Increased Risk Of Nonalcoholic Fatty Liver Disease Research Articles

Variant adiponutrin confers genetic protection against cholestatic itch.

Lysophosphatidic acid (LPA) mediates cholestatic pruritus. Recently the enzyme PNPLA3, expressed in liver and skin, was demonstrated to metabolise LPA. Here we assess the association of the PNPLA3 variant p.Ile148Met, known to be associated with (non-)alcoholic fatty liver disease (NAFLD) in genome-wide association studies, with cholestatic itch in 187 patients with primary biliary cirrhosis (PBC) and 250 PBC-free controls as well as 201 women with intrahepatic cholestasis of pregnancy (ICP) and 198 female controls without a history of ICP. Our hypothesis was that the intensity of cholestatic itch differs in carriers of distinct PNPLA3 p.Ile148Met genotypes. Patients with PBC carrying the allele p.148Met that confers an increased NAFLD risk reported less itching than carriers of the p.148Ile allele (ANOVA P = 0.048). The PNPLA3 p.148Ile allele increased the odds of requiring plasmapheresis for refractory pruritus (OR = 3.94, 95% CI = 0.91–17.00, P = 0.048). In line with these findings, the PNPLA3 p.148Met allele was underrepresented in the ICP cohort (OR = 0.66, 95% CI = 0.47–0.92, P = 0.013). Notwithstanding the need for further replication of these findings, we conclude that the PNPLA3 allele p.148Met might confer protection against cholestatic pruritus, possibly due to increased LPA-acyltransferase activity in liver and/or skin.

Patent Foramen Ovale is Associated with an Increased NAFLD Risk for Health of Young Men

Between March 2012 and July 2013, 1000 asymptomatic young military male underwent hepatic ultrasonography and echocardiography at Medical Check-up Center for general young health screening. Blood biochemistry, arterial blood pressure and anthropometric measurements were studied. All analyses were performed using the statistical package SPSS 15.0, where the statistical significance was assessed at the two-tailed 0.05 threshold. It was found that among 1000 persons, 60 had patent foramen ovale (PFO) and 110 subjects had symptoms of nonalcoholic fatty liver disease (NAFLD). The PFO-group consisted of 20 male with 33.3% of NAFLD symptoms, while the group without PFO consisted of 90 male with 9.6% of NAFLD symptoms only. There were significant differences between two groups: p<0.001. Moreover, such factors as the mean age, BMI, triglycerides, hemoglobin, and aspartate aminotransferase level, the mean HDL cholesterol, alanine aminotransferase, platelet count did not differ between the two groups. The main cause of the pathogenesis of nonalcoholic fatty liver disease (NAFLD) has not been sufficiently elucidated. Serotonin of plasma is removed from circulation in capillary beds, predominantly in the lung. Nevertheless, metabolism of serotonin can be by-passed by patent foramen ovale (PFO) that can lead to NAFLD. Therefore, the aim of this study was to test the hypothesis that echocardiographic diagnosed PFO predicts the subsequent NAFLD, which can be diagnosed by ultrasonography. The statistical analysis of the 1000 young male supports the hypothesis that PFO can be associated with increased NAFLD risk for the health of young men.

Association of INSIG2 rs9308762 With ALT Level Independent of BMI

An increasing number of people are at risk for developing nonalcoholic fatty liver disease (NAFLD). Because obesity is a risk factor for NAFLD, the common variants of obesity-susceptible genes may be associated with NAFLD. Our aim was to identify whether the obesity-susceptible gene variants (rs9939609, rs9930506, and rs4783819 in fat mass and obesity-associated gene (FTO); rs12970134 and rs17782313 in melanocortin-4 receptor gene (MC4R); and rs7566605, rs13428113, and rs9308762 in insulin-induced gene 2 [INSIG2]) were associated with NAFLD. The case-control study recruited 1027 Chinese children ages 7 to 18 years, including 162 children with NAFLD and 865 children without NAFLD. Anthropometric measurements, alanine transaminase (ALT) detection, liver ultrasound examination, and genotyping of 8 gene variants were performed. The A-allele of FTO rs9939609 was associated with increased NAFLD risk (P = 0.029, odds ratio 1.43), but was not significant after being adjusted for body mass index (BMI) (P = 0.268). We also found an association between the 2 variants (rs12970134 in MC4R and rs9308762 in INSIG2) and ALT level. For rs12970134, each additional A-allele increased ALT level by 1.87 IU/L (P = 0.032). For rs9308762, the homozygotes of the C-allele had a higher ALT level than the T-allele carriers (β = 3.19, P = 0.007). After adjustment for BMI, the former association did not exist, whereas the latter reminded significant (P = 0.003). The FTO rs9939609 A-allele increased risk of NAFLD and MC4R rs12970134 was associated with ALT level through an effect on BMI. The association between INSIG2 rs9308762 and ALT level was independent of BMI. The results provided evidence for identifying genetic factors of NAFLD and may be useful for risk assessment and personalized medicine of NAFLD.

Long-Term Dietary Potential Renal Acid Load During Adolescence Is Prospectively Associated with Indices of Nonalcoholic Fatty Liver Disease in Young Women 3

Nonalcoholic fatty liver disease (NAFLD), frequently already present in young subjects, has been linked to reduced growth hormone levels and signaling. Similar hormonal changes occur during metabolic acidosis (MA), which may thus contribute to an increased NAFLD risk. Because subclinical MA can be diet induced, we aimed to examine whether a higher diet-dependent acid load during adolescence is prospectively associated with several currently used NAFLD surrogates in young adulthood. Dietary acidity during adolescence (boys:10–15 y, girls: 9–14 y) was calculated as potential renal acid load (PRAL) from at least three 3-d weighed dietary records according to a published algorithm considering dietary protein and minerals in 145 healthy participants. Routine measurements derived from blood analysis and anthropometric data in participants’ young adulthood (18–25 y) were used to determine the NAFLD surrogates alanine-aminotransferase (ALT), hepatic steatosis index (HSI), and fatty liver index (FLI). Sex-stratified linear regression models, adjusted for dietary fiber, saturated fat, protein, and adolescent BMI SD scores, were run with PRAL as the independent variable. Dietary PRAL during puberty was positively associated with ALT (P= 0.02), HSI (P= 0.002), and FLI (P= 0.005) in adult females but not males. Females with an adolescent dietary acid load in the highest tertile had 3.5, 4.4, and 4.5 higher values of ALT, HSI, and FLI as adults, respectively, compared to females with the lowest PRAL. The present findings suggest that higher dietary acidity in adolescence may be prospectively associated with hepatic lipid accumulation in females. Whether this relationship is due to the higher proton load or rather represents an unhealthy dietary pattern requires further investigation.