Non-alcoholic fatty liver disease and cardiovascular risk: Pathophysiological mechanisms and implications

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and, indeed, worldwide. It has become a global public health issue. In the United States, the prevalence in the general population is estimated at approximately 20%, while that in the morbidly obese population at approximately 75-92% and in the pediatric population at approximately 13-14%. The progressive form of NAFLD, nonalcoholic steatohepatitis, is estimated at approximately 3-5%, with approximately 3-5% of these having progressed to cirrhosis. Thus, the numbers of individuals at risk for end-stage liver disease and development of primary liver cancer is large. NAFLD is an independent risk factor for cardiovascular disease, leads to increased all-cause mortality, and to increased liver-related mortality. This review focuses on recent advances in our understanding of the NAFLD disease spectrum, including etiology, diagnosis, treatment, and genetic and environmental risk factors and suggests future directions for research in this important area.

Liver enzymes, nonalcoholic fatty liver disease, and incident cardiovascular disease

Biomarkers in Fatty Liver Disease—Here is the Skinny

We aimed to elucidate the frequency of polymorphic genotypes and alleles of patatin-like phospholipase domain containing 3 rs738409 polymorphism and its possible associations with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis in a cohort from Turkey.We enrolled 200 patients diagnosed with NAFLD and genotyped for rs738409 I148M polymorphism by real-time polymerase chain reaction, particularly by melting curve analysis. SPSS analysis software was used for statistical significance. Continuous variable values were expressed as mean ± standard deviation. Significant statistical level was chosen as p = 0.05.Our results demonstrate in a cohort from Turkey that rs738409 C > G polymorphism (I148M) of patatin-like phospholipase domain containing 3 gene is significantly able to affect individuals to have NAFLD in unadjusted regression model.Consistent with the previous studies in other populations, our study group showed a significantly higher risk of having NAFLD in unadjusted regression model but not in the adjusted model indicating that non-genetic factors such as age and sex may be responsible for the association. However, independent studies need to validate our findings with a larger group of NAFLD patients, as well as in different ethnic cohorts.

1915-P: High-but-Normal Serum Thyrotropin Levels Increased the Risk of Nonalcoholic Fatty Liver Disease in Euthyroid Subjects with Type 2 Diabetes

Association between folate and non-alcoholic fatty liver disease among US adults: a nationwide cross-sectional analysis.

We explored the role of the adiponutrin (PNPLA3) nonsynonymous-rs738409 single nucleotide polymorphism (SNP) in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) and whether this SNP contributes to the severity of histological disease. Two hundred sixty-six individuals were evaluated in a case-control association study, which included 172 patients with features of NAFLD and 94 control subjects. The rs738409 G allele was significantly associated with NAFLD (P < 0.001; OR 2.8 95%, CI 1.5-5.2), independent of age, sex, body mass index (BMI), and Homeostasis Model Assessment (HOMA) index. When we tested the hypothesis of a relation between the SNP and the histological spectrum of NAFLD, a significant association was observed [chi2 19.9, degree of freedom (df): 2, P < 5 x 10(-5), adjusted for HOMA and BMI]. The degree of liver steatosis, as evaluated by liver biopsy, was significantly associated with the rs738409 G allele. Patients with CC genotype showed a lower steatosis score (14.9% +/- 3.9) in comparison with the CG genotype (26.3% +/- 3.5) and GG genotype (33.3% +/- 4.0) (P < 0.005). The proportion of the total variation attributed to rs738409 genotypes was 5.3% (beta 0.23 +/- 0.07; P < 0.002). Our data suggest that the rs738409 G allele is associated not only with fat accumulation in the liver but also with liver injury, possibly triggered by lipotoxicity.

Non-alcoholic fatty liver DISEASE (NAFLD) is the most common chronic liver disease in Western countries and affects approximately 25% of the adult population. Since NAFLD is frequently associated with further metabolic comorbidities such as obesity, type 2 diabetes mellitus, or dyslipidemia, it is generally considered as the hepatic manifestation of the metabolic syndrome. In addition to its potential to cause liver-related morbidity and mortality, NAFLD is also associated with subclinical and clinical cardiovascular disease (CVD). Growing evidence indicates that patients with NAFLD are at substantial risk for the development of hypertension, coronary heart disease, cardiomyopathy, and cardiac arrhythmias, which clinically result in increased cardiovascular morbidity and mortality. The natural history of NAFLD is variable and the vast majority of patients will not progress from simple steatosis to fibrosis and end stage liver disease. However, patients with progressive forms of NAFLD, including non-alcoholic steatohepatitis (NASH) and/or advanced fibrosis, as well as NAFLD patients with concomitant types 2 diabetes are at highest risk for CVD. This review describes the underlying pathophysiological mechanisms linking NAFLD and CVD, discusses the role of NAFLD as a metabolic dysfunction associated cardiovascular risk factor, and focuses on common cardiovascular manifestations in NAFLD patients.

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To the Editor: I read with interest the article by Brea et al1 regarding the strong relationship between nonalcoholic fatty liver disease (NAFLD) and carotid atherosclerosis (as measured by intima-media thickness [IMT] and plaque prevalence) in a sample of predominantly obese and hypertensive subjects. Notably, they reported substantially similar results to those recently published by our group in a sample of nonobese healthy men,2 thus further supporting the notion that people with NAFLD are at increased risk of CVD. However, I partly disagree with the authors’ conclusions suggesting that NAFLD is a strong risk factor for carotid atherosclerosis beyond its association with the metabolic syndrome (MetS). In both studies, patients with NAFLD had, other than several features resembling MetS, a marked increase in carotid IMT values compared with those without NAFLD. However, in the study by Brea et al1 the increase in carotid IMT (but not that in the prevalence of carotid plaques) remained statistically significant after adjustment for the presence of MetS (as defined by ATP-III or WHO criteria). On the contrary, in our study the increase in carotid IMT was largely mediated by the extent of visceral fat accumulation, as measured by computed tomography (CT).2 It is known that WHO and ATP-III definitions of …

BackgroundWe aim to investigate the association between TyG(Triglyceride-Glucose index) and TyG-BMI(Triglyceride-Glucose-Body Mass Index) indices and the risk of non-alcoholic fatty liver disease (NAFLD) in patients undergoing percutaneous coronary intervention (PCI), an area where their predictive value is currently unclear, despite their established link to insulin resistance, metabolic syndrome, and cardiovascular disease.MethodsIn this cross-sectional study, 776 patients who underwent coronary angiography and PCI were categorized into NAFLD+PCI and PCI groups based on abdominal ultrasound. They were further classified by TyG and TyG-BMI indices. Continuous variables were compared using ANOVA, Wilcoxon-Mann-Whitney, or t-tests, while categorical variables were analyzed with χ² or Fisher exact tests. Logistic regression identified independent factors for NAFLD in PCI patients. ROC curves evaluated the predictive efficacy of TyG and TyG-BMI for NAFLD. Linear correlation and multiple linear regression assessed relationships among NAFLD fibrosis score (NFS), TyG, and TyG-BMI.ResultsAmong 776 patients, NAFLD was detected in 305. After adjusting for age, smoking, hypertension, diabetes, sex, and cardiovascular disease, multivariate logistic regression showed the TyG index was a significant risk factor for NAFLD in PCI patients (OR = 2.04; 95% CI, 1.62-2.55; P < 0.001). Similarly, the TyG-BMI index, total cholesterol, triglycerides, LDL cholesterol, fasting blood glucose, and BMI were associated with increased NAFLD risk. Each unit increase in the TyG index raised the NAFLD risk by 2.63-fold (OR = 2.63; 95% CI, 1.78-3.8; P<0.001), and each unit increase in the TyG-BMI index by 3.80-fold (OR = 3.80; 95% CI, 2.55-5.68; P < 0.001). Multivariate linear regression indicated that in the PCI-NAFLD group, each unit increase in the TyG index increased the NFS value by 0.247 (β = 0.247; 95% CI, 0.19-0.45; P < 0.001), and each unit increase in the TyG-BMI index increased the NFS value by 0.344 (β = 0.344; 95% CI, 0.28-0.59; P < 0.001).ConclusionsThe TyG index and TyG-BMI were positively associated with the risk of NAFLD in patients treated with PCI, reflecting the severity of liver fibrosis.

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

Background: Non-alcoholic fatty liver disease (NAFLD) as a severe health problem is the leading cause of morbidity and mortality from the chronic liver disease worldwide. NAFLD is tightly associated with dyslipidemia although the etiology is still unclear. ATP binding cassette subfamily A member 1 (ABCA1) is involved in cholesterol efflux, fatty acid oxidation, and inflammation. Although some reports show that the ABCA1 polymorphisms affect the lipids metabolism and severity of clinical liver diseases, the effects of ABCA1 polymorphisms on the development of NAFLD are unknown. Objectives: The current study was performed to investigate the association between the ABCA1 polymorphisms and the development of NAFLD and the effect of the four ABCA1 SNPs on the serum lipid levels. Methods: The ABCA1 polymorphisms (rs1800977, rs2066714, rs2066715, and rs2230808) were determined in 265 NAFLD patients and 126 healthy controls using the sequencing and polymerase chain reaction analysis. Serum lipid profiles and liver enzymes were examined using standard clinical laboratory methods. Results: There was a significant difference (P < 0.05) in the genotype of the ABCA1 rs1800977 G/A polymorphisms between NAFLD patients and healthy controls. No significant differences were found in genotypes and allele frequencies of the ABCA1 rs2066714T/C, rs2066715T/C, and rs2230808C/T between NAFLD patients and healthy controls. The ABCA1 rs1800977 A was independently associated with NAFLD after adjusting for the effects of age, gender, and BMI. Compared to the noncarriers in NAFLD patients, the carriers of ABCA1 rs2066714 C showed a significantly higher level of LDL (P = 0.045) and the carriers of ABCA1 rs2230808 T showed a significantly lower level of HDL (P = 0.039). Conclusions: We first demonstrated the association between the ABCA1 polymorphisms and the risk of NAFLD in a Chinese Han population. The ABCA1 rs1800977 may be a protective factor against the development of NAFLD. The ABCA1 rs2066714 C allele could increase the serum LDL cholesterol level, and the ABCA1 rs2230808 T allele could decrease the serum HDL cholesterol level in NAFLD patients.

BackgroundGenetic factors affect the risk of non-alcoholic fatty liver disease (NAFLD) and colorectal adenoma (CRA) importantly. Transmembrane protein 6 superfamily member 2 (TM6SF2) rs58542926 is a significant genetic susceptibility site for NAFLD. The relationships of TM6SF2 rs58542926 with the risk of NAFLD and CRA in Chinese Han population were unclear. The aim of this study was to investigate the association of TM6SF2 rs58542926 with the risk of NAFLD and CRA, and the effect of CRA on TM6SF2 rs58542926 carried NAFLD patients.ResultsA total of 839 Chinese Han population were included in this retrospective study. TM6SF2 rs58542926 polymorphism was genotyped in B-type ultrasonography proven NAFLD patients with or without CRA, CRA patients and healthy controls, using polymerase chain reaction. Serum lipid profiles were determined using biochemical methods. Statistical analyses were performed using SPSS statistical software, version 16.0 for mac. There was a significant difference in the distribution of genotype and allele of TM6SF2 rs58542926 in NAFLD and NAFLD&CRA patients compared to controls. The CT + TT genotypes were tightly associated with the risk of NAFLD and NAFLD&CRA. TM6SF2 rs58542926 T allele promotes the abnormal regulation of lipids metabolism and liver injury in NAFLD patients and NAFLD&CRA patients. CRA aggravates the clinical performance of NAFLD in T allele carriers.ConclusionsWe demonstrated the significant association between TM6SF2 rs58542926 polymorphism and the risk of NAFLD and NAFLD&CRA in a Chinese Han population. The TM6SF2 rs58542926 T allele promotes the abnormal regulation of lipid profiles and liver injury in NAFLD patients, NAFLD&CRA patients, and overall subjects.

Nonalcoholic Fatty Liver Disease and Fibrosis Progression: The Good, the Bad, and the Unknown