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The efficacy of systemic therapy for unresectable advanced hepatocellular carcinoma (aHCC) has not been proven in patients with Child-Pugh (C-P) B cirrhosis. Nevertheless, in real-world these patients are treated both with tyrosine kinase inhibitors (TKIs) and with metronomic capecitabine (MC). This study aimed to compare sorafenib and MC outcomes versus best supportive care (BSC) in C-P B patients. Between 2008 and 2020, among 774 C-P B patients with aHCC not amenable/responsive to locoregional treatments, 410 underwent sorafenib, 62 MC, and 302 BSC. The propensity score matching method was used to correct the baseline unbalanced prognostic factors. In the unmatched population, median OS was 9.7 months in patients treated with sorafenib, 8.0 with MC, and 3.9 months with BSC. In sorafenib vs. BSC-matched patients (135 couples), median OS was 7.3 (4.9–9.6) vs. 3.9 (2.6–5.2) months (p <0.001). ECOG-Performance Status, tumor size, macrovascular invasion, AFP, treatment-naive, and sorafenib were independent predictors of survival. In MC vs. BSC-matched patients (40 couples), median OS was 9.0 (0.2–17.8) vs.3.0 (2.2–3.8) months (p <0.001). Median OS did not differ (p = 0.283) in sorafenib vs. MC-matched patients (55 couples). C-P B patients with aHCC undergoing BSC have poor survival. Both Sorafenib and MC treatment improve their prognosis. [ABSTRACT FROM AUTHOR]

Gluten-free diet (GFD) is the one therapy in coeliac disease (CeD). Unfortunately, some patients adopt GFD before the diagnostic work-up. The guidelines suggest a 14-day gluten intake > 3 gr to get CeD diagnosis, although many subjects refuse this approach. Other evidence showed that the intake of 50 mg/day of gluten for 3 months could be useful for CeD diagnosis. We performed a dietary study, administering a low dose of gluten in form of "crackers" (about 60–120 mg of gluten/day) for 3 months, to get a final diagnosis of CeD in subjects already on GFD. We enrolled adult patients with a suspicion of CeD on self-prescribed GFD. All subjects performed the crackers challenge for 3 months. At the end, all patients were analysed for CeD serology and if positive underwent endoscopy/histology. Also, we recorded the grade of satisfaction for the gluten challenge and the onset of adverse events. We enrolled 120 patients. All patients concluded the challenge without relevant adverse events. Serological positivity was detected in 54 patients (45%). Histology showed atrophy in 87% and Marsh 1–2 grade in 13% of patients. Ninety-nine patients (83%) were satisfied by this challenge. The "crackers challenge" is a useful and safe diagnostic approach in people on self-administered GFD. [ABSTRACT FROM AUTHOR]

Metabolic dysfunctions, particularly hyperlipidemia, are a common finding in Primary Biliary Cholangitis (PBC). In presence of metabolic components of fatty-liver-disease (MAFLD), the liver fibrosis progression risk is higher. The aim of this study was to evaluate lifestyle of PBC patients compared to controls. In a prospective, multicenter study 107 PBC patients were enrolled; among these, 54 subjects were age-and sex-matched with 54 controls with a propensity-score-matching-analysis. Eating habits and physical activity were evaluated, respectively, with a food-frequency-questionnaire and with a short pre-validated-questionnaire. The adherence to Mediterranean diet was assessed with the alternate Mediterranean diet score. The total fat intake was higher in controls than in PBC (p =0.004), unless above the national recommendations in both groups. Moreover, in PBC monounsaturated-fat and polyunsaturated-fatty-acid intakes and the adherence to Mediterranean diet were significantly lower than in controls (p <0.001, p =0.005 and p <0.001 respectively). Regarding physical activity, PBC subjects had a sedentary behavior as well as controls. The lifestyle of both PBC and controls is at high risk of developing MAFLD. Therefore, hepatologists should regularly evaluate eating habits and physical activity in PBC patients and promote a lifestyle change to reduce liver disease progression risk. [ABSTRACT FROM AUTHOR]

Vascular liver diseases are an heterogenous group of diseases that collectively represent an important health issue in the field of liver diseases. This narrative review was elaborated by the Special Interest Group (SIG) "Gender in Hepatology" of the Italian Association for the Study of the Liver (AISF). We aimed to review the current knowledge regarding the potential role of biological sex in patients with vascular liver diseases such as splanchnic vein thrombosis, hepatic vein thrombosis, porto-sinusoidal vascular disorder, and hereditary hemorrhagic telangiectasia. As vascular liver diseases commonly affect young individuals, including women in childbearing age, we also included a specific section on the management of pregnancy in these challenging patients. [ABSTRACT FROM AUTHOR]

Comprehensive and contemporary data pertaining large populations of patients with Primary Biliary Cholangitis (PBC) and hepatocellular carcinoma (HCC) are missing. To describe main characteristics and outcome of PBC patients with HCC diagnosed in the new millennium. Analysing the Italian Liver Cancer registry we identified 80 PBC patients with HCC diagnosed after the year 2000, and described their clinical characteristics, access to treatment and survival. Median age of patients was 71 years and 50.0% were males. Cirrhosis was present in 86.3% of patients, being well-compensated in 58.0%. Median HCC diameter was smaller in patients under surveillance (2.6 vs 4.0 cm, P = 0.007). Curative treatment, feasible in 50.0% of patients, was associated with improved survival compared to palliative and supportive care (42 vs 33 vs 6 months, P <0.0001). Surveillance was associated with a non-significant improved survival (36 vs 23 months), likely due to similar rate of curative treatment in patients under (51.4%) and outside surveillance (42.6%). PBC patients with HCC are often elderly males with well-preserved liver function. Feasibility of curative treatment is high and associated with improved prognosis. Description of these patients may help focus surveillance to identify earlier tumours, increase their curability, and improve prognosis. [ABSTRACT FROM AUTHOR]

Sarcopenia, defined as progressive and generalized loss of muscle mass and strength, is common in chronic liver disease. It significantly impacts the quality of life and increases the risk of liver-related complications and mortality in cirrhotic patients. Moreover, recent studies showed a negative impact of sarcopenia on patients awaiting liver transplantation (LT), on post-LT outcomes, and on response to hepatocellular carcinoma therapies. Data about the influence of sex on the incidence, prevalence, diagnosis and treatment of sarcopenia in chronic liver diseases are poor and conflicting. The aims of this review of the literature are to define sex differences in sarcopenic cirrhotic patients and to highlight the necessity of a sex stratified analysis in future studies. This analysis of the literature showed that most of the studies are retrospective, with a higher prevalence of sarcopenia in males, probably due to anatomical differences between the sexes. Moreover, diagnostic criteria for sarcopenia are different between studies, as there is not a defined cut-off and, as a consequence, no comparable results. In conclusion, sex seems to have an impact on sarcopenia, and future studies must accurately investigate its role in identifying and treating high-risk patients, reducing the negative impact of sarcopenia on the survival and quality of life of cirrhotic patients. [ABSTRACT FROM AUTHOR]

Mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave (PSPW) index are able to increase the diagnostic yield of impedance-pH and are associated to proton pump inhibitor (PPI) response. Few data concerning these variables in patients with extra-esophageal symptoms (EES) are available. To evaluate, in EES patients, the role of the conventional and new impedance-pH variables in diagnosing GERD and the predictive value of impedance-pH variables for PPI response. Consecutive patients presenting suspected GERD-related EES underwent impedance-pH. Patients treated in the last six months with double dose PPI therapy were enrolled. The presence of concomitant typical symptoms was assessed. 239 EES patients were studied; 102 responders and 137 non-responders. Eighty-one (34%) were affected by non-erosive reflux disease (NERD), 61 (26%) presented reflux hypersensitivity (RH) and 97 (40%) were non-GERD. In NERD and RH groups, a significantly higher proportion of patients with pathological PSPW index or MNBI values compared to non-GERD group was observed. 24 (25%) non-GERD patients presented a pathological PSPW index and/or MNBI. Pathological PSPW index, MNBI and presence of typical symptoms were associated to PPI response. MNBI and PSPW index measurement increases the diagnostic yield of impedance-pH; abnormal values are associated with a satisfactory response to acid-suppressive therapy in EES patients. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) recurrence is common in patients treated with liver resection (LR). Salvage liver transplantation (LT) may be an option provided that a transplantable recurrence has occurred. We aimed to assess incidence and preoperative predictors of recurrence beyond Milan criteria (MC) in patients with small (≤ 5 cm) single HCC treated with first-line LR. Data of 512 patients with single HCC ≤5 cm treated with frontline LR were retrieved from the Italian Liver Cancer (ITA.LI.CA) database. Incidence and predictors of recurrence beyond MC was compared across two groups according to tumor diameter (HCC ≤3 cm vs. >3 cm). During a median follow-up of 4.2 years, the overall recurrence rate was 55.9%. Only 18.0% of patients had a first recurrence beyond MC (14.0% in the ≤3 cm group and 23.9% in the >3 group; p=0.005), while the overall recurrence rate beyond MC was 30.3% (25.1% and 38.0% patients in the ≤3 cm and >3 cm groups, respectively; p=0.002) (Figure). Compared to those with larger tumors, patients with HCC ≤3 cm had a longer recurrence-free survival (4.0 [95% CI 3.3-4.7] vs. 2.5 [95% CI 2.0-3.0] years; p=0.002) and overall survival (9.9 [95% CI 6.5-13.4] vs. 7.8 [95% CI 5.7-9.9] years; p=0.008). HCC size and alpha-fetoprotein (AFP) level at the time of LR were independent predictors of recurrence beyond MC. A subanalysis in patients with "ab initio" potentially transplantable HCC confirmed these results. Despite the high recurrence rate, LR for single HCC ≤ 5 cm offers excellent long-term survival. Recurrence beyond MC is predicted by HCC size and AFP levels. Referral for salvage LT should be immediate at the first HCC recurrence, but high-risk patients (HCC >3 cm and high AFP) could be considered for frontline LT or listed for transplantation even before recurrence. [ABSTRACT FROM AUTHOR]

In Italy, the prevalence of HDV infection in HBsAg carriers is about 9.9% (6.4% in Italian natives and 26.4% in immigrants). However, the actual prevalence is probably underestimated because the anti-HDV test is not performed routinely in all HBsAg carriers. The HDV causes a rapidly progressive liver disease and as new antiviral therapies are coming, it is fundamental to known the exact HDV prevalence. The aim of this study was to assess the real HDV prevalence in the AOU Federico II. From April 2021 to July 2022, reflex test for the detection of total HDV antibodies was performed in all HBsAg positive subjects observed at AOU Federico II. Demographic, clinical and laboratory data were collected. Liver fibrosis was evaluated with FIB-4. Sera were evaluated with ADVIA Centaur HBsAgII Qualitative, Liaison Murex HBsAg Quantitative and Liaison Murex Total Anti-HDV Qualitative. Of 365 HBsAg carriers, 46 (12.6%) resulted positive for total anti-HDV. The majority of them (89.2%) were Italian natives and only 5 (10.8%) of them were immigrants. Twenty-one (45.6%) were males with a median age of 62.2 years. Thirty-five (76%) patients were already aware of HBV/HDV coinfection. HDV-RNA was performed in 18 (39.1%) subjects and resulted detectable in 15 (83.3%) of them, with a median HDV-RNA level of 84.300 [25th – 75th percentiles: 1.685-547.796] IU/ml. Twenty (43.5%) anti-HDV positive subjects had advanced liver fibrosis. Our data showed that the HDV prevalence is higher than expected, demonstrating that the reflex test in HBsAg carriers could be a useful approach to identify the real prevalence of HDV infection. Moreover, the HDV-RNA is performed only in the minority of the anti-HDV positive subjects. In this setting, due to the forthcoming approval of specific anti-HDV drugs, a reflex test for HDV-RNA should be implemented to identify viremic patients needing antiviral treatment. [ABSTRACT FROM AUTHOR]

Growing evidence supports the potential role of intestinal microbiota in the pathophysiology of inflammatory bowel diseases (IBD) even if the literature does not reveal uniform alterations. The aim of the study was to evaluate the mucosal (MM) and faecal microbiota (FM) composition in a cohort of IBD patients compared to healthy controls (CTRLs). Faecal and mucosal samples were collected from 14 IBD patients and 11 CTRLs. The V1-V3 region of 16S rRNA locus was amplified on a 454-Junior Genome Sequencer. Reads were grouped into operational taxonomic units (OTUs) at a sequence similarity level of 97% for taxonomic assignment, and aligned for OTUs matching against Greengenes database. Irrespective of disease localization and activity, in the MM of IBD patients a statistically significant increase of Proteobacteria (especially Enterobacteriaceae, Acidaminococcus , Veillonella dispar) and decrease of Firmicutes (especially Roseburia and Faecalibacterium prausnitzii) and Actinobacteria was found compared to CTRLs. In the colon district some specific bacterial biomarkers were identified: Enterobacteriaceae for IBD stools, Bacteroides for IBD biopsies, Mogibacteriaceae, Ruminococcaceae and Prevotella for CTRL stools, Ruminococcaceae for CTRL biopsies. The profiles of FM were more similar to CTRLs, suggesting that microbiota adhering to the gut mucosa better discriminates patients from controls, with the identification of some interesting biomarkers. [ABSTRACT FROM AUTHOR]

Abstract Background In liver cirrhosis, the renin-angiotensin-aldosterone system is involved in the pathogenesis of portal hypertension. Its effector, angiotensin II, is generated by angiotensin-converting enzyme (ACE). Serum ACE levels are affected by I/D polymorphism of its gene, with alleles I and D being associated, respectively, with lesser and greater activity of the enzyme. In cirrhotic patients carrying the ACE I allele, an increased risk for gastro-oesophageal varices was observed. Aim The aim of our study was to evaluate whether ACE I/D polymorphism influenced portal pressure. Methods Fifty-one consecutive cirrhotic patients were divided based on ACE genotype (DD, ID, and II). Kidney and liver function tests, upper endoscopy, and hepatic venous pressure gradient measurement (HVPG) were performed in all patients. Results The presence of the ACE I allele was associated with a higher HVPG value (18.7 ± 6.4 vs 10.3 ± 6.3 mmHg; P <.001), higher frequency of large gastrooesophageal varices (59.3% vs 25.0%; P <.05), and higher frequency of variceal bleeding (63.0% vs 29.2%; P <.05). No significant differences were found between patients with and those without the ACE I allele regarding Child-Pugh score, MELD score, ascites, and hepatic encephalopathy. Conclusion ACE I/D polymorphism seems to influence the severity of portal hypertension and the risk of variceal bleeding in liver cirrhosis, regardless of the severity of liver disease. [ABSTRACT FROM AUTHOR]

Abstract Although studies suggest decreased incident hepatocellular carcinoma (HCC) after treatment with direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection, data are conflicting regarding risk and aggressiveness of recurrence in patients who have a history of treated HCC. This review analyses data available in literature in order to elucidate the impact of DAAs on the risk of HCC recurrence after successful treatment of the tumor. Overall 24 papers were identified. The available data cannot be considered definitive, but the initial alarmist data indicating an increased risk of recurrence have not been confirmed by most subsequent studies. The suggested aggressive pattern (rapid growth and vascular invasion) of tumor recurrence after DAAs still remains to be confirmed. Several limitations of the available studies were highlighted, and should drive future researches. The time-to-recurrence should be computed since the last HCC treatment and results stratified for cirrhosis and sustained viral response. Any comparison with historical series is of limited interest because of a number of biases affecting these studies and differences between enrolled patients. Prospective intention-to-treat analyses will be probably the best contribution to drive clinical practice, provided that a randomized trial can be difficult to design. [ABSTRACT FROM AUTHOR]

Background Available data on HBV prevalence in Italy are outdated and assessed with studies conducted in small towns. We aimed to evaluate prevalence of and risk factors for HBV infection in the metropolitan area of Naples, 24 years after the introduction of mass vaccination campaign against Hepatitis B in Italy. Methods A random systematic sample of the adult general population of Naples was selected from the register of 3 general practitioners in 3 different socio-economic districts. Independent predictors of the likelihood of HBV infection were identified by logistic regression analysis. Results Among 900 selected subjects, 772 (85.8%) participated in the study. The overall HBsAg and anti-HBc prevalences were 1.7% and 14.4%, respectively. Both markers were more likely detected in the district at low socioeconomic status than in those at medium–high status (p < 0.01). Anti-HBc prevalence linearly increased from 0% in subjects 30 years old or younger to 28.0% in those older than 60 years of age (p < 0.01). At multivariate analysis, age >60 years (OR3.38; 95%CI:1.98–5.74), low socioeconomic district of residence (OR3.26; 95%CI:1.72–6.18), and low educational qualification (OR2.73; 95%CI:1.45–5.16) were independent predictors of anti-HBc positivity. Conclusion Differences in socioeconomic conditions have played a major role in the past spread of HBV infection in Naples. Hepatitis B vaccination has resulted very effectively in preventing HBV infection, regardless of the district of residence, as none of the subjects in the vaccinated cohorts was exposed to the infection. [ABSTRACT FROM AUTHOR]

Background Altered body composition is frequently observed in Crohn’s disease (CD) patients. Aims To investigate the nutritional status, and the effect of different therapeutic regimes in adult CD patients. Methods Fat free mass (FFM) and BIA-derived phase angle (PhA) were assessed in 45 CD patients, 22 on conventional therapy (CT) and 23 on maintenance therapy with infliximab (MT). Nutritional status was also assessed in 12 CD patients before and following the induction protocol with infliximab. BIA data of CD patients were compared with those of 20 healthy asymptomatic volunteers. In CD patients C Reactive Protein (CRP) and albuminaemia dosage were obtained. Results The mean values of PhA and of FFM were significantly lower in CT patients when compared with control group and MT patients. Following infliximab treatment FFM increased, although not significantly, while mean phase angle value significantly increased from 4.6 ± 0.3 to 6.2 ± 0.4 (p < 0.05). CRP was significantly lower in MT patients compared to that in CT patients. Conclusion CD patients on conventional therapy showed a lower FFM and a lower mean phase angle score compared to those on infliximab therapy. Following infliximab treatment the mean phase angle score normalized. PhA is a reliable nutritional indicator in IBD patients and could be considered as an additional tool for assessing response to treatment. [ABSTRACT FROM AUTHOR]

Emerging reports suggest a relationship between thyroid hormones (TH) signalling pathways and liver diseases, including hepatocellular carcinoma (HCC). Although it has been proven that the expression of deiodinases type 1 and 3 (D1-3) changes during induced liver injury, their role is still poorly understood in hepatocarcinogenesis. We aimed to evaluate the role of deiodinases and their regulation in liver carcinogenesis. This is a proof of knowledge introductory to an ongoing monocentric prospective study. We enrolled 19 patients underwent liver surgery for HCC (10 cases) or for other non-neoplastic liver diseases in non-cirrhotic context (9 controls). We evaluated genes and protein expression of the main TH metabolism factors (D1, Monocarboxylate transporter-MCT8, Thyroid receptors-TR alpha and beta and Kruppel-like factor-KLF-9), with RT-PCR and Western blot analysis in HCC, cirrhotic tissue and healthy liver samples. RT -PCR analysis showed a progressive statistically significant decrease of D1 (p=0.004), MCT-8 (p=0.001) and TRα (p=0.02) mRNA expression from healthy liver to HCC. The expression of KLF9, involved in cell differentiation and proliferation, decreased accordingly (p=0.03). Western Blot analysis showed a decreased expression of D1 protein in all cirrhotic samples (p=0.01), while D3 increased in 50% of HCC (p=0.02). Among HCC patients, D3 expression was associated with more severe liver stiffness (32 kPa, IQR:23.47-35.5, p=0.002) and high BMI (p=0.004). A statistically significant overall survival (OS) difference between D3 positive and D3 negative HCC patients was observed (log rank p=0.003), with a median OS of 17.9 (IQR:15.5-18.7) months for D3 positive vs 41.3 (IQR:35.1-43.8) months in D3 negative. Furthermore, a shorter Progression Free Survival and an increased recurrence rate was observed in D3 positive patients, even if not statistically significant. These preliminary data showed that D3 expression could define a more severe phenotype of HCC and it could be used in clinical practice as negative prognostic biomarker. [ABSTRACT FROM AUTHOR]

Several studies showed that patients with liver cirrhosis have an immune dysregulation leading to poor immunological response to vaccination. However, in literature there are few data about the response to SARS-CoV-2 vaccination in patients with chronic liver disease (CLD). Aims of the study are (is) the evaluation of safety and immunogenicity of booster dose in patients with CLD. From September 2021 to April 2022, all consecutive outpatients with CLD who completed the primary vaccination course and the booster dose for anti-SARS-CoV-2 vaccination were enrolled. Blood samples were collected 12-16 weeks after second dose and after booster dose. Collected samples were analyzed for detecting anti-Spike protein IgG using LIAISON TrimericS IgG chemiluminescent assay (Diasorin, Italy). We enrolled 340 patients (187 Males, mean age:64.32±17.34years). Stratified by the presence of cirrhosis, 249 had CLD and 91 were cirrhotic whose 57 (62.24%) had portal hypertension. At the end of the primary vaccination course, 60 patients (17.65%) did not develop a protective antibody titer, with no statistically significant differences between the two groups (19.7% in cirrhotic vs 16.8% in non-cirrhotic; p=0.076). The majority of them (53/60 patients; 88.3%) developed a protective titer after booster dose, without differences between cirrhotics and non-cirrhotics (p=0.089). At multivariate analysis, factors associated with a higher humoral response after booster dose were young age (p=0.0098); porto-sinusoidal vascular disorder (p=0.005), none or a single comorbidity rather than two or more (p=0.05) and Spikevax booster dose compared with Comirnaty (p=0.001). Moreover, the antibody titer is inversely related to age (p=0.000). In a large cohort of patients with CLD booster dose of anti-Sars-CoV-2 vaccine has an excellent immunogenicity and leads to an adequate antibody response even in those who had not produced a protective titer after the primary vaccination course. Cirrhosis is not associated with a reduced humoral response. [ABSTRACT FROM AUTHOR]

Abstract: Background: Impairment of gastrointestinal motility is frequently observed in patients with severe infection. Aim: To assess whether exposure of human colonic mucosa to pathogenic lipopolysaccharide affects smooth muscle contractility. Methods: Human colonic mucosa and submucosa were sealed between two chambers, with the luminal side facing upwards and covered with Krebs solution, with or without lipopolysaccharide from a pathogenic strain of Escherichia coli (O111:B4; 1000ng/mL), and with the submucosal side facing downwards into Krebs. The solution on the submucosal side was collected following 30-min mucosal exposure to Krebs without (N-undernatant) or with lipopolysaccharide (lipopolysaccharide undernatant). Undernatants were tested for lipopolysaccharide and hydrogen peroxide levels and for their effects on smooth muscle cells in the presence of catalase, indomethacin or MG132. Results: Smooth muscle cells incubated with N-undernatant had a maximal contraction of 32±5% that was reduced by 62.9±12% when exposed to lipopolysaccharide undernatant. Inhibition of contraction was reversed by catalase, indomethacin and MG132. Lipopolysaccharide levels were higher in the lipopolysaccharide undernatant (2.7±0.7ng/mL) than in N-undernatant (0.45±0.06ng/mL) as well as hydrogen peroxide levels (133.75±15.9 vs 82±7.5nM respectively). Conclusions: Acute exposure of colonic mucosa to pathogenic lipopolysaccharide impairs muscle cell contractility owing to both lipopolysaccharide mucosal translocation and production of free radicals. [Copyright &y& Elsevier]

Abstract: Background: Dilation of intercellular space diameters of oesophageal epithelium detected at transmission electron microscopy morphometry is a marker of tissue injury in non-erosive reflux disease patients. Semi-quantitative evaluation of intercellular space diameters using light microscopy seems to provide promising results. Aim/methods: To comparatively evaluate intercellular space diameters in the same patients, by means of morphometry and semi-quantitative analysis, both on light microscopy and transmission electron microscopy microphotographs, biopsies were taken in 29 non-erosive reflux disease patients at distal and proximal oesophagus. Twelve asymptomatic controls underwent the same protocol. Results: Morphometric analysis on transmission electron microscopy microphotographs showed mean intercellular space diameter values of patients, at distal and proximal oesophagus, 3- and 2-fold, respectively, higher than those in controls (p <0.001). On light microscopy microphotographs, mean intercellular space diameter values of patients at distal oesophagus were higher than those in controls, an overlap between patients and controls being observed. The semi-quantitative score was positive in 79% of patients and in 25% of controls at distal esophagus. Conclusions: Intercellular space diameter morphometric analysis at light microscopy is widely available, allows intercellular space diameter to be quantitatively measured with good sensitivity and specificity and could represent a useful tool in non-erosive reflux disease diagnosis. Despite satisfactory sensitivity, the semi-quantitative score at light microscopy is hampered by much lower specificity than transmission electron microscopy- and light microscopy-morphometry. [Copyright &y& Elsevier]

Abstract: Chronic intestinal pseudo-obstruction represents a cause of persistent functional intestinal failure either “secondary” to specific conditions or “chronic intestinal idiopathic pseudo-obstruction” in origin. The diagnosis is mainly clinical, supported by radiological and/or endoscopic findings excluding any mechanical cause of intestinal obstruction. We reported a case of a 39-year-old woman with chronic intestinal idiopathic pseudo-obstruction, who underwent colectomy with ileorectal anastomosis; histological examination of the surgical specimen did not reveal myogenic or neurogenic defects or other pathological abnormalities indicative of an underlying neuromuscular impairment. Because of the apparent integrity of the gut neuromuscular layer, we tested whether a functional impairment affected colonic single smooth muscle cells. Muscle cells were isolated from the right colon and their contractile response to a receptor-dependent agonist evaluated in comparison to that obtained from controls. The cell contraction induced by acetylcholine in a dose response manner was markedly decreased in the patient affected by chronic intestinal idiopathic pseudo-obstruction compared with cells from controls (percentage of cell shortening with maximal dose of acetylcholine [10−6 M]: 10.7±3% versus 34.2±4%, respectively). The present findings indicate a specific defect of colonic smooth muscle cells likely related to an ineffective response to acetylcholine. [Copyright &y& Elsevier]