05) (Supporting Fig. 6). In contrast, IL-10 was significantly lower in mice that received Con EX 527 A only (P < 0.05), whereas there was no significant difference in the serum level of TNFα between experimental groups. We also examined whether TD139 would affect the infiltration of MNCs into the livers of

mice after Con A injection (Fig. 7). Although there was no significant difference in the total number of liver-infiltrating MNCs, CD3+ T cells, NK1.1+ NK and CD3+NK1.1+ NKT cells, CD11c+ DCs and CD11c+CD80+CD86+ activated DCs, F4/80+ macrophages (data not shown), and Gal-3 INH profoundly reduced CD4+- and CD8+ T-cell infiltration into the liver parenchyma (Fig. 7). The total number of IFNγ- and IL-17- and -4-producing CD4+ T cells and IFNγ-producing CD8+ T lymphocytes was significantly lower in TD139-treated mice (Fig. 7). However, https://www.selleckchem.com/products/Gefitinib.html the total number of CD4+ IL-10-producing cells was significantly higher in TD139-treated mice (P < 0.05). There was no difference in the total number of TNFα- producing CD4+ T cells, IFNγ- and IL-4-producing CD3+NK1.1

NKT cells, IFNγ-producing NK1.1+ NK cells, IL-12- and -10-producing CD11c+ DCs, and F4/80+ macrophages between TD139-treated mice and mice that received Con A only (data not shown). In line with results obtained from Gal3−/− mice (Fig. 5A), we found a significantly higher percentage and total number of F4/80+ CD206+ alternatively activated (i.e., M2-polarized) macrophages in livers of TD139-treated mice, compared to mice treated with Con A only (Fig. 8A). However, there was no difference in the total number of IL-12- and -10-producing macrophages (data not shown). We also found that TD139 prevented apoptosis of liver-infiltrating MNCs (Fig. 8B) 8 hours after Con A injection. Significantly lower percentages of Annexin V+ PI+ liver-infiltrating MNCs (P < 0.01) were observed in TD139-treated mice, compared to mice treated with Con A only. Here, we provided

the first evidence that Gal-3 plays an important role in the pathogenesis of Con A–induced hepatitis, a model of acute, fulminate hepatitis in humans.1 Targeted disruption of Gal-3 gene attenuated liver injury by reducing the number of effector cells, including T lymphocytes (both CD4+ and CD8+), B lymphocytes, DCs, and NK and NKT cells, and increasing the number of IL-10-producing CD4+ T cells Uroporphyrinogen III synthase and alternatively activated (i.e., M2-polarized) macrophages that was accompanied with lower serum levels of TNFα, IFNγ, and IL-17, but also IL-4. In addition, pretreatment of WT mice with TD139 attenuated Con A–induced liver injury (Fig. 6). IP injection of TD139 in WT mice 2 hours before and immediately after Con A injection suppressed the infiltration of IFNγ- and IL-17- and -4-producing CD4+ and IFNγ-producing CD8+ lymphocytes (Fig. 7), increased the total number of IL-10-producing CD4+ T cells (Fig. 7), attenuated serum levels of IFNγ and IL-17 and -4, elevated the serum level of IL-10 (Supporting Fig.

“
“Summary.  Life expectancy for haemophilia has increased significantly in many countries. DAPT manufacturer This represents a major success

of the improved safety of therapeutic materials to treat haemophilia and of improved quality of care. This improved longevity will generate a population of older individuals with haemophilia with complex medical problems associated with age and managing such clinical issues is likely to be challenging. The world population is ageing in an unprecedented way in part, as a result of a major increase in life expectancy through decreased infant mortality and improvements in healthcare, housing and diet. Globally, the number of older persons is expected to exceed the number of children by 2047, but in developed countries this milestone was passed in 1998. [1] An ageing

population is likely to have wide ranging consequences for the economic and social environment of society and as older individuals have more chronic illness, the impact of a larger population of elderly individuals will be significant for healthcare systems. [1,2] The world population of persons with haemophilia (pwh) is also likely to have benefited from the general factors contributing to health improvement but have also benefited more specifically from advances in haemophilia care such as the availability Selleckchem HDAC inhibitor of safe, effective factor concentrate, the development of comprehensive care programmes and therapeutic modalities such as home treatment and prophylaxis. There is clear evidence that life expectancy has increased for individuals with haemophilia. In the early part of the last century, the prevalence of haemophilia was estimated to be only 4 per 100 000 males while the prevalence in the 1990s was 13–18 per 100 000 [3]. More recent studies estimating life expectancy

for individuals with severe haemophilia not infected PAK6 with HIV in the period 1977–2001 have ranged from 63 years for the UK, to 70 years (Netherlands) and 73 years (Canada). [4–6] However, because improvements in haemophilia care have been relatively recent and the high mortality rate from bleeding and transfusion transmitted infection, particularly HIV in past decades, there is, at present, in many countries, a relatively small population of severely affected individuals with haemophilia at advanced age and thus, relatively little experience in managing age-related medical problems in this group of individuals. As much as 88% of the general population over the age of 65 years have one or more chronic medical condition [7] and for the first time, many countries have seen the emergence of a significant middle aged and elderly population of persons with haemophilia.

Eight Japanese early-onset ataxia patients with ARSACS confirmed molecularly were investigated. We performed neurological examination, SACS gene analysis, and MRI in the patients. Hypointensity

lesions in the middle cerebellar peduncles in addition to the pons were observed in T2-weighted and FLAIR images in all eight cases. Although superior cerebellar atrophy was seen in all cases, this MRI finding might not be specific for ARSACS. Upper cervical cord and medulla oblongata atrophy was not observed in 3 of the 7 patients examined. Not only pontine but also middle cerebellar peduncle hypointensity lesions observed in T2-weighted and FLAIR images could be specific findings for ARSACS even in cases with variable clinical phenotypes. www.selleckchem.com/products/nivolumab.html “
“Despite current developments in neuroradiology, the sources of infarctions go undiagnosed in 28% of cases. An embolic source in the setting of minimal stenosis

at the carotid bifurcation has rarely been reported. The authors report a previously healthy 48-year-old woman, without any risk factors for cerebrovascular events, sustained multiple cerebral infarctions in the right LY2157299 anterior and middle cerebral artery territory. Repeated imaging of the heart and cerebral vessels missed a very small abnormality arising from the posterior wall of the internal carotid artery, until it was diagnosed by computed tomographic angiography. This is problematic because by North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria, minimal stenosis

essentially excludes the carotid artery as an embolic Evodiamine source. Despite maximum antiplatelet and anticoagulation therapy, she continued to have neurological deteriortation by progression of her strokes. She underwent standard carotid endarterectomy and sustained no new embolic phenomena. Histopathological examination showed an endothelial hyperplasia with organizing thrombus, which on the posterior wall of the internal carotid artery, is likely a hemodynamically induced on top of preexisting atherosclerotic plaque. “
“Hyperperfusion is a rare but serious complication following cerebrovascular angioplasty and stent placement. Radiographically identifying hyperperfusion before the development of severe sequelae is difficult, as few diagnostic criteria have been established. A 50-year-old woman, initially presenting with 6 weeks of right-sided hemiparesis and dysarthria, was treated for severe stenosis of the left internal carotid and middle cerebral arteries with intracranial angioplasty and placement of a balloon mounted Wingspan Stent (Boston Scientific, Fremont, CA). Continuous transcranial Doppler monitoring after stent placement indicated developing cerebral hyperperfusion. Concurrent angiography revealed markings consistent with dilatations of small arteries in the vascular territory of the stented arteries. Aggressive blood pressure management started in the procedure and continued postprocedure led to an approximately 40% reduction in systolic blood pressure.

Future studies will also have to address whether these compounds have direct effects on cholangiocellular bile secretion resulting from their BA-signaling properties. In contrast to INT-767, the selective FXR agonist, INT-747, enhanced liver injury and fibrosis in the Mdr2−/− model. Although low-dose INT-747 had no impact on liver damage in Mdr2−/− mice (data not shown), a high dose (0.03% w/w) aggravated it, despite the induction of Fgf15 and inhibition of BA synthesis. Interestingly, INT-747 did not induce hepatic Shp gene expression, suggesting

Wnt beta-catenin pathway that in contrast to INT-767, which efficiently activates Fxr in the intestine and liver, INT-747 is less likely to have hepatic activity in Mdr2−/− mice. However, Ntcp gene expression was inhibited by INT-747, which may reflect selleck kinase inhibitor direct repression by BAs or by proinflammatory cytokines caused by induced liver injury.49 In addition, INT-747 had no impact on Ca14 gene expression in vivo and in vitro (data not shown). Together, these findings point out to a differential regulation of Fxr-dependent genes by INT-747 and INT-767. Ligand binding to FXR can favor receptor conformations that, in turn, allow only specific cofactor recruitment, depending on the DNA-binding sequence,

therefore resulting in selective modulation of gene expression.50 Our findings suggest that INT-767 acts as a specific FXR modulator in a way similar to other natural or synthetic FXR modulators.51-53 BA hydrophobicity is another important factor directly linked to BA detergent properties.54, 55 Hydrophobic BAs are toxic to hepatocytes at micromolar concentrations.56 Endogenous BAs and INT-747 are hydrophobic BAs, whereas INT-767 is hydrophilic.23 INT-767 reduces bile toxicity and prevents further progression of liver injury via strong inhibition of endogenous BA synthesis, replacing Methocarbamol hydrophobic BAs with the hydrophilic INT-767 and inducing HCO-rich bile secretion. In contrast, accumulation of the hydrophobic INT-747 in the liver without stimulation of hepatoprotective mechanisms may act as an additional important factor for the promotion of liver damage

in Mdr2−/− mice. Nevertheless, preliminary data from clinical phase II trials reported a beneficial effect of INT-747 on serum liver enzymes in patients with primary biliary cirrhosis.57 However, Fxr-mediated stimulation of bile flow may be deleterious in obstructive cholestasis.58 Importantly, despite promoting bile infarcts (because of increased bile flow) in the CBDL model, INT-767 even moderately reduced serum ALT levels and ameliorated proinflammatory cytokine expression, possibly because of low concentrations of endogenous hydrophobic BA and high HCO content. Because TGR5 signals through cAMP, an important regulator of chloride channel CFTR,10 we expected increased bile flow and HCO output by the selective TGR5 agonist, INT-777.

Methods: In the present study we use MassARRAY technology to detect the methylation status of smad4 gene promoter in 33 cases of Kazak esophageal squamous cell carcinoma and 38 cases of local normal esophageal tissue that selected

from esophageal high incidence-Ili Kazak Autonomous Prefecture of Xinjiang. Results: ① Selleckchem MK2206 The average methylation rate of smad4 gene promoter CpG units were 3.4% in Kazak esophageal cancer and 2.5% in control groups, the difference was not statistically significant (P > 0.05). ② The average methylation rate of smad4 gene in Kazak esophageal CpG units of CpG units 1, CpG units 16–17–18–19, CpG units 27–28, CpG units 31–32–33 were 1.6%, 4.3%, 4.8%, 6.8%, and the average methylation rate is significantly higher than the control group (0.7%, 2.2%, 3.0%, 5.5%), the difference was statistically significant (P < 0.05). Conclusion: From the above, our finding that smad4 gene promoter methylation in Kazak esophageal cancer may support an association with cancer development, the change in status that smad4 gene promoter methylation

in CpG Unit 1, CpG units 16–17–18–19, CpG units 27–28, CpG units 31–32–33 may connected with the development of Xinjiang Kazakh esophageal cancer. Key Word(s): 1. Kazak; 2. esophageal cancer; 3. smad4 gene; 4. methylation; Presenting Author: VARDA SHALEV Additional this website Authors: YARON KINAR, NIR KALKSTEIN, PINCHAS AKIVA, ELIZABETHE HALF, INBAL GOLDSHTEIN, GABRIEL CHODICK Corresponding Author: PINCHAS AKIVA Affiliations: Medial-Research; Medial Research; Rambam Health Care Campus; Maccabi Health Care Services Objective: Gastric and colorectal cancers account for over one quarter of the cancer incidence in East Asia. The compliance rates in screening programs for these cancers, where available,

are sub-optimal, with the majority of cases not detected through screening. Here, we propose a method that could significantly selleck chemical increase the early detection rate of these digestive cancers based solely on computational analysis of widely available parameters such as age, gender, and complete blood counts (CBCs). Methods: We devised a machine learning method for stratifying the probability of individuals having gastric or colorectal cancers using only age, gender, and CBCs values (current and past tests). Specifically, the method was developed using data from 860,000 Israelis above 40 years of age and performance was assessed by cross validation. As external validation, we tested our model on an additional 180,000 primary care patients from the UK’s Health Information Network (THIN) database. Results: We evaluated the performance of our method using the standard area under the receiver-operator curve (AUC), and obtained a value of 0.81 ± 0.01.

pylori vaccine using a nontoxic double mutant of E. coli toxin (R192G/L211A) (dm2T) as the mucosal adjuvant. An H. pylori vaccine using the dm2T as the mucosal adjuvant was

as effective as the gold standard H. pylori vaccine containing cholera toxin. These investigators also demonstrated the potential of employing sublingual immunization as a new route of mucosal immunization. In addition to the work by Ottsjo et al. [41], highlighting the potential utility of the sublingual route of immunization, Zhang et al. [42] have extended the mucosal immunization field to incorporate the concept of an edible vaccine. GSK126 Lactococcus lactis is commonly used for the production of fermented milk products and is routinely ingested. A recombinant L. lactis containing both the H. pylori urease antigen UreB and IL-2, a known mucosal adjuvant, resulted in a significant increase in anti-urease antibodies when ingested by mice. This was also accompanied by Pexidartinib ic50 a significant drop in bacterial load following challenge. Although additional studies

are needed, this approach might result in an effective, as well as inexpensive, vaccine to prevent or treat H. pylori. Altman et al. [43] recently demonstrated that synthetic glycoconjugates based on delipidated lipopolysaccharide (LPS) of H. pylori and containing an α(1-6)-glucan chain induced broadly cross-reactive functional antibodies in immunized animals and provided evidence that dextran-based conjugates might be of some usefulness in the development of carbohydrate-based vaccines against H. pylori. Two recent publications by Muhsen et al. [44, 45] Depsipeptide chemical structure explore the impact of H. pylori infection on the host immune response

to other oral immunizations such as the live cholera vaccine or an attenuated Salmonella typhi vaccine. Using Ty21a, an oral attenuated typhoid vaccine, these investigators demonstrated that in this adult study seroconversion was significantly higher among H. pylori-infected subjects. H. pylori-infected individuals had more than a 3-fold increased rate of conversion to the typhoid vaccine. This appears in some way to be due to the gastritis associated with H. pylori infection. In fact, evidence of severe corpus gastritis was associated with a 6-fold increased likelihood of seroconversion. In contrast, the second study by Muhsen et al. [45] evaluated the impact of H. pylori infection on the immune response to a live oral cholera vaccine. This study suggested that the gastric inflammation associated with H. pylori promoted seroconversion particularly in the older child. When examining children aged 6 months to 4 years, the likelihood of vibriocidal antibody seroconversion was quite low. Taken together, these two reports [44, 45] demonstrate that active H. pylori infection can impact the efficacy of other vaccines. This appears to be an area where much more research is needed. One additional manuscript focusing on the host immune response to H. pylori infection is worth noting. Freire de Melo et al.

4 Recent epidemiological studies showed an association between urinary levels of BPA and the prevalence of diabetes, cardiovascular diseases, and elevated markers of liver toxicity.5, 6 These studies pointed to metabolic disorders as a potential impact of exposure to low doses of BPA. In agreement with this hypothesis, experimental evidence has accumulated that BPA can alter several aspects of metabolic functions in rodents. Animal studies

showed an increased body weight in offspring of mothers exposed to BPA during gestation and/or lactation period.7 The increase in body weight was more pronounced and persistent in females than males and the effects were stronger at low compared with high doses of exposure. Such nonmonotonic dose-response relationship have been reported for many actions of BPA.8-11 How perinatal BPA exposure may exert these effects remains EX 527 datasheet to be determined, but potential target tissues of BPA action including adipose tissue and pancreas have been studied. Gestational exposure to BPA was shown to increase adipose tissue mass at weaning associated with adipocyte hypertrophy and overexpression of lipogenic genes.9, 10, 12 Low BPA doses were also shown to increase leptin and to decrease adiponectin secretion.9,

13In vitro studies documented learn more an increased lipid accumulation and adipocyte differentiation after exposure of 3T3L1 preadipocytes Interleukin-3 receptor to BPA and other endocrine-disrupting chemicals.14-16 Nadal and colleagues showed that BPA increases insulin synthesis and secretion with concurrent impacts on glucose homeostasis.17, 18In vivo injection of 1, 10, or 100 μg/kg/day of BPA to adult male mice resulted in a significant dose-dependent decrease in glycemia in parallel to an increase in insulin from 30 minutes after injection.19 Isolated islets

of pancreatic β-cells exposed to a range of BPA doses showed increased insulin content following an inverted U-shape dose-response curve.20 The same group recently reported on similar effects in pregnant mice and their offspring exposed to 10 or 100 μg/kg/day of BPA.21 Thus, both the adipose tissue and the pancreas have emerged as important targets of low BPA doses. Despite the important roles of the liver in whole body energy homeostasis, little is known about the hepatic impacts of exposure to environmentally relevant doses of BPA. Here we evaluated the effects of oral exposure to 50 μg/kg/day (TDI) or 5,000 μg/kg/day (NOAEL) of BPA on mouse liver transcriptome. Initial genome-wide microarray screenings evidenced a predominant impact of low BPA doses on lipid biosynthesis pathways. Using a wide range of doses, we showed that these effects are specific to low, environmentally relevant doses of BPA and correlate with an increased hepatic accumulation of neutral lipids.

Our data in surgically resected human HCC and a mouse model of selleck carcinogen-induced HCC support a potential tumor suppressor function of Col18a1. Further studies are underway to establish what roles Col18a1 may play in controlling the rates of HCC progression. Disclosures: Lewis R. Roberts – Grant/Research Support: Bristol Myers Squibb, ARIAD Pharmaceuticals, BTG, Wako Diagnostics, Inova Diagnostics, Gilead Sciences The following people have nothing to disclose: Michael Duncan, Renumathy Dhanasekaran, Priyanka Thakur Background & Aims: Recent single nucleotide polymorphism (SNP) studies revealed several host genetic risk factors for hepatocellular carcinoma (HCC); however, the majority

of genetic factors remain unclear. MicroRNAs (miRNAs) are small non-coding RNAs that control

gene expression post-transcrip-tionally. As for HCC, two common SNPs in mature miRNAs (rs2910164 in miR-146a and rs11614913 in miR-196a2) have been extensively studied, but published results are inconsistent and inconclusive. Almost all these studies compared hepatitis B virus (HBV)-related HCC patients and healthy controls in China. We aimed to investigate the association between these Napabucasin SNPs and HBV-related as well as hepatitis C virus (HCV)-related HCC risk in a Japanese population using a large number of patients. Methods: We analyzed the effect of rs2910164 and rs11614913 on HCC development in over 1,500 chronic HBV patients, including 407 with HCC (cases) and 1,141 without HCC (controls), and over 3,300 chronic HCV patients, including 1,026 cases and 2,349 controls, by multiplex-PCR-based Invader assay. Results: According to 1000Genomes database, risk allele frequencies (AFs) of rs2910164 and 3-mercaptopyruvate sulfurtransferase rs11614913 vary among ethnic groups: 0.22 and 0.41 in Europeans, 0.54 and 0.58 in Han Chinese, and 0.60 and 0.60 in Japanese, respectively. Estimated statistical power is 60% and over 90% for our HBV and HCV studies, respectively. First, we analyzed chronic HBV patients and found that risk AF of rs2910164 was significantly higher in cases than in controls (P = 0.040, odds ratio [OR] = 1.19).

We also found a similar result for rs11614913 (P = 0.017, OR = 1.21). Because both of age and male ratio were significantly higher in cases than controls, we adjusted for age and gender and again found significant associations with HBV-related HCC for both SNPs (P = 0.014 and 0.037, OR = 1.23 and 1.19, respectively). Next, we analyzed chronic HCV patients, but we could not find any significant differences between risk AFs of cases and those of controls for either SNP (P = 0.266 and 0.861, respectively), despite sufficient statistical power. After adjusting for age and gender, we again observed no association. Finally, we investigated the association between these two SNPs and expression of possible target genes using expression quantitative trait loci (eQTL) with public databases, but we failed to find any supporting evidence.

9 Moreover, neutrophil or CD4+ cell depletion prevented

necrosis in infected IL-10 KO mice 9 (Fig. 5). Thus, our data support a model in which, in the absence of IL-10, CD4+ T cells activated within GALT migrate to the liver and elaborate cytokines that regulate both neutrophil accumulation and the state of activation. In support of this, we reported that adoptive transfer of intestinal CD4+ T cells from infected IL-10 KO mice to WT mice led to a mild hepatitis upon infection, whereas the transfer of WT cells to IL-10 KO recipients was protective. 9 To determine whether IL-10 was required for protective activity, we transferred WT CD4+ T cells into IL-10 KO mice that had received PBS, an irrelevant antibody, or α-IL-10R Ibrutinib purchase antibody. Animals that received WT CD4+ T cells had decreased ALT activity and hepatic leukocyte content (total and intestinally-derived CD4+ cells) in comparison with IL-10 KO mice that did not receive cells FK506 (Fig. 6). Additionally, the development of necrotic

lesions was suppressed in IL-10 KO recipients that received cells in comparison with those given PBS (data not shown). Interestingly, cultured hepatic leukocytes from adoptively transferred mice released less IL-4, and this suggested that the transferred WT CD4+ T cells controlled IL-4 production (Fig. 6D). In vivo blockade of the IL-10R did not compromise protection, indicating that IL-10 was important during T cell activation in GALT rather than for T cell function in the liver. Because neutrophil depletion blocked the development of hepatic necrosis, we hypothesized that the transfer of intestinal CD4+ T cells from WT Liothyronine Sodium mice would reduce neutrophil numbers and decrease hepatic necrosis. Indeed, IL-10 KO recipients accumulated significantly fewer Ly6-G+F4/80− cells in the liver (Fig. 6E). Furthermore, blockade of IL-10 signaling did not reverse this effect. To aid in the interpretation of these results, we included a group of WT recipients that were administered α-IL-10R antibodies. These animals experienced hepatocellular damage and

an influx of CD4+α4β7+ cells similar to those experienced by IL-10 KO mice. Hepatic IL-4 levels were greater in WT mice versus IL-10 KO mice that received cells but less than those in PBS-injected IL-10 KO animals. Additionally, two-thirds of WT mice developed small necrotic foci (data not shown). Thus, the α-IL-10R antibody preparation antagonized the effects of IL-10. Overall, our data indicate that intestinally derived CD4+ T cells, activated in an IL-10 sufficient environment, can protect the liver against hepatic injury and necrosis by regulating effector cell trafficking and function. Clinically significant liver disease may result from a multitude of insults, including infection, alcohol, drugs, and ischemia/reperfusion.

14 A P value equal to or less than 0.05 was considered statistically significant. All calculations were performed using the Comprehensive Meta-Analysis computer program (Biostat, Englewood, NJ). We evaluated 16 studies that met the selection criteria and that were identified using the search strategy described in Supporting Fig. 1. Studies characteristics are shown in Table 1. Data from one study that fulfilled the eligibility criteria was included after personal contact with the investigators15; data on one further study was unavailable because in the article the authors did not disclose the raw data and our attempts to contact the authors were unsuccessful.16 All the studies scored well in

terms of adequate descriptions of selection criteria and reference selleck screening library test, blind assessment of the reference test, and the availability of clinical data. A general critique concerns the observation that information about

genotype counts per evaluated phenotype was scarcely found across the studies. Eleven studies were hospital-based case-control studies,2-6, 15, 17-21 and the other five were population-based case-control studies,1, 22-24 or family-based studies.25 Information about liver biopsy was available in six studies,2-6, 17 and data about disease severity was analyzed in 2,651 patients with NAFLD; ALT levels according to the rs738409 genotypes were available in 11 studies.1, 2, 5, 6, 15, 17-21, 24 Genotyping for rs738409 was carried out across studies using Taqman assay in 111, 5, Navitoclax 6, 17-24 studies, by allele-specific oligonucleotides in two studies,2, 15 and by Sequenom MassARRAY iPLEX Gold platform (Sequenom, San Diego, CA) in the remaining three studies.3, 4, 25 Data regarding fatty liver disease as a disease trait extracted from 11 studies included 5,100 individuals,2-4, 6, 15, 17, 18, 20, 23-25 and, as expected, the analysis showed a significant association between fatty liver and the rs738409 variant either in the fixed or the random model (P < 1 × 10−9) (Fig. 1a); details of the association stratified by age are shown in Supporting Fig. 2. At any rate, we did not observe heterogeneity

among studies stiripentol as assessed by the Q statistic (P = 0.33), I2: 11.97. From the Begg and Mazumdar’s rank correlation test (two-tailed P = 0.15), it seems that there was no publication bias. The evaluation of the risk associated with heterozygosity for the variant and fatty liver as a dichotomic variable also showed a significant association with the G allele. Interestingly, this analysis suggests that rs738409 exerts an additive effect on the susceptibility to develop NAFLD (Fig. 7); the details of the association analysis results for NAFLD and the CG versus CC genotypes are given in Supporting Table 1. In addition, we found five homogeneous reports (P = 0.22, I2: 27.5) that reported retrieval data about the measurement of liver fat content (determined using hydrogen magnetic resonance spectroscopy [H-MRS]) according to the rs738409 genotypes.