Background: An association between environmental pollutants and alcohol-related liver disease (ALD) has not been determined until now. The objectives of this study were to examine the association of the pollutants with ALD, and whether the pollutants together increased the risk of ALD. Methods: Data were extracted from the Korea National Health and Nutrition Examination Survey (2010–2013 and 2016–2017; n = 11,993). Blood levels of lead, cadmium, and mercury were measured. ALD was defined by a combination of excessive alcohol consumption and ALDon-alcoholic fatty liver disease index > 0. The aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 score were used to evaluate ALD FIB. Results: The odds ratios (ORs) of ALD for the highest versus the lowest quartiles of exposure were for lead, 7.39 (95% confidence interval [CI], 5.51–9.91); cadmium, 1.68 (95% CI, 1.32–2.14); and mercury, 5.03 (95% CI, 3.88–6.53). Adjusting for age, gender, smoking, occupation, education, and personal income attenuated the associations but indicated significant positive trends (all P trend < 0.001). A positive additive interaction between cadmium and lead was observed. The relative excess OR due to the interaction was 0.96 (95% CI, 0.41–1.51); synergy index = 2.92 (95% CI, 0.97–8.80). Among 951 subjects with ALD, advanced FIB was associated with lead and cadmium (OR, 3.46, 95% CI, 1.84–6.53; OR, 8.50, 95% CI, 2.54–28.42, respectively), but not with mercury. The effect estimates for lead and cadmium remained significant even after adjustment for daily alcohol intake. Conclusion Blood levels of lead, cadmium, and mercury were significantly associated not only with the risk of ALD but also with ALD FIB. Cadmium and lead have synergistic effects that increase the risk of ALD.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is closely related to gut-microbiome. There is a paucity of research on which strains of gut microbiota affect the progression of NAFLD. This study explored the NAFLD-associated microbiome in humans and the role of Lactobacillus in the progression of NAFLD in mice. Methods: The gut microbiome was analyzed via next-generation sequencing in healthy people (n=37) and NAFLD patients with elevated liver enzymes (n=57). Six-week-old male C57BL/6J mice were separated into six groups (n=10 per group; normal, Western, and four Western diet + strains [109 colony-forming units/g for 8 weeks; L. acidophilus, L. fermentum, L. paracasei, and L. plantarum]). Liver/body weight ratio, liver pathology, serum analysis, and metagenomics in the mice were examined. Results: Compared to healthy subjects (1.6±4.3), NAFLD patients showed an elevated Firmicutes/Bacteroidetes ratio (25.0±29.0) and a reduced composition of Akkermansia and L. murinus (P<0.05). In the animal experiment, L. acidophilus group was associated with a significant reduction in liver/body weight ratio (5.5±0.4) compared to the Western group (6.2±0.6) (P<0.05). L. acidophilus (41.0±8.6), L. fermentum (44.3±12.6), and L. plantarum (39.0±7.6) groups showed decreased cholesterol levels compared to the Western group (85.7±8.6) (P<0.05). In comparison of steatosis, L. acidophilus (1.9±0.6), L. plantarum (2.4±0.7), and L. paracasei (2.0±0.9) groups showed significant improvement of steatosis compared to the Western group (2.6±0.5) (P<0.05). Conclusions Ingestion of Lactobacillus, such as L. acidophilus, L. fermentum, and L. plantarum, ameliorates the progression of nonalcoholic steatosis by lowering cholesterol. The use of Lactobacillus can be considered as a useful strategy for the treatment of NAFLD.

Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF. Post treatment with PMOC sequentially ameliorated hepatic inflammation, apoptosis of hepatocytes, severe liver injury and shock-mediated death in ALF-induced mice. As a mechanism, PMOC inhibited the catalytic activity of TGF-β-activated kinase 1 (TAK1) in a competitive manner with respect to ATP, displaced fluorescent ATP probe from the complex with TAK1, and docked at the ATP-binding active site on the crystal structure of TAK1. Moreover, PMOC inhibited TAK1 auto-phosphorylation, which is an axis in the activating pathways of nuclear factor-κB (NF-κB) or activating protein 1 (AP1), in the liver with ALF in vivo or in primary liver cells stimulated with TLR agonists in vitro. PMOC consequently suppressed TAK1-inducible NF-κB or AP1 activity in the inflammatory injury, an early pathogenesis leading to ALF. The results suggested that PMOC could contribute to the treatment of TLR/MyD88-associated ALF with the ATP-binding site of TAK1 as a potential therapeutic target.
Adenosine Triphosphate ; Animals ; Apoptosis ; Catalytic Domain ; Chalcone ; Death, Sudden ; Escherichia coli ; Hepatocytes ; In Vitro Techniques ; Inflammation ; Liver ; Liver Failure, Acute* ; Mice ; Myeloid Differentiation Factor 88 ; Phosphotransferases ; Plants, Medicinal ; Toll-Like Receptors

PURPOSE: We investigated whether suprarenal and infrarenal aortic angles change after the endovascular aneurysm repair (EVAR) procedure and during follow-up, and investigated the correlation between infrarenal aortic angle after EVAR and type Ia endoleaks. METHODS: Data collected on 70 EVAR procedures for a fusiform infrarenal aortic aneurysm performed between May 2006 and December 2012 were supplemented with a retrospective review of charts and radiographs. RESULTS: The greater the preoperative infrarenal aortic angle, the greater the suprarenal aortic angle (r = 0.72, P < 0.001). The infrarenal aortic angle decreased after the EVAR procedure and continued to decrease slowly thereafter (all P < 0.001). Suprarenal aortic angle decreased immediately after the EVAR procedure and continued to decrease during the first month (P < 0.001). No differences in angulation were observed based on stent graft type. Type Ia endoleaks occurred with significantly greater incidence in patients with a larger post EVAR infrarenal angle (P = 0.037). CONCLUSION: The infrarenal aortic angle decreased significantly immediately after the EVAR procedure and continued to decrease slowly thereafter. Suprarenal aortic angle decreased immediately after the EVAR procedure and continued to decrease during the first month. We found a correlation between infrarenal and suprarenal aortic angle. Type Ia endoleaks occurred with greater incidence in patients with a larger infrarenal angle immediately after EVAR.
Aneurysm* ; Aortic Aneurysm ; Blood Vessel Prosthesis ; Endoleak ; Endovascular Procedures ; Follow-Up Studies ; Humans ; Incidence ; Retrospective Studies

Whether the metabolic syndrome (MetS) has prognostic value for coronary artery disease (CAD) beyond its individual components is controversial. We compared the relationship between the number of MetS components and CAD severity as assessed by angiography in non-diabetic and diabetic subjects. We consecutively enrolled 527 patients who underwent their first coronary angiography. Patients were divided into four groups according to the number of MetS components: 0/1, 2, 3, and 4/5. A coronary atherosclerosis score was used to quantify the extent of atherosclerotic involvement. The relationship between the MetS score and angiographic CAD severity or clinical presentation was compared between non-diabetic and diabetic subjects. Individuals with the MetS (n = 327) had a higher prevalence of CAD (60% vs 32%, P < 0.001), multi-vessel disease (34% vs 16%, P < 0.001), and acute coronary syndromes (49% vs 26%, P < 0.001) than those without the MetS. In the non-diabetic group, atherosclerosis score increased with the MetS score (1.0 +/- 2.1, 2.0 +/- 2.9, 2.8 +/- 2.9, and 3.6 +/- 3.9, P < 0.001) whereas there was no significant difference in the diabetic group (0.5 +/- 1.0, 5.2 +/- 4.7, 4.2 +/- 2.9, and 4.4 +/- 3.5, P = 0.102). The MetS score is related to CAD severity in non-diabetic patients but the association between the MetS score and angiographic CAD severity may be obscured in the presence of diabetes.
Adult ; Aged ; *Coronary Angiography ; Coronary Artery Disease/complications/*radiography ; Diabetes Mellitus, Type 2/*complications ; Female ; Humans ; Male ; Metabolic Syndrome X/*complications/diagnosis ; Middle Aged ; Odds Ratio ; Prognosis ; Republic of Korea ; Risk Factors ; *Severity of Illness Index

PURPOSE: The glutathione-S-transferase (GST)P1, GSTM1, and GSTT1 genotypes have been associated with an increased risk of prostate, bladder, and lung cancers. The aim of this study was to investigate the association between the GSTP1, GSTM1, and GSTT1 genotypes and the risk of prostate cancer in Korean men. MATERIALS AND METHODS: The study group consisted of 166 patients with histologically confirmed prostate cancer. The control group consisted of 327 healthy, cancer-free individuals. The diagnosis of prostate cancer was made by transrectal ultrasound-guided biopsy. Patients with prostatic adenocarcinoma were divided into organ-confined (< or =pT2) and non-organ-confined (> or =pT3) subgroups. The histological grades were subdivided according to the Gleason score. The GSTP1, GSTM1, and GSTT1 genotypes were determined by using polymerase chain reaction-based methods. The relationship among GSTP1, GSTM1, and GSTT1 polymorphisms and prostate cancer in a case-control study was investigated. RESULTS: The frequency of the GSTM1 null genotype in the prostate cancer group (54.2%) was higher than in the control group (odds ratio=1.53, 95% confidence interval=1.20-1.96). The comparison of the GSTP1, GSTM1, and GSTT1 genotypes and cancer prognostic factors, such as staging and grading, showed no statistical significance. CONCLUSIONS: An increased risk for prostate cancer may be associated with the GSTM1 null genotype in Korean men, but no association was found with the GSTT1 or GSTP1 genotypes.
Adenocarcinoma ; Biopsy ; Case-Control Studies ; Genotype ; Glutathione Transferase ; Humans ; Lung Neoplasms ; Male ; Neoplasm Grading ; Prostate ; Prostatic Neoplasms ; Urinary Bladder