BackgroundFatty liver disease (FLD) including non-alcoholic fatty liver disease (NAFLD), a rapidly emerging and widely recognized liver disease today, is regarded as a hepatic manifestation of metabolic syndrome. Helicobacter pylori, one of the most common pathogens worldwide, has been reported to be associated with metabolic syndrome, but whether there is a direct association with FLD is as of yet unclear. The aim of this study was to clarify the association of FLD and NAFLD with causative background factors including Helicobacter pylori infection.MethodsThis was a cross-sectional study of Japanese adults who received medical checkups at a single medical center in 2010.Univariate and multivariate statistical analysis was performed to evaluate background factors for ultrasonography diagnosed FLD. Subjects free from alcohol influence were similarly analyzed for NAFLD.ResultsOf a total of 13,737 subjects, FLD was detected in 1,456 of 6,318 females (23.0 %) and 3,498 of 7,419 males (47.1%). Multivariable analyses revealed that body mass index (standardized coefficients of females and males (β-F/M) =143.5/102.5), serum ALT (β-F/M = 25.8/75.7), age (β-F/M = 34.3/17.2), and platelet count (β-F/M = 17.8/15.2) were positively associated with FLD in both genders. Of the 5,289 subjects free from alcohol influence, NAFLD was detected in 881 of 3,473 females (25.4%) and 921 of 1,816 males (50.7%). Body mass index (β-F/M = 113.3/55.3), serum ALT (β-F/M = 21.6/53.8), and platelet count (β-F/M = 13.8/11.8) were positively associated with NAFLD in both genders. Metabolic syndrome was positively associated with FLD and NAFLD only in males. In contrast, Helicobacter pylori infection status was neither associated with FLD nor NAFLD regardless of gender.ConclusionsBody mass index, serum ALT and platelet count were significantly associated with FLD and NAFLD, whereas infection of Helicobacter pylori was not.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-015-0247-9) contains supplementary material, which is available to authorized users.

Dynamic metabolic changes occur in the liver during the transition between fasting and feeding. Here we show that transient ER stress responses in the liver following feeding terminated by Sdf2l1 are essential for normal glucose and lipid homeostasis. Sdf2l1 regulates ERAD through interaction with a trafficking protein, TMED10. Suppression of Sdf2l1 expression in the liver results in insulin resistance and increases triglyceride content with sustained ER stress. In obese and diabetic mice, Sdf2l1 is downregulated due to decreased levels of nuclear XBP-1s, whereas restoration of Sdf2l1 expression ameliorates glucose intolerance and fatty liver with decreased ER stress. In diabetic patients, insufficient induction of Sdf2l1 correlates with progression of insulin resistance and steatohepatitis. Therefore, failure to build an ER stress response in the liver may be a causal factor in obesity-related diabetes and nonalcoholic steatohepatitis, for which Sdf2l1 could serve as a therapeutic target and sensitive biomarker.

Both Helicobacter pylori (H. pylori) infection and liver diseases, including nonalcoholic fatty liver disease (NAFLD), viral hepatitis, and hepatocellular carcinoma (HCC), have high prevalences worldwide, and the relationship between H. pylori infection and liver disease has been discussed for many years. Although positive correlations between H. pylori and NAFLD have been identified in some clinical and experimental studies, negative correlations have also been obtained in high-quality clinical studies. Associations between H. pylori and the pathogenesis of chronic viral hepatitis, mainly disease progression with fibrosis, have also been suggested in some clinical studies. Concerning HCC, a possible role for H. pylori in hepatocarcinogenesis has been identified since H. pylori genes have frequently been detected in resected HCC specimens. However, no study has revealed the direct involvement of H. pylori in promoting the development of HCC. Although findings regarding the correlations between H. pylori and liver disease pathogenesis have been accumulating, the existing data do not completely lead to an unequivocal conclusion. Further high-quality clinical and experimental analyses are necessary to evaluate the efficacy of H. pylori eradication in ameliorating the histopathological changes observed in each liver disease.

The expression levels of the BA export transporter BSEP were inversely correlated with NAS in NAFLD patients. Such down-regulation may cause excessive BA levels in hepatocytes, leading to cell injury. Our findings may afford new insights into the pathogenesis of NASH.

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We recently reported that the intronic splice-site mutation IVS3-8G>A of CHRNA1 that encodes the muscle nicotinic acetylcholine receptor alpha subunit disrupts binding of a splicing repressor, hnRNP H. This, in turn, results in exclusive inclusion of the downstream exon P3A. The P3A(+) transcript encodes a non-functional alpha subunit that comprises 50% of the transcripts in normal human skeletal muscle, but its functional significance remains undetermined. In an effort to search for a potential therapy, we screened off-label effects of 960 bioactive chemical compounds and found that tannic acid ameliorates the aberrant splicing due to IVS3-8G>A but without altering the expression of hnRNP H. Therefore, we searched for another splicing trans-factor. We found that the polypyrimidine tract binding protein (PTB) binds close to the 3' end of CHRNA1 intron 3, that PTB induces skipping of exon P3A and that tannic acid increases the expression of PTB in a dose-dependent manner. Deletion assays of the PTB promoter region revealed that the tannic acid-responsive element is between positions -232 and -74 from the translation initiation site. These observations open the door to the discovery of novel therapies based on PTB overexpression and to detecting possible untoward effects of the overexpression.

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