Showing papers in "Digestive Diseases in 2021"

Biomarkers of inflammation in Inflammatory Bowel Disease: how long before abandoning single-marker approaches?

Abstract: Background Inflammatory bowel disease (IBD) is a chronically relapsing disease with a continuous need for proactive monitoring to decide appropriate treatments and follow-up strategies. To date, gastrointestinal endoscopy with histological examination of biopsies and contrast-enhanced imaging are mandatory techniques for the diagnosis and the activity assessment of IBD. Summary In recent decades, many research efforts in the IBD field have been placed on finding non-invasive and reliable biomarkers of disease burden that can be easily tested in body fluids without impacting the quality of life of patients. Unfortunately, the ideal biomarker is yet to be discovered and recent studies have investigated the possibility to increase the accuracy of such measurements by combining different markers. In this review, we provide an update about the current knowledge on biomarkers of intestinal inflammation in IBD, focusing on disease diagnosis, correlation with endoscopic findings and prediction of relapse. We also summarise composite scores of clinical and laboratory markers that have been recently proposed in various scenarios of disease activity. Key messages To date, only C-reactive protein and faecal calprotectin can be considered reliable markers of disease activity with demonstrated utility in IBD management. The combination of different parameters has recently shown higher accuracy and might substitute single-marker approaches in the future of research and clinical practice.

NASH/liver fibrosis prevalence and incidence of non-liver comorbidities among people with NAFLD and incidence of NAFLD by metabolic comorbidites: Lessons from South Korea.

Abstract: BACKGROUND NAFLD incidence, NASH prevalence, NAFLD fibrosis prevalence, incidence of metabolic comorbidities, and mortality data in the NAFLD population remain limited AIMS We used a meta-analytic approach to "stage" NAFLD among the Korean population METHODS We searched PubMed, Embase, Cochrane Library, and KoreaMed from inception until June 29, 2019, and calculated pooled estimates via the random-effects model RESULTS We screened 1,485 studies and analyzed 191 eligible studies: 179 (3,556,579 participants) for NAFLD prevalence and outcome analysis and 32 (1,089,785 participants) for NAFLD incidence analysis NAFLD prevalence was 3146% overall and 50-60% in those with metabolic risks The incidence (per 1,000 person-years) of NAFLD was 428 overall and 70-77% in those with metabolic risk The incidence (per 1,000 person-years) of new-onset T2DM, hypertension, cardiovascular disease, and chronic kidney disease was found to be 169, 479, 1006, and 139, respectively From biopsy data, 3021% of the NAFLD population had moderate-to-severe steatosis (9 studies, 2,461 participants) and 5227% had NASH (7 studies, 1,168 participants) and 8541% had fibrosis

The Behavior of MMP-2, MMP-7, MMP-9, and Their Inhibitors TIMP-1 and TIMP-2 in Adenoma-Colorectal Cancer Sequence.

Abstract: BACKGROUND We and others have previously shown that matrix metalloproteinases (MMPs) play a role in colorectal cancer (CRC) invasion and metastasis. However, the serum changes of various MMPs and their inhibitors (TIMPs) have scarcely been concomitantly investigated in identical blood samples in the normal colon-adenoma-CRC sequence. METHODS The MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 serum antigen concentrations were determined concomitantly in 19 tumor-free control patients, 19 patients with high-risk colorectal adenoma, and 47 patients with CRC by ELISA technique. The analyzed parameters were also investigated in correlation with CRC stages. Statistical analysis with one-way ANOVA and Student's t test was performed. p values <0.05 were considered significant. RESULTS Serum antigen levels of MMPs and TIMPs were significantly increased in patients with CRC and adenomas compared to controls (mean values, ng/mL) (MMP-7: 5.88, 4.44, and 2.89, respectively, p = 0.001; MMP-9: 1,075.81, 999.22, and 845.97, respectively, p = 0.01; TIMP-1: 241.80, 205.98, and 166.53, respectively, p = 0.001; TIMP-2: 83.40, 80.30, and 69.62, respectively, p = 0.01). The elevated serum MMP-7, MMP-9, TIMP-1, and TIMP-2 levels significantly correlated with advanced tumor stages (p < 0.05). No statistically significant differences were observed in MMP-2 levels. CONCLUSIONS We demonstrate that serum antigen concentrations of MMP-7, MMP-9, TIMP-1, and TIMP-2 were significantly increased in patients with CRC and adenomas compared to controls. These results suggest that MMPs and their inhibitors TIMP-1 and TIMP-2 play an important role in CRC invasion; however, they are also activated in premalignant adenomas. Furthermore, MMP-7, MMP-9, TIMP-1, and TIMP-2 may have a potential prognostic impact in CRC.

Mild versus Severe Liver Injury in SARS-CoV-2 Infection

Abstract: BACKGROUND: Abnormal liver function has been reported in patients with COVID-19 infection The aim of our study was to report on the prevalence of liver injury in our cohort, to evaluate the association of mild versus severe liver injury with mortality in COVID-19 patients and to scrutinize the temporal pattern of viral detection and liver injury METHODS: We present data from a German cohort of 147 SARS-CoV-2 infected patients The patients were divided into 3 groups according to their liver status during treatment The first group included patients without elevated alanine aminotransferase or bilirubin, the third group patients meeting the biochemical criteria of acute liver failure (ALF), and the second group all other patients RESULTS: Liver injury was detected in 75 (50 7%) and 93 (63%) patients by admission and during treatment, respectively ALF was associated with the male sex, younger age, and higher BMI Mortality was associated with the presence of ALF (OR = 9 423, 95% CI: 2 410-36 858) in contrast to milder liver injury (OR 1 101, 95% CI: 0 435-2 791) In 30% of patients with mild liver injury and in 50% of ALF patients, peak liver injury was observed at a time point when the virus was no longer detectable in the respiratory tract CONCLUSION: Mild liver injury was not associated with worse outcome in our cohort, and the pattern of liver injury did not fit well to the theory of SARS-CoV-2 directly causing liver impairment Instead, severe liver injury in our cohort was associated multiple-organ failure and acute vascular events

Validity of International Classification of Diseases, Tenth Revision, Codes for Cirrhosis.

Abstract: Introduction Accurate identification of patients with cirrhosis is important for research using administrative databases. We aimed to examine the accuracy of several major ICD-10 codes for cirrhosis diagnosis in a large and diverse patient cohort; there is little existing research on this topic. Methods Using data from 3396 patients with chronic liver disease (hepatitis B, C or non-alcoholic fatty liver disease) from one university and several community medical centers, we calculated sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUROC) for several major ICD-10 codes for cirrhosis, which was verified by individual chart review. We performed a secondary validation in a general cohort of 1560 randomly selected patients. Results While each of the individual study ICD-10 codes were specific (98.08 - 100%), none of the codes were sufficiently sensitive (0.27 - 55.70%). PPVs were high in the chronic liver disease cohort (88.41 - 100%) but lower in the general population (55.53 - 66.76%). The AUROC for having at least one code was higher (0.79) than any code alone (0.50 - 0.65). Discussion/conclusion Individual ICD-10 codes are suboptimal for identifying patients with cirrhosis in the general patient population. We recommend conditioning ICD-10 code searches with a chronic liver disease diagnosis code and/or combining diagnostic codes to maximize performance.

Real-Life Comparison of Different Anti-TNF Biologic Therapies for Ulcerative Colitis Treatment: A Retrospective Cohort Study

Abstract: Background: Head-to-head comparison studies evaluating the effectiveness and tolerability of anti-tumor necrosis factor (anti-TNF) drugs in inflammatory bowel disease patients are lacking. Aim: To compare the effectiveness and tolerability of anti-TNF-α drugs used in clinical practice in a cohort of patients with moderate-to-severe ulcerative colitis (UC). Methods: Retrospectively, 122 UC patients treated with infliximab (IFX) originator and biosimilar, adalimumab (ADA), and golimumab (GOL) were included. We performed an ITT analysis to evaluate clinical response and remission, steroid-free clinical remission, and endoscopy response according to the different time points of the follow-up. Baseline and post indErledigt ((Please, could you write "post induction" and remove "postinduction"?))uction predictor factors of these outcomes were evaluated using multivariate logistic regression models. Moreover, a propensity score-based weighting analysis was performed. Data were analyzed using R and STATA11 software. Results: The overall clinical response was 77% after induction, 81.4% at 30 weeks, and 76.9% at 52 weeks, while the steroid-free clinical remission was 39.7, 46, and 54.6%, respectively. After induction, a higher rate of treatment failure was observed in the GOL group. At the end of follow-up, lower rates of steroid-free clinical remission and clinical response were obtained by GOL. At week 52, endoscopic response was achieved by 46.5% of the population. Conclusions: Among the different anti-TNF treatments, moderate-to-severe UC seems to respond better to IFX and ADA, whereas GOL seems to be less effective, despite a similar good safety profile.

Prevalence, Resistance Rates, and Risk Factors of Pathogens in Routine Bile Cultures Obtained during Endoscopic Retrograde Cholangiography.

Abstract: INTRODUCTION AND OBJECTIVE Acute cholangitis is a life-threatening condition. The early initiation of antibiotic therapy significantly impacts the course of disease. Only few data are available on distribution and resistance profiles of bile pathogens. Here, we report on an analysis of routinely acquired bile specimens and provide an overview of the prevalence, resistance rates, and risk factors for the presence of pathogens in bile. METHODS Bile cultures obtained from 388 endoscopic retrograde cholangiographies (ERCs) with corresponding clinical data were analysed in 208 patients. RESULTS The majority (84.8%) of cultures yielded positive for at least 1 organism. Abundance was highest for Enterococcus faecalis, Enterococcus faecium, and Escherichia coli. Multiresistant organisms were present in 14.9%. The initial antibiotic regimen was changed in 44.1%, which increased the length of hospital stay significantly (***p < 0.001). Pre-existing papillotomy (EPT) or biliary drainage was associated with higher frequency of bile pathogens (**p < 0.01) in a univariate analysis. Multivariate analysis confirmed these results for EPT and revealed significantly more positive results for pathogens, gram-negative bacteria, and fungi in patients with biliary drainage. Significant differences in the prevalence of pathogens were observed between relevant subgroups of ERC indications. The highest susceptibility rates were observed for linezolid and tigecycline in gram-positive bacteria and for meropenem and gentamicin in gram-negative bacteria. CONCLUSIONS Our study provides a comprehensive analysis of the distribution, resistance profiles, and risk factors for the detection of bile pathogens. The frequent change in initial antibiotic treatment highlights the importance of routine bile culture and indicates that current schemas of empirical treatment might not cover the contemporary spectrum of pathogens in bile.

High Prevalence of Small Intestinal Bacterial Overgrowth among Functional Dyspepsia Patients.

Abstract: BACKGROUND Small intestinal bacterial overgrowth (SIBO), characterized by either increased numbers or presence of colonic type bacteria in the small bowel has been previously described in functional dyspepsia (FD), based on breath testing. In this study, we aim to examine the prevalence of SIBO among FD patients using small bowel aspirate culture. METHODS We prospectively enrolled outpatients fulfilling Rome IV criteria for FD. Severity of symptoms was graded using the patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) questionnaire. Patients underwent upper gastrointestinal endoscopy and duodenal fluid was aspirated in sterile traps. SIBO was defined as ≥103 colony forming units/mL of duodenal aspirate and/or presence of colonic type bacteria. Patients undergoing gastroscopy due to gastroesophageal reflux symptoms - control group (CG) - and patients with irritable bowel syndrome (IBS) fulfilling Rome IV criteria were also recruited. RESULTS We enrolled 227 FD subjects, 30 CG, and 90 IBS patients. Among FD patients, 144 (63.4%), 64 (28.2%), and 19 (8.4%) had postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and overlapping PDS-EPS syndrome, respectively. SIBO prevalence was 20.8%, 12.5%, and 31.6% among PDS, EPS, and overlapping PDS-EPS FD subtypes, respectively. Overall, SIBO prevalence was significantly higher in FD (44/227 [19.4%]) compared to CG (1/30 [3.3%]) (p = 0.037) and similar to IBS (44/227 [19.4%] vs. 15/90 [16.7%], p = 0.63) subjects. SIBO presence was associated neither with total nor with any subscale score of the PAGI-SYM questionnaire. CONCLUSION In a cohort of Greek FD patients, SIBO prevalence was similar to that of IBS subjects and higher compared to that of controls.

Increasing Age and Nonliver Comorbidities in Patients with Chronic Hepatitis B in Taiwan: A Nationwide Population-Based Analysis.

Abstract: BACKGROUND Data from the USA suggest that chronic hepatitis B (CHB) patients have aged in the past decade. However, the burden of nonliver comorbidities has not been well characterized in Taiwan, where CHB is very prevalent. AIM Our study examined this issue as it presented between 2001 and 2011 in Taiwan. METHODS This study identified adult patients (≥18 years) who were diagnosed with CHB in 2001, 2006, and 2011, from the Taiwan National Health Insurance Research Database (NHIRD). Changes in demographic characteristics, prevalence of nonliver comorbidities, and medication usage over the decade were examined. Non-CHB controls were adults without CHB diagnosis from the Longitudinal Health Insurance Database 2000 (LHID2000). RESULTS A total of 102,158, 252,809, and 338,200 eligible patients were identified in 2001, 2006, and 2011, respectively. The mean age significantly advanced from 45.4 to 52.3 years over the decade (p < 0.001). The prevalence of comorbidities, including diabetes mellitus, hypertension, stroke, chronic kidney disease, and bone fracture, significantly increased between 2001 and 2011 (all p < 0.001), as so were medication usage (all p < 0.001). Moreover, within each study period, compared to non-CHB controls, CHB patients were also older and more likely to have metabolic and cardiovascular comorbidities (all p < 0.001). In addition, the annual nonliver mortality in the CHB population significantly increased from 2001 to 2011. CONCLUSIONS Over a decade, the CHB population in Taiwan has aged with a higher nonliver comorbidity burden and increasing nonliver mortality. These findings may provide information to care providers in the monitoring and management of CHB patients.

Antimitochondrial Rather than Antinuclear Antibodies Correlate with Severe Drug-Induced Liver Injury.

Abstract: Introduction A proportion of patients with drug-induced liver injury (DILI) present with autoantibodies, which has led to the current concept of autoimmune-like DILI. However, no standardized definition exits and the clinical relevance has not been studied in detail yet. Methods 1434 patients with DILI enrolled in a prospective study were analyzed. DILI diagnosis was based on the monocyte-derived hepatocyte-like (MH) cell test and supported by Roussel Uclaf Causality Assessment Method (RUCAM) and expert adjudication. Testing for antinuclear antibodies (ANA) and anti-mitochondrial antibodies (AMA) were performed using immunofluorescence. ANA titers ≥ 1:100 were considered positive and ≥ 1:400 clinically relevant; AMA positivity was considered at titers ≥ 1:100. Results 67 % exhibited ANA ≥ 1:100 and 298 % ANA ≥ 1:400; 102 % were AMA positive. There was no significant correlation between the ANA titers and the causative drug, while AMA positive patients had taken nonsteroidal anti-inflammatory drugs more frequently. No difference was seen regarding clinical characteristics or laboratory parameters in patients with ANA ≥ 1:400, while patients with positive AMA presented with higher aminotransferases, bilirubin and INR. Significantly higher proportions of patients with ANA ≥ 1:400 or AMA positivity exhibited elevated IgG levels were observed for patients with ANA ≥ 1:400 or AMA positivity. Both ANA titers ≥ 1:400 and AMA positivity but not elevated ANA titers correlated with a higher proportion of Hy's law positivity. Conclusion A closer look in a causality proven DILI cohort provided no evidence that presence of ANA titers is specific for DILI by a certain medication. AMA rather than ANA positivity was related to a more pronounced liver injury.

Influence of COVID-19 pandemic on endoscopic procedures in two European large-capacity endoscopy units: "keep calm, keep safe and scope on"?

Abstract: Background The COVID19-pandemic poses challenges to the medical system and especially to endoscopic staff and patients. National, European and International societies provided recommendations on how to safely perform endoscopic procedures during the current pandemic. Until now, the effect of the current pandemic on tertiary endoscopy centers has not been reported. Objective To analyze the influence of the early SARS-CoV2- pandemic on endoscopic care and work flow in two European tertiary endoscopy units. Methods Data from two tertiary endoscopy units (Katowice, Munich) were retrospectively collected during the early pandemic and compared to an equivalent pre-pandemic period. Data include procedures, complications, benchmarks, and influence on endoscopy training. Results During the early pandemic, we noted a highly significant decrease (49.1%) in the overall number of all endoscopies with a significant increase in therapeutic procedures. Besides, there were no significant differences in the number of urgent ERCP or interventional EUS procedures. The exceptional situation reduced endoscopic procedures performed by trainees significantly. Conclusions The SARS-CoV2-pandemic halved the endoscopy service of two tertiary centers while maintaining an urgent therapeutic service. Recommended personal safety measures in endoscopy proved to be efficient and safe in preventing SARS-CoV2 infection of staff or spreading. Unnecessarily, the SARS-CoV2 pandemic prevented routine endoscopy training.

Combination of a Probiotic and an Antispasmodic Increases Quality of Life and Reduces Symptoms in Patients with Irritable Bowel Syndrome: A Pilot Study.

Abstract: BACKGROUND Probiotics and antispasmodics have been tested extensively in the management of symptoms of irritable bowel syndrome (IBS), but they have rarely been evaluated in combination. The objective of this pilot study was to assess the efficacy of treatment with the probiotic formulation i3.1 (Lactobacillus plantarum CECT7484 and CECT7485 and Pediococcus acidilactici CECT7483), with or without the addition of the antispasmodic alverine/simethicone, in improving IBS-related quality of life (QoL) and reducing abdominal pain and diarrhea in patients with IBS. METHODS This was a randomized, placebo-controlled clinical trial with 3 parallel arms (probiotic, probiotic plus antispasmodic, and placebo). Patients with IBS (N = 55) were recruited at the Gastroenterology Department of the Juarez Hospital (Mexico City). QoL was assessed with the IBS-QoL questionnaire, abdominal pain with a visual analog scale, and stool consistency with the Bristol scale. RESULTS The IBS-QoL rate of response (ITT analysis) was 50.0% for patients in the group with probiotic alone, 68.4% in the group with probiotic plus antispasmodic, and 16.7% in the group with placebo after 6 weeks of treatment (p = 0.005). Response to abdominal pain was reported by 38.9% of patients treated with probiotic, 57.9% with probiotic plus antispasmodic, and 16.7% with placebo (p = 0.035). Regarding stool consistency, a response to treatment was reported by 44.4% of patients treated with probiotic, 57.9% with probiotic plus antispasmodic, and 16.7% with placebo (p = 0.032). CONCLUSION The results are consistent with previous studies on the use of the i3.1 probiotic formulation for the management of symptoms in IBS patients, and the addition of an antispasmodic improves its observed effects.

Natural History of Cirrhosis: Changing Trends in Etiology Over the Years.

Abstract: BACKGROUND AND GOALS The aims of the present study were to investigate the natural history of cirrhosis and to determine trends in the etiology of cirrhosis. METHODS Between January 2001 and January 2018, a total of 1,341 patients had been diagnosed with cirrhosis and were included. RESULTS A total of 898 cirrhotic patients, who were followed up for at least 6 months were included into the analysis. The median age was 54 years. The median Child-Pugh and MELD scores were 7.5 and 11, respectively. Ascites (51%) was the most common causes of decompensation. Chronic viral hepatitis was the most frequent cause of cirrhosis (58%). Hepatitis B virus (HBV) infection was the main etiology (34%), followed by hepatitis C virus (HCV) infection (18%). Among 129 patients with cryptogenic cirrhosis (CC), 60 had metabolic abnormalities. If these 60 patients with CC were considered to have nonalcoholic fatty liver disease (NAFLD)-related cirrhosis, the proportion of NAFLD-related cirrhosis increased from 1.8 to 8.0%. At admission, 74 patients (8%) had been diagnosed with hepatocellular carcinoma (HCC). A new HCC developed in 80 patients during the follow-up period. The probability of developing HCC was 3.9% at 12 months. Logistic regression analysis showed that the development of HCC was significantly associated with older age (p < 0.001), male gender (p < 0.001), viral etiology (p = 0.026), and baseline high aspartate aminotransferase level (p = 0.01). Overall, 104 cirrhotic patients died. CONCLUSION HBV and HCV remain the leading causes of etiology in cirrhosis and HCC. However, NAFLD-related cirrhosis is recognized as a growing burden.

Delayed-Release Phosphatidylcholine Is Effective for Treatment of Ulcerative Colitis: A Meta-Analysis.

Abstract: Background Phosphatidylcholine (PC) is intrinsically missing in intestinal mucus of patients with ulcerative colitis. Topical supplementation with delayed intestinal release PC formulations is assumed to compensate this lack. Three monocenter randomized controlled trials (RCTs) with a 30% PC containing lecithin were successful, whereas 1 trial with > 94% PC containing lecithin failed. Objectives Evaluation of 30% PC-containing lecithin provided in a delayed intestinal release formulation for treatment efficacy of ulcerative colitis evaluated by meta-analysis of three RCT's. Methods Meta-analysis of 3 studies was performed using RevMan 5.3 software. Odds ratio (OR) and 95% Cl were calculated for remission, clinical and endoscopic improvement, histology and life quality. p-values less than 0.05 were accepted as significant. Results The meta-analysis of 3 RTCs with 160 included patients with ulcerative colitis verified that PC improved the rate of remission (OR = 9.68), as well as clinical (OR = 30.58) and endoscopic outcome (OR = 36.73). Within the available patient population also histology and quality of life became better. All effects were significant over placebo. Achieved remission was maintained in a higher percentage of patients under intestinal release PC formulation compared to placebo. The profile of adverse events was identical to the placebo population. Conclusions A 30% PC containing lecithin in delayed intestinal release formulation improves clinical and endoscopic outcomes, histologic activity and quality of life in patients with ulcerative colitis. For the patients lack of adverse events is an important consideration.

An Improved Scoring System Based on Platelet-Albumin-Bilirubin in Predicting Posthepatectomy Liver Failure Outcomes.

Abstract: BACKGROUND Posthepatectomy liver failure (PHLF) is one of the major complications of liver resection that causes perioperative mortality. Accurate preoperative assessment of PHLF is of great significance to reduce the complication rate after hepatectomy and improve the survival rate. METHODS A retrospective study of patients who received hepatectomy from January 2016 to October 2019 at Tang Du Hospital was performed. The area under the receiver operating characteristic (ROC) curve was used to compare the predictive effects of various scoring models on PHLF. RESULTS The area under the ROC curve of platelet-albumin-bilirubin (PALBI) score, new platelet-albumin-bilirubin (I-PALBI) score, ALBI score, and MELD score was, respectively, 0.647, 0.772, 0.677, and 0.686 (p < 0.01). The I-PALBI score was significantly better than the other scores. CONCLUSIONS I-PALBI score can be used as a predictive score of PHLF, and its prediction accuracy is better than other scoring systems.

Co-Medication and Nutrition in Hepatocellular Carcinoma: Potentially Preventative Strategies in Hepatocellular Carcinoma.

Abstract: Background Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide with about 841,000 new cases and 782,000 deaths annually. Given the clearly defined population at risk, mostly patients with liver cirrhosis, prevention of HCC could be highly effective. Summary Besides regular ultrasound surveillance, numerous publications have suggested protective effects of diverse drugs and nutrients. However, none of those preventive options has made it into clinical routine or practice guidelines. We therefore summarize the current status on preventive effects of drugs such as statins, acetylsalicylic acid (ASA), and metformin, but also dietary aspects and nutrients such as coffee, tea, and vitamin D supplementation. A successful implementation of some of these strategies may potentially lead to improved prevention of HCC development in patients with liver cirrhosis. Key messages: Accumulating data suggest, that particularly ASA, antidiabetic therapies, and statins may substantially decrease HCC incidence in patients at risk.

Characteristics and healthcare costs in the aging hepatitis B population of Japan: A nationwide real-world analysis.

Abstract: INTRODUCTION Advancing age, comorbidity, and financial burden have been observed in chronic hepatitis B (CHB) patients globally. As Japan is leading the world in aging demographics, similar real-world data are urgently needed for its CHB population to inform all stakeholders. METHODS This cross-sectional study characterized the demographics, comorbidities, and healthcare costs of a large Japanese real-world adult (≥18 years) CHB patient (ICD-10: B18.1) population from the Medical Data Vision database from 01/01/2012 to 31/12/2016. Comorbidities were identified by ICD-10 codes and the annual point-prevalence and Charlson Comorbidity Index (CCI) score were calculated. Annual mean and median all-cause healthcare utilization and costs per-patient were calculated. Comparison tests were conducted for CCI scores, prevalence of comorbidities and healthcare resource utilization and costs. RESULTS We identified 11,125 CHB patients. Between 2012 and 2016, the mean age increased from 62.0±13.3 to 65.2±13.2 years, and the percentage of those aged ≥65 years increased from 45.6% to 60.7%. The prevalence of cirrhosis remained similar (5.8% in 2012 and 5.6% in 2016, p=0.69) while hepatocellular carcinoma decreased from 6.3% to 4.5% (p<0.01). The prevalence of non-liver comorbidities increased (40.9% to 52.0% for cancer (p<0.01), 12.1% to 17.7% for osteoporosis (p<0.01), and 10.7% to 15.0% for renal impairment (p<0.01). Healthcare resource utilization and costs also increased, with a 119.3% increase in the median total healthcare costs from ¥229,143 in 2012 to ¥502,467 in 2016 (p<0.01). CONCLUSIONS The CHB population of Japan is predominantly elderly and carry a high non-liver comorbidity burden, while incurring increasing healthcare costs.

Opioid Use is More Common in Non-Alcoholic Fatty Liver Disease Patients with Cirrhosis, Higher Body Mass Index and Psychiatric Disease

Abstract: BACKGROUND Opioid use is a topic of growing concern among patients with nonalcoholic fatty liver disease (NAFLD). Given safety concerns of opioids, proactively identifying subgroups of patients with an increased probability of opioid use may encourage practitioners to recommend alternative therapies for pain, thus reducing the likelihood of opioid misuse. This work assessed the prevalence and patient characteristics associated with opioid use in a real-world cohort of patients with NAFLD. METHODS TARGET-NASH, an observational study of participants at 55 academic and community sites in the United States, includes patients with NAFLD defined by pragmatic case definitions. Opioid use was defined as any documented opioid prescriptions in the year prior to enrollment. The association between patient characteristics and the odds of opioid use were modeled with stepwise multivariable logistic regression and tree ensemble methods (Classification and regression tree/Boosted Tree). RESULTS The cohort included 3,474 adult patients with NAFLD including 18.0% with documented opioid use. Variables associated with opioid use included presence of cirrhosis (OR 1.51, 95% CI 1.16-1.98), BMI ≥32 kg/m2 (OR 1.29, 95% CI 1.05-1.59), depression (OR 1.87, 95% CI 1.50-2.33), and anxiety (OR 1.59, 95% CI 1.27-1.98). In the boosted tree analysis, history of back pain, depression, and fibromyalgia had the greatest relative importance in predicting opioid use. CONCLUSION Prescription opioids were used in nearly 1 of 5 patients with NAFLD. Given the safety concerns of opioids in patients with NAFLD, alternative therapies including low-dose acetaminophen and nonpharmacologic treatments should be considered for these patients.

Mucin Secretion in Cystic Fibrosis: A Systematic Review.

Abstract: Background Mucus protects the epithelium against invaders and toxic materials. Sticky and thick mucus is characteristic of CF. Objective The aim of this systematic review is to characterize the specific mucins secreted in the lung and intestinal tract of CF patients. Methods A systematic literature search was conducted up to December 31, 2019. The following terms were used: "cystic fibrosis" AND "mucin." Case-control studies comparing mucin expression in CF patients to healthy controls were included. Results We found 741 eligible studies, 694 studies were rejected because they were performed in animals and not in full text, and 32 studies were excluded being editorials, duplications, review articles, meta-analysis, or not in English. Fifteen studies were eligible for our study, including 150 CF patients compared to 82 healthy controls, all fulfilled the inclusion criteria. The main mucin types expressed in the sinus submucosal glands, sputum, tracheobronchial surface epithelium, and lung submucosal glands were MUC5AC and MUC5B. Increase in the number of sinusoidal submucosal glands and expression of MUC5B was found in CF patients, but no such difference from healthy controls was found for the number of goblet cells in the surface epithelium nor in the expression of -MUC5AC. The opposite was found in the tracheobronchial surface epithelium and in the lungs. Conclusions Increased expression of MUC5AC in the surface epithelium and of MUC5B in the subepithelial glands may be the result of higher secretion rate of mucin into the lumen of the respiratory tract, causing mucus plaque, infection, and inflammation.

Evaluation of Ki67 Index in Endoscopic Ultrasound-Guided Fine Needle Aspiration Samples for the Assessment of Malignancy Risk in Gastric Gastrointestinal Stromal Tumors.

Abstract: BACKGROUND The risk of malignancy in resected gastrointestinal stromal tumors (GISTs) depends on tumor size, location, and mitotic index. Reportedly, the Ki67 index has a prognostic value in resected GISTs. We aimed to analyze the accuracy of endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) samples with reference to Ki67 index, using surgical specimens as the gold standard. METHODS Fifty-five patients who underwent EUS-FNA followed by surgical resection for gastric GISTs were retrospectively analyzed. Patients' age and sex; tumors' size and location; mitotic index, cell type, cellularity, pleomorphism, presence of ulceration, hemorrhage, necrosis, mucosal or serosal invasion, growth pattern, and Ki67 index based on pathology were investigated. RESULTS Location in fundus, ulceration, hemorrhage, mucosal invasion, and Ki67 index in surgical specimens were significant in predicting high-risk groups (p < 0.05) on univariate analysis. Frequency of bleeding (p = 0.034) and the Ki67 index (p = 0.018) were the only independent significant factors in multivariate analysis. The optimal cutoff level of Ki67 was 5%, with 88.2% sensitivity and 52.8% specificity (p = 0.021). The mean Ki67 index was lower in EUS-FNA samples than in surgical specimens (2% [1-15] versus 10% [1-70], p = 0.001). The rank correlation coefficient value of Ki67 was 0.199 (p = 0.362) between EUS-FNA and surgical samples and showed no reliability for EUS-FNA samples. CONCLUSION The Ki67 index in resected specimens correlated with high-risk GISTs, although it had no additive value to the current criteria. The Ki67 index in EUS-guided FNA samples is not a reliable marker of proliferation in GISTs.

Acute Diverticulitis in Elderly Patients: Does Age Really Matter?

Abstract: Objective: Contrasting results are reported on the clinical course of acute diverticulitis (AD) in the geriatric population. The aim of this study is to compare the AD clinical outcomes between patients aged up to 80 years and those ≥80 years. Methods: A total of 1,139 patients were enrolled: 276 patients aged ≥80 years were compared with a group of 863 patients aged <80 years. The primary outcome was to compare the overall mortality. Secondary outcomes included major complications, in-hospital length of stay (LOS), and need for surgical procedures. Results: Patients ≥80 years with AD had different clinical presentation compared with younger patients: they had less fever (21.4 vs. 35.2%; p < 0.001) and abdominal pain (47.8 vs. 65.6%; p < 0.001) rates, but a higher digestive tract bleeding (31.5 vs. 12.3%; p < 0.001) and fatigue (12.7 vs. 7.1%; p = 0.004) rates. Median LOS, cumulative major complications, and mortality rates were higher for patients ≥80 years.Multivariate analysis identified age, absence of abdominal pain, and dyspnea at presentation as independent predictors of intrahospital death or major complications. Conclusions: Patients with AD and age ≥80 years have a higher mortality rate and cumulative major complications as compared with younger patients. Invasive treatments were associated to a poor prognosis in this group.

Patient Engagement with Interactive Text Message System Improves Successful Colonoscopy Rates in an Outpatient Endoscopy Center.

Abstract: INTRODUCTION Text message-based interventions reduce colonoscopy no-show rates and improve bowel preparation scores. In this non-randomized study, we assessed whether an interactive text messaging system could improve colonoscopy outcomes. METHODS Colonoscopy pre-procedural instructions were programmed into a dedicated software platform created for this study. In the intervention arm, text messages were sent to veterans during a 4-week study period. Validated pre-procedural satisfaction questionnaires were completed by patients during standard protocol and intervention periods. Demographics and colonoscopy outcomes data were compared between the standard protocol and intervention arms, including procedure completion rate on scheduled date, Boston bowel preparation score (BPPS), adenoma detection rate, and satisfaction. RESULTS Of 241 patients, 128 were in the standard protocol arm and 113 in the intervention arm. Higher proportions of patients receiving text messages underwent colonoscopy on their scheduled date (69.9%) compared to the ones in the standard protocol (50.8%, p = 0.015). Patients with ≥3 interactions with the system had 80.6% likelihood of completing colonoscopy on the scheduled date compared to 56.9% with 65 years) and younger patients (p = 1.0). Among older patients, colonoscopy was completed successfully in 84.2% when alert-based human interactions occurred compared to 65.6% in those without and 47.9% with standard protocol (p = 0.018). More than 90% indicated they would recommend the system to patients undergoing future colonoscopy. CONCLUSION An interactive text messaging system improves successful colonoscopy rates in a VA setting, with greatest impact in older patients.

Dual Clarithromycin and Metronidazole Resistance Is the Main Cause of Failure in Ultimate Helicobacter pylori Eradication.

Abstract: BACKGROUND/AIM Antimicrobial resistance significantly affects the cure rate of Helicobacter pylori (H. pylori) eradication. We evaluated the risk factor of failure in ultimate H. pylori eradication and assessed the efficacy of current regimens to overcome antibiotic resistance. METHODS Patients with H. pylori infection were prospectively enrolled in a single center. They were classified into 3 groups according to the previous history of H. pylori eradication, and antibiotic susceptibility was evaluated by culture and minimum inhibitory concentrations (MICs). RESULTS Ninety-seven patients were successfully cultured for H. pylori and 81 (83.5%), 7 (7.2%), and 9 (9.3%) were classified into primary resistance, 1st eradication failure, and 2nd or more eradication failure groups; the resistance to clarithromycin (CLA), metronidazole (MET), and levofloxacin increased in the 1st eradication failure (85.7, 57.1, and 42.9%) and 2nd or more eradication failure (88.9, 88.9, and 55.6%) groups. The prevalence of MDR was 21.0% (17/81), 57.1% (4/7), and 88.9% (8/9) in the primary, 1st eradication failure, and 2nd or more eradication failure groups, respectively. In multivariate analysis, dual CLA/MET resistance (CLA/MET-R) (OR = 31.432, 95% CI: 3.094-319.266, p = 0.004) was an independent risk factor for ultimate H. pylori eradication failure. In patients with dual CLA/MET-R, the eradication ratio of concomitant therapy was 57.1% (4/7), whereas that of bismuth-containing quadruple therapy was 27.3% (3/11) (p = 0.350). CONCLUSIONS Dual CLA/MET-R was the main cause of failure in ultimate H. pylori eradication, and 7-day bismuth quadruple or concomitant regimen would not be suitable for H. pylori eradication in the dual CLA/MET-R group.

Plasma Oncostatin M, TNF-α, IL-7, and IL-13 Network Predicts Crohn's Disease Response to Infliximab, as Assessed by Calprotectin Log Drop.

Abstract: Background: Cytokines emerge as possible biomarkers of response in Crohn’s disease (CD). We aimed to determine the plasmatic cytokine profiles of active CD patients who started infliximab (IFX) treatment and their capacity to predict the response to IFX. Methods: A total of 30 active CD patients receiving an induction therapy of IFX were enrolled in the study. Peripheral blood samples pretreatment were collected. Concentrations of 15 cytokines were measured by Luminex technology. Responses to IFX were evaluated by the drop in fecal calprotectin based on its logarithm-transformed values. A random forest (RF) predictive model was used for data analyses. Results: Samples of 22 patients were analyzed. The RF model ranked the following cytokines as the top predictors of the response: tumor necrosis factor alpha (TNFα), interleukin (IL)-13, oncostatin M (OSM), and IL-7 (p < 0.005). Partial dependency plots showed that high levels of IL-13 pretreatment, low TNFα levels, and low IL-7 levels were associated with a favorable IFX response. Increased levels of OSM and TNFα predicted unfavorable responses to IFX. Conclusions: We here show that a log drop in calprotectin strongly correlates with clinical parameters and it can be proposed as a useful objective clinical response predictor. Plasma TNFα, IL-13, Il-7, and OSM network could predict CD response to IFX before induction therapy, as assessed by calprotectin log drop.

Visceral Adipose Tissue Index and Hepatocellular Carcinoma Are Independent Predictors of Outcome in Patients with Cirrhosis Having Endoscopic Treatment for Esophageal Varices.

Abstract: Background: The relationship between the amount of adipose tissue and advanced-stage liver cirrhosis with esophageal varices (EV) is unknown. We aimed to reveal the prognostic significance of adipose tissues in patients with liver cirrhosis. Methods: We enrolled 87 patients with EV who received initial endoscopic treatment and underwent scheduled treatments in our hospital. Computed tomography (CT) images were obtained of a 5-mm slice at the umbilical level. We evaluated the effect of mortality based on the visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue ratio (VSR). Results: Cox hazard multivariate analysis showed that the presence of hepatocellular carcinoma (HCC; hazard ratio [HR]: 4.650, 95% confidence interval [CI]: 1.750–12.353, p = 0.002), γ-GTP (HR: 1.003, 95% CI: 1.001–1.006, p = 0.026), and VATI (HR: 1.057, 95% CI: 1.030–1.085, p < 0.001) significantly affected mortality. Cox hazard multivariate analysis for liver-related death was also significantly affected by HCC (HR: 1.057, 95% CI: 1.030–1.085, p < 0.001) and VATI (HR: 1.052, 95% CI: 1.019–1.086, p = 0.002). The difference between the Child-Pugh scores 12 months after treatment and that during initial treatment were significantly positively correlated with VATI ( r = 0.326, p = 0.027). Patients with high VATI had a significantly higher frequency of HCC after EV treatment by Kaplan-Meier analysis ( p = 0.044). Conclusion: Our findings suggest that VATI measured by CT could significantly predict mortality in cirrhosis patients through decreasing liver function and increasing HCC frequency, and appropriately controlling VATI could improve their prognosis.