Can vitamin B6 alleviate the adverse reactions of quadruple anti-Helicobacter pylori regimen? : randomized controlled trial.

BACKGROUND: Vitamin B6 is an essential water-soluble vitamin for humans. It is often used to prevent a variety of neuropathies, relieve vomiting, and relieve symptoms such as hand and foot neuritis. AIM: To evaluate whether vitamin B6 can alleviate the adverse reactions caused by the quadruple anti-Helicobacter pylori treatment regimen containing minocycline and metronidazole. METHODS: In this randomized controlled trial, 280 patients with H. pylori infection were randomly placed into one of two treatment groups-the conventional treatment group and the vitamin B6 supplement treatment group-for 2 weeks. The primary endpoint was the total incidence of adverse reactions up to 2 weeks after treatment initiation. The study was designed according to CONSORT Medicinal Interventions. And it was registered with Chinese Clinical Trial Registry under the number ChiCTR2100053833. RESULTS: In terms of efficacy, vitamin B6 does not affect the efficacy of conventional regimen. In the vitamin B6 supplement treatment group, the incidence of adverse reactions was 56.92%, which was significantly lower than the 74.62% observed in the conventional treatment group. In addition, the severity of adverse reactions was also significantly reduced. The proportion of moderate to severe central nervous system symptoms decreased from 58.7 to 14.63%. And, the proportion of moderate to severe gastrointestinal reactions decreased from 33.33 to 0%. We speculate that the mechanism of vitamin B6 of reducing adverse reaction may be related to the production of GABA in the brain. CONCLUSIONS: Vitamin B6 can alleviate adverse reactions of the quadruple anti-H. pylori regimen containing minocycline and metronidazole.

Reliability and validity of the Chinese version of chronic liver disease questionnaire-nonalcoholic fatty liver disease in patients with nonalcoholic fatty liver disease: a multicenter cross-sectional survey in China.

PURPOSE: The Chronic Liver Disease Questionnaire (CLDQ)-Nonalcoholic Fatty Liver Disease (NAFLD) is a disease-specific instrument to assess the health-related quality of life (HRQL) of patients with NAFLD. In order to provide further evidence for the cross-cultural utility of this instrument in the Chinese population, we translated the CLDQ-NAFLD into Chinese and examined its reliability and validity. METHODS: Patients with NAFLD in 90 hospitals across China were enrolled in this multicenter cross-sectional survey. Eligible patients completed the Chinese version of CLDQ-NAFLD at enrollment to assess HRQL. Internal consistency of the questionnaire was assessed using Cronbach's alpha coefficient and split-half reliability. Convergent and discriminant validity were assessed using Spearman correlation coefficient. Factor analysis was used to test the construct validity. RESULTS: Between March and August 2019, 5181 patients with a mean age of 43.8 ± 13.3 years were enrolled. All domains exhibited good internal consistency, with Cronbach's alpha and split-half reliability greater than 0.70. The scaling success rate of all domains was 100% for convergent validity and 99.4% (179/180) for discriminant validity. The inter-scale correlations indicated a significant correlation between all CLDQ-NAFLD domains (r = 0.608 to 0.832, all p < 0.001). Factor analysis of 36 items extracted 6 factors, which explained 69.14% of the total variance. CONCLUSION: The Chinese version of CLDQ-NAFLD is a reliable and valid instrument for assessing the HRQL of Chinese patients with NAFLD.

The impact of Helicobacter pylori infection and eradication therapy containing minocycline and metronidazole on intestinal microbiota.

BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with remodeling of gut microbiota. Many studies have found H. pylori infection and eradication therapy can alter the gut microbiota. However, few studies explored the impact of eradication therapy containing minocycline and metronidazole on gut microbiota. AIM: The objective of the present study was to explore the changes of gut microbiota after H. pylori infection. Besides, learn more about the dynamic changes of gut microbiota during different stages of eradication treatment containing minocycline, metronidazole, bismuth agents and proton pump inhibitors. METHODS: Sixty stool samples from the patients with H. pylori infection before eradication, 14 and 42 days after eradication, and ten stool samples from non-infected individuals were collected. Subsequently, we performed 16S rRNA gene amplicon sequencing to analyze these samples, and the results were evaluated by using alpha diversity, beta diversity and microbial composition analyses. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was also used to predict the metabolic pathways according to the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: The alpha and beta diversity of the microbiota changed significantly in H. pylori infected individuals, but returned to baseline 42 days after eradication therapy. At the genus level, the abundances of Bacteroidetes, [Ruminococcus]_gnavus_group, Ruminococcaceae_Incertae_Sedis, Tuzzrealla, Butyricicoccus were significantly lower in the H. pylori infected group. Bacterial abundance was also dynamically changing during eradication treatment. In addition, PICRUST analysis found the levels of uronic acid metabolism, uncharacterized transport system, and biosynthesis of unsaturated fatty acids were higher in H. pylori infected individuals than in the non-infected group. CONCLUSIONS: Intestinal microbiota diversity, composition, functional predictions altered significantly after H. pylori infection, and gradually returned to healthy control levels after the application of eradication therapy containing minocycline and metronidazole in one month and a half.

Health-related quality of life in Chinese population with non-alcoholic fatty liver disease: a national multicenter survey.

BACKGROUND: Health Related Quality of Life (HRQL) is a multi-dimensional construct that can comprehensively evaluate the patient's health status, including physical, emotional, mental and social well-being. In this study, we aimed to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on HRQL in a Chinese population. METHODS: In this national multicenter cross-sectional survey, patients with NAFLD were enrolled. Chronic Liver Disease Questionnaire (CLDQ)-NAFLD was used to qualify HRQL. Univariate and multivariate analysis were used to identify independent risk factors of HRQL. RESULTS: A total of 5181 patients with NAFLD from 90 centers were enrolled in this study (mean age, 43.8 ± 13.3 years; male, 65.8%). The overall CLDQ score was 5.66 ± 0.89. Multivariate logistic regression analysis showed that body mass index (BMI: HR, 1.642; 95% CI, 1.330-2.026), alanine transaminase (ALT: HR, 1.006; 95% CI, 1.001-1.011), triglyceride (HR, 1.184; 95% CI, 1.074-1.305), disease severity (HR, 3.203; 95% CI, 1.418-7.232) and cardiovascular disease (HR, 4.305; 95% CI, 2.074-8.939) were independent risk factors for overall CLDQ score. In the logistic analyses of individual domain, BMI and triglyceride were independent risk factors of all domains. ALT, disease severity, diabetes, depression and cardiovascular disease were influencing factors for the CLDQ score of several domains. CONCLUSIONS: This national multicenter cross-sectional survey in China indicated that the HRQL in patients with NAFLD was impaired. HRQL was found to be significantly associated with sociodemographic and clinical factors. Attention should be paid to the optimally managing care of patients with NAFLD to improve their HRQL.

linc-SCRG1 accelerates liver fibrosis by decreasing RNA-binding protein tristetraprolin.

The biologic roles of long noncoding RNAs (lncRNAs) in liver fibrosis remained unknown. Through microarray analysis, linc-SCRG1 (a lncRNA with transcript length 3118 bp) was found up-regulated 13.62-fold in human cirrhotic tissues. Quantitative PCR verified that linc-SCRG1 increased along with liver fibrosis progression in human tissues and in activated LX2 cells induced by TGF-ß1. Knockdown of linc-SCRG1 significantly reversed the effects of TGF-ß1 on LX2, including inhibiting activation, promoting apoptosis, reducing proliferation, lessening invasion, and down-regulating genes [fibrosis-related mRNA: α-smooth muscle actin ( α-SMA), type I collagen, and B-cell lymphoma-2; invasion-related mRNA: matrix metallopeptidase-2 ( MMP-2), MMP-9, and MMP-13; inflammation-related mRNA: TNF-α, IL-6, and IL-10]. linc-SCRG1 had binding sites with tristetraprolin (TTP), a kind of RNA-binding protein, and specifically combined to TTP proteins. Overexpression of linc-SCRG1 would cause TTP mRNA unstably and proteins decreasing. TTP mRNA was proved having negative relevance with linc-SCRG1 and was gradually reduced during human liver fibrosis progression. Overexpressing TTP resulted in knockdown of lincSCRG1 and degraded downstream target genes ( MMP-2 and TNF-α) in activated LX2. Overexpressing TTP had the same effects as small interfering RNA-lincSCRG1 (si- lincSCRG1), whereas knockdown of TTP had reversal effects on si- lincSCRG1 in activated LX2. In summary, linc-SCRG1 reduced TTP and restricted its degradation of target genes TNF-α and MMP-2. Therefore, linc-SCRG1 had a repressing TTP-elicited inactivation effect on hepatic stellate cell (HSC) phenotypes. Inhibition of linc-SCRG1 may be a novel therapeutic approach to inactivate HSCs and extenuate human liver fibrosis.-Wu, J.-C., Luo, S.-Z., Liu, T., Lu, L.-G., Xu, M.-Y. linc-SCRG1 accelerates liver fibrosis by decreasing RNA-binding protein tristetraprolin.

Prediction of hepatic necroinflammatory activity in patients with chronic hepatitis B by a simple noninvasive model.

BACKGROUND: A model was constructed using clinical and serum variables to discriminate between chronic hepatitis B (CHB) patients with and without significant necroinflammatory activity (score 4-18 vs. score 0-3). METHODS: Consecutive CHB patients who underwent liver biopsy were divided into two sequential groups: a training group (n = 401) and a validation group (n = 401). Multivariate analysis identified alanine aminotransferase, γ-glutamyltransferase, prothrombin time and albumin as independent predictors of necroinflammatory activity. RESULTS: The area under the receiver operating characteristic curve was 0.826 for the training group and 0.847 for the validation group. Using a cut-off score of H ≤ 0.375, significant necroinflammatory activity (score 4-18) was excluded with high accuracy [78.2% negative predictive value (NPV), 72% positive predictive value (PPV), and 90.8% sensitivity] in 238 (59.4%) of 401 patients in the training group and with the same certainty (88.1% NPV, 61.2% PPV, and 95.1% sensitivity) among 204 (50.9%) of 401 patients in the validation group. Similarly, applying a cut-off score of H > 0.720, significant necroinflammatory activity was correctly identified with high accuracy (90.8% PPV, 57.7% NPV, and 92.0% specificity) in 150 (37.4%) of 401 patients in the training group and with the same certainty (91.8% PPV, 64.6% NPV, and 95.4% specificity) in 188 (46.9%) of 401 patients in the validation group. CONCLUSIONS: A predictive model based on easily accessible variables identified CHB patients with and without significant necroinflammatory activity with a high degree of accuracy. This model may decrease the need for liver biopsy for necroinflammatory activity grading in 72.1% of CHB patients.

Accuracy of transient elastography in the assessment of chronic hepatitis C-related liver cirrhosis.

PURPOSE: Staging liver cirrhosis is essential for the management of chronic hepatitis C (CHC). The current meta-analysis evaluated the accuracy of transient elastography for detecting liver cirrhosis in patients with CHC. METHODS: Either prospective or retrospective studies, including cohort and cross sectional studies, in patients diagnosed with chronic hepatitis C, as assessed by transient elastography, were searched from Medline, Cochrane, EMBASE, and Google Scholar databases until March 3, 2015, using the terms "transient elastography, chronic hepatitis C and liver cirrhosis". The primary outcome analyzed was the diagnostic performance, which included sensitivity, specificity, diagnostic odds ratio and area under the receiver-operating characteristic (ROC) curve. RESULTS: Data from 24 articles included in the meta-analysis demonstrated high sensitivity (84%) and specificity (90%) of transient elastography (TE) for assessing liver cirrhosis patients with HCV. Subgroup analysis of patients by underlying diseases revealed a sensitivity and specificity of 91% and 92% (HCV alone), 100% and 75% (HCV-liver transplant), 83.6% and 89.7% (HIV/HCV co-infection) and 97.1% and 90.7% (recurrent CHC after liver transplantation). The pooled diagnostic odds ratio was 61.57 (95% CI, 39.5 - 96.00) and the area under the summary ROC curves was 0.952 ± 0.008, suggesting high diagnostic accuracy of TE. CONCLUSION: Transient elastography can accurately predict liver cirrhosis in patients with hepatitis C, with a sensitivity and specificity of 84% and 90%, respectively. The present results further validate the utility of TE in staging liver cirrhosis in chronic HCV infections.

Stat3 signaling activation crosslinking of TGF-ß1 in hepatic stellate cell exacerbates liver injury and fibrosis.

BACKGROUND/AIMS: The role of signal transducer and activator of transcription 3 (Stat3) in liver fibrosis is still controversial. Since hepatic stellate cells (HSCs) and transforming growth factor-ß1 (TGF-ß1) are central to the fibrogenesis, our goal was to clarify the mechanism of Stat3 crosslinking of TGF-ß1 signaling. METHODS: Stat3, TGF-ß1 mRNA and protein expressions were examined in liver tissues of chronic hepatitis B (CHB) patients and diethylinitrosamine (DEN)-induced rat fibrosis model. The effect of Stat3 activation or suppression on TGF-ß1 signaling in HSCs was tested in vitro and in vivo. RESULTS: Stat3 expression as well as TGF-ß1 was increased in CHB patients and DEN-induced fibrosis rat model. This was strongly correlated with increase in fibrosis staging. TGF-ß1, a mediator of fibrosis, was enhanced by Stat3, but suppressed by siRNA-mediated RNA knockdown of Stat3 (siStat3) or Janus kinase 2 inhibitor (AG490) both in vivo and in vitro. Stat3 crosslinking TGF-ß1 signaling plays an important role in HSC activation and increasing fibrosis related products. TGF-ß1 could not achieve profibrogenic cytokine and anti-apoptosis characteristics without Stat3 activation in HSCs. CONCLUSION: We provide a novel role of Stat3 cooperating TGF-ß1 in activation and anti-apoptotic effect of HSCs. Stat3 worsens liver fibrosis through the up-regulation of TGF-ß1 and fibrotic product expression.

Safety and efficacy of a novel plastic stent coated with stone-dissolving agents for the treatment of biliary stones in a porcine model.

BACKGROUND AND STUDY AIM: We previously reported on a plastic stent that was coated with ethylenediaminetetraacetic acid (EDTA) and sodium cholate, which dissolved common bile duct (CBD) stones ex vivo. The aim of this study was to investigate the safety and efficacy of such stents on biliary stones in a live porcine model. METHODS: Stents without coating or with degradable membranes containing 0 % or 50 % EDTA and sodium cholate were inserted together with human CBD stones into the porcine CBD. Serum laboratory variables, histological examinations of the bile duct, and the weight change in stones were compared during and after stent placement for 6 months. RESULTS: A total of 16 pigs were included (5 no coating, 5 0 % coating, 6 50 % coating). Biliary stones showed decreased weight in all groups; however, stones in the group with 50 % coated stents showed a greater reduction in weight compared with the no coating and the 0 % coating groups (269 ±â€Š66 mg vs. 179 ±â€Š51 mg [P = 0.09]; 269 ±â€Š66 mg vs. 156 ±â€Š26 mg [P = 0.01], respectively). CONCLUSIONS: The plastic stent coated with 50 % agent enhanced CBD stone dissolution in vivo and may be a promising tool for patients with difficult biliary stones.

The effect of a novel drug-eluting plastic stent on biliary stone dissolution in an ex vivo bile perfusion model.

BACKGROUND: Temporary plastic stent insertion has been considered a safe and effective bridge therapy for difficult common bile duct (CBD) stones. Infusing chemicals to directly dissolve stones through the bile duct might also be effective. However, there are no studies on the efficacy of the combination of these 2 approaches. OBJECTIVE: To investigate the efficacy of a novel ethylenediaminetetraacetic acid (EDTA) and sodium cholate-eluting plastic stent on biliary stones. DESIGN: Ex vivo model by using different doses of active ingredient. SETTING AND INTERVENTIONS: An ex vivo bile duct model perfused with porcine bile was created. Stents coated with degradable membranes containing various concentrations of EDTA and sodium cholate were placed in the model with CBD stones. MAIN OUTCOME MEASUREMENTS: The change in the weight of stents and stones was measured every week during perfusion until the coated membranes were completely biodegraded. RESULTS: The time that the stents required to be fully degraded and the efficiency of stone dissolution were positively correlated with the percentage of EDTA and sodium cholate in the stent membrane. However, the 50% EDTA and sodium cholate stents achieved the greatest percentage of stone weight loss when the drugs were completely released. LIMITATIONS: Ex vivo study. CONCLUSIONS: The EDTA and sodium cholate-eluting plastic stent effectively dissolved CBD stones and has prospect in the therapy for patients with difficult CBD stones.

Endoscopic ultrasound for the diagnosis and treatment of primary hepatocellular carcinoma.

Chronic liver disease has emerged as a significant global concern, with primary hepatocellular carcinoma (HCC) representing a critical consequence of this disease. However, early detection of HCC remains challenging in clinical practice. Recently, there has been a growing interest in applying endoscopic ultrasound (EUS) as a diagnostic tool for gastrointestinal diseases. Nevertheless, using EUS to diagnose and treat HCC is uncommon. In this review we described the diagnostic and therapeutic applications of EUS in primary HCC and evaluated its clinical significance. The diagnostic procedures primarily involve EUS-guided fine-needle biopsy or aspiration, assessment of metastatic lymph nodes and portal vein thrombosis, portal pressure monitoring, and portal vein blood collection. Treatment mainly includes EUS-guided tumor ablation, brachytherapy, injectable chemotherapy, and managing variceal hemorrhage related to portal hypertension.

Serum dihydroxyacetone kinase peptide m/z 520.3 as predictor of disease severity in patients with compensated chronic hepatitis B.

BACKGROUND AND AIM: Due to known limitations of liver biopsy, reliable non-invasive serum biomarkers for chronic liver diseases are needed. We performed serum peptidomics for such investigation in compensated chronic hepatitis B (CHB) patients. METHODS: Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) was used to identify differentially expressed peptides in sera from 40 CHB patients (20 with S0G0-S1G1 and 20 with S3G3-S4G4). Ion pair quantification from differentially expressed peptides in a validation set of sera from 86 CHB patients was done with multiple reaction monitoring (MRM). RESULTS: 21 differentially represented peptide peaks were found through LC-MS/MS. Ion pairs generated from eleven of these peptides (m/z < 800) were quantified by MRM. Summed peak area ratios of 6 ion pairs from peptide m/z 520.3 (176.1, 353.7, 459.8, 503.3, 351.3, 593.1), which was identified as dihydroxyacetone kinase (DAK) fragment, decreased from mild to advanced stages of fibrosis or inflammation. Area Under Receiver Operating Characteristic Curves (AUROCs) of five ion models discriminating fibrosis degrees were 0.871 ~ 0.915 (S2-4 versus S0-1) and 0.804 ~ 0.924 (S3-4 versus S0-2). AUROCs discriminating inflammation grades were 0.840 ~ 0.902 (G2-4 versus G0-1) and 0.787 ~ 0.888 (G3-4 versus G0-2). The diagnostic power of these models provides improved sensitivity and specificity for predicting disease progression as compared to aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Forn's index and serum DAK protein. CONCLUSIONS: The peptide fragment (m/z 520.3) of DAK is a promising biomarker to guide timing of antiviral treatment and to avoid liver biopsy in compensated CHB patients.

Prediction of significant fibrosis and cirrhosis in hepatitis B e-antigen negative patients with chronic hepatitis B using routine parameters.

AIM: As liver biopsy has considerable limitations in the assessment of liver fibrosis, non-invasive models have achieved great progress in the past. However, many tests consist of variables that are not readily available, and there are few data about patients with hepatitis B e-antigen (HBeAg) negative chronic hepatitis B (CHB). The aim of this study was to develop a model using routine data to predict liver fibrosis in HBeAg negative CHB patients. METHODS: We randomly divided 349 patients who underwent liver biopsy into training (n = 200) and validation (n = 149) sets. Multivariable logistic regression and receiver-operator curve (ROC) analyses were used to develop a model for predicting both significant fibrosis (stages 2-4) and cirrhosis (stage 4) in the training set. The model was validated in 149 patients in comparison to FIB-4, Forn's, S and aspartate aminotransferase-to-platelet ratio index indices using ROC. RESULTS: Multivariable logistic regression analysis showed that the parameters of the model for predicting both significant fibrosis and cirrhosis included sex, age, prothrombin time, platelet count, cholesterol and γ-glutamyltransferase. In the training set, the areas under the ROC (AUC) for predicting significant fibrosis and cirrhosis were 0.856 and 0.956, respectively. In the validation group, the AUC for predicting significant fibrosis and cirrhosis were 0.889 and 0.937, respectively. Using the best cut-off values, significant fibrosis and cirrhosis can be accurately predicted in 40.9% and 91.3% of patients, respectively. CONCLUSION: Our model can accurately predict both significant fibrosis and cirrhosis and may decrease the need of liver biopsy in a considerable proportion of patients with HBeAg negative CHB.

[Aspartate-ornithine granules in the treatment of nonalcoholic steatohepatitis: a multiple-dose parallel controlled clinical trial].

OBJECTIVE: To investigate the therapeutic efficacy and safety of aspartate-ornithine granules in patients with nonalcoholic steatohepatitis (NASH). METHODS: Seventy-two patients with NASH were included in this multiple-dose parallel controlled clinical trial and received a 12-week course of aspartate-ornithine granule treatment at either high-dose (6 g bid po; n = 38) or low-dose (3 g bid po; n = 34). Clinical efficacy was assessed by monitoring data from urinalysis, serologic tests (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and triglyceride (TG)), and abdominal computed tomography (CT) scan. Safety was assessed by occurrence of adverse events (fatigue, anorexia, abdominal distension, nausea, and vomiting). Statistical analyses were conducted to determine the significance of differences between parameters before (baseline) and after treatment. RESULTS: After 12 weeks of treatment, the liver and spleen CT ratios in both the high-dose group (0.89 +/- 0.19) and the low-dose group (0.80 +/- 0.15) were significantly higher than at baseline (S = 329, P less than 0.0001 and S = 246, P less than 0.0001); the overall improvement was more robust in the high-dose group (52.63%) than in the low-dose group (38.23%) (Z = -2.1042, P less than 0.05). After 6 and 12 weeks of treatment, the serum ALT levels in both the high-dose group and the low-dose group were significantly lower than at baseline (6 weeks: S = 324.5, P less than 0.0001 and S = 223, P less than 0.0001; 12 weeks: S = 370.5, P less than 0.0001 and S = 297.5, P less than 0.0001); the overall improvement was more robust in the high-dose group (79.0%) than in the low-dose group (53.0%) (Z = -2.0533, P less than 0.05). Similar trends were seen for the serum levels of AST and GGT after 6 and 12 weeks of treatment (all P less than 0.01) and serum levels of TG after 12 weeks of treatment. The rate of adverse reactions was low and similar between the two groups (high-dose: 4.8% and low-dose: 4.4%; all gastrointestinal). CONCLUSION: Aspartate-ornithine granule therapy was an effective and safe treatment of nonalcoholic steatohepatitis, with the higher dose of 6 g bid po providing more robust clinical benefit without affecting the safety profile.

Favorable impact of a novel endoscopic auxiliary system (NEAS) on fluoroscopy-guided lithotripsy for difficult bile duct stones: A pilot study.

OBJECTIVES: Laser lithotripsy under fluoroscopic guidance is difficult to perform and risky due to its invisibility. In this study we aimed to investigate the efficacy and safety of a novel endoscopic auxiliary system (NEAS)-assisted lithotripsy under fluoroscopy for treating difficult common bile duct (CBD) stones. METHODS: Patients with difficult CBD stones who were treated with NEAS-assisted laser lithotripsy (NEAS group) or conventional mechanical lithotripsy (ML) under fluoroscopy (ML group) were retrospectively evaluated. The primary outcome was the complete stone clearance rate and the secondary outcomes included operation time, complications, and medical cost. RESULTS: Seventeen patients were treated with NEAS-assisted laser lithotripsy and 144 patients underwent ML. Using the propensity score matching analysis, 17 pairs of cases treated with NEAS-assisted lithotripsy and ML were included. Patients in the NEAS group showed a higher stone clearance rate than the ML group (94.1% vs 58.8%, P = 0.039), as well as shorter operation time (41.9 min vs 49.4 min, P < 0.001) and lower medical cost (USD 4607 vs USD 5014, P < 0.001). There was no significant difference in the complication rate between the two groups (5.9% vs 17.6%, P = 0.601). CONCLUSION: NEAS-assisted fluoroscopy-guided laser lithotripsy is feasible and safe, which may be a promising technique in fluoroscopy-guided laser lithotripsy for difficult CBD stones.

Diagnostic value of FibroTouch in identifying hepatic steatosis in NAFLD with MRI-PDFF as the reference standard.

OBJECTIVE: To estimate the performance of the FibroTouch-based ultrasound attenuation parameter (UAP) for assessing hepatic steatosis in nonalcoholic fatty liver disease (NAFLD), with magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. METHODS: This prospective, cross-sectional study included 275 individuals in the training group and 110 individuals in the validation group, all of whom completed a standardized research visit, laboratory tests, MRI-PDFF, and UAP measurements over 1 month. Pearson correlation coefficient and Bland-Altman analysis were used to assess the agreement between UAP and MRI-PDFF for the detection of hepatic steatosis. The diagnostic value of UAP was evaluated by the area under the receiver operating characteristic (ROC) curve (AUROC). Confounding factors to UAP performance were identified by ROC curves and regression analyses. RESULTS: The AUROC of UAP for detecting MRI-PDFF at ≥5%, ≥10%, and ≥20% were 0.95 (95% confidence interval [CI] 0.92-0.97), 0.86 (95% CI 0.81-0.90), and 0.90 (95% CI 0.86-0.93), respectively, and their optimal thresholds were 259, 274, and 295 dB/m, respectively. The UAP measurements had higher diagnostic accuracy in participants with lower waist circumference (≤90 cm for men and ≤80 cm for women) compared to those with higher waist circumference (AUROC values: 0.97 vs 0.84, P < 0.05). Bland-Altman analysis showed good agreement between UAP and MRI-PDFF (bias 0.00021). According to established regression analyses, hepatic steatosis could be accurately diagnosed using UAP estimation. CONCLUSIONS: FibroTouch-UAP has a high diagnostic potential for hepatic steatosis in NAFLD patients and helps clinical assessment and monitoring.

Stages of psychological change among patients with non-alcoholic fatty liver disease in China: a national cross-sectional study.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is becoming the leading cause of chronic liver disease worldwide. However, treatment of NAFLD is potentially influenced by psychological conditions. Using the simplified version of the University of Rhode Island Change Assessment (URICA-SV) scale, this study aimed to evaluate the stage of psychological change as a prerequisite to refining implementation strategies for psychological change. DESIGN: A multicentre cross-sectional survey. SETTING: Ninety hospitals in China. PARTICIPANTS: 5181 patients with NAFLD were included in this study. OUTCOME MEASURES: All patients completed the URICA-SV questionnaire and were assigned to one of the three stages of change (precontemplation, contemplation or action) according to their readiness scores. A stepwise multivariate logistic regression analysis was used to identify independent factors associated with the stage of psychological change. RESULTS: A total of 4832 (93.3%) patients were included in the precontemplation stage and only 349 (6.7%) considered making a change or preparing to make one. There were significant differences in gender (Cohen's d=0.039, p=0.005), age (Cohen's d=-0.327, p<0.001), waist circumference (Cohen's d=0.143, p=0.003), alanine transaminase (Cohen's d=0.347, p=0.001), triglyceride (Cohen's d=0.351, p=0.002), body mass index (BMI; Cohen's d=0.056, p<0.001), proportion of hyperlipidaemia (Cohen's d=0.068, p<0.001) and cardiovascular disease (Cohen's d=0.032, p=0.029), therapeutic regimen (Cohen's d=0.136, p<0.001), and Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease overall score (Cohen's d=-0.420, p<0.001) between patients with NAFLD in the precontemplation stage and those in the contemplation/action stage. Logistic regression identified BMI (HR 0.659, 95% CI 0.469 to 0.928, p=0.017), cardiovascular disease (HR 2.161, 95% CI 1.089 to 4.287, p=0.027) and triglyceride (HR 0.751, 95% CI 0.591 to 0.955, p=0.020) as independent factors predicting psychological change. CONCLUSIONS: The results demonstrated that very few patients with NAFLD presented psychological condition in the stage of action. Psychological condition was found to be significantly related to BMI, cardiovascular disease and triglyceride factors. Integrated diversity considerations for evaluating psychological change are necessary.

Effect of ursodeoxycholic acid administration after liver transplantation on serum liver tests and biliary complications: a randomized clinical trial.

BACKGROUND/AIMS: Endogenous hydrophobic bile acids are suspected to be one of the pathogenetic factors of biliary complications after orthotopic liver transplantation (OLT). This study was designed to investigate the effects of hydrophilic ursodeoxycholic acid (UDCA) administration early after OLT on serum liver tests and the incidence of biliary complications. METHODS: 112 adult patients undergoing OLT from donation after cardiac death (DCD) were randomized to UDCA (13-15 mg/kg/day for 4 weeks; 56 patients) or placebo (56 patients). Serum liver tests and serum bile acids of all patients and biliary bile acids in patients with T-tube drainage were determined during the 4 weeks after OLT. Biliary complications as well as patient and graft survival were analyzed during a mean follow-up of 41.6 months. RESULTS: UDCA treatment decreased ALT, AST and GGT (p < 0.05) during the 4 weeks after OLT and the incidence of biliary sludge and casts within the 1st year (p < 0.05). However, no differences in the incidence of other biliary complications as well as 1-, 3- and 5-year graft and patient survival were observed. CONCLUSIONS: UDCA administration early after DCD-OLT improves serum liver tests and decreases the incidence of biliary sludge and casts within the 1st postoperative year but does not affect overall outcome up to 5 years after OLT.

Transforming growth factor beta1 gene variation Leu10Pro affects secretion and function in hepatic cells.

BACKGROUND: Our previous work revealed transforming growth factor beta1 (TGFß1) gene polymorphisms are associated with susceptibility to hepatocellular carcinoma and liver cirrhosis. However, no further study of functional substitution in hepatic cells has yet been reported. AIMS: This study was designed to uncover the functional mechanisms of TGFß1 gene polymorphisms in the pathogenesis of liver diseases. METHODS: Two recombinant TGFß1 expression plasmids containing TGFß1 codon 10 Leu/Pro variation were constructed with CMV promoter and transfected into human hepatoma cell lines (HepG2 and SMMU 7721), hepatic stellate cells (LX-2), and immortalized hepatocytes (L02). The secretion capacities of TGFß1 protein in the transfected cells were determined by ELISA. Apoptosis, proliferative activity, and expression of CD 105, CD83, and CD80 were also measured by use of flow cytometry. RESULTS: The ELISA results showed that cells transfected with CMV-Pro10 were more capable of TGFß1 secretion than those transfected with CMV-Leu10. Functionally, CMV-Pro10 was more apoptosis-protective and induced more proliferation than CMV-Leu10 in transfected hepatic cells. Pro10 up-regulated expression of CD105 and down-regulated expression of CD83. CONCLUSIONS: TGFß1 gene Leu10Pro variation in signal peptide has significant effects on TGFß1 secretion and functions in hepatic cells.

18α-glycyrrhetinic acid down-regulates expression of type I and III collagen via TGF-Β1/Smad signaling pathway in human and rat hepatic stellate cells.

OBJECTIVE: To investigate the effects of 18α-glycyrrhetinic acid (18α-GA) on the expression of type I and III collagen in human and rat hepatic stellate cells (HSC) and to explore the role of TGF-ß1/Smad signaling pathway involved. METHODS: Following 18α-GA treatment, the cell viability and cell growth were detected to determine the optimal concentration of 18α-GA. The expressions of TGF-ß1/Smad signaling-related genes including type I and III collagen in human and rat HSCs before and after 18α-GA treatment were measured by real time PCR. The expression of related proteins was verified by western blot assay. The phosphorylation level of Smad2 and Smad3 was detected by immunocytochemistry. The DNA binding activities of SP-1, AP-1 and NF-κB were measured by both EMSA and ArrayStar transcription factor activity assay. RESULTS: 18α-GA could decrease the mRNA and protein expression of Smad3, type I and III collagen, increase the Smad7 expression in human and rat HSCs (P<0.05), and reduce phosphorylation level of Smad3 at 24 h and 48 h after treatment. The DNA binding activities of transcription factors were suppressed by 18α-GA in human and rat HSCs at 24 h, and the activities reduced in a time dependent manner with the lowest activities at 48 h, especially for SP-1. CONCLUSION: 18α-GA could inhibit the mRNA and protein expression of type I and III collagen in human and rat HSCs, which may be attributed to down-regulation of Smad3, up-regulation of Smad7, and inhibition of DNA binding activities of SP-1, AP-1 and NF-κB.