Spleen stiffness can be employed to assess the efficacy of spontaneous portosystemic shunts in relieving portal hypertension

Introduction: Spleen stiffness (SS) has been found to mirror dynamic changes in portal pressure after transjugular intrahepatic portosystemic shunt (TIPS) placement. However, there is no data available regarding SS in patients with spontaneous portosystemic shunting (SPSS), especially in regards to prediction of hepatic decompensation. Methods: We retrospectively selected patients with confirmed SPSS and esophageal varices (EVs) at endoscopic examination, and recorded any decompensating event (i.e., variceal hemorrhage, overt hepatic encephalopathy, refractory ascites, spontaneous bacterial peritonitis, hepatorenal syndrome) in the first twelve months following liver and spleen elastography. Results: The patients who presented decompensating events showed lower platelet count (94.5 vs. 121.5 g/L, p < 0.001), higher SS (44 vs. 30 kPa, p < 0.001), higher probability of EVs according to SS (77 vs. 2 %, p < 0.001), and higher spleen diameter (14 vs. 12 cm, p = 0.043). They also showed a higher prevalence of splenorenal shunts (66.7 vs. 31.2%), and a significantly wider SPSS major diameter (14.5 vs. 8 mm, p < 0.001). Conclusion: SS could predict SPSS efficacy in relieving portal pressure, and could predict decompensating events in patients with SPSS

Spleen Stiffness Probability Index (SSPI): A simple and accurate method to detect esophageal varices in patients with compensated liver cirrhosis

8noIntroduction and objectives: Recent findings pointed out that even low-risk esophageal varices (EVs) are markers of severe prognosis. Accordingly, we analyzed spleen stiffness (SS) as a non-invasive method to predict EVs of any grade in a cohort of patients with compensated liver cirrhosis. Method: We measured SS and liver stiffness (LS) using point-Shear-Wave Elastography (pSWE) with Philips Affiniti 70 system in 210 cirrhotic patients who had undergone endoscopic screening for EVs. We compared SS and LS predictive capability for EVs of any grade. Results: SS was higher in cirrhotic patients with EVs if compared to patients without EVs (p < 0.001). The cut-off analysis detected 31 kPa (100% sensitivity and negative predictive value) as the value to rule-out EVs and 69 kPa (100% specificity and positive predictive value) to rule-in EVs. Besides, we developed the Spleen Stiffness Probability Index (SSPI), that can provide a probability of presence/absence of EVs. SSPI was the best model according to all discriminative and calibration metrics (AIC = 120, BIC = 127, AUROC = 0.95, Pseudo-R2 = 0.74). SS demonstrated higher correlation with spleen bipolar diameter and spleen surface (r = 0.52/0.55) if compared to LS (r = 0.30/0.25) – and with platelet count as well (r = 0.67 vs r = 0.4). Conclusion: SS showed significantly higher performance than other parameters, proving to be the best non-invasive test in the screening of EVs: by directly applying SS cut-off of 31 kPa, our department could have safely avoided endoscopy in 36% of patients. Despite cut-off analyses, it was possible to create a probability model that could further stratify low-risk from high-risk patients (for any grade of EVs).openopenGiuffrè M.; Macor D.; Masutti F.; Abazia C.; Tine F.; Bedogni G.; Tiribelli C.; crocèGiuffrè, M.; Macor, D.; Masutti, F.; Abazia, C.; Tine, F.; Bedogni, G.; Tiribelli, C.; Croce', Saveri

Evaluation of spleen stiffness in healthy volunteers using point shear wave elastography

Introduction and Objectives: This study aims to measure the values of spleen stiffness (SS) in healthy subjects, the inter-operator agreement in SS measurement, and to detect statistically significant correlations between SS and age, sex, weight, BMI, portal vein dynamics and splenic dimensions. Materials and methods: The study included 100 healthy volunteers who had no substantial alcohol intake (<30 g/daily for man, <20 g/daily women), were negative on hepatitis B, hepatitis C, HIV blood serology, and had any history of lymphoproliferative disorders. Abdominal ultrasound, liver and spleen elastography were performed on each patient to search for focal splenic lesions, bile tract or portal vein dilatation, moderate/severe liver steatosis, and to measure liver and spleen stiffness. Results: The mean value was 18.14 (+/- 3.08) kPa. In the group of men (n= 49), the mean was 17.73 (+/- 2.91) kPa, whereas in the group of women (n= 51) it was 16.72 (+/- 3.32) kPa. Statistical analyses showed no correlation between spleen stiffness and sex, age, weight, and BMI. Regarding their splenoportal axis, statistically significant differences in SS were found in the means of the two subgroups of subjects stratified by their portal flow velocity (p= 0.003) and spleen area (p < 0.001). Spearman's rank showed a weak association between SS and portal flow velocty (r= 0.271) and splenic area (r = -0.237). ICC showed excellent (0.96) inter-operator agreement and Bland-Altman plot demonstrated no systematic over/under-estimation of spleen stiffness values. Conclusions: Our results may serve as a reference point in the evaluation of SS especially in patients affected by advanced liver disease

Alanine aminotransferase and spleno-portal dynamics affect spleen stiffness measured by point shear-wave elastography in patients with chronic hepatitis C in the absence of significant liver fibrosis

Background: Spleen stiffness (SS) has gained a lot of interest in the context of liver cirrhosis and portal hypertension stratification. However, there is a paucity of data on confounding factors that may alter SS values. Methods: Between January 2018 and October 2019, we enrolled 120 healthy subjects and 117 patients with hepatitis C virus (HCV) infection who did not have significant liver fibrosis (i.e., F0–1). Abdominal ultrasound evaluation was performed on each individual to measure portal vein diameter, portal flow velocity, spleen bipolar diameter, and splenic area. We also performed liver and spleen elastography. Results: HCV patients had higher SS (p 32 IU/L. Besides, the relationship between SS and ALT was described by cubic polynomial regression according to the following equation: 11.735 + 0.404 (ALT)1 − 0.002 (ALT)2 + 4.26 × 10–6 (ALT)3. Conclusions: Our results bring new light to the role of inflammation as a confounding factor for SS measurement. Therefore, particular attention should be paid to serum transaminase for a correct evaluation of spleen elastography

Effect of chronic administration of tacrolimus and cyclosporine on human gastrointestinal permeability.

The antirejection drug tacrolimus (FK506) has been reported to impair intestinal permeability in an early stage after orthotopic liver transplantation (OLT), and cyclosporine (CsA) has shown a similar effect in animals. We studied the chronic effect of FK506 and CsA on gastroduodenal and intestinal permeability and on blood endotoxin levels in patients 2 to 3 years after OLT. Thirty-two OLT patients (22 men and 10 women; mean age, 44.8 +/- 7.1) who had received CsA (n = 19) or FK506 (n = 13) and 10 healthy volunteers (6 male and 4 female, mean age 41.7 +/- 5.4) were assessed for gastroduodenal permeability by recovery in urine of sucrose after oral administration and for intestinal permeability by recovery in urine after oral loads of rhamnose and lactulose, which evaluate the intracellular and paracellular routes, respectively. In all subjects, plasma levels of endotoxins also were assessed. Gastroduodenal permeability was similar in patients and controls (0.03 +/- 0.003 versus 0.04 +/- 0.01%, P = NS). In regard to intestinal permeability, passage through the intracellular route was significantly reduced in OLT patients compared with controls (1.13 +/- 0.06 versus 2.74 +/- 0.17%, P &lt;.01), but paracellular permeability was unchanged (0.14 +/- 0.007 versus 0.13 +/- 0.01%, P = NS). Serum endotoxin levels were similar in all subjects. We conclude that chronic administration of FK506 or CsA induces a clinically irrelevant, selective dysfunction of monosaccharide absorption, but does not affect gastroduodenal or intestinal permeabilit

Increased intestinal permeability and NOD2 variants in familial and sporadic Crohn's disease

Abnormal barrier function may be genetically determined in Crohn's disease. To examine the role of abnormal intestinal permeability in genetic predisposition in multiplex vs. sporadic Crohn's disease families. Intestinal permeability was measured in patients, relatives and partners by means of lactulose/mannitol test. Healthy subjects from the hospital staff served as controls. CARD15 mutations were investigated in sporadic and familial Crohn's disease patients and in a group of blood donors. The median lactulose/mannitol ratio was increased significantly in Crohn's disease patients vs. their relatives [0.03 (0.01-0.24) vs. 0.01 (0.003-0.19), P = 0.005]. The percentage of abnormal tests was significantly higher in familial vs. sporadic first-degree relatives of Crohn's disease patients (29% vs. 11%, P = 0.0281). Abnormal permeability occurred significantly more frequent in patients with familial Crohn's disease carrying the frameshift mutation. The frameshift mutation 3020msC was associated with increased permeability in 75% in the multiplex and in 61% of the sporadic CD patients. One partner had abnormal lactulose/mannitol ratio. Intestinal permeability is raised in Crohn's disease patients and relatives, with higher rates in familial vs. sporadic healthy relatives. CARD15 mutations are associated with abnormal permeability in ileal Crohn's disease