Prevalence of Non-alcoholic Fatty Liver Disease Detected by Computed Tomography in the General Population Compared with Ultrasonography.

Objective To assess the prevalence and clinical correlates of non-alcoholic fatty liver disease (NAFLD) identified by computed tomography (CT) in the general population compared with ultrasonography (US). Methods Four hundred and fifty-eight subjects who received health checkups at Meijo Hospital in 2021 and underwent CT within a year of US in the past decade were analyzed. The mean age was 52.3±10.1 years old, and 304 were men. Results NAFLD was diagnosed in 20.3% by CT and in 40.4% by the US. The NAFLD prevalence in men was considerably greater in subjects 40-59 years old than in those ≤39 years old and in those ≥60 years old by both CT and US. The NAFLD prevalence in women was substantially higher in the subjects 50-59 years old than in those ≤49 years old or those ≥60 years old on US, while no significant differences were observed on CT. The abdominal circumference, hemoglobin value, high-density lipoprotein cholesterol level, albumin level, and diabetes mellitus were independent predictors of NAFLD diagnosed by CT. The body mass index, abdominal circumference, and triglyceride level were independent predictors of NAFLD diagnosed by the US. Conclusion NAFLD was found in 20.3% of CT cases and 40.4% of US cases among recipients of health checkups. An "inverted U curve" in which the NAFLD prevalence rose with age and dropped in late adulthood was reported. NAFLD was associated with obesity, the lipid profile, diabetes mellitus, hemoglobin values, and albumin levels. Our research is the first in the world to compare the NAFLD prevalence in the general population simultaneously by CT and US.

Independent evolution of multi-dominant viral genome species observed in a hepatitis C virus carrier.

The viral genome quasispecies composition of hepatitis C virus (HCV) could have important implications to viral pathogenesis and resistance to anti-viral treatment. The purpose of the present study was to profile the HCV RNA quasispecies. We developed a strategy to determine the full-length HCV genome sequences co-existing within a single patient serum by using next-generation sequencing technologies. The isolated viral clones were divided into the groups that can be distinguished by core amino acid 70 substitution. Subsequently, we determined HCV full-length genome sequences of three independent dominant species co-existing in the sequential serum with a 7-year interval. From phylogenetic analysis, these dominant species evolved independently. Our study demonstrated that multiple dominant species co-existed in patient sera and evolved independently.

Prevalence of nonalcoholic fatty liver disease and its association with age in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a risk factor for nonalcoholic fatty liver disease (NAFLD). AIM: To determine the prevalence and clinical correlates of NAFLD in a large cohort of patients with T2DM. METHODS: Four hundred thirty-seven participants with T2DM who consulted at Meijo Hospital from April 2019 to September 2020 and underwent computed tomography (CT) were assessed. The mean age was 74 ± 13 years, and 269 were men. Hepatic attenuation minus splenic attenuation (CTL-S) less than 1 Hounsfield unit was considered fatty liver. NAFLD was defined as fatty liver in the absence of significant alcohol consumption and hepatitis virus infection. A multiple logistic regression was used to assess the independent factors associated with NAFLD. RESULTS: NAFLD was identified in 25.2% of the participants. Young age (odds ratio [OR] = -0.945; 95% confidence interval [CI]: 0.922-0.969), higher hemoglobin levels (OR = 1.501, 95%CI: 1.278-1.764), lower high-density lipoprotein (HDL) cholesterol levels (OR = 0.971, 95%CI: 0.953-0.989), and the absence of dialysis (OR = 0.109, 95%CI: 0.014-0.856) were independent predictors of NAFLD. CONCLUSION: NAFLD was detected with CT in 25.2% of the participants. NAFLD was associated with younger age, higher hemoglobin levels, lower HDL cholesterol levels, and an absence of dialysis.

The case of a liver-transplant recipient with severe acute respiratory syndrome coronavirus 2 infection who had a favorable outcome.

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in 2019; thereafter, the COVID-19 outbreak became a health emergency of international concern. The impact of COVID-19 on liver-transplant recipients is unclear. Thus, it is currently unknown whether liver-transplant recipients are at a higher risk of developing complications related to COVID-19. Here, we report the case of liver-transplant recipients who were infected with SARS-CoV-2. A 20-year-old man who had undergone living-donor liver transplantation from his father at 5 years of age because of congenital biliary atresia was referred to our hospital for SARS-CoV-2 infection. Chest computed tomography did not show any abnormalities; however, laboratory results revealed liver dysfunction. He received tacrolimus as maintenance therapy that was continued at the same dose. He has not developed severe pulmonary disease and was discharged after 10 days of hospitalization. Limited data are available on post-transplant patients with COVID-19, and this case of a young patient without metabolic comorbidities did not show any association of severe COVID-19 under tacrolimus treatment. The progression of COVID-19 in liver-transplant recipients is complex, and COVID-19 risk should be evaluated in each patient until the establishment of optimal guidelines.

The role of early video capsule endoscopy in the diagnosis and prognosis of obscure gastrointestinal bleeding: A multi-center propensity score matching study.

BACKGROUND AND AIM: Video capsule endoscopy (VCE) is a first-line procedure for the diagnosis of obscure gastrointestinal bleeding (OGIB). The opinions on the timing for such diagnostic evaluation remain unclear. We aimed to explore the role of early VCE in OGIB patients. METHODS: A total of 997 patients that underwent VCE at Renji Hospital and Nagoya University from May 15, 2002, to December 28, 2016, were included in this study. We matched patients that underwent early VCE within 14 days of bleeding (early group, n = 678) to patients that did not (late group, n = 319) via 1:1 propensity score matching (PSM). We then compared VCE diagnostic rates and the prevalence of post-VCE rebleeding in patients with initial negative VCE findings within 1 year between these groups before and after PSM. RESULTS: Following PSM, early VCE was associated with a significantly higher rate of OGIB diagnosis (56.4% vs 45.5%, P = 0.001) and with a significantly lower incidence of rebleeding within 1 year following treatment (24.7% vs 36.7%, P = 0.041). In univariate and multivariate analyses, VCE timing (odds ratio 0.648; 95% confidence interval 0.496-0.847, P = 0.001 and odds ratio 0.666; 95% confidence interval 0.496-0.894, P = 0.007, respectively) was found to be linked with a higher rate of positive findings. CONCLUSION: Early VCE can improve the reliability of OGIB diagnosis while also reducing rates of post-VCE rebleeding. This suggests that timely and accurate diagnosis can help to improve OGIB patient treatment and prognosis.

Tag-less patency capsule for suspected small bowel stenosis: Nationwide multicenter prospective study in Japan.

STUDY AIMS: The PillCam patency capsule (PPC) is an Agile tag-less patency capsule used to evaluate gastrointestinal (GI) patency. We determined the appropriate use of PPC to preclude subsequent small bowel capsule endoscopy (SBCE) retention. METHODS: This prospective multicenter study consecutively enrolled patients indicated for SBCE with suspected or established small bowel stenosis. Excretion of an intact PPC or its radiologic visualization in the large bowel was considered GI patency. Primary and secondary study endpoints were SBCE retention rates in patients with confirmed patency and identification of factors associated with patency and SBCE retention, respectively. RESULTS: Of 1096 patients enrolled in the study, patency was confirmed in 976 (89.1%). PPC excretion occurred in 579 patients. Of the remaining 517 patients, patency was confirmed using imaging modalities in 401 (77.5%). SBCE retention occurred in five (0.51%) of 963 patients who underwent SBCE: 1.0% in established Crohn's disease (CD) patients, 0% in suspected CD, 0% in tumors, and 1.6% in patients with obscure GI bleeding, for which PPC localization had been radiographically misinterpreted. The non-confirmation of patency was associated with established CD, stenosis identified using imaging modalities, abdominal fullness, serum albumin levels <4.0 g/dL, and previous small bowel obstruction (adjusted odds ratios: 4.21, 2.60, 2.47, 2.12, and 2.00; 95% confidence intervals: 2.62-6.78, 1.62-4.17, 1.43-4.27, 1.32-3.40, and 1.15-3.47, respectively). CONCLUSIONS: The PillCam™ patency capsule helped preclude SBCE retention in most patients, but its accurate localization was essential for cases without excretion (Study registered the University Hospital Medical Information Network, #UMIN000010513).

Low ETV1 mRNA expression is associated with recurrence in gastrointestinal stromal tumors.

Although the majority of gastrointestinal stromal tumors (GISTs) possess KIT mutations that induce constitutive signal transduction, the clinical outcomes are variable. The ETS translocation variant 1 (ETV1) gene encodes a transcription factor that is reported to cooperate with KIT in GISTs. However, the clinical role of ETV1 is largely unknown. The aim of this study was to examine ETV1 expression and its associations with clinical features in GISTs. We conducted a cohort study involving 64 patients with GISTs who underwent surgical resection between October 2008 and February 2015. ETV1 mRNA expression was compared with that in non-GISTs and was analyzed among risk classifications or clinical outcomes. The GIST samples exhibited significantly higher ETV1 mRNA expression than the non-GIST samples (P < 0.0001). Sixty-four GISTs were stratified into high or low ETV1 mRNA expression groups based on the median relative abundance of ETV1 mRNA. The multivariate analysis showed that low ETV1 expression, as well as tumor size and mitotic index, was an independent factor of recurrence (hazard ratio: 8.1). Patients with high ETV1 expression achieved significantly longer recurrence-free survival (RFS) times than those with low ETV1 expression (P = 0.025). Our study revealed that low ETV1 expression is an independent factor of recurrence after surgery in patients with GISTs, and thus, low ETV1 expression might be a marker of more aggressive malignant GISTs.

Detection of indocyanine green fluorescence to determine tumor location during laparoscopic gastrectomy for gastric cancer: Results of a prospective study.

INTRODUCTION: In laparoscopic gastrectomy, a method to locate the margin of an early-stage cancerous lesion that is invisible from the serosal surface and impalpable during laparoscopic procedures is needed to determine an appropriate transection line. We conducted a prospective study to develop a new marking method using preoperative submucosal injection of indocyanine green (ICG). METHODS: Patients undergoing laparoscopic gastrectomy for T1 gastric cancer were recruited. The first 11 patients comprised the learning set and the subsequent 18 patients the validation set. ICG was endoscopically injected in the submucosal layer of the stomach approximately 1 cm away from the tumor edge 1 or 3 days before surgery. The diameters of the visualized ICG were compared with those of a conventional marking method using India ink in 10 historical controls. RESULTS: In the learning set, the optimal amount of ICG was determined to be 0.1 mL at a concentration of 0.5 mg/mL. In the validation set, the same procedure was repeated. No technical problems or adverse reactions related to ICG injection were observed. In all cases, ICG was successfully detected, and negative surgical margins were pathologically confirmed. The mean long diameter of the visualized ICG fluorescence measured at the mucosal surface of the stomach was significantly smaller in the current study than in the historical controls in whom India ink was used (21 vs 52 mm, P < 0.0001). CONCLUSIONS: The preoperative submucosal ICG marking was safely performed and successfully detected without excessive blurring during laparoscopic gastrectomy.

Generation of magnifying endoscopic images of gastric neoplasms based on an all-in-focus algorithm.

BACKGROUND AND AIM: Magnifying endoscopy is useful for diagnosis of early gastrointestinal neoplasms by visualizing microvascular (MV) and microsurface (MS) structures of the mucosa when combined with image-enhanced endoscopy. However, precise control of the endoscope is needed because the depth of focus is narrow and the target may move. These problems may be overcome by the all-in-focus (AIF) technique, which was developed in the engineering field. The aim of the study was to evaluate magnifying endoscopic image with AIF algorithm. METHODS: Twenty gastric neoplasms were examined. Images were acquired at 80× magnification and converted to endoscopic images with an AIF algorithm (EI-AIF). The focus area and MV and MS patterns in the original image and the EI-AIF were compared on a 5-point Likert scale, where 5 indicates that the EI-AIF was superior. Intraclass correlation coefficients (ICCs) were used to assess the inter-evaluator reliability. An image quality measurement value was calculated for each image as an indicator of the degree of focus. RESULTS: The scores for focus area, MV, and MS were 4.78 ± 0.45 (ICC = 0.63), 4.12 ± 0.76 (ICC = 0.70), and 4.72 ± 0.52 (ICC = 0.45), respectively, with the EI-AIF significantly superior for all three items (P < 0.05 by Student's t-test). ICCs for the focus area and MV were > 0.60, indicating strong inter-evaluator reliability. Image quality measurement was higher for the EI-AIF compared with the original image in every case. CONCLUSIONS: Endoscopic observation with AIF algorithm gives a better image quality that allows easier evaluation of MV and MS patterns. This technique may resolve the difficulties with magnifying endoscopic observation.

An International Study on the Diagnostic Accuracy of the Japan Narrow-Band Imaging Expert Team Classification for Colorectal Polyps Observed with Blue Laser Imaging.

BACKGROUND: The Japan narrow-band imaging Expert Team (JNET) classification of colorectal polyps based on magnifying endoscopy is used in Japan, but not worldwide. The objective of this study was to clarify differences of diagnostic accuracy between JNET users in Japan and non-JNET users in other countries. METHODS: A total of 185 colorectal tumors were assessed. Six endoscopists (3 each from Japan and Taiwan) participated in the study. The Japanese endoscopists normally used the JNET classification and the Taiwanese endoscopists normally used the narrow-band imaging International Colorectal Endoscopic classification for diagnosis of colorectal tumors. After receiving a lecture on the JNET classification, they all observed one blue laser imaging magnified image per lesion and performed diagnosis based on the JNET classification. RESULTS: Diagnostic ability was equivalent for Type 1, Type 2A, and Type 2B. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of Type 3 for deep submucosal invasive carcinoma was, respectively, 44.4, 98.3, 57.1, and 97.2% in Group J and 70.0, 94.7, 40.4, and 98.4% in Group T. The PPV for diagnosis of Type 3 with a high confidence was significantly higher in Group J than in Group T (81.8% [55.4-94.6] vs. 44.4% [33.6-50.9], p < 0.05). CONCLUSIONS: The PPV for Type 3 differed between the 2 groups, suggesting the need to become familiar with differentiation between Type 2B and Type 3.

The Prevalence of Mixed Hepatitis C Virus Genotype Infection and Its Effect on the Response to Direct-Acting Antivirals Therapy.

BACKGROUND: The incidence of mixed hepatitis C virus (HCV) genotype infection is variable, and a few reports exist regarding the efficacy of direct-acting antivirals (DAA) therapy for mixed genotype. We aimed to investigate the prevalence of mixed genotype and its impact on the virologic response to DAA therapy. METHODS: A total of 365 patients with chronic HCV infection who completed antiviral therapy were recruited. Nested polymerase chain reaction with universal and specific primers of genotypes 1b and 2 and direct sequencing were used for HCV genotyping. RESULTS: Direct sequencing with universal primers defined genotypes 1b (n = 230), 2a (n = 95), and 2b (n = 40). Direct sequencing of genotype 2 was performed in patients with genotype 1b, and direct sequencing of genotype 1b in patients with genotype 2. Four patients with genotype 1b underwent amplification for genotype 2, and direct sequencing identified genotypes 1b (n = 1), 2a (n = 1), and 2b (n = 2). None with genotype 2 underwent amplification for genotype 1b. Three cases were confirmed to have mixed genotype. CONCLUSIONS: Mixed genotype was rare, and hence the impact of mixed genotype on treatment outcome with DAA therapy is expected to be minimal.

Phase II study of chemoradiotherapy combined with gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic ductal adenocarcinoma (NUPAT 05 Trial): study protocol for a single arm phase II study.

The efficacy of nab-paclitaxel combined with gemcitabine (GnP) and of chemoradiotherapy (CRT) for unresectable locally advanced pancreatic ductal adenocarcinoma (UR-LA PDAC) is still unclear. We previously conducted a phase I study of CRT using GnP and determined the recommended dose and have now designed a phase II trial to evaluate the efficacy of CRT incorporating GnP for UR-LA PDAC. Eligibility criteria are chemotherapy-naïve patients with UR-LA PDAC as defined by the NCCN guidelines version 2. 2016. Study patients will receive 100 mg/m2 nab-paclitaxel and 800 mg/m2 gemcitabine on Days 1, 8, and 15 per 4-week cycle with concurrent radiation therapy (total dose of 50.4 Gy in 28 fractions of 1.8 Gy per day, 5 days per week). Treatment will be continued until disease progression or surgery, which is to be performed only for patients in whom the disease is well-controlled at 8 months from beginning the protocol treatment. Primary endpoint is 2-year overall survival rate and co-primary endpoint is resection rate. Secondary endpoints are overall survival, progression free survival, time to treatment failure, response rate, disease control rate, early tumor shrinkage, depth of response, reduction of SUV-max on PET-CT, serum tumor markers, relative dose intensity, safety, and Quality of life. This study will show the efficacy and safety of chemoradiotherapy combined with GnP.

The utility of ultrathin endoscopy with flexible spectral imaging color enhancement for early gastric cancer.

Many researchers suggested that ultrathin endoscopy improves patient acceptance of endoscopic examinations. However, ultrathin endoscopy provides less image resolution and luminous intensity. Therefore, we focused on the visibility of early gastric cancer on ultrathin endoscopy with Flexible spectral imaging color enhancement (FICE) in this study. Thirty-six patients with early gastric cancer were prospectively enrolled. One endoscopist performed the endoscopic examinations by white light conventional endoscopy (W-CE), white light ultrathin endoscopy (W-UE), FICE ultrathin endoscopy (F-UE) and white light plus FICE ultrathin endoscopy (WF-UE) in the patients. Four other endoscopists were asked to evaluate the visibility of gastric cancer on the W-CE, W-UE, F-UE and WF-UE images with a 5-point Likert scale. The lesions were classified as uncolored, normocolored or reddish. We examined the color difference between early gastric cancer and the surrounding mucosa. To examine the relationship between the color difference and the vessel density, we also measured the difference in vessel density using pathologic specimens stained with hematoxylin and eosin. The Likert score of WF-UE was significantly higher than those of the other three methods (p<0.001). The color difference of F-UE was higher than that of W-CE in the reddish group (p=0.049). The difference in vessel density was higher in the reddish group than in the normocolored group (p=0.048). In conclusion, the visibility of early gastric cancer from the surrounding mucosa using ultrathin endoscopy with FICE was better than that using white light conventional endoscopy, especially for reddish lesions.

Increased hardness of the underlying pancreas correlates with the presence of intraductal papillary-mucinous neoplasm in a limited number of cases.

PURPOSE: Pancreatic fibrosis or fibrosing reactions have been reported in intraductal papillary-mucinous neoplasm (IPMN) patients. We assessed whether a higher elastic modulus (EM) measured using shear wave elastography (SW-EG) correlated with the existence of branch-duct (BD) IPMN. METHODS: In total, 183 normal pancreas (NP) and 123 BD-IPMN cases were enrolled. First, we assessed the difference in pancreatic EM (PEM) at different sites (head or tail side of the cyst). Second, a comparison was done between the median PEM of the NP and the BD-IPMN cases. Receiver-operating characteristic analysis was performed to determine the BD-IPMN diagnostic capabilities. Finally, in patients whose cyst was not visualized, the test-positive rate was determined. RESULTS: No significant difference was seen between the cyst head side PEM (4.61 kPa) and the tail side PEM (5.35 kPa) (P = 0.471). Among these cases matched by age, 73 were selected each from NP and BD-IPMN cases (median age 65 years). The median PEM of the BD-IPMN cases (5.18 kPa) was significantly higher than that of the NP cases (3.17 kPa) (P < 0.001). When the cut-off value was set at 4.75 kPa, the sensitivity, specificity, PPV, NPV, and accuracy were 75.3%, 64.4%, 72.3%, 67.9%, and 69.9%, respectively. The cut-off value of 4.75 kPa helped for the indirect selection of BD-IPMN patients (10/17, 58.8%) whose cyst was not detected on B-mode ultrasonography. CONCLUSION: SW-EG measurement of the underlying pancreatic parenchyma may correlate with the presence of BD-IPMN.

Colorectal endoscopic submucosal dissection in special locations.

Colorectal endoscopic submucosal dissection (ESD) is considered one of the most challenging endoscopic procedures for novice endoscopists. When compared with the stomach, the colon and rectum have a narrower tubular lumen, greater angulation at the flexures, and a thinner muscle layer. These factors make endoscopic control and maneuverability difficult. ESD of the colorectum was considered more difficult than gastric and esophageal ESD. However, with learning from the experts, practicing, and selecting an appropriate technique, most of colorectal ESD could be performed successfully. Nevertheless, some colorectal locations are extremely specialized either from unique anatomy or given unstable scope position. Accordingly, the objective of this review was to provide endoscopists with an overview of the techniques and outcomes associated with ESD at these special colorectal locations. ESD at the discussed special locations of the ileo-colo-rectum was found to be feasible, and outcomes were comparable to those of ESD performed in non-special locations of the ileo-colo-rectum. Practice for skill improvement and awareness of the unique characteristics of each special location is the key to performing successful ESD.

The Propagation Display Method Improves the Reproducibility of Pancreatic Shear Wave Elastography.

Evaluation of the pancreatic elastic modulus (PEM) using shear wave elastography (SWE) requires at least 5 measurements to ensure reproducibility. The aim of this study was to evaluate improvement in reproducibility of SWE, using the propagation display method in normal pancreas ([NP] phase 1) and to examine the differences in PEM between NP and chronic pancreatitis (CP), intraductal papillary mucinous neoplasm (IPMN) and autoimmune pancreatitis ([AIP] phase 2). In phase 1, the measurement success rate, median PEM in repeated measurements and appropriate number of SWE measurements were determined in 109 cases with NP. In phase 2, PEM was measured in CP (n = 10), IPMN (n = 31) and AIP (n = 5), using the required number of SWE measurements determined in phase 1. In phase 1, the measurement success rate was 93.9% (92/109 cases). The median PEM for NP was 14.6 kPa and the appropriate number of SWE measurements was at least 3. In phase 2, the median PEMs in CP, IPMN and AIP were 19.6, 18.1 and 17.2 kPa, respectively, with significant differences between NP and CP (p = 0.0133) and between NP and IPMN (p = 0.0436). Use of the propagation display method in SWE improves the reproducibility of measurement of PEM.

Preoperative endoscopic predictors of severe submucosal fibrosis in colorectal tumors undergoing endoscopic submucosal dissection.

Background and study aims Endoscopic submucosal dissection (ESD) enables en bloc removal of colorectal neoplasms regardless of size. Submucosal fibrosis is a significant factor for technical difficulty and poor outcomes. We assessed the predictive factors for severe submucosal fibrosis and the ESD outcomes. Patients and methods Patients undergoing ESD from January 2006 to September 2017 were retrospectively reviewed. The degree of submucosal fibrosis was classified into three types: no fibrosis (F0), mild fibrosis (F1), and severe fibrosis (F2). F0 and F1 cases were grouped as non-severe fibrosis for comparison with the severe fibrosis group. Predictors of severe submucosal fibrosis and ESD outcomes were evaluated. Results ESD was performed in 524 lesions (60 % male; mean age, 67.8 years). Eighty lesions with severe fibrosis (15.3 %) were observed. The overall en bloc resection rate and curative resection rate were 94.3 % and 77.7 %, respectively. Rates of en bloc resection (91.2 % vs. 94.8 %, P  = 0.2) and perforation (7.5 % vs. 5.6 %, P  = 0.45) were no different between severe fibrosis and non-severe fibrosis groups. However, incidences of non-curative resection and low resection speed were significantly higher in the severe fibrosis group. Among protruding lesions, tumor height and volume were significantly greater in the severe counterparts. A diameter ≥ 40 mm, endoscopic finding of the tumor beyond fold, and fold convergence were independent risk factors for severe fibrosis. Conclusions Severe submucosal fibrosis is a significant risk factor for non-curative resection and a long procedural time. Tumor size and morphology might help to predict the severity of fibrosis.

ATAD2 is associated with malignant characteristics of pancreatic cancer cells.

Pancreatic cancer is one of the most aggressive human cancers and is associated with a poor prognosis. To develop a novel strategy for pancreatic cancer treatment, it is essential to elucidate the molecular mechanisms underlying the invasion and proliferation of cancer cells. ATPase family AAA domain containing protein 2 (ATAD2) is a highly conserved protein with an AAA+ domain and a bromodomain. Accumulating studies have demonstrated that ATAD2 is associated with the progression of multiple cancers. The present study demonstrated that ATAD2 depletion suppressed cell invasion and migration. In addition, ATAD2 knockdown suppressed anchorage-independent growth of pancreatic cancer cells. Finally, ATAD2 depletion was demonstrated to sensitize pancreatic cancer cells to gemcitabine. The results of the present study indicate that ATAD2 is involved in the malignant characteristics of pancreatic cancer.

Antifibrotic Effects of 1,25(OH)2D3 on Nonalcoholic Steatohepatitis in Female Mice.

BACKGROUND: Postmenopausal women have a higher risk of nonalcoholic steatohepatitis (NASH) along with an increase in age, and vitamin D deficiency occurs in some patients with NASH. AIM: We performed ovariectomy (OVX) surgery on female mice to mimic menopause, fed them a choline-deficient high-fat (CDHF) diet to induce NASH, and then investigated the effects of treatment with 1,25(OH)2D3. METHODS: Seven-week-old C57BL/6J female mice were separated into five experimental groups: SHAM, OVX, and OVX + intraperitoneal (i.p.) injection of 1,25(OH)2D3 (0.0008, 0.004, and 0.02 µg/kg). All groups were fed a CDHF diet for 8 weeks. Injections took place twice per week throughout the experimental period. Blood samples and liver tissue were collected for analyzing liver histological changes, serum biochemical indicators of hepatic function, and hepatic genes associated with fibrosis. RESULTS: Supplementation of 1,25(OH)2D3 in CDHF-diet mice showed decreased serum levels of ALT, AST, indicating the improvement in overall liver function, and suppressed histological NASH regarding fibrosis stage, lobular inflammation, and steatosis compared to the OVX group. Primary fibrotic markers of TGF-ß, TIMP-1, α-SMA, and COL1A1 were significantly lower in the 1,25(OH)2D3 groups than in the OVX group. Furthermore, down-regulated levels of SMAD2 and SMAD3 were also observed in 1,25(OH)2D3 groups. CONCLUSION: Supplementation of 1,25(OH)2D3 may ameliorate liver fibrosis and improve liver function in OVX mice with NASH induced by a CDHF diet, suggesting the therapeutic effects on postmenopause with NASH.

Influence of proton pump inhibitors on microbiota in chronic liver disease patients.

BACKGROUND: Current knowledge suggests that proton pump inhibitors (PPIs) are associated with an increased risk of hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). These conditions and PPI use are related to gut microbiota. The aim of this study is to research the changes in gut microbiota caused by PPI in patients with chronic liver disease. METHODS: From 198 Japanese patients, 31 patients in the PPI and non-PPI groups were matched using propensity score matching (PSM) based on age, sex, and Child-Turcotte-Pugh class. We investigated the gut microbial composition of stool samples using the Illumina MiSeq sequencing platform and compared them using linear discriminant analysis effect size and phylogenetic investigation of communities by reconstruction of unobserved states. RESULTS: Before PSM, Child-Turcotte-Pugh score (p = 0.038), ascites (p = 0.049), encephalopathy (p = 0.023), and esophageal varices (p < 0.01) were significantly higher in the PPI group than in the non-PPI group. After PSM, six genera, consisting of Lactobacillus, Streptococcus, Selenomonas, Veillonella, Campylobacter, and Haemophilus were enriched in the PPI group. Eggerthella, Paraprevotella, Turicibacter, Dorea, Anaerotruncus, and Ruminococcus were less abundant in the PPI group. We identified five types of level 3 KEGG pathways predicted to be significantly different. CONCLUSIONS: Part of microbial changes caused by PPI use was common to the changes by progression of liver cirrhosis. Increases in oral bacterial flora and decreases in autochthonous flora may produce the intestinal environment which tends to make the risk factor for HE or SBP.