Eleonora Scaioli

Measurement of Spleen Stiffness to Evaluate Portal Hypertension and the Presence of Esophageal Varices in Patients With HCV-Related Cirrhosis

BACKGROUND & AIMS The hepatic vein pressure gradient (HVPG) is the standard used to determine the degree of portal hypertension (PH) and an important prognostic factor for patients with cirrhosis; HVPG values correlate with the presence of esophageal varices (EV). However, HVPG can only be accurately determined at specialized centers; noninvasive methods are needed to predict HVPG values and the presence of EV. We compared the diagnostic performance of spleen stiffness (SS) measurement by transient elastography with that of liver stiffness (LS) and of other recently proposed noninvasive tests. METHODS We measured SS and LS in 100 consecutive patients with hepatitis C virus-induced cirrhosis. Patients were also assessed by FibroScan, HVPG, esophagogastroduodenoscopy, and liver biopsy. We also analyzed LS-spleen diameter to platelet ratio score and platelet count to spleen diameter. RESULTS SS and LS were more accurate than other noninvasive parameters in identifying patients with EV and different degrees of PH. A linear model that included SS and LS accurately predicted HVPG values (R(2) = 0.85). The results were internally validated using bootstrap analysis. CONCLUSIONS Measurement of SS can be used for noninvasive assessment and monitoring of PH and to detect EV in patients with hepatitis C virus-induced cirrhosis.

Review article: the diagnosis of non‐alcoholic fatty liver disease – availability and accuracy of non‐invasive methods

Non‐alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of clinical conditions, actually representing an emerging disease of great clinical interest. Currently, its diagnosis requires liver biopsy, an invasive procedure not free from potential complications. However, several non‐invasive diagnostic strategies have been proposed as potential diagnostic alternatives, each with different sensitivities and accuracies.

Natural history of gallstone disease: Expectant management or active treatment? Results from a population-based cohort study

Background and Aims:  The knowledge of natural history is essential for disease management. We evaluated the natural history (e.g. frequency and characteristics of symptoms and clinical outcome) of gallstones (GS) in a population‐based cohort study.

Pre-operative liver biopsy in cirrhotic patients with early hepatocellular carcinoma represents a safe and accurate diagnostic tool for tumour grading assessment

BACKGROUND & AIMS Knowledge of pre-operative tumour grade is crucial in the management of hepatocellular carcinoma (HCC) because it can influence recurrence and survival after surgery. The accuracy of pre-operative needle core biopsy (NCB) in tumour grading has been assessed in only a few studies with conflicting results. Our aim was to determine the long-term safety and the overall accuracy of NCB in assessing tumour grading in subjects who had undergone liver resection for a single HCC. METHODS Eighty-one cirrhotic patients with HCC who had undergone NCB before liver resection were selected. Only patients with a single HCC and with at least a five-year-follow-up were included. Tumour grading was scored according to a modified Edmondson-Steiner classification: well/moderately (low grade) vs poorly-differentiated (high grade). RESULTS In the 81 patients with a solitary HCC (mean size 4.1 ± 2.3cm) tumour grade was correctly identified by NCB in 74 out of 81 (91.4%) HCCs. NCB overall sensitivity and specificity were 65% and 98.1%, respectively, with a PPV of 92% and an NPV of 91%. No major complications (in particular tumour seeding) were observed. The overall survival rates at 1, 3, and 5 years were 83%, 62%, and 44%, respectively; the recurrence rate after a 5-year-follow-up was 56.2% for low grade and 82.3% for high grade tumours (p<0.007). CONCLUSIONS Pre-operative NCB can be performed on early (<5 cm) HCC cirrhotic patients because it provides histologically useful information for HCC management with good accuracy and a low complication rate.

Gut Microbiota and Its Pathophysiology in Disease Paradigms

The gut flora carries out important functions for human health, although most of them are still unknown, and an alteration of any of them, due to a condition of dysbiosis, can lead to relevant pathological implications. Commensal bacteria in the gut are essential for the preservation of the integrity of the mucosal barrier function and an alteration in the anatomic functional integrity of this barrier has been implicated in the pathophysiologic process of different diseases. The gut microflora plays a role in modulating the intestinal immune system; in fact, it is essential for the maturation of gut-associated lymphatic tissue, the secretion of IgA and the production of antimicrobial peptides. The enteric flora represents a potent bioreactor which controls several metabolic functions, even if most of them are still unknown. The main metabolic functions are represented by the fermentation of indigestible food substances into simple sugars, absorbable nutrients, and short-chain fatty acids. Furthermore, the gut microbiota exerts important trophic and developmental functions on the intestinal mucosa. This overview focuses briefly on the physiological role of the gut microbiota in maintaining a healthy state and the potential role played by disturbances of both the function and composition of the gut microbiota in determining important pathological conditions, such as irritable bowel syndrome, inflammatory bowel disease, metabolic syndrome, obesity, and cancer.

Gut microbiota, metabolome and immune signatures in patients with uncomplicated diverticular disease

Objective The engagement of the gut microbiota in the development of symptoms and complications of diverticular disease has been frequently hypothesised. Our aim was to explore colonic immunocytes, gut microbiota and the metabolome in patients with diverticular disease in a descriptive, cross-sectional, pilot study. Design Following colonoscopy with biopsy and questionnaire phenotyping, patients were classified into diverticulosis or symptomatic uncomplicated diverticular disease; asymptomatic subjects served as controls. Mucosal immunocytes, in the diverticular region and in unaffected sites, were quantified with immunohistochemistry. Mucosa and faecal microbiota were analysed by the phylogenetic platform high taxonomic fingerprint (HTF)-Microbi.Array, while the metabolome was assessed by 1H nuclear magnetic resonance. Results Compared with controls, patients with diverticula, regardless of symptoms, had a >70% increase in colonic macrophages. Their faecal microbiota showed depletion of Clostridium cluster IV. Clostridium cluster IX, Fusobacterium and Lactobacillaceae were reduced in symptomatic versus asymptomatic patients. A negative correlation was found between macrophages and mucosal Clostridium cluster IV and Akkermansia. Urinary and faecal metabolome changes in diverticular disease involved the hippurate and kynurenine pathways. Six urinary molecules allowed to discriminate diverticular disease and control groups with >95% accuracy. Conclusions Patients with colonic diverticular disease show depletion of microbiota members with anti-inflammatory activity associated with mucosal macrophage infiltration. Metabolome profiles were linked to inflammatory pathways and gut neuromotor dysfunction and showed the ability to discriminate diverticular subgroups and controls. These data pave the way for further large-scale studies specifically aimed at identifying microbiota signatures with a potential diagnostic value in patients with diverticular disease.

Gut Microbiota and Celiac Disease

Recent evidence regarding celiac disease has increasingly shown the role of innate immunity in triggering the immune response by stimulating the adaptive immune response and by mucosal damage. The interaction between the gut microbiota and the mucosal wall is mediated by the same receptors which can activate innate immunity. Thus, changes in gut microbiota may lead to activation of this inflammatory pathway. This paper is a review of the current knowledge regarding the relationship between celiac disease and gut microbiota. In fact, patients with celiac disease have a reduction in beneficial species and an increase in those potentially pathogenic as compared to healthy subjects. This dysbiosis is reduced, but might still remain, after a gluten-free diet. Thus, gut microbiota could play a significant role in the pathogenesis of celiac disease, as described by studies which link dysbiosis with the inflammatory milieu in celiac patients. The use of probiotics seems to reduce the inflammatory response and restore a normal proportion of beneficial bacteria in the gastrointestinal tract. Additional evidence is needed in order to better understand the role of gut microbiota in the pathogenesis of celiac disease, and the clinical impact and therapeutic use of probiotics in this setting.

Autoimmune liver diseases in a paediatric population with coeliac disease - a 10-year single-centre experience.

Backgroud  Coeliac disease (CD) can be associated with liver disease. Gluten‐free diet (GFD) normalizes cryptogenic forms, but most likely not autoimmune hepatitis (AIH). For this condition, immunosuppressants represent the treatment. However, when these are stopped, AIH generally relapses.

Natural history of small gallbladder polyps is benign: evidence from a clinical and pathogenetic study.

OBJECTIVES:Little is known about the natural history and pathogenesis of small gallbladder polyps (<10 mm, usually of the cholesterol type), particularly in Western populations. It is unclear if these polyps and gallstones represent different aspects of the same disease. The aim of this study was to characterize the natural history and pathogenesis of small gallbladder polyps.METHODS:Fifty-six Caucasian patients with small gallbladder polyps, 30 matched gallstone patients, and 30 controls were enrolled in this 5-year prospective study. Patients underwent a symptomatic questionnaire, abdominal ultrasonography, and ultrasonographic evaluation of gallbladder motility at baseline and yearly intervals for 5 years. Cholesterol saturation index, cholesterol crystals in bile, and apolipoprotein E genotype were also determined.RESULTS:Most patients with polyps (mean size: 5.3 mm) were men (61%), asymptomatic, and had multiple polyps (57%). Polyps did not change in 91% of patients during follow-up. No subject experienced biliary pain or underwent cholecystectomy; four developed gallstones. Cholesterol saturation index was higher in patients with polyps or gallstones than in controls (P<0.05). Cholesterol crystals were more frequent in patients with polyps than in controls (P<0.0001) but less common than in gallstone patients (P<0.0001). Polyps and gallstones were associated with nonapolipoprotein E4 phenotypes.CONCLUSIONS:The natural history of small gallbladder polyps was benign, as no patient developed specific symptoms and/or morphological changes in polyps. Consequently, a “wait and see” policy is advisable in these patients. Polyps have some pathogenetic mechanisms in common with gallstones, but few patients developed gallstones.

Non-invasive methods can predict oesophageal varices in patients with biliary atresia after a Kasai procedure

BACKGROUND After a Kasai procedure, 70% of patients with biliary atresia develop chronic liver disease with portal hypertension and oesophageal varices. AIMS To investigate the role of new non-invasive parameters in predicting the presence of varices in patients with biliary atresia after a Kasai procedure and to identify the cut-off values of these parameters in predicting the presence of varices. METHODS 31 patients with biliary atresia who had undergone a Kasai portoenterostomy were studied. Clinical, biochemical and abdominal ultrasound examination, liver stiffness measurement (LSM), LSM-spleen diameter to platelet ratio score (LSPS) and upper digestive endoscopy were performed. RESULTS 15 (47%) patients had oesophageal varices (Group A) and 16 had no varices (Group B). Median values of LSM (kPa) and LSPS were significantly higher in Group A than in Group B (LSM: 17.0 vs. 7.5, respectively; p=0.0001; LSPS: 19.62 vs. 2.94, respectively; p=0.0001). The optimal cut-offs for predicting oesophageal varices were: LSM>10.6 kPa (sensitivity: 87%, specificity: 87.5%, PPV: 87%, NPV: 87.5%, and AUC: 0.92) and LSPS ≥9.2 (sensitivity: 91%, specificity: 92%, PPV: 91%, NPV: 92%, and AUC: 0.96). CONCLUSIONS Non-invasive methods can predict the presence of oesophageal varices in patients with biliary atresia; the sequential use of two non-invasive methods improves accuracy.