Abstract
Objective. Chemerin and vaspin are new adipokines which may modulate inflammatory response and insulin sensitivity in non-alcoholic fatty liver disease (NAFLD). The aims of this study were ...to assess: (1) circulating levels of chemerin and vaspin and their association with liver histology and markers of liver injury in NAFLD patients; and (2) the relationship between the analyzed adipokines and insulin resistance. Material and methods. A total of 41 NAFLD patients with body mass index (BMI) 30.4 ± 3.3 kg/m2 20 with non-alcoholic steatohepatitis (NASH) and BMI 30.3 ± 3.3 kg/m2 and 21 with simple steatosis/uncertain NASH (SS/UN) and BMI 30.5 ± 3.4 kg/m2 and 10 healthy volunteers with BMI 24.0 ± 2.9 kg/m2 were included in the study. Results. Serum chemerin concentration was significantly higher in NAFLD patients compared to healthy volunteers (p = 0.009). Serum chemerin was significantly higher in patients with NASH compared to patients with SS/UN (p = 0.009). The homeostasis model assessment for insulin resistance (HOMA-IR) value was higher in patients with NASH than in patients with SS/UN (p = 0.01). Serum chemerin and HOMA-IR were positively associated with NAFLD activity score (r = 0.40, p = 0.02; and r = 0.43, p = 0.008, respectively). Serum chemerin was associated with hepatocyte ballooning degeneration (r = 0.37; p = 0.03), total cholesterol (r = 0.45; p = 0.008) and diastolic blood pressure (r = 0.41; p = 0.02). HOMA-IR was related to fibrosis stage (r = 0.51; p = 0.001) and inflammatory activity grade in portal tracts (r = 0.40; p = 0.01). Serum vaspin correlated with hepatocyte ballooning degeneration (r = 0.31; p = 0.04), alanine aminotransferase and aspartate aminotransferase (r = 0.33, p = 0.03; and r = 0.32, p = 0.04, respectively) and diastolic blood pressure (r = 0.39, p = 0.01). Conclusions. This study shows for the first time that chemerin and vaspin serum concentrations are altered in patients with NAFLD. The analyzed adipokines appear to play a pivotal role in the pathogenesis of NAFLD, not only as regulators of insulin sensitivity, but also as mediators of the inflammatory process.
Background & Aims
Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non‐invasive tests to quantify liver injury in women with PCOS and analyse whether ...FLD‐associated genetic variants contribute to liver phenotypes in PCOS.
Methods
Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan assays. Liver stiffness measurements (LSM), controlled attenuation parameters (CAP) and non‐invasive HSI, FLI, FIB‐4 scores were determined to assess hepatic steatosis and fibrosis.
Results
A total of 42 German (age range 18–53 years) and 143 Polish (age range 18–40 years) women with PCOS, as well as 245 German and 289 Polish controls were recruited. In contrast to Polish patients, Germans were older, presented with more severe metabolic profiles and had significantly higher LSM (median 5.9 kPa vs. 3.8 kPa). In the German cohort, carriers of the PNPLA3 p.I148M risk variant had an increased LSM (p = .01). In the Polish cohort, the minor MTARC1 allele was linked with significantly lower serum aminotransferases activities, whereas the HSD17B13 polymorphism was associated with lower concentrations of 17‐OH progesterone, total testosterone, and androstenedione (all p < .05).
Conclusions
FLD is common in women with PCOS. Its extent is modulated by both genetic and metabolic risk factors. Genotyping of variants associated with FLD might help to stratify the risk of liver disease progression in women suffering from PCOS.
Heterotopic gastric mucosa in the upper esophagus (cervical inlet patches - CIP) may be easily missed during esophagogastroduodenoscopy (EGD) due to low awareness of this usually, but not invariably, ...benign lesion. Narrow-band imaging (NBI) emphasizes contrast between normal esophageal mucosa and CIP. The purpose of this study was to investigate how NBI use and enhanced attention of operator during inspection of upper esophagus impacts cervical inlet patch detection rate (CIPDR).
This is a prospective, randomized study in which we enrolled 1000 patients, qualified for diagnostic EGD. The trial was divided into two parts; the first, when 6 operators performed EGD with standard attention (SA), and the second, when the same operators were asked to step up with attention at CIP (enhanced attention - EA). In both parts of the study, patients were randomized to NBI and white light endoscopy (WLE) in 1:1 ratio. The study is registered in ClinicalTrials.gov (No. NCT03015571).
Differences in CIPDR between WLE and NBI in SA and EA were not statistically different (5.6% vs 7.6%; p = 0.3, and 7.6% vs 11.6%; p = 0.1, respectively). In multivariate regression analysis, the only factors improving CIPDR were NBI with EA (NBIEA, OR 3.31; 95%CI 1.57–6.98; p = 0.003) and sedation (OR 1.97; 95%CI 1.27–3.05; p = 0.002).
The use of NBI combined with EA significantly improves CIPDR.
Precancerous conditions for esophageal (EA) and gastric adenocarcinoma (GA) are Barrett's esophagus (BE) and atrophic gastritis (AG), respectively. Their surveillance is crucial for the detection of ...early lesions.
The study aimed to assess whether one‑timeesophagogastroduodenoscopy (EGD) in search for precancerous conditions would be effective in the population with low‑to‑moderate esophageal and gastric cancer risk.
A total of 5984 individuals who underwent diagnostic EGD in 3 endoscopic centers, from March 2018 to October 2019, were analyzed to assess the age of occurrence of precancerous conditions and cancers. Age distribution of the patients with malignant gastric and esophageal tumors registered in the national cancer registry from 2014 to 2017 was analyzed.
In comparison with individuals below 40 years old, the risk of EA and GA diagnosis increased at the age of 60 to 64 years (odds ratio OR, 12.1; 95% CI, 1.5-98.6), gastric and esophageal dysplasia at the age of 55 to 59 years (OR, 3.6; 95% CI, 1.3-9.7), and BE and AG at the age of 40 to 44 years (OR, 1.6; 95% CI, 1.04-2.4). The number of procedures per 1 cancer that could be potentially avoided was 236, 235, 290, 360, 394, and 344 for the age groups of 40-44 years, 45-49 years, 50-54 years, 55-59 years, 60-64 years, and 65-69 years, respectively. The assessed potential benefit‑to‑harm ratio was 47, 38, 31, 28, and 32 for the age groups of 40-49 years, 50-54 years, 55-59 years, 60-64 years, and 65-69 years, respectively.
One‑time EGD in search for precancerous conditions could be potentially applicable in individuals between 40 and 69 years of age.
INTRODUCTION The etiology of autoimmune hepatitis (AIH) is unclear, with molecular mimicry between host and viral/drug antigens being the most plausible mechanism initiating the immune cascade ...that induces hepatocyte injury. Finding a serologic parameter that closely relates to the liver histology would be beneficial for monitoring AIH activity and optimizing treatment. OBJECTIVES We studied serum interleukin (IL)-17 levels and IL‑17 activators (IL‑6 and transforming growth factor β1 TGF-β1) in treatment-naive and immunosuppressed patients with AIH. We also analyzed the relationships between these cytokines and histological inflammation scores. PATIENTS AND METHODS A total of 44 patients with confirmed AIH were enrolled to the study (22 treatment-naive patients and 22 patients in clinical remission after at least 3 years of immunosuppression). Liver biopsies were performed, and the histological grading of inflammatory activity was performed by a single pathologist. The control group comprised 30 healthy age- and sex‑matched subjects. Serum IL‑17, IL‑6, and TGF‑β1 levels were measured by a quantitative sandwich enzyme immunoassay. RESULTS Serum IL‑17, IL‑6, and TGF‑β1 levels were higher in treatment-naive patients compared with controls (23.2 pg/ml vs 15.3 pg/ml, P = 0.0001; 5.20 pg/ml vs 1.42 pg/ml, P = 0.0001; and 40.5 ng/ml vs 30.1 ng/ml, P = 0.04; respectively). In treatment-naive patients, serum IL‑17 negatively correlated with hepatic inflammation (r = -0.63, P = 0.01). A reduced serum IL‑17 concentration correlated with an increased TGF‑β1 concentration in patients in clinical remission (r = -0.51, P = 0.03). CONCLUSIONS Serum IL‑17 levels may be a useful parameter for assessing disease activity in patients with AIH.
Introduction: Gastric antral vascular ectasia (GAVE) is a rare vasculopathy that associates several diseases, most commonly liver cirrhosis. It usually presents as an occult gastrointestinal bleeding ...leading to profound iron deficiency anemia. We hypothesized that GAVE is local mucosal pathology dependent on genetic mechanisms, and the purpose of the study was to characterize miRNAs expression in gastric tissue of patients with cirrhosis and GAVE.
Materials and methods: Thirteen patients with GAVE and cirrhosis and 35 healthy subjects were recruited. Microarray analysis and comparative microRNA study was done by quantitative polymerase chain reaction (qPCR). The microarray scores were grouped with use of the hierarchical clusterization analysis and miRNA target prediction was done with TargetScan 6.2 algorithm and Gene Ontology analysis (DIANA-miRPath).
Results: Concentration of miR-3677 in GAVE-affected mucosa was higher by 72% in comparison with GAVE-free mucosa of patients with cirrhosis (33.7 vs. 35.6 PCR cycles; p < .001) and by 45% in comparison with normal mucosa (33.7 vs. 34.9 PCR cycles; p < .05). According to Gene Ontology analysis miR-3677 was related to angiopoietin-like protein 4 (ANGPTL4) gene.
Conclusion: GAVE in liver cirrhosis is associated with increased expression of miR-3667 that may be linked with ANGPTL4 gene.
Corticosteroids are used widely to treat many types of disease. In general, these drugs are considered safe for the liver; however, recent reports have demonstrated that high-dose methylprednisolone ...(MT) may cause severe liver injury. Here, we report a case of a 24-year-old female who was given pulsed MT therapy for multiple sclerosis. MT induced icteric hepatitis and impaired liver synthetic function. Hepatotoxicity developed several weeks after drug exposure, and the causal association with MT was confirmed by unintentional rechallenge test. A brief review of the literature on corticosteroid-induced hepatotoxicity is presented.
Corticosteroids are used widely to treat many types of disease. In general, these drugs are considered safe for the liver; however, recent reports have demonstrated that high-dose methylprednisolone ...(MT) may cause severe liver injury. Here, we report a case of a 24-year-old female who was given pulsed MT therapy for multiple sclerosis. MT induced icteric hepatitis and impaired liver synthetic function. Hepatotoxicity developed several weeks after drug exposure, and the causal association with MT was confirmed by unintentional rechallenge test. A brief review of the literature on corticosteroid-induced hepatotoxicity is presented.
Summary Objective Portal vein thrombosis (PVT) is a common complication of cirrhosis, but its pathogenesis is unclear. We tested the hypotheses that PVT is the result of platelet hyperactivity or ...intestinal barrier disruption. Methods This study included 49 patients with cirrhosis (15 females) of mixed etiology. Based on spiral computed-tomography, the patients were divided into two groups: with PVT ( n = 16) and without PVT ( n = 33). Serum biomarkers of intestinal barrier integrity were endotoxins and zonulin, and platelet activity was assessed with multiple electrode aggregometry. Results The levels of endotoxin (43.5 ± 18.3 ng/ml vs. 36.9 ± 7.5 ng/ml; P = 0.19) and zonulin (56.3 ± 31.1 ng/ml vs. 69.3 ± 63.1 ng/ml; P = 0.69) were not different between the patients with and without PVT. Moreover, endotoxin and zonulin did not correlate with the coagulation and platelet parameters. The platelet aggregability measured with the TRAP and the ADP tests was decreased in PVT patients. In the logistic regression analysis the PVT incidence was related to the levels of D-dimer and bilirubin as well as the TRAP test results. Patients with PVT presented with significantly higher levels of D-dimer (4.45 ± 2.59 vs. 3.03 ± 2.97 mg/l; P < 0.05) and prothrombin levels (175 ± 98.8 μg/ml vs. 115 ± 72.9 μg/ml; P < 0.05) than patients without thrombosis. PVT could be excluded with a 90% negative predictive value when the D-dimer level was below 1.82 mg/l. Conclusions Endotoxemia and platelet activity are not determinants of PVT in patients with cirrhosis. The D-dimer measurement has diagnostic significance for PVT in patients with liver cirrhosis.
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