Chest CT opportunistic biomarkers for phenotyping high-risk COVID-19 patients: a retrospective multicentre study.

OBJECTIVE: To assess the value of opportunistic biomarkers derived from chest CT performed at hospital admission of COVID-19 patients for the phenotypization of high-risk patients. METHODS: In this multicentre retrospective study, 1845 consecutive COVID-19 patients with chest CT performed within 72 h from hospital admission were analysed. Clinical and outcome data were collected by each center 30 and 80 days after hospital admission. Patients with unknown outcomes were excluded. Chest CT was analysed in a single core lab and behind pneumonia CT scores were extracted opportunistic data about atherosclerotic profile (calcium score according to Agatston method), liver steatosis (≤ 40 HU), myosteatosis (paraspinal muscle F < 31.3 HU, M < 37.5 HU), and osteoporosis (D12 bone attenuation < 134 HU). Differences according to treatment and outcome were assessed with ANOVA. Prediction models were obtained using multivariate binary logistic regression and their AUCs were compared with the DeLong test. RESULTS: The final cohort included 1669 patients (age 67.5 [58.5-77.4] yo) mainly men 1105/1669, 66.2%) and with reduced oxygen saturation (92% [88-95%]). Pneumonia severity, high Agatston score, myosteatosis, liver steatosis, and osteoporosis derived from CT were more prevalent in patients with more aggressive treatment, access to ICU, and in-hospital death (always p < 0.05). A multivariable model including clinical and CT variables improved the capability to predict non-critical pneumonia compared to a model including only clinical variables (AUC 0.801 vs 0.789; p = 0.0198) to predict patient death (AUC 0.815 vs 0.800; p = 0.001). CONCLUSION: Opportunistic biomarkers derived from chest CT can improve the characterization of COVID-19 high-risk patients. CLINICAL RELEVANCE STATEMENT: In COVID-19 patients, opportunistic biomarkers of cardiometabolic risk extracted from chest CT improve patient risk stratification. KEY POINTS: • In COVID-19 patients, several information about patient comorbidities can be quantitatively extracted from chest CT, resulting associated with the severity of oxygen treatment, access to ICU, and death. • A prediction model based on multiparametric opportunistic biomarkers derived from chest CT resulted superior to a model including only clinical variables in a large cohort of 1669 patients suffering from SARS- CoV2 infection. • Opportunistic biomarkers of cardiometabolic comorbidities derived from chest CT may improve COVID-19 patients' risk stratification also in absence of detailed clinical data and laboratory tests identifying subclinical and previously unknown conditions.

AI-SCoRE (artificial intelligence-SARS CoV2 risk evaluation): a fast, objective and fully automated platform to predict the outcome in COVID-19 patients.

PURPOSE: To develop and validate an effective and user-friendly AI platform based on a few unbiased clinical variables integrated with advanced CT automatic analysis for COVID-19 patients' risk stratification. MATERIAL AND METHODS: In total, 1575 consecutive COVID-19 adults admitted to 16 hospitals during wave 1 (February 16-April 29, 2020), submitted to chest CT within 72 h from admission, were retrospectively enrolled. In total, 107 variables were initially collected; 64 extracted from CT. The outcome was survival. A rigorous AI model selection framework was adopted for models selection and automatic CT data extraction. Model performances were compared in terms of AUC. A web-mobile interface was developed using Microsoft PowerApps environment. The platform was externally validated on 213 COVID-19 adults prospectively enrolled during wave 2 (October 14-December 31, 2020). RESULTS: The final cohort included 1125 patients (292 non-survivors, 26%) and 24 variables. Logistic showed the best performance on the complete set of variables (AUC = 0.839 ± 0.009) as in models including a limited set of 13 and 5 variables (AUC = 0.840 ± 0.0093 and AUC = 0.834 ± 0.007). For non-inferior performance, the 5 variables model (age, sex, saturation, well-aerated lung parenchyma and cardiothoracic vascular calcium) was selected as the final model and the extraction of CT-derived parameters was fully automatized. The fully automatic model showed AUC = 0.842 (95% CI: 0.816-0.867) on wave 1 and was used to build a 0-100 scale risk score (AI-SCoRE). The predictive performance was confirmed on wave 2 (AUC 0.808; 95% CI: 0.7402-0.8766). CONCLUSIONS: AI-SCoRE is an effective and reliable platform for automatic risk stratification of COVID-19 patients based on a few unbiased clinical data and CT automatic analysis.

Myosteatosis Significantly Predicts Persistent Dyspnea and Mobility Problems in COVID-19 Survivors.

Background: Persistent symptoms including dyspnea and functional impairment are common in COVID-19 survivors. Poor muscle quality (myosteatosis) associates with poor short-term outcomes in COVID-19 patients. The aim of this observational study was to assess the relationship between myosteatosis diagnosed during acute COVID-19 and patient-reported outcomes at 6 months after discharge. Methods: Myosteatosis was diagnosed based on CT-derived skeletal muscle radiation attenuation (SM-RA) measured during hospitalization in 97 COVID-19 survivors who had available anthropometric and clinical data upon admission and at the 6-month follow-up after discharge. Dyspnea in daily activities was assessed using the modified Medical Research Council (mMRC) scale for dyspnea. Health-related quality of life was measured using the European quality of life questionnaire three-level version (EQ-5D-3L). Results: Characteristics of patients with (lowest sex- and age-specific tertile of SM-RA) or without myosteatosis during acute COVID-19 were similar. At 6 months, patients with myosteatosis had greater rates of obesity (48.4 vs. 27.7%, p = 0.046), abdominal obesity (80.0 vs. 47.6%, p = 0.003), dyspnea (32.3 vs. 12.5%, p = 0.021) and mobility problems (32.3 vs. 12.5%, p = 0.004). Myosteatosis diagnosed during acute COVID-19 was the only significant predictor of persistent dyspnea (OR 3.19 [95% C.I. 1.04; 9.87], p = 0.043) and mobility problems (OR 3.70 [95% C.I. 1.25; 10.95], p = 0.018) at 6 months at logistic regression adjusted for sex, age, and BMI. Conclusion: Myosteatosis diagnosed during acute COVID-19 significantly predicts persistent dyspnea and mobility problems at 6 months after hospital discharge independent of age, sex, and body mass. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04318366].

Efficacy of Endoscopic Ultrasound-Guided Ablation with the HybridTherm Probe in Locally Advanced or Borderline Resectable Pancreatic Cancer: A Phase II Randomized Controlled Trial.

Endoscopic ultrasound-ablation with HybridTherm-Probe (EUS-HTP) significantly reduces tumour volume (TV) in locally-advanced pancreatic ductal adenocarcinoma (LA-PDAC). We aimed at investigating the clinical efficacy of EUS-HTP plus chemotherapy versus chemotherapy (HTP-CT and CT arms) in LA- and borderline-resectable (BR) PDAC, with 6-months progression-free survival (6-PFS) rate as primary endpoint. In a phase-II randomized-controlled-trial, 33 LA/BR-PDAC patients per-arm were planned to verify 20% improved 6-PFS rate. Radiological response (Choi criteria), TV and serum CA19.9 were assessed up to 6-months. Seventeen and 20 LA/BR-PDAC patients were randomized to HTP-CT or CT. Baseline and CT-related features were balanced. At 6-months, 6-PFS rate was 41.2% and 30% in HTP-CT and CT arms (p = 0.48), respectively. A decrease ≥50% of serum CA19.9 was achieved in 75% and 64.3% of HTP-CT and CT patients (p = 0.53), respectively. TV reduced up to 6-months in 64.3% and 47.1% of HTP-CT and CT patients (p = 0.35), respectively. Resection rate, PFS-time and overall survival (OS-time) were similar. HTP-CT achieves a non-significant 11.2%, 10.7% and 17.2% improved 6-PFS, CA19.9 decrease ≥50% and TV reduction rates over CT, without any impact on resection rate, PFS-time and OS-time. As the study was underpowered, these results suggest further investigation of EUS-local ablation in selected patients with localized disease after induction CT.

Dynamic changes of mitral valve annulus geometry at preprocedural CT: relationship with functional classes of regurgitation.

BACKGROUND: We investigated mitral valve annular geometry changes during the cardiac cycle in patients with severe mitral regurgitation (MR) who underwent cardiac computed tomography angiography (CCTA) prior to percutaneous mitral valve replacement or annuloplasty. METHODS: Fifty-one patients with severe MR and high surgical risk (Carpentier classification: 3 type I, 16 type II, 16 type IIIa, 16 type IIIb) underwent multiphase electrocardiographically gated (0-90%) CCTA, using a second generation dual-source CT scanner, as pre-procedural planning. Twenty-one patients without MR served as controls. The mitral valve annulus was segmented every 10% step of the R-R interval, according to the D-shaped segmentation model, and differences among groups were analysed by t-test or ANOVA. RESULTS: Mitral annular area and diameters were larger in MR patients compared to controls, particularly in type II. Mitral annular area varied in MR patients throughout the cardiac cycle (mean ± standard deviation of maximum and minimum area 15.6 ± 3.9 cm2 versus 13.0 ± 3.5 cm2, respectively; p = 0.001), with greater difference between annular areas versus controls (2.59 ± 1.61 cm2 and 1.98 ± 0.6 cm2, p < 0.001). The largest dimension was found in systolic phases (20-40%) in most of MR patients (n = 27, 53%), independent of Carpentier type (I: n = 1, 33%; II: n = 10, 63%; IIIa: n = 8, 50%; IIIb: n = 8, 50%), and in protodiastolic phases (n = 14, 67%) for the control group. CONCLUSIONS: In severe MR, mitral annular area varied significantly throughout the cardiac cycle, with a tendency towards larger dimensions in systole.

Advanced cardiac imaging in athlete's heart: unravelling the grey zone between physiologic adaptation and pathology.

Over the last decades, interest toward athlete's heart has progressively increased, leading to improve the knowledge on exercise-induced heart modifications. Sport may act as a trigger for life-threatening arrhythmias in patients with structural or electrical abnormalities, hence requiring to improve the diagnostic capability to differentiate physiological from pathological remodeling. Pathological alterations are often subtle at the initial stages; therefore, the challenge is to promptly identify athletes at risk of sudden cardiac death during the pre-participation screening protocols. Advanced imaging modalities such as coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) can non-invasively depict coronary vessels and provide a deep morpho-functional and structural characterization of the myocardium, in order to rule out pathological life threatening alterations, which may overlap with athletes' heart remodeling. The purpose of the present narrative review is to provide an overview of most frequent diagnostic challenges, defining the boundaries between athlete's heart remodeling and pathological structural alteration with a focus on the role and importance of CCTA and CMR.

The hidden interplay between sex and COVID-19 mortality: the role of cardiovascular calcification.

Recent clinical and demographical studies on COVID-19 patients have demonstrated that men experience worse outcomes than women. However, in most cases, the data were not stratified according to gender, limiting the understanding of the real impact of gender on outcomes. This study aimed to evaluate the disaggregated in-hospital outcomes and explore the possible interactions between gender and cardiovascular calcifications. Data was derived from the sCORE-COVID-19 registry, an Italian multicentre registry that enrolled COVID-19 patients who had undergone a chest computer tomography scan on admission. A total of 1683 hospitalized patients (mean age 67±14 years) were included. Men had a higher prevalence of cardiovascular comorbidities, a higher pneumonia extension, more coronary calcifications (63% vs.50.9%, p<0.001), and a higher coronary calcium score (391±847 vs. 171±479 mm3, p<0.001). Men experienced a significantly higher mortality rate (24.4% vs. 17%, p=0.001), but the death event tended to occur earlier in women (15±7 vs. 8±7 days, p= 0.07). Non-survivors had a higher coronary, thoracic aorta, and aortic valve calcium score. Female sex, a known independent predictor of a favorable outcome in SARS-CoV2 infection, was not protective in women with a coronary calcification volume greater than 100 mm3. There were significant differences in cardiovascular comorbidities and vascular calcifications between men and women with SARS-CoV2 pneumonia. The differences in outcomes can be at least partially explained by the different cardiovascular profiles. However, women with poor outcomes had the same coronary calcific burden as men. The presumed favorable female sex bias in COVID-19 must therefore be reviewed in the context of comorbidities, especially cardiovascular ones.

Epicardial adipose tissue characteristics, obesity and clinical outcomes in COVID-19: A post-hoc analysis of a prospective cohort study.

BACKGROUND AND AIMS: Obesity-related cardiometabolic risk factors associate with COVID-19 severity and outcomes. Epicardial adipose tissue (EAT) is associated with cardiometabolic disturbances, is a source of proinflammatory cytokines and a marker of visceral adiposity. We investigated the relation between EAT characteristics and outcomes in COVID-19 patients. METHODS AND RESULTS: This post-hoc analysis of a large prospective investigation included all adult patients (≥18 years) admitted to San Raffaele University Hospital in Milan, Italy, from February 25th to April 19th, 2020 with confirmed SARS-CoV-2 infection who underwent a chest computed tomography (CT) scan for COVID-19 pneumonia and had anthropometric data available for analyses. EAT volume and attenuation (EAT-At, a marker of EAT inflammation) were measured on CT scan. Primary outcome was critical illness, defined as admission to intensive care unit (ICU), invasive ventilation or death. Cox regression and regression tree analyses were used to assess the relationship between clinical variables, EAT characteristics and critical illness. One-hundred and ninety-two patients were included (median [25th-75th percentile] age 60 years [53-70], 76% men). Co-morbidities included overweight/obesity (70%), arterial hypertension (40%), and diabetes (16%). At multivariable Cox regression analysis, EAT-At (HR 1.12 [1.04-1.21]) independently predicted critical illness, while increasing PaO2/FiO2 was protective (HR 0.996 [95% CI 0.993; 1.00]). CRP, plasma glucose on admission, EAT-At and PaO2/FiO2 identified five risk groups that significantly differed with respect to time to death or admission to ICU (log-rank p < 0.0001). CONCLUSION: Increased EAT attenuation, a marker of EAT inflammation, but not obesity or EAT volume, predicts critical COVID-19. TRIAL REGISTRATION: NCT04318366.

Impact of clinical and subclinical coronary artery disease as assessed by coronary artery calcium in COVID-19.

BACKGROUND AND AIMS: The potential impact of coronary atherosclerosis, as detected by coronary artery calcium, on clinical outcomes in COVID-19 patients remains unsettled. We aimed to evaluate the prognostic impact of clinical and subclinical coronary artery disease (CAD), as assessed by coronary artery calcium score (CAC), in a large, unselected population of hospitalized COVID-19 patients undergoing non-gated chest computed tomography (CT) for clinical practice. METHODS: SARS-CoV 2 positive patients from the multicenter (16 Italian hospitals), retrospective observational SCORE COVID-19 (calcium score for COVID-19 Risk Evaluation) registry were stratified in three groups: (a) "clinical CAD" (prior revascularization history), (b) "subclinical CAD" (CAC >0), (c) "No CAD" (CAC = 0). Primary endpoint was in-hospital mortality and the secondary endpoint was a composite of myocardial infarction and cerebrovascular accident (MI/CVA). RESULTS: Amongst 1625 patients (male 67.2%, median age 69 [interquartile range 58-77] years), 31%, 57.8% and 11.1% had no, subclinical and clinical CAD, respectively. Increasing rates of in-hospital mortality (11.3% vs. 27.3% vs. 39.8%, p < 0.001) and MI/CVA events (2.3% vs. 3.8% vs. 11.9%, p < 0.001) were observed for patients with no CAD vs. subclinical CAD vs clinical CAD, respectively. The association with in-hospital mortality was independent of in-study outcome predictors (age, peripheral artery disease, active cancer, hemoglobin, C-reactive protein, LDH, aerated lung volume): subclinical CAD vs. No CAD: adjusted hazard ratio (adj-HR) 2.86 (95% confidence interval [CI] 1.14-7.17, p=0.025); clinical CAD vs. No CAD: adj-HR 3.74 (95% CI 1.21-11.60, p=0.022). Among patients with subclinical CAD, increasing CAC burden was associated with higher rates of in-hospital mortality (20.5% vs. 27.9% vs. 38.7% for patients with CAC score thresholds≤100, 101-400 and > 400, respectively, p < 0.001). The adj-HR per 50 points increase in CAC score 1.007 (95%CI 1.001-1.013, p=0.016). Cardiovascular risk factors were not independent predictors of in-hospital mortality when CAD presence and extent were taken into account. CONCLUSIONS: The presence and extent of CAD are associated with in-hospital mortality and MI/CVA among hospitalized patients with COVID-19 disease and they appear to be a better prognostic gauge as compared to a clinical cardiovascular risk assessment.

Coronary and total thoracic calcium scores predict mortality and provides pathophysiologic insights in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide determining dramatic impacts on healthcare systems. Early identification of high-risk parameters is required in order to provide the best therapeutic approach. Coronary, thoracic aorta and aortic valve calcium can be measured from a non-gated chest computer tomography (CT) and are validated predictors of cardiovascular events and all-cause mortality. However, their prognostic role in acute systemic inflammatory diseases, such as COVID-19, has not been investigated. OBJECTIVES: The aim was to evaluate the association of coronary artery calcium and total thoracic calcium on in-hospital mortality in COVID-19 patients. METHODS: 1093 consecutive patients from 16 Italian hospitals with a positive swab for COVID-19 and an admission chest CT for pneumonia severity assessment were included. At CT, coronary, aortic valve and thoracic aorta calcium were qualitatively and quantitatively evaluated separately and combined together (total thoracic calcium) by a central Core-lab blinded to patients' outcomes. RESULTS: Non-survivors compared to survivors had higher coronary artery [Agatston (467.76 â€‹± â€‹570.92 vs 206.80 â€‹± â€‹424.13 â€‹mm2, p â€‹< â€‹0.001); Volume (487.79 â€‹± â€‹565.34 vs 207.77 â€‹± â€‹406.81, p â€‹< â€‹0.001)], aortic valve [Volume (322.45 â€‹± â€‹390.90 vs 98.27 â€‹± â€‹250.74 mm2, p â€‹< â€‹0.001; Agatston 337.38 â€‹± â€‹414.97 vs 111.70 â€‹± â€‹282.15, p â€‹< â€‹0.001)] and thoracic aorta [Volume (3786.71 â€‹± â€‹4225.57 vs 1487.63 â€‹± â€‹2973.19 mm2, p â€‹< â€‹0.001); Agatston (4688.82 â€‹± â€‹5363.72 vs 1834.90 â€‹± â€‹3761.25, p â€‹< â€‹0.001)] calcium values. Coronary artery calcium (HR 1.308; 95% CI, 1.046-1.637, p â€‹= â€‹0.019) and total thoracic calcium (HR 1.975; 95% CI, 1.200-3.251, p â€‹= â€‹0.007) resulted to be independent predictors of in-hospital mortality. CONCLUSION: Coronary, aortic valve and thoracic aortic calcium assessment on admission non-gated CT permits to stratify the COVID-19 patients in-hospital mortality risk.

Chest CT-derived pulmonary artery enlargement at the admission predicts overall survival in COVID-19 patients: insight from 1461 consecutive patients in Italy.

OBJECTIVES: Enlarged main pulmonary artery diameter (MPAD) resulted to be associated with pulmonary hypertension and mortality in a non-COVID-19 setting. The aim was to investigate and validate the association between MPAD enlargement and overall survival in COVID-19 patients. METHODS: This is a cohort study on 1469 consecutive COVID-19 patients submitted to chest CT within 72 h from admission in seven tertiary level hospitals in Northern Italy, between March 1 and April 20, 2020. Derivation cohort (n = 761) included patients from the first three participating hospitals; validation cohort (n = 633) included patients from the remaining hospitals. CT images were centrally analyzed in a core-lab blinded to clinical data. The prognostic value of MPAD on overall survival was evaluated at adjusted and multivariable Cox's regression analysis on the derivation cohort. The final multivariable model was tested on the validation cohort. RESULTS: In the derivation cohort, the median age was 69 (IQR, 58-77) years and 537 (70.6%) were males. In the validation cohort, the median age was 69 (IQR, 59-77) years with 421 (66.5%) males. Enlarged MPAD (≥ 31 mm) was a predictor of mortality at adjusted (hazard ratio, HR [95%CI]: 1.741 [1.253-2.418], p < 0.001) and multivariable regression analysis (HR [95%CI]: 1.592 [1.154-2.196], p = 0.005), together with male gender, old age, high creatinine, low well-aerated lung volume, and high pneumonia extension (c-index [95%CI] = 0.826 [0.796-0.851]). Model discrimination was confirmed on the validation cohort (c-index [95%CI] = 0.789 [0.758-0.823]), also using CT measurements from a second reader (c-index [95%CI] = 0.790 [0.753;0.825]). CONCLUSION: Enlarged MPAD (≥ 31 mm) at admitting chest CT is an independent predictor of mortality in COVID-19. KEY POINTS: • Enlargement of main pulmonary artery diameter at chest CT performed within 72 h from the admission was associated with a higher rate of in-hospital mortality in COVID-19 patients. • Enlargement of main pulmonary artery diameter (≥ 31 mm) was an independent predictor of death in COVID-19 patients at adjusted and multivariable regression analysis. • The combined evaluation of clinical findings, lung CT features, and main pulmonary artery diameter may be useful for risk stratification in COVID-19 patients.

Impact of Ascending Aorta Dilation on Mid-Term Outcome After Transcatheter Aortic Valve Implantation.

BACKGROUND: Severe aortic stenosis (AS) is often associated with ascending aorta dilation (AAD). AAD is amenable to surgical correction combined with aortic valve replacement. Transcatheter aortic valve implantation (TAVI) might represent a valid therapeutic option in these patients when AAD correction Is not indicated. The aim of the present study is to evaluate the impact of concomitant AAD on early and mid-term outcomes after TAVI for symptomatic severe AS. METHODS: This is a single-center observational study including patients undergoing transfemoral TAVI. All patients with previous surgery on the left ventricular outflow tract, aortic valve, or ascending aorta (except coronary artery bypass graft surgery) were excluded from the analysis. Patients undergoing TAVI for congenital aortic valve defects or subjects in whom a computed tomography (CT) scan was not available were excluded from the analysis. Ascending aortas were measured on CT scans using appropriate multiplanar reconstructions. Ascending aortas were qualified as dilated if the measurement was >40 mm. Study outcomes were death from any cause, significant paravalvular leaks (PVLs), and new permanent pacemaker (PPM) implant. RESULTS: The final population consisted of 680 subjects, 61% females, mean age 82 ± 7 years. One hundred subjects (15%) had AAD. No differences in terms of significant PVL or PPM implantation were found between subjects with or without AAD (P>.99 and P=.13, respectively). At a median follow-up of 498 ± 216 days, no significant difference in terms of mortality was found between subjects with or without AAD (P=.78). CONCLUSIONS: AAD does not appear to impact the mid-term outcomes in a cohort of subjects undergoing TAVI.

Natural history of patients with non cirrhotic portal hypertension: Comparison with patients with compensated cirrhosis.

BACKGROUND: The knowledge of natural history of patients with portal hypertension (PH) not due to cirrhosis is less well known than that of cirrhotic patients. AIM: To describe the clinical presentation and the outcomes of 89 patients with non-cirrhotic PH (25 with non-cirrhotic portal hypertension, INCPH, and 64 with chronic portal vein thrombosis, PVT) in comparison with 77 patients with Child A cirrhosis. METHODS: The patients were submitted to a standardized clinical, laboratory, ultrasonographic and endoscopic follow-up. Variceal progression, incidence of variceal bleeding, portal vein thrombosis, ascites and survival were recorded. RESULTS: At presentation, the prevalence of varices, variceal bleeding and ascites was similar in the 3 groups. During follow-up, the rate of progression to varices at risk of bleeding (p < 0.0001) and the incidence of first variceal bleeding (p = 0.02) were significantly higher in non-cirrhotic then in cirrhotic patients. A PVT developed in 32% of INCPH patients and in 18% of cirrhotics (p = 0.02). CONCLUSIONS: In the patients with non-cirrhotic PH variceal progression is more rapid and bleeding more frequent than in cirrhotics. Patients with INCPH are particularly prompt to develop PVT. This observational study suggests that the management of patients with non-cirrhotic PH should take into consideration the natural history of portal hypertension in these patients and cannot be simply derived by the observation of cirrhotic patients.

Idiopathic noncirrhotic portal hypertension: current perspectives.

The term idiopathic noncirrhotic portal hypertension (INCPH) has been recently proposed to replace terms, such as hepatoportal sclerosis, idiopathic portal hypertension, incomplete septal cirrhosis, and nodular regenerative hyperplasia, used to describe patients with a hepatic presinusoidal cause of portal hypertension of unknown etiology, characterized by features of portal hypertension (esophageal varices, nonmalignant ascites, porto-venous collaterals), splenomegaly, patent portal, and hepatic veins and no clinical and histological signs of cirrhosis. Physicians should learn to look for this condition in a number of clinical settings, including cryptogenic cirrhosis, a disease known to be associated with INCPH, drug administration, and even chronic alterations in liver function tests. Once INCPH is clinically suspected, liver histology becomes mandatory for the correct diagnosis. However, pathologists should be familiar with the histological features of INCPH, especially in cases in which histology is not only requested to exclude liver cirrhosis.

Hepatic encephalopathy in patients with non-cirrhotic portal hypertension: Description, prevalence and risk factors.

BACKGROUND: Hepatic encephalopathy (HE) is a common complication of cirrhosis but it is less studied in patients with non-cirrhotic portal hypertension (NCPH). AIMS: To describe the prevalence of cognitive impairment (overt and covert HE) in NCPH patients and to identify the risk factors for its development. METHODS: 51 patients with NCPH, 35 with chronic portal vein thrombosis (PVT) and 16 with idiopathic non-cirrhotic portal hypertension (INCPH), were evaluated for the presence of previous or present overt HE (OHE). The psychometric hepatic encephalopathy score and the SCAN battery were used to detect the presence of covert HE (CHE). 34 compensated cirrhotic patients were used as control. In NCPH patients, abdominal scans were performed to detect the presence of shunts. RESULTS: None of the patients experienced OHE at evaluation while 5.7% of PVT and 12.5% of INCPH patients referred at least one documented episode of previous OHE, similarly to patients with cirrhosis (14.7%). Even if lower than in patients with cirrhosis (64.7%), a considerable proportion of patients with chronic PVT (34.3%) and INCPH (25%) had CHE (p=0.008). The presence of a large portal-systemic shunt was the only factor significantly correlated to cognitive impairment in NCPH patients. CONCLUSION: HE is a tangible complication of NCPH and is mainly related to the presence of portal-systemic shunts.

Cognitive Impairment Predicts The Occurrence Of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt.

OBJECTIVES: Hepatic encephalopathy (HE) is a major problem in patients treated with TIPS. The aim of the study was to establish whether pre-TIPS covert HE is an independent risk factor for the development of HE after TIPS. METHODS: Eighty-two consecutive cirrhotic patients submitted to TIPS were included. All patients underwent the PHES to identify those affected by covert HE before a TIPS. The incidence of the first episode of HE was estimated, taking into account the nature of the competing risks in the data (death or liver transplantation). RESULTS: Thirty-five (43%) patients developed overt HE. The difference of post-TIPS HE was highly significant (P=0.0003) among patients with or without covert HE before a TIPS. Seventy-seven percent of patients with post-TIPS HE were classified as affected by covert HE before TIPS. Age: (sHR 1.05, CI 1.02-1.08, P=0.002); Child-Pugh score: (sHR 1.29, CI 1.06-1.56, P=0.01); and covert HE: (sHR 3.16, CI: 1.43-6.99 P=0.004) were associated with post-TIPS HE. Taking into consideration only the results of PHES evaluation, the negative predicting value was 0.80 for all patients and 0.88 for the patients submitted to TIPS because of refractory ascites. Thus, a patient with refractory ascites, without covert HE before a TIPS, has almost 90% probability of being free of HE after TIPS. CONCLUSIONS: Psychometric evaluation before TIPS is able to identify most of the patients who will develop HE after a TIPS and can be used to select patients in order to have the lowest incidence of this important complication.