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 < 0.001), portal vein diameter (p = 0.031), portal flow velocity (p = 0.035), spleen bipolar diameter (p = 0.042) and area (p = 0.025), and ALT levels (p < 0.001). Linear regression models showed that SS increased by 3.220 kPa for each mm of portal vein diameter, by 0.7 kPa for each cm/s of portal flow velocity, by 2.239 kPa for each cm of spleen bipolar diameter, and by 0.233 kPa for each cm2 of spleen area. Patients with HCV infection were stratified according to median ALT levels (i.e. 32 IU/L). SS and spleno-portal axis parameters were significantly higher in patients with an ALT level > 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.

The role of elastography in alcoholic liver disease: fibrosis staging and confounding factors, a review of the current literature.

INTRODUCTION: Alcohol-related liver disease (ALD) was estimated to have a prevalence of 2% among the USA population. Since severe fibrosis in compensated patients is the main predictor of long-term survival, it is of utmost importance to early detect patients with severe fibrosis before decompensation occurs. Liver elastography has been used to stage liver fibrosis. However, there is a widespread lack in guidelines for the correct use of liver stiffness (LS) in ALD. EVIDENCE ACQUISITION: A structured search was carried out on MEDLINE/PubMed database. From the original 225 research articles identified, only 12 studies met the inclusion criteria, with 10 studies being eventually included. EVIDENCE SYNTHESIS: According to reported data, patients with aspartate aminotransferase (AST)>100 IU/L and 50 IU/L showed significantly higher values of LS if compared to patients with the same fibrosis stage. Also, excessive alcohol consumption greatly influences elastography, leading to false fibrosis staging. When LS values >5-6 kPa are detected, several aspects should be taken into account. First of all, the patient should be asked about the current alcohol consumption (i.e. active vs. abstinence, determination of abstinence period, and quantification of alcohol intake), and if the patient is an active drinker, liver elastography can be repeated after a complete abstinence period of at least two weeks. and if the patient is an active drinker, liver elastography can be repeated after a complete abstinence period of at least two weeks. Secondly, clinicians should check liver transaminases level, and if AST are above 100 IU/L, they should be aware of a possible overestimation of fibrosis. However, whether transaminases-adapted cut-off values should be used for ad-hoc decisions in patients with no time or option to withdraw from alcohol consumption is still a matter of debate. CONCLUSIONS: We hope that our review article may serve as a reference point in the prospect of futures guidelines.

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.

Comparison between hepatocellular carcinoma prognostic scores: A 10-year single-center experience and brief review of the current literature.

BACKGROUND: Hepatocellular carcinoma (HCC) represents the most common primitive liver malignancy. A relevant concern involves the lack of agreement on staging systems, prognostic scores, and treatment allocation algorithms. AIM: To compare the survival rates among already developed prognostic scores. METHODS: We retrospectively evaluated 140 patients with HCC diagnosed between February 2006 and November 2017. Patients were categorized according to 15 prognostic scoring systems and estimated median survivals were compared with those available from the current medical literature. RESULTS: The median overall survival of the cohort of patients was 35 (17; 67) mo, and it was statistically different in relation to treatment choice, ultrasound surveillance, and serum alpha-fetoprotein. The Italian Liver Cancer (ITA.LI.CA) tumor staging system performed best in predicting survival according to stage allocation among all 15 evaluated prognostic scores. Using the ITA.LI.CA prognostic system, 28.6%, 40.7%, 22.1%, and 8.6% of patients fell within stages 0-1, 2-3, 4-5 and > 5 respectively. The median survival was 57.9 mo for stages 0-1, 43 mo for stages 2-3, 21.7 mo for stages 4-5, and 10.4 mo for stage > 5. The 1-, 3-, and 5-year survival rates were respectively 95%, 65%, and 20%, for stages 0-1; 94.7%, 43.9% and 26.3% for stages 2-3; 71%, 25.8% and 16.1% for stages 4-5; and 50%, 16.7% and 8.3% for stage > 5. At the same time, although statistically significant in prognostic stratification, the most commonly used Barcelona Clinic Liver Cancer system showed one of the most relevant differences in median survival, especially for stages A and C, when compared to the medical literature. In fact, 10.7%, 59.3%, 27.1%, 1.4%, and 0% of patients were stratified into stages 0, A, B, C, and D respectively. The median survival was > 81.1 mo for stage 0, 44.9 mo for stage A, 21.3 mo for stage B, and 3.1 mo for stage C. The 1-, 3-, and 5-year survival rates were respectively 86.7%, 60%, and 46.7% for stage 0; 91.6%, 50.6%, and 20.5% for stage A; 73.7%, 23.7% and 13.2% for stage B; and 2%, 0% and 0% for stage C. CONCLUSION: Survival analysis shows excellent prognostic ability of the ITA.LI.CA scoring system compared to other staging systems.

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

INTRODUCTION 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 31kPa (100% sensitivity and negative predictive value) as the value to rule-out EVs and 69kPa (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 31kPa, 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).

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 (<30g/daily for man, <20g/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.

Simultaneous gas-chromatographic measurement of rhamnose, lactulose and sucrose and their application in the testing gastrointestinal permeability.

BACKGROUND: As it is important to test gastric and intestinal permeability simultaneously in gastrointestinal disorders such as Celiac disease, we developed a gas-chromatographic (GC) method to estimate rhamnose (L-rh), lactulose (Lacl) and sucrose (Suc) in urine. METHODS: The method is based on the use of alditol acetate derivatives giving a lower number of GC peaks than reducing sugars do. Acetate derivatives are more stable and less expensive than GC silylates and keep the flame-detector cleaner. We checked the chemical stability of alditol acetates by verifying the reproducibility of the standard curve of a sugar derivative sample which had been stored for 2 months at -20 degrees C. RESULTS: The calibration proved linear over the range 0.1-1 microg of sugar injected. Analytical sugar recovery was 88%+/-19.4% (mean+/-S.D.) for rhamnose, 105%+/-7.4% for sucrose and 102%+/-2.4% for lactulose. Mean within-day precision (CV) was 7.7% for rhamnose, 5.7% for sucrose and 1.9% for lactulose, and between-day (CV) was 6.7% for rhamnose, 3.9% for sucrose and 1.6% for lactulose. The rhamnose, lactulose and sucrose as the lactulose/rhamnose ratio clearly differentiated 25 healthy controls from 36 patients with active gluten-sensitive enteropathy. CONCLUSIONS: A fast, reliable and cheap gas-chromatographic method is presented here to evaluate gastric and intestinal permeability.

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 <.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 permeability.