Extrahepatic autoimmune diseases in primary biliary cholangitis: Prevalence and significance for clinical presentation and disease outcome.

BACKGROUND AND AIM: The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). METHODS: The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. RESULTS: A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5% vs 86.1%, P < 0.001) and seropositive for anti-mitochondrial antibodies (88% vs 84%, P = 0.05) and antinuclear antibodies and/or smooth muscle antibodies (53.8% vs 43.6%, P = 0.005). At presentation, patients with EHAIDs had significantly lower levels of alkaline phosphatase (1.76 vs 1.98 × upper limit of normal [ULN], P = 0.006), aspartate aminotransferase (1.29 vs 1.50 × ULN, P < 0.001), and total bilirubin (0.53 vs 0.58 × ULN, P = 0.002). Patients with EHAIDs and without EHAIDs had similar rates of GLOBE high-risk status (12.3% vs 16.1%, P = 0.07) and Paris II response (71.4% vs 69.4%, P = 0.59). Overall, event-free survival was not different in patients with and without EHAIDs (90.8% vs 90.7%, P = 0.53, log rank). Coexistence of each autoimmune thyroid diseases (10.6%), Sjögren disease (8.3%), systemic sclerosis (2.9%), rheumatoid arthritis (2.7%), systemic lupus erythematosus (1.7%), celiac disease (1.7%), psoriasis (1.5%), and inflammatory bowel diseases (1.3%) did not influence the outcome. CONCLUSIONS: Our study confirms that EHAIDs are frequently diagnosed in patients with PBC. The presence of EHAIDs may influence the clinical phenotype of PBC at presentation but has no impact on PBC outcome.

Multicenter cohort study of patients with buried bumper syndrome treated endoscopically with a novel, dedicated device.

BACKGROUND AND AIMS: Buried bumper syndrome (BBS) is a rare adverse event of percutaneous endoscopic gastrostomy (PEG) placement in which the internal bumper migrates through the stomal tract to become embedded within the gastric wall. Excessive tension between the internal and external bumpers, causing ischemic necrosis of the gastric wall, is believed to be the main etiologic factor. Several techniques for endoscopic management of BBS have been described using off-label devices. The Flamingo set is a novel, sphincterotome-like device specifically designed for BBS management. We aimed to evaluate the effectiveness of the Flamingo device in a large, homogeneous cohort of patients with BBS. METHODS: A guidewire was inserted through the external access of the PEG tube into the gastric lumen. The Flamingo device was then introduced into the stomach over the guidewire. This dedicated tool can be flexed by 180 degrees, exposing a sphincterotome-like cutting wire, which is used to incise the overgrown tissue until the PEG bumper is exposed. A retrospective, international, multicenter cohort study was conducted on 54 patients between December 2016 and February 2019. RESULTS: The buried bumper was successfully removed in 53 of 55 procedures (96.4%). The median time for the endoscopic removal of the buried bumper was 22 minutes (range, 5-60). Periprocedural endoscopic adverse events occurred in 7 procedures (12.7%) and were successfully managed endoscopically. A median follow-up of 150 days (range, 33-593) was performed in 29 patients (52.7%), during which no significant adverse events occurred. CONCLUSIONS: Through our experience, we found this dedicated novel device to be safe, quick, and effective for minimally invasive, endoscopic management of BBS.

High anti-TNF alfa drugs trough levels are not associated with the occurrence of adverse events in patients with inflammatory bowel disease.

Objectives: Up to 40% of inflammatory bowel disease (IBD) patients treated with anti-TNF drugs lose response within 1 year of treatment, therefore requiring drug optimization. Although higher drug trough levels (TLs) are associated with sustained clinical outcomes, there are concerns that they may be associated with a higher risk of adverse events (AEs). The aim was to evaluate the presence of a possible association between drug TLs and the occurrence of AEs in IBD patients treated with anti-TNF drugs.Methods: We retrospectively studied a cohort of 113 IBD patients treated with adalimumab or infliximab, of whom 27 were in combination therapy with immunosuppressants. TLs were measured using a homogeneous mobility shift assay.Results: During a median follow-up of 16 months (range 1-144), we observed 103 AEs occurring in 58 patients. We found no statistically significant difference (p = .21) in median TLs between patients who did 6.7 mcg/mL; range 0.0-36.2) or did not (7.7 mcg/mL; range 0.0-20.7) experience an AE. No difference was observed in the rate of AEs between patients in mono- or combination therapy (p = .38), as well as between elderly (i.e., >65 years) and younger patients (p = .32). Considering a TL cutoff of 7 mcg/mL for infliximab and 12 mcg/mL for adalimumab, or even double these TL values, we observed no statistically significant difference in the rate of AEs occurrence.Conclusion: Our study suggests that, when clinically required, anti-TNF drug dosage may be increased without particular concerns regarding the risk of AEs occurrence in IBD patients, even in patients on combination therapy and elderly ones.

Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis.

INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.

Proton pump inhibitors: use and misuse in the clinical setting.

INTRODUCTION: The introduction of proton pump inhibitors (PPIs) into clinical practice has greatly improved our therapeutic approach to acid-related diseases for their efficacy and safety. Areas Covered: The following evidence-based indications for PPI use are acknowledged by many scientific societies: treatment of the various forms and complications of gastroesophageal reflux disease, eradication of H. pylori infection in combination with two or more antibiotics, short- and long-term therapy of H. pylori-negative peptic ulcers, healing, and prevention of NSAID/COXIB-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger Ellison syndrome. Expert Commentary: Despite the above well-defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and the endless expansion of the PPI market has created important problems for many regulatory authorities for two relevant features: the progressive increase of the costs of therapy and the greater potential harms for the patients. The major reasons for the misuse of PPIs are the prevention of gastro-duodenal ulcers in patients without risk factors and the stress ulcer prophylaxis in non-intensive care units, steroid therapy alone, anti-platelet or anti-coagulant treatment in patients without risk of gastric injury and the overtreatment of functional dyspepsia.

A safety review of proton pump inhibitors to treat acid-related digestive diseases.

INTRODUCTION: Proton pump inhibitors (PPIs) have become the first choice medical treatment of acid-related disease and, as with any pharmacological agent, they have been reported to be associated with some adverse events mainly linked to their chronic use. The most important postulated harms are represented by serum electrolyte alterations, vitamin B12 and iron deficiency, gastric tumors, enteric infections, spontaneous bacterial peritonitis, pneumonia, ischemic heart attacks, bone fractures, chronic kidney disease, dementia, and Alzheimer disease. Specific pathophysiological mechanisms have been identified for some of them and not for other manifestations. AREAS COVERED: However, studies on PPIs safety have generally important limitations because of their frequent retrospective design and other methodological drawbacks, such as patients' selection and residual confounders. EXPERT OPINION: Obviously, in the vast majority of the cases, adverse drug reactions cannot be assessed by means of randomized clinical trials due to the high costs, ethical reasons, and difficulties in performing prospective observational studies. So far, assessment of retrospective observational investigations remains the only method to evaluate adverse events with any drug in general and, although the weaknesses of these studies are evident, the awareness of the reported associations with the medications analyzed is important for physicians in order to manage adequately their individual patients.

The appropriate use of proton-pump inhibitors.

The introduction of proton-pump inhibitors (PPIs) into clinical practice since about thirty years has greatly improved our therapeutic approach to acid-related diseases for their well recognized efficacy and safety. Accordingly, the role of surgery has been enormously reduced in this field. The main indications for PPI use are universally acknowledged by many scientific societies and are the following: treatment of gastroesophageal reflux disease in its various forms and complications, eradication of H. pylori infection in combination with two or more antibiotics, therapy of H. pylori-negative peptic ulcers, healing and prevention of NSAID-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger-Ellison Syndrome. Despite the above well-defined indications, however, the use of PPIs continues to grow every year in both Western and Eastern countries and this phenomenon poses serious queries about the appropriate prescription of these drugs worldwide. In fact, the endless expansion of PPI market has created important problems for many regulatory authorities for two relevant features: the progressive and irreversible increase of the costs of therapy with this class of drugs and the greater potential harms for the patients. So, there is the need for a reappraisal of PPI correct indications for both general practitioners and various specialists in order to re-establish a correct use of these effective drugs in daily clinical practice, according to the best evidence-based guidelines.

Long-Term Follow-Up Study of Liver-Related Outcome After Bilio-Pancreatic Diversion in Patients with Initial, Significant Liver Damage.

BACKGROUND: Obesity is associated with NAFLD, and bariatric surgery has significant impact on this liver disease, with reported improvement in hepatic fibrosis. AIMS: To investigate the effects of bariatric surgery on long-term liver disease-related outcome in obese patients with nonalcoholic fatty liver disease (NAFLD) and significant liver damage. METHODS: This study included 56 NAFLD patients who underwent bilio-pancreatic diversion for morbid obesity and who had significant fibrosis at intraoperative liver biopsy. Data were analyzed at 1, 3, and 5 years of follow-up, and at the latest available visit in patients who had longer follow-up. We assessed the incidence of clinically relevant liver events (ascites, hepatic encephalopathy, portal hypertension-related bleeding, and jaundice) as well as modifications of a validated biochemical index such as the NAFLD score. RESULTS: During a median follow-up of 78 months, median weight decreased from 119 to 78 kg (P < 0.0001), and median body mass index decreased from 45.2 to 29.0 kg/m2 (P < 0.0001). None of the patients developed clinical complications of liver disease, and none died due to liver-related causes. Median NAFLD score significantly decreased (P = 0.0005) during follow-up from - 0.929 (- 1.543 to - 0.561) to - 1.609 (- 2.056 to - 1.102). The NAFLD score category was unchanged in 32 patients (57%), improved in 18 (32%), and worsened in 6 (11%). CONCLUSIONS: Patients with NAFLD and proven histological liver damage at surgery do not develop complications of liver disease in long term after bilio-pancreatic diversion. Moreover, noninvasive parameters of liver damage improve. Thus, preexisting liver damage does not seem to be a contraindication to bilio-pancreatic diversion.

Drugs for improving esophageal mucosa defense: where are we now and where are we going?

In the past, the attention of physiologists and doctors has been mainly focused on the key role of acid in the pathogenesis of gastroesophageal reflux disease (GERD), but increasing evidence that 20-40% of reflux patients respond not at all or only partially to proton pump inhibitors (PPIs) has underlined the concept that factors other than acid are implicated in its development and the elicitation of symptoms. Among these, impaired mucosal integrity, particularly in most patients with non-erosive reflux disease, has recently been reincluded and the reinforcement of defensive mechanisms and/or its protection has been reappointed as a renewed therapeutic target for the management of GERD patients. In this review we will summarize the existing knowledge of the old and novel compounds able to produce this therapeutic effect, including sucralfate, alginate-based drugs, and a new medical device consisting of hyaluronic acid and chondroitin sulfate dispersed in a bioadhesive carrier, together with the potential indications for their use. It is to be stressed, however, that, although these compounds may represent a real alternative to PPI therapy in GERD, the combination of mucosal protection with acid suppression may help manage many cases with a partial or unsatisfactory response to PPIs alone.

Complexity and diversity of gastroesophageal reflux disease phenotypes.

Gastroesophageal reflux disease (GERD) is defined as a condition which develops when the reflux of gastric contents causes troublesome symptoms, impairs quality of life, or leads to mucosal damage or complications. There are two main phenotypic presentations of GERD, the erosive (ERD) and non-erosive reflux disease (NERD), with the latter one representing up to 70% of GERD spectrum. Moreover, patients with GERD can be clinically subdivided into two distinct syndromes: patients with esophageal and extraesophageal symptoms. The diagnosis of NERD should be supported by the evidence that symptoms are due to reflux episodes on the basis of an excess of acid into the esophagus or a positive correlation between symptoms and acid and/or weakly acidic reflux episodes as evidenced by 24-hour impedance-pH monitoring. Patients with normal esophageal acid exposure and no correlation between heartburn and any kind of chemical reflux are considered affected by functional heartburn and do not pertain to the realm of NERD. They do not usually respond to PPI therapy as further empirical criterion and are included in the large group of functional digestive disorders with the expression of altered generation or perception of symptoms at the esophageal level and can often overlap with functional dyspepsia and irritable bowel syndrome.

Epidemiology and natural history of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is highly prevalent in Western countries, particularly when considering its most classic symptom that is heartburn. This symptom is very frequent in the community and ranges from 10% to more than 30%, according to the various population-based studies. This disease is much more represented in Europe and USA than in Asiatic countries. It has been shown that GERD prevalence increases in parallel with the remarkable growth of obesity, as this condition is able to favor all the pathogenetic mechanisms leading to it. Current information regarding the phenotypic presentation of GERD shows that there are two main phenotypic manifestations, that are erosive reflux disease (ERD) and non-erosive reflux disease (NERD) and the latter includes the majority of patients (up to 70%). The major complication of GERD is the development of Barrett esophagus, a pre-malignant lesion potentially leading to esophageal adenocarcinoma. Data from medical literature on the natural history of this disease are scant and mainly retrospective, so the interpretation of them is very difficult. However, they seem to suggest that both NERD and mild esophagitis tend to remain as such overtime and the progression from NERD to ERD, from mild to severe ERD and from ERD to Barrett's esophagus may occur only in a small number of cases, ranging from 0% to 30%, 10-22% and 1-13%, respectively. Future studies should help us in elucidating better the real transition from one category to another and to do this, we have to exclude from the world of GERD all the functional conditions that nowadays can be easily recognized by means of impedance-pH monitoring.

Risk of microangiopathy in type 2 diabetes mellitus patients with or without chronic hepatitis C: Results of a retrospective long-term controlled cohort study.

BACKGROUND: Patients with chronic hepatitis C have an increased risk of diabetes mellitus but the type and risk of developing diabetes-related complications have not yet been evaluated. METHODS: In order to compare the incidence of diabetic microangiopathy in patients with new onset diabetes without microangiopathy we recruited 54 hepatitis C virus (HCV)-positive and 119 HCV-negative patients from January 2005 to December 2006. All patients were followed-up every 6 months for liver and diabetic complications and incidence of cardiovascular diseases up to December 2012 when data were retrospectively analyzed. RESULTS: The two cohorts were comparable at enrolment except for mean body mass index, obesity rate and family history of diabetes (p=0.007). After 7.2 years of follow-up, 13 HCV-positive (24.1%) and 37 HCV-negative patients (31%) showed at least one microangiopathic complication (p=0.34); 5 HCV-positive (9.3%) and 13 HCV-negative patients (10.8%) reported cardiovascular diseases (p=0.2); 14 HCV-positive (24.5%) compared to 0 HCV-negative patients developed liver-related complications (p=0.0003). One HCV-positive patient died due to liver cancer, 1 HCV-negative patient died from myocardial infarction (p=0.3). Increasing age (HR=1.04, 95% CI: 1.00-1.07, p=0.04) and smoking (HR=2.94, 95% CI: 1.06-8.17, p=0.04) were positively associated to diabetic complications. CONCLUSIONS: Incidence of microangiopathy is not significantly different in diabetics with or without chronic hepatitis C.

Narrow band imaging vs. high definition colonoscopy for detection of colorectal adenomas in patients with positive faecal occult blood test: a randomised trial.

BACKGROUND: The impact of narrow band imaging in improving the adenoma detection rate in a screening scenario is still unclear. AIM: To evaluate whether narrow band imaging compared with high definition white light colonoscopy can enhance the adenoma detection rate during screening colonoscopy. METHODS: Consecutive patients presenting for screening colonoscopy were included into this study and were randomly assigned to the narrow band imaging group (Group 1) or standard colonoscopy group (Group 2). Primary end point was the adenoma detection rate and secondary aim was the detection rate of advanced adenomas. RESULTS: Overall, 117 patients were allocated to Group 1 and 120 to Group 2. Both the adenoma detection rate and the detection rate of advanced adenomas were not significantly different between the two groups (respectively, 52.1% vs. 55%, RR=0.95, 95% CI 0.75-1.20; 32.5% vs. 44.2%, RR=0.74, 95% CI 0.53-1.02). No significant difference between the proportions of polypoid and flat adenomas was found. Male gender, no prior history of screening, and endoscopist's adenoma detection rate were independent predictive factors of higher advanced adenoma detection rate. CONCLUSIONS: In a screening scenario, narrow band imaging did not improve the adenoma nor advanced adenoma detection rates compared to high definition white light colonoscopy.

Comprendiendo las percepciones de los usuarios adictos a drogas, respecto a su experiencia en psicoeducación / Understanding drug addicted perceptions about their experience in psychoeducation

Las adicciones a drogas (alcohol e ilicitas) son un problema grave y crónico que aumenta cada día. Los pacientes que logran comprometerse con un tratamiento tienen mayor probabilidad de éxito en lograr abstinencia y rehabilitarse. El modelo de tratamiento y rehabilitación que aplica la Unidad de adicciones de la Pontificia Universidad Católica de Chile, contempla varias estrategias entre las cuales se encuentra la psicoeducación, basada en el modelo cognitivo conductual, que pretende crear consciencia racional de enfermedad a través del trabajo grupal de temas previamente establecidos. Esta investigación se propuso explorar las percepciones de los usuarios adictos a drogas respecto a su experiencia de psicoeducación en ese centro, para construir una comprensión que rescate las experiencias más significativas en este proceso. Se realizó un grupo focal con 8 participantes y al análisis de los testimonios, se identificaron 5 categorías principales: Percepción de las características del método: se reconoce como método no tradicional obligatorio, que enseña conceptos de enfermedad adictiva, es complementario a las otras estrategías del tratamiento y tiene credibilidad