Liver steatosis in celiac disease: the open door.

Non-alcoholic fatty liver disease (NAFLD) is a common disease of unknown origin characterized by histological features similar to alcoholic-like liver injury but in the absence of significant alcohol intake. Non-alcoholic fatty liver disease refers to a spectrum of diseases of the liver ranging from simple steatosis (i.e., fatty infiltration of the liver) to nonalcoholic steatohepatitis (i.e., steatosis with inflammation and hepatocyte necrosis) to cirrhosis. Non-alcoholic fatty liver disease is frequently associated with disorders such as insulin resistance, obesity, type 2 diabetes mellitus, hyperlipidemia and protein-calorie malnutrition. However, in a subgroup of NAFLD patients, the true relevant cause remains undetermined. Celiac disease (CD) is a common immune-mediated disorder and develops in genetically susceptible subjects after the ingestion of gluten proteins. Celiac disease has been found in about 10% of patients with unexplained abnormal liver tests, and in about 3.5% of patients with NAFLD as the only manifestation of the disease. The frequency of subclinical or silent presentations in older children and adults highlights the importance of CD screening in patients with unexplained chronic abnormal liver function tests and NAFLD without any specific etiology. The pathogenesis of liver steatosis in CD is uncertain. The aims of this review are to describe the possible mechanisms involved in the occurrence and progression of liver steatosis in CD patients.

The Apparent Asymmetrical Relationship Between Small Bowel Bacterial Overgrowth, Endotoxemia, and Liver Steatosis and Fibrosis in Cirrhotic and Non-Cirrhotic Patients: A Single-Center Pilot Study.

Introduction: Gut microbiota are a complex ecosystem harboring our intestine. They maintain human body equilibrium, while their derangement, namely, "dysbiosis", has been associated with several gastrointestinal diseases, such as liver steatosis (NAFLD) and liver cirrhosis. Small intestinal bacterial overgrowth (SIBO) is an example of dysbiosis of the upper gastrointestinal (GI) tract. Aim: The aim of this study is to evaluate the relationship between SIBO and levels of endotoxemia and grade of liver steatosis (LS) and liver fibrosis (LF) in hepatologic patients. Materials and Methods: Consecutive outpatients referred to our hepatology clinic were tested for SIBO by the lactulose breath test (LBT) and peripheral blood levels of endotoxemia; LS grading and LF were assessed by abdominal ultrasound and transient elastography, respectively. Results: Fifty-two consecutive patients (17 with alcohol abuse (4.5 ± 0.8 alcohol units per day), 4 with HCV and 2 with HBV infection, 24 of metabolic origin, 2 of autoimmune origin, and 3 with cholangiopathies; mean age 54.7 ± 8.3 years, 31 F, BMI 24.1 ± 1.1 Kg/m2) and 14 healthy volunteers (HV) (mean age 50.1 ± 4.3 years, 9 F, BMI 23.3 ± 1.1 Kg/m2) were enrolled. SIBO prevalence was significantly higher in cirrhotic (LC) vs. non-cirrhotic (LNC) patients and vs. HV (all, p < 0.05), with a significant positive trend according to Child-Pugh status (all, p < 0.05). SIBO prevalence was not correlated with LS stages (all, p = NS). Consensually, endotoxin levels were significantly higher in LC vs. LNC and vs. HV (all, p < 0.05) and significantly correlated with LF in patients with LC, according to Child-Pugh status (all, p < 0.05). Conclusion: This study shows that SIBO prevalence and relative endotoxin blood levels seem to be significantly associated with the grade of LF vs. LS in LC. SIBO is also present under pre-cirrhotic conditions, but its prevalence seems to correlate with liver disease irreversible derangement.

Quality of endoscopic screening for colorectal cancer in Italy: A national survey.

BACKGROUND: Colorectal cancer (CRC) is a major healthcare problem all over the world and screening is effective in reducing mortality and increasing survival. Since colonoscopy has a central role in faecal immunochemical test (FIT)-based CRC screening and surveillance, consistent quality measures are essential to ensure quality and outcomes. Nevertheless, screening modalities in clinical practice may differ according to the centers experience and the local availability of instrumentation and devices. AIMS: to assess the quality of endoscopic screening for CRC and adherence to international guidelines across Gastroenterology Departments in Italy. METHODS: All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a web-based survey. RESULTS: Data from 64 hospitals from 17 Italian regions were analyzed. 32/64 (50.0%) were from northern, 12/64 (18.75%) from central and 20/64 (31.25%) from southern Italy. Each center is equipped with a median of 5.0 (3.5-7.0) endoscopists involved in CRC screening, 71.4% of which are gastroenterologists. After a positive FIT, most centers (93.8%) schedule a colonoscopy within 3 months. High-definition video endoscopy is routinely performed in 68.8% and chromoendoscopy in 53.1% of centers. Withdrawal time is ≥6 min in 79.9% and cecal intubation rate is ≥90% in 94.4% of departments. Finally, in 92.7% of centers adenoma detection rate (ADR) overcome the minimum standard of 25%. Analyzing the data by regional areas, a significant higher number of median endoscopic examinations/year (6500 vs 4000 and 3000, respectively, p = 0.024) and of endoscopists per center (6.5 vs 5.0 and 3.5, respectively, p < 0.001) has been registered in the northern compared to central-southern centers. CONCLUSIONS: Data from this survey show adequacy and good quality of endoscopic screening for CRC in Italy, highlighting, at the same time, relevant deficiencies and a discrepancy in procedural attitudes between the different centers. These findings call for a urgent action to overcome the shortcomings, refine and homogenize the behaviour of all screening centers in the national territory and improve the outcomes.

Multifaceted pathogenesis of liver steatosis in inflammatory bowel disease: a systematic review.

OBJECTIVE: Non-Alcoholic Fatty Liver Disease (NAFLD), as a hepatic manifestation of metabolic syndrome (MET)-related obesity, insulin resistance, dyslipidemia, and hypertension, is the main cause of chronic liver disease. Inflammatory Bowel Diseases (IBD), (Crohn's Disease (CD) and Ulcerative Colitis (UC)), are often associated with extraintestinal manifestations. Of these, NAFLD is one of the most frequently reported. To highlight the etiopathogenesis of NAFLD in IBD, we performed a systematic review emphasizing the relationship between NAFLD genetic alterations, metabolic syndrome, and drugs. MATERIALS AND METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria, we performed a systematic literature search on PubMed, Google Scholar, and Web of Science for literature updated from 2010 to 1 March 2021. Inclusion criteria for studies were observational design and Randomized Controlled Trials (RCTs); written in English; primary research only; based on adult patients, and human research only. RESULTS: We identified nine studies on the link between NAFLD and IBD. Among these, two described the genetic predisposition to NAFLD of patients with IBD. Four reported an association between MetS and NAFLD in IBD patients. Regarding medications, none of four studies included, detected a relationship between NAFLD onset and IBD treatment (corticosteroids, immunomodulators, methotrexate, or biologics).  However, a retrospective study showed a protective effect of anti-TNF alpha therapies against altered liver enzymes. CONCLUSIONS: In this interplay between genetic, metabolic, drug, and inflammatory factors, the underlying pathogenic mechanisms behind NAFLD in IBD are still far from clear. Further studies are needed to better clarify the role of individual components influencing the development of NAFLD in IBD.

The role of gluten-free diet in nonalcoholic fatty liver disease development.

OBJECTIVE: Celiac Disease (CD) is an autoimmune disease involving the small bowel, generated by the ingestion of gluten-containing foods in genetically predisposed subjects. Currently, the unique therapy for CD is the absolute adherence to gluten-free diet, but this treatment has been related to the onset of non-alcoholic fatty liver disease (NAFLD). In this systematic review, we provide an update from the most recent studies on the risk of developing NAFLD patients adhering to GFD. MATERIALS AND METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria, we performed a systematic literature search on PubMed and Google Scholar from 2012 to 2021. RESULTS: In the present systematic review, eight studies investigated how GFD in CD patients may be a risk factor for the onset of NAFLD from a minimum of six months to the maximum follow-up period represented by a median of 10 years. CONCLUSIONS: Present systematic review evaluates how GFD plays a key role in NAFLD for consumption of products rich in saturated fats and carbohydrates that promotes accumulation of lipids and lead to hepatic steatosis and inflammation.

Trends and characteristics associated with dietary triggers and psychological distress in patients with irritable bowel syndrome: a cross-sectional study.

OBJECTIVE: Diet, visceral sensitivity, and psychological distress play an important role in Irritable Bowel Syndrome (IBS). This study focused on the relation between IBS severity, foods, visceral sensitivity, and anxiety/depression. PATIENTS AND METHODS: Patients with IBS were investigated through (1) IBS-symptoms severity score (SSS), (2) self-reported food intolerance, (3) visceral sensitivity index (VSI), and (4) Hospital Anxiety and Depression Scale (HADS). Seventy-seven patients agreed to participate in the survey. Of them, 64 (83%) showed IBS according to Rome IV criteria and were included in the final analysis. Patients with IBS-D were 30 (47%), with IBS-C 27 (42%), and with IBS-M 7 (11%). RESULTS: Fifty-eight patients (90%) considered at least one foodstuff as IBS trigger. Amine-rich foods represented a symptom trigger for 77% of patients, those with lectin for 70%, IACs by 48%, and capsaicin by 37%. Overweight was significantly associated with amine-rich foods (p=0.015), age >45 years (p=0.001) and non-smoking condition (p=0.033) with lectin-rich foods, male gender (p=0.005) and overweight (p=0.027) with capsaicin-containing foods. A positive VSI score was found in 59% of patients, and non-smoking condition was significantly associated (OR 10.03; p=0.009). No factors were associated with a positive HADS score, shown by 80% of patients. Severe IBS was shown by 63% of patients, being amine-rich foods (p=0.024), overweight (p=0.020), and female gender (p=0.029) independent risk factors while marriage/cohabiting a protective one (p=0.038). Amine-rich foods are an independent risk factor for severe IBS, along with overweight and female gender. CONCLUSIONS: Clinicians should pay more attention to self-reported food intolerance in IBS patients. A personalized therapy including dietary advice as part of treatment could be of great benefit.

Real-life efficacy and safety of Ustekinumab as second- or third-line therapy in Crohn's disease: results from a large Italian cohort study.

OBJECTIVE: Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn's Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics. PATIENTS AND METHODS: 194 CD patients (108 males and 86 females, mean age 48 years (range 38-58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients. RESULTS: At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up. A logistic regression, UST therapy as third-line therapy (after both anti-TNFα and vedolizumab), FC >200 µg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment. CONCLUSIONS: UST seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.

Modulated ventricular parasystole as a mechanism for concealed bigeminy.

Concealed extrasystolic ventricular bigeminy reflects a distributional pattern of ventricular extrasystoles where intervening sinus beats are always in odd numbers. This has been explained on bigeminal rhythm associated with exit block. This presentation reflects a modification of this concept in that the distributional pattern may be explained on the basis of complex concealed modulation of ventricular parasystole, the concealment being due to impulses falling within the refractory period rather than suffering true exit block.

Supernormal modulation of ventricular parasystole: the triphasic phase-response curve.

Modulation of ventricular parasystole by sinus beats has been shown both in vitro and in vivo to result in a classic biphasic phase-response curve. The first clinical presentation of 3 cases of supernormal modulation of ventricular parasystole resulting in a triphasic phase response curve is reported. Supernormal modulation reflects an unexpected early enhancement expedition of the ectopic ventricular impulses. An alternative explantation for the triphasic phase-response curve is the discharge and resetting of the parasystolic focus by critically timed sinus impulses.

Low Prevalence of p-ANCA in Unaffected Relatives of Patients with Ulcerative Colitis from a Mediterranean Area.

: Antineutrophil-cytoplasmic-autoantibodies (p-ANCA) are strongly associated with ulcerative colitis (UC) and may represent an indicator of genetic susceptibility to UC. To further examine whether p-ANCA may serve as a genetic marker of UC we evaluated the frequency of p-ANCA in unaffected family members of UC from a defined geographic area. A total of 110 patients with UC and 90 unaffected family members (first- or second-degree relatives) were tested. Controls included: 58 Crohn's disease (CD) patients with 25 unaffected relatives and 52 irritable bowel syndrome (IBS) patients with 20 healthy family members. p-ANCA were detected by enzyme-linked immunoassay followed by immunofluorescence. p-ANCA were detected in 57 UC patients (51.8%). Six of 90 (6.6%) unaffected relatives were positive for p-ANCA and 4 of these were from two families. In 3 of 35 families the proband and at least one unaffected relative were p-ANCA-positive. In five families with more than one member affected by UC, p-ANCA were detected in 2 of 19 (10.5%) unaffected relatives. Six CD patients (10.3%) and one (1.9%) in the IBS group were positive for p-ANCA. One family member was positive in the CD family group and 1 was positive in the control family group. In the group of families recruited for this study, p-ANCA were not more frequent in unaffected relatives of UC patients than in controls, suggesting that at least in the geographic area considered for this study p-ANCA may not represent a definite subclinical marker of susceptibility for UC.

Pseudo-atrioventricular dissociation caused by interpolated ventricular extrasystoles in the presence of dual atrioventricular nodal pathway.

This report describes a patient manifesting with ventricular extrasystoles. The pause occasioned by extrasystoles often is followed by narrow QRS complexes not preceded by P waves, but at times is followed by a sinus P wave. At first glance, the pattern suggests a diagnosis of atrioventricular (A-V) junctional escape complexes. Analysis reveals that ventricular extrasystoles are, in fact, interpolated; the sinus P wave that follows the extrasystole is conducted to the ventricles with a very prolonged P-R interval (up to 0.80 s). The phenomenon is due to the presence of a dual A-V nodal pathway. The sinus impulse that follows the extrasystole is blocked in the fast pathway but may still be conducted to the ventricles through the slow pathway, resulting i a very prolonged P-R interval.

Sinoatrial block with complicating sinoatrial reciprocation.

This presentation reflects an atypical manifestation of sinoatrial block in a patient with chronic renal failure and hyperkalemia (7.8 mEq/L). An allorhythmic distribution of P-P intervals permits the interpretation of sinoatrial block complicated by sinoatrial reciprocation.

Wedensky facilitation. Electrotonic potentiation during complete A-V block.

The electrocardiogram recorded from a patient with third degree A-V block reflected almost regular A-V junctional escape rhythm. Some of the R-R cycles were slightly shorter than the basic escape cycle. A QRS complex ending such a relatively short R-R interval was always preceded by a sinus P wave, and had a QRS configuration which was minimally different from that of the escape complexes. The His bundle recording demonstrated that these minimally premature complexes were associated with an H-V interval which was shorter than that of the escape complexes. This indicates that the premature QRS complex could not be a capture beat. The relationship between the slightly premature QRS complex and the preceding sinus P-waves is explained on the basis of electrotonic potentiation or modulation to due Wedensky facilitation.

Concealed ventricular bigeminy with exceptions due to time-dependent modulation of an ectopic rhythm.

This presentation reflects a case of atypical concealed bigeminy, where some interectopic intervals contain even numbers of sinus beats. Exceptions to the rule of concealed bigeminy only occur during slowing of the sinus node. The pattern is explained on the basis of modulated parasystole, by drawing a phase-response curve which explains all the interectopic intervals on the basis of the modulating effect exerted by the sinus impulses upon a parasystolic focus.

Bigeminal and trigeminal distribution of ventricular extrasystoles as an expression of "atypical" concealed bigeminy.

This report reflects a case of bigeminal and trigeminal ventricular extrasystoles where bigeminal extrasystoles are associated with short coupling intervals, while trigeminal extrasystoles manifest long coupling intervals. The arrhythmia is interpreted as an "atypical" form of concealed bigeminy.

Atrial parasystole and tachycardia. Modulation and automodulation of a parasystolic focus.

This report deals with a patient reflecting atrial parasystole and episodes of atrial tachycardia. The P' waves during tachycardia were identical to the parasystolic P' waves. Atrial parasystole was at times regular, as revealed by a precise mathematical relationship between the interectopic intervals, and on other occasions irregular. Irregularity was due to modulation, namely electrotonic influence exerted by the sinus impulses upon the parasystolic focus. Atrial tachycardia occurred only during the periods when atrial parasystole was modulated. Atrial tachycardia has been interpreted as due to automodulation, a situation where the propagated parasystolic impulse exerts an electrotonic influence on the ectopic focus itself, leading to a marked unexpected acceleration of the ensuing parasystolic discharge.

Lansoprazole and Helicobacter pylori infection.

Helicobacter pylori-associated gastritis is present in virtually all patients with duodenal ulcer (DU). Eradication of H pylori is associated with a highly significant decline in the recurrence rates of DU, indicating that treatments aimed at eradicating H pylori are mandatory in these patients. The novel proton pump inhibitor lansoprazole exhibits a potent antiulcer effect and, in vitro, a direct antibacterial effect against H pylori. Conflicting data have been reported on the question of whether lansoprazole is bactericidal against H pylori in vivo when administered alone. The aim of this double-blind trial was to address this issue further by comparing the effects of two different 4-week regimens (lansoprazole alone or in combination with amoxicillin) on H pylori infection in patients with DU. Patients were assessed before and after the 4-week treatment and 3 months after stopping the study medication. The ulcer healing rates at 4 weeks were similar for the two treatments while there was a trend for higher recurrence rates at 4 months in patients receiving lansoprazole alone. The frequency of high-grade H pylori infection was significantly lower in the lansoprazole and amoxicillin group both at 4 weeks (84% clearing) and 4 months. After 4 weeks of treatment there were no patients with residual H pylori-positive active antral gastritis in the lansoprazole and amoxicillin group compared with 25% in the lansoprazole alone group. Neither treatment significantly affected the IgG antibody response to H pylori either at the circulatory or the mucosal level. In contrast, the mucosal H pylori-specific IgA response was significantly enhanced after 4 weeks and more markedly after treatment with lansoprazole.(ABSTRACT TRUNCATED AT 250 WORDS)

Lansoprazole-based triple therapy versus ranitidine bismuth citrate-based dual therapy in the eradication of Helicobacter pylori in patients with duodenal ulcer: a multicenter, randomized, double-dummy study.

BACKGROUND: The optimal treatment regimen for eradication of Helicobacter pylori in patients with duodenal ulcer has yet to be determined. Based on a search of MEDLINE, no studies have been performed comparing a proton pump inhibitor-based triple therapy regimen with a ranitidine bismuth citrate (RBC)-based dual therapy regimen, both containing clarithromycin. OBJECTIVE: This study was undertaken to compare the efficacy of lansoprazole (LAN)-based triple therapy with that of RBC-based dual therapy in H pylori-infected patients with duodenal ulcer. METHODS: Patients were randomized to receive either 1 week of triple therapy with LAN 30 mg BID, clarithromycin 500 mg BID, and tinidazole 500 mg BID, followed by 3 weeks of LAN 30 mg BID, or 2 weeks of dual therapy with RBC 400 mg BID plus clarithromycin 500 mg BID, followed by 2 weeks of RBC 400 mg BID. Eradication of H pylori was defined as negative results on both the urease quick test and histologic examination > or =4 weeks after the end of treatment. Duodenal healing and recurrence rates were assessed endoscopically at 8 weeks and 6 months. A per-protocol (PP) analysis was conducted for each efficacy end point. Also conducted were an intent-to-treat (ITT) analysis in which patients with missing data were considered failures, and an observed analysis (OBS), which included patients with an evaluable result after treatment, regardless of compliance. RESULTS: One hundred eighty-five patients (126 men, 59 women; age range, 18-76 years; mean age, 43 years) were enrolled and randomized to treatment. In the LAN and RBC groups, respectively, H. pylori eradication rates were 92.6%, 93.1%, and 72.8% versus 78.6%, 77.9%, and 64.5% in the PP (P = 0.02), OBS (P = 0.01), and ITT analyses. The corresponding duodenal ulcer healing rates were 98.6%, 98.7%, and 83.7% versus 90.8%, 91.5%, and 81.7%; these differences were not statistically significant. Side effects were mild, occurring in 20.7% of LAN patients and 17.2% of RBC patients. Ulcer recurred in 2 RBC patients. No difference was observed between treatments in terms of the occurrence of gastritis or improvement of symptoms. CONCLUSION: Based on the results of the PP and OBS analyses, LAN-based triple therapy was superior to RBC-based dual therapy for the eradication of H. pylori in patients with duodenal ulcer.

High seroprevalence of Helicobacter pylori infection in non-institutionalised children with mental retardation.

Eighty-four children with mental retardation (34 boys, 50 girls; age range 2-18 years, median 6 years) and 84 age- and gender-matched outpatient controls were studied. All children were living at home, had never stayed in an institution, and came from the same urban area. Seropositivity for Helicobacter pylori was found in 42 (50%) of 84 mentally retarded children and 16 (19%) of 84 controls (p < 0.01). Socio-economic factors did not differ between the two groups. The findings indicated that a higher prevalence of H. pylori infection occurs in children with mental retardation, regardless of whether they are institutionalised.

Salivary specific IgG is a sensitive indicator of the humoral immune response to Helicobacter pylori.

In humans, salivary antibodies are secreted during humoral immune response. Helicobacter pylori infection is associated with systemic humoral immune response reflected by raised serum levels of specific IgG. The present study was aimed at exploring whether salivary concentrations of specific H. pylori IgG are a reliable indicator of H. pylori infection. Serum and salivary samples were obtained from 291 subjects attending the GI clinic and tested for H. pylori-specific IgG by a direct ELISA (94% sensitivity, 95% specificity for serum determinations) using a crude H. pylori sonicate as antigen. Data are given as optical density (mean +/- S.D.). Levels of salivary H. pylori IgG paralleled those of circulating specific IgG in the 291 subjects studied (0.981 +/- 0.431 vs. 0.777 +/- 0.682, respectively). A significant positive correlation was found between specific H. pylori IgG in sera and saliva samples (r = 0.981, P < 0.0001). An overall concordance between circulating and salivary H. pylori IgG was observed in 238 out of the 291 (81.7%) subjects. Salivary H. pylori IgG represent a sensitive marker of specific humoral immune response and they may substitute circulating H. pylori IgG measurement when sera samples are not available.