it is first reported that elevated weight was inversely associated with GSD in patients with hypercholesterolemia. The results of this study suggest that effective control of hyperlipidemia is of greater significance than weight loss, which might make the situation worse, in the prevention of GSD in obese patients with hyperlipidemia.

A cohort study on the correlation between body mass index trajectories and new-onset non-alcoholic fatty liver disease

Objective: To explore the correlation between the body mass index (BMI) trajectories and new-onset non-alcoholic fatty liver disease (NAFLD) so as to provide a scientific basis for the prevention and treatment of NAFLD. Methods: A total of 16388 observation subjects that met the inclusion criteria in the Kailuan study were used to form a cohort study. According to the BMI values of the observed subjects during annual physical examinations from 2006 to 2007, 2008 to 2009 and 2010 to 2011, SAS Proc Traj was used to determine four different BMI trajectories groups, namely, the low-stable medium-stable, medium-high and high-stable group. NAFLD incidence in each group was followed up during annual physical examinations from 2012 to 2013, 2014-2015 and 2016-2017. A total of 14998 observation subjects were finally included in the statistical analysis. The cumulative incidences of NAFLD differences in the four groups were compared. The Cox's proportional hazards regression model was used to analyze the correlation between different BMI trajectories and new-onset NAFLD. One-way analysis of variance was used to compare the intergroup difference of measurement data, and pairwise comparisons were conducted. LSD test was used for the homogeneity of variance. Dunnett's T3 test was used for heterogeneity of variances. χ (2) test was used to compare the count data, and the difference of NAFLD cumulative incidence rate between the different BMI trajectories groups was compared by log-rank test. Results: (1) the cumulative incidence of NAFLD was increased with the increase of BMI trajectories, which were 31%, 47%, 63%, 77%, respectively, and the difference was statistically significant (P < 0.01). (2) after adjusting for multiple confounding factors such as age and gender with the Cox's proportional hazards regression model, the risk of NAFLD in the BMI medium stable, medium-high, and high stable group was still 1.757 times [95% confidence interval (CI): 1.589 ~ 1.942], 2.612 (95%CI: 2.353 ~ 2.900), 3.566 (95%CI: 3.129 ~ 4.064) of the low-stable group (P < 0.01). Conclusion: The risk of NAFLD increases with increase of BMI trajectories, and long-term high levels of BMI are independent risk factors for the onset of NAFLD.