Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors.
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ABSTRACT:
SUBMITTER: Juanola O
PROVIDER: S-EPMC8155932 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and is strongly associated with metabolic deregulation. More recently, a significant impact of parental NAFLD in the offspring was demonstrated and has been widely discussed. However, pathogenetic pathways implicated in the inheritance by the offspring and relatives are still under debate. Probably, multiple mechanisms are involved as well as in NAFLD pathogenesis itself. Among the multifactorial involved mechanisms, genetic, epigenetic and environmental backgrounds are strongly related to NAFLD development in the offspring. Thus, based on recent evidence from the available literature concerning genetic, epigenetic and environmental disease modifiers, this review aimed to discuss the relationship between parental NAFLD and its impact on the offspring.
| S-EPMC9280730 | biostudies-literature
Project description:Recurrent or de novo non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) following liver transplantation (LT) is a frequent event being increasingly recognized over the last decade, but the influence of recurrent NASH on graft and patient outcomes is not yet established. Taking into consideration the long term survival of liver transplanted patients and long term complications with associated morbidity and mortality, it is important to define and minimize risk factors for recurrent NAFLD/NASH. Metabolic syndrome, obesity, dyslipidemia, diabetes mellitus are life style risk factors that can be potentially modified by various interventions and thus, decrease the risk of recurrent NAFLD/NASH. On the other hand, genetic factors like recipient and/or donor PNPLA3, TM6SF2, GCKR, MBOAT7 or ADIPOQ gene polymorphisms proved to be risk factors for recurrent NASH. Personalized interventions to influence the different metabolic disorders occurring after LT in order to minimize the risks, as well as genetic screening of donors and recipients should be performed pre-LT in order to achieve diagnosis and treatment as early as possible.
| S-EPMC8795078 | biostudies-literature
Project description:BackgroundAlthough many studies on non-alcoholic fatty liver disease (NAFLD) are underway worldwide, and several existing studies have investigated the association between NAFLD and cardiovascular risk factors, studies comparing NAFLD and alcoholic fatty liver disease (AFLD) are scarce. This study aimed to evaluate differences between the incidence of cardiovascular risk factors and metabolic syndrome in NAFLD and AFLD.MethodsA retrospective analysis of 913 patients who underwent abdominal computed tomography (CT) was performed to compare the incidence of cardiovascular risk factors and metabolic syndrome between NAFLD and AFLD. Subjects were divided into three groups based on criteria: healthy (n = 572), NAFLD (n = 295), and AFLD (n = 46). The healthy group had no liver disease. NAFLD was defined as fatty liver diagnosed on CT and drinking less than 140 g/week for men or 70 g/week for women. AFLD was defined as fatty liver diagnosed on CT and drinking more than 140 g/week for men or 70 g/week for women. We compared the incidence of cardiovascular risk factors and metabolic syndrome between the three groups. The relationship between each group and the metabolic syndrome risk was analyzed through multivariate logistic regression analysis.ResultsNo significant differences in several cardiovascular risk factors were observed between the NAFLD and AFLD groups. Upon analyzing the metabolic syndrome status in each group after making appropriate adjustments, the odds ratios (ORs) in the NAFLD (OR = 2.397, P = 0.002) and AFLD groups (OR = 4.445, P = 0.001) were found to be significantly higher than that in the healthy group; the incidence rate of metabolic syndrome was similar in the NAFLD and AFLD groups.ConclusionsBoth the NAFLD and AFLD groups had more cardiovascular risk factors and higher metabolic syndrome risk than the healthy group. Thus, the prevention of fatty liver disease, regardless of the specific type, should involve the identification of cardiovascular and metabolic syndrome risk factors. If abdominal CT reveals a fatty liver, whether NAFLD or AFLD, the risk of cardiovascular disease and metabolic syndrome should be assessed.
| S-EPMC8088638 | biostudies-literature
Project description:Lifestyle choices such as the intake of sweets, history of diseases, and genetic variants seem to play a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). To explore which genetic and environmental factors are associated with NAFLD in a Chinese Han population, we conducted this study. We collected the medical reports, lifestyle details, and blood samples of individuals and used the polymerase chain reaction-ligase detection reaction method to genotype the single-nucleotide polymorphism (SNPs) from the 2113 eligible people. The GG genotype of the additive model of rs7493 in the PON2, the CC genotype of the additive and recessive models of rs7593130 in the ADCY3, together with dyslipidemia, regular intake of egg and sweets and hypertension, increased the risk of NAFLD (adjusted OR > 1, p < 0.05). The TT genotype of the additive and dominant models of rs11583680 in the PCSK9, together with the regular intake of vegetable, reduced the risk of NAFLD (adjusted OR < 1, p < 0.05). In addition, interactions between some variables were found. Eventually, we identified three SNPs and six environmental factors associated with NAFLD. These results provide the theoretical basis for gene and other risk factors screening to prevent NAFLD.
| S-EPMC7399983 | biostudies-literature
Project description:BACKGROUND & AIMS:Little is known regarding the risk of hepatic steatosis (HS) among adult children of affected parents. We examined the association between parental and offspring HS in the multigenerational Framingham Heart Study, which characterized HS using computed tomography. METHODS:We performed multivariable logistic regression models adjusted for age, sex, alcohol use, and body mass index to generate the odds of HS according to parental HS. We determined the proportion of participants with HS according to parental HS and the presence or absence of hypertension, diabetes, or obesity (BMI ?30 kg/m2 ). After excluding heavy alcohol use (n = 126) and missing covariates (n = 1), 785 offspring with at least one parent were included. RESULTS:Approximately 23% (183/785) had at least one parent with HS and 1.1% had two affected parents (9/785). In adjusted models, participants with at least one parent with HS had a nearly two-fold increased odds of HS compared to participants without a parental history of HS (OR 1.86, 95% confidence interval 1.15-3.03). Among participants without hypertension, diabetes, or obesity, a higher proportion had HS if they had a parental history of HS compared to those without (16.1% vs 5.2%, P < 0.001). However, for participants with cardiometabolic risk factors, we did not observe a difference in HS among those with and without parental HS (30.3% vs 28.5%, P = 0.78). CONCLUSIONS:Individuals with a parental history of HS are at increased risk for HS. Specifically, a parental history of HS may be an important factor among those that are otherwise metabolically healthy.
| S-EPMC6758911 | biostudies-literature
Project description:BackgroundThe incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide parallel to the global obesity epidemic. NAFLD encompasses a range of liver pathologies and most often originates from metabolically driven accumulation of fat in the liver, or non-alcoholic fatty liver (NAFL). In a subset of NAFL patients, the disease can progress to non-alcoholic steatohepatitis (NASH), which is a more severe form of liver disease characterized by hepatocyte injury, inflammation, and fibrosis. Significant progress has been made over the past decade in our understanding of NASH pathogenesis, but gaps remain in our mechanistic knowledge of the precise metabolic triggers for disease worsening.Scope of reviewThe transition from NAFL to NASH likely involves a complex constellation of multiple factors intrinsic and extrinsic to the liver. This review focuses on early metabolic events in the establishment of NAFL and initial stages of NASH. We discuss the association of NAFL with obesity as well as the role of adipose tissue in disease progression and highlight early metabolic drivers implicated in the pathological transition from hepatic fat accumulation to steatohepatitis.Major conclusionsThe close association of NAFL with features of metabolic syndrome highlight plausible mechanistic roles for adipose tissue health and the release of lipotoxic lipids, hepatic de novo lipogenesis (DNL), and disruption of the intestinal barrier in not only the initial establishment of hepatic steatosis, but also in mediating disease progression. Human genetic variants linked to NASH risk to date are heavily biased toward genes involved in the regulation of lipid metabolism, providing compelling support for the hypothesis that NASH is fundamentally a metabolic disease.
| S-EPMC8324696 | biostudies-literature
Project description:This study was performed for investigation the relationship between variants of MTP gene polymorphism and the development of NAFLD in patients with and without MS. The study was included 174 NAFLD patients (106 with MS and 68 without MS), and 141 healthy control subjects. The 493 G/T polymorphism of MTP gene was evaluated by PCR-RFLP method. The frequency of MTP TT genotype and T allele were significantly higher in NAFLD patients when compared to healthy controls. Moreover, a significant association in MTP gene polymorphism was observed in NAFLD patients with MS compared to NAFLD patients without MS and controls. Our study suggested that MTP 493 G/T gene polymorphism may act as susceptibility biomarker for NAFLD and MS.
| S-EPMC6147179 | biostudies-literature
Project description:Background and aimNon-alcoholic fatty liver disease (NAFLD) is a significant cause of hepatic dysfunction and liver-related mortality. As there is a lack of population-based prevalence data in a representative sample of general population, we aimed to estimate the prevalence and risk factors of NAFLD in Bangladesh.MethodsA cross-sectional study was conducted both in urban and rural areas of Bangladesh from December 2015 to January 2017. Data were collected using a pretested structured questionnaire followed by ultrasonography of hepatobiliary system for screening of NAFLD. Multivariate logistic regression was used to estimate the risk factors of NAFLD.ResultsA total of 2782 (1694 men and 1088 women) participants were included in the study, with a mean age of 34.21 (±12.66) years. The overall prevalence of NAFLD was 33.86% (95% confidence interval [CI]: 32.12, 35.64). Females living in the rural areas and midlife adults (45-54 years) had the highest prevalence of NAFLD (P < 0.05). Multivariable logistic regression model demonstrated that increasing age, diabetes, elevated body mass index, and married individuals are significantly associated with NAFLD. Individuals with diabetes (adjusted odds ratio: 2.71, 95% CI: 1.85, 3.97) and hypertension were at a higher risk of having NAFLD. The odds of having NAFLD were 4.51 (95% CI: 3.47, 5.86) and 10.71 (95% CI: 7.80, 14.70) times higher among overweight and obese participants, respectively, as compared to normal-weight participants.ConclusionsAbout one-third of the population of Bangladesh is affected by NAFLD. Individuals with higher body mass index (overweight and obese), diabetics, midlife adults, married individuals, and rural women were more at risk of having NAFLD than others.
| S-EPMC6206991 | biostudies-literature
Project description:Background: Adolescent non-alcoholic fatty liver disease (NAFLD) is associated with cardiometabolic risk factors. The association between adolescent NAFLD and a wide range of metabolic biomarkers is unclear. We have attempted to determine the differences in metabolic profile of adolescents with and without markers of NAFLD. Methods: We performed cross-sectional analyses in a sample of 3,048 participants from the Avon Longitudinal Study of Parents and Children at age 17. We used three indicators of NAFLD: ALT >40 U/l; AST >40 U/l and ultrasound scan-assessed steatosis. Associations between each measure of NAFLD and 154 metabolic traits, assessed by Nuclear Magnetic Resonance, were analyzed by multivariable linear regression, adjusting for age, sex and BMI. Results: All three indicators of NAFLD were associated with ~0.5 standard deviation (SD) greater concentrations of all extremely large to small very low-density lipoproteins (VLDL) measures. ALT >40U/l was associated with ~0.5SD greater concentrations of very small VLDLs, intermediate-density lipoproteins and low-density lipoproteins. Concentrations of most cholesterols, including remnant cholesterol, all triglycerides and monounsaturated fatty acids, in addition to glycoprotein acetyls (inflammatory marker), were also higher in participants with NAFLD. Conclusions: We have identified differing metabolic profiles between adolescents with and without indicators of NAFLD. These results provide the foundations for future research to determine whether these differences persist and result in adverse future cardiometabolic health.
| S-EPMC6338132 | biostudies-literature
Project description: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.
| S-EPMC10496397 | biostudies-literature