Publications by authors named "Paolo Angeli"

222 Publications

Reply to JHEPAT-D-21-00702 and JHEPAT-D-21-00793.

J Hepatol 2021 Jul 17. Epub 2021 Jul 17.

Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Padova, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2021.07.010DOI Listing
July 2021

COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study.

Gut 2021 Jul 19. Epub 2021 Jul 19.

Department of Gastroenterology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Lombardia, Italy.

Objective: Explore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course.

Design: Data from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed.

Results: From 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10-30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15-19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44-102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31-170).

Conclusions: Increased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).
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http://dx.doi.org/10.1136/gutjnl-2021-324879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300535PMC
July 2021

Untargeted lipidomics uncovers lipid signatures distinguishing severe versus moderate forms of acutely decompensated cirrhosis.

J Hepatol 2021 Jul 7. Epub 2021 Jul 7.

European Foundation for the Study of Chronic Liver Failure (EF Clif) and Grifols Chair, Barcelona, Spain.

Background And Aim: Acutely decompensated of cirrhosis is a heterogeneous clinical entity associated with moderate mortality. In some patients, this condition develops quickly into a more often deadly acute-on-chronic liver failure (ACLF), in which other organs such as the kidneys or brain fail. The aim of this study was to characterize the blood lipidome in a large series of patients with cirrhosis and identify specific signatures associated with acute decompensation and ACLF development.

Methods: Serum untargeted lipidomics was performed in 561 patients with acutely decompensated (AD) cirrhosis (518 without and 43 with ACLF) (discovery cohort) and in 265 AD patients (128 without and 137 with ACLF) in whom serum samples were available to perform repeated measurements during the 28-day follow-up (validation cohort). Analyses were also performed in 78 AD patients included in a therapeutic albumin trial, 43 patients with compensated cirrhosis and 29 healthy subjects.

Results: The circulating lipid landscape associated with cirrhosis was characterized by a generalized suppression, which was more manifest during acute decompensation and in non-surviving patients. By computing discriminating accuracy and the variable importance projection score for each of the 223 annotated lipids, we identified a sphingomyelin fingerprint specific for AD cirrhosis and a distinct cholesteryl ester and lysophosphatidylcholine fingerprint for ACLF. Liver dysfunction, mainly, and infections were the principal net contributors to these fingerprints, which were dynamic and interchangeable between AD patients whose condition worsened to ACLF and those who improved. Notably, blood lysophosphatidylcholine levels increased in these patients after albumin therapy.

Conclusions: Our findings provide insights into the lipid landscape associated with decompensation of cirrhosis and ACLF progression and identify unique noninvasive diagnostic biomarkers of advanced cirrhosis.

Lay Summary: Analysis of lipids in blood from patients with advanced cirrhosis reveals a general suppression of their levels in the circulation of these patients. A specific group of lipids known as sphingomyelins are useful to distinguish compensated from decompensated patients with cirrhosis. Another group of lipids designated cholesteryl esters further distinguish patients with decompensated patients who are at risk of developing organ failures.
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http://dx.doi.org/10.1016/j.jhep.2021.06.043DOI Listing
July 2021

A step forward in the choice of fluid for early resuscitation of critically ill patients with cirrhosis.

Authors:
Paolo Angeli

Hepatol Int 2021 Jul 7. Epub 2021 Jul 7.

Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Teaching Hospital of Padova, Padova, Italy.

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http://dx.doi.org/10.1007/s12072-021-10211-9DOI Listing
July 2021

Coagulopathy is not predictive of bleeding in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure.

Liver Int 2021 Jul 5. Epub 2021 Jul 5.

Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, Padova, Italy.

Background & Aims: Understanding factors responsible for the increased bleeding tendency in acute-on-chronic liver failure (ACLF) would improve the management of these complications. We investigated coagulation alterations in ACLF and assessed whether they were predictive of bleeding.

Methods: Cirrhosis patients with ACLF (cases) and acute decompensation (AD, controls) were prospectively recruited and underwent an extensive haemostatic assessment including standard tests, pro and anticoagulant factors, thrombomodulin-modified thrombin generation (TG) and thromboelastometry (ROTEM ). In study part 1 (case-control), we compared coagulation in ACLF vs AD. In study part 2 (prospective), all patients were followed for bleeding, and predictors of outcome were assessed.

Results: Ninety-one patients were included (51 with ACLF, 40 with AD). Infections and ascites/renal dysfunction were the most common precipitating and decompensating events. Platelet count was lower while INR and activated partial thrombin time were longer in ACLF cohort vs AD. Regarding clotting factors, fibrinogen and factor VIII were comparable between groups while protein C and antithrombin were significantly reduced in ACLF. Endogenous thrombin potential by TG was comparable between groups. Clotting formation time and clot stability by ROTEM were significantly lower in ACLF, indicative of a more hypocoagulable state. No haemostasis alteration could discriminate between patients who had bleeding complications during hospitalization and those who did not.

Conclusion: We found coagulation changes in ACLF to largely overlap with that of AD and evidence of preserved coagulation capacity in both groups. ROTEM alterations were indicative of a more pronounced hypocoagulable state in ACLF; however, no correlation was found between such alterations and bleeding.
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http://dx.doi.org/10.1111/liv.15001DOI Listing
July 2021

Comparison of fondaparinux and low molecular weight heparin in the treatment of portal vein thrombosis in cirrhosis.

Am J Med 2021 Jun 28. Epub 2021 Jun 28.

Unit of Internal Medicine and Hepatology Department of Medicine-DIMED, Padua University Hospital, Padua, Italy.

Background: Portal vein thrombosis is the most common thrombotic complication in cirrhosis. About 60% of anticoagulated patients can achieve recanalization. Despite fondaparinux (FPX) theoretical advantages, data are lacking regarding safety and efficacy for treatment of portal vein thrombosis in cirrhosis.

Methods: Cirrhotic patients with portal vein thrombosis treated with FPX or low molecular heparin (LMWH) were retrospectively included. The extension of thrombosis at baseline and its evolution during anticoagulant treatment were evaluated. Patients were treated with LMWH or FPX at therapeutic dosage and reduction was considered in selected cases.

Results: One-hundred and twenty-four patients were included. Main PV branch, splenic and superior mesenteric veins were involved in 84%, 13% and 36% of cases, respectively. Forty-one patients (33%) were treated with FPX and eighty-three (67%) with LMWH. The probability of resolution of thrombosis at 36 months was significantly higher in patients treated with FPX than in those treated with LMWH (77% vs 51%; p=0.001), particularly when prescribed at reduced dose. With multivariate analysis, the treatment with FPX (HR=2.38; p=0.002) and use of a full dose (HR=1.78; p=0.035) were independent predictors of portal vein full recanalization. Bleeding rate was higher in patients treated with FPX than in those treated with LMWH (27% vs 13%; p=0.06).

Conclusions: FPX appears to be more effective than LMWH in the treatment of portal vein thrombosis when used at reduced dose, also in complete thrombosis. FPX should be considered amongst possible treatments for portal vein thrombosis in cirrhosis.
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http://dx.doi.org/10.1016/j.amjmed.2021.05.013DOI Listing
June 2021

Coronary artery calcium on standard chest computed tomography predicts cardiovascular events after liver transplantation.

Int J Cardiol 2021 Jun 26. Epub 2021 Jun 26.

Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Italy. Electronic address:

Aims: Cardiac complications are a leading cause of mortality after orthotopic liver transplantation (LT) and pre-operative risk stratification is challenging. We evaluated whether coronary artery calcium (CAC) score calculated on a standard (non-thin layer, non-ECG gated) chest computed tomography (CT) predicted cardiac outcome after LT.

Methods: We included a consecutive series of LT recipients who underwent pre-operative cardiac evaluation including stress-testing or cardiac catheterization in high-risk patients. Patients with a history of coronary artery disease or coronary revascularization were excluded. The CAC score was calculated from the chest CT routinely performed before LT. CAC values were not available at the time of pre-transplant cardiac evaluation and did not affect LT eligibility. The primary end-point included peri-operative arrhythmic cardiac arrest and sustained ventricular arrhythmias; heart failure, myocardial infarction and cardiac death within 1-year after LT.

Results: The study population consisted of 301 patients (median age 56 years, 76% males). At chest CT, 49% had CAC = 0; 27% had CAC = 1-99, 15% had CAC = 100-399 and 9% CAC > 400. The primary end-point incidence increased from 7% in patients with CAC = 0 to 27% in patients with CAC > 400 (p = 0.007). At multivariable analysis including traditional risk factors, CAC remained an independent predictor of cardiac events (p = 0.01).

Conclusions: CAC score calculated on a standard chest CT stratified the risk of cardiac events in patients who underwent LT after negative pre-transplant cardiac evaluation. These findings suggest that evaluation of CAC from a standard chest CT performed for other reasons can be used as an early cardiac risk stratification tool before LT.
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http://dx.doi.org/10.1016/j.ijcard.2021.06.046DOI Listing
June 2021

Why have we performed a randomized controlled trial on our own dissemination policy?

Authors:
Paolo Angeli

J Hepatol 2021 Aug 19;75(2):261. Epub 2021 Jun 19.

Unit of Internal Medicine and Hepatology (UIMH), University of Padova, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2021.05.021DOI Listing
August 2021

TOWARDS A NEW DEFINITION OF DECOMPENSATED CIRRHOSIS.

J Hepatol 2021 Jun 19. Epub 2021 Jun 19.

Department of Medicine, Unit of Internal Medicine and Hepatology (UIMH), University of Padova, Italy. Electronic address:

There is a universal agreement on the fact that the occurrence of clinical complications, such as ascites, hepatic encephalopathy, gastrointestinal bleeding, and jaundice mark the transition from the compensated to the decompensated stage of liver cirrhosis. Decompensation is associated with a substantial worsening of patient prognosis, and is therefore considered the most important stratification variable for the risk of death. However, this classification sounds as an oversimplification, as it does not discriminate between the prognostic subgroups that characterize the course of decompensation, which depends on the type and number of decompensating events. A deeper insight into the clinical course of decompensated cirrhosis is provided by observational studies characterizing acute decompensation (AD) which occurs mostly in patients who have already experienced decompensating events. Decompensation presents as AD in a portion of patients while in many others it presents as a slow development of ascites or mild hepatic encephalopathy grade 1 or 2, or jaundice, not requiring hospitalization. Thus, we propose that decompensation of cirrhosis occurs through two distinguished pathways: a non-acute (NAD) and an acute one (AD, which includes ACLF). Moreover, while NAD is the most frequent pathway of the first decompensation, AD mostly represents further decompensation.
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http://dx.doi.org/10.1016/j.jhep.2021.06.018DOI Listing
June 2021

Reply to: HEP-21-0945.R1.

Hepatology 2021 Jun 7. Epub 2021 Jun 7.

Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University of Padova, Italy.

We appreciate the interest of Jindal et al. in our article recently published in Hepatology on response to terlipressin and albumin and post-transplant outcomes in patients with hepatorenal syndrome (AKI-HRS). They raised four important points. The first one allow us to strengthen further the message that a liver transplant (LT) allocation policy based on weekly updates of MELD/MELD-Na score may have a negative impact on responders to treatment with terlipressin and albumin. This is the reason why baseline MELD/MELD-Na score (pre-treatment value) is currently used for LT prioritization in responders to terlipressin and albumin in some regions.
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http://dx.doi.org/10.1002/hep.31989DOI Listing
June 2021

Sustained Complete Response after Biological Downstaging in Patients with Hepatocellular Carcinoma: XXL-Like Prioritization for Liver Transplantation or "Wait and See" Strategy?

Cancers (Basel) 2021 May 17;13(10). Epub 2021 May 17.

Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgical, Oncological, and Gastroenterological Sciences, Padua University Hospital, 35128 Padova, Italy.

The XXL trial represents the first prospective validation of "biological downstaging" in liver transplantation (LT) for hepatocellular carcinoma. The aim of this study was to compare the Padua downstaging protocol to the XXL protocol in terms of downstaging failure rates and patient outcome. A total of 191 patients undergoing aggressive surgical downstaging and potentially eligible for LT from 2012 to 2018 at our center were retrospectively selected according to XXL trial criteria. Unlike the XXL trial, patients with a complete response to downstaging did not receive any prioritization for LT. Downstaging failure was defined as stable progressive disease or post-treatment mortality. The statistical method of "matching-adjusted indirect comparison" was used to match the study group to the XXL population. Downstaging failure rate was considerably lower in the study group than in the XXL trial (12% vs. 32%, value = |0.683|). The survival curves of our LT group ( = 68) overlapped with those of the LT-XXL group ( = 0.846). Survival curves of non-LT candidates with a sustained complete response ( = 64) were similar to those of transplanted patients ( = 0.281). Our study represents a validation of the current Padua and Italian policies of denying rapid prioritization to patients with complete response to downstaging. Such a policy seems to spare organs without worsening patient outcome.
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http://dx.doi.org/10.3390/cancers13102406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156031PMC
May 2021

New clinical and pathophysiological perspectives defining the trajectory of cirrhosis.

J Hepatol 2021 Jul;75 Suppl 1:S14-S26

European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain.

Traditionally, the complications of cirrhosis, namely variceal bleeding, ascites and hepatic encephalopathy, were thought to result predominantly from circulatory dysfunction and altered organ perfusion arising as a result of portal hypertension. Over the past 20 years, large, international prospective studies have indicated the importance of systemic inflammation and organ immunopathology as additional determinants of organ dysfunction in cirrhosis, which not only manifests in the liver, brain, circulation and the kidneys, but also the immune system, gut, muscles, adrenal glands, reproductive organs, heart and lungs. This review provides an overview of the traditional and emerging concepts around the initiation and maintenance of organ dysfunction in cirrhosis and proposes a new paradigm based upon a better understanding of acute decompensation of cirrhosis. The interaction between the traditional concepts and the emerging perspectives remains a matter of great interest and the basis for future research.
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http://dx.doi.org/10.1016/j.jhep.2021.01.018DOI Listing
July 2021

Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: Results of the ELITA/EF-CLIF collaborative study (ECLIS).

J Hepatol 2021 May 2. Epub 2021 May 2.

Department of Hepatogastroenterology, Hepatology and Liver Transplantation Unit, HCL Hopital de la Croix-Rousse, Lyon, France.

Background & Aims: Liver transplantation (LT) has been proposed as an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to assess the current clinical practice and outcomes of patients with ACLF who are wait-listed for LT in Europe.

Methods: This was a retrospective study including 308 consecutive patients with ACLF, listed in 20 centres across 8 European countries, from January 2018 to June 2019.

Results: A total of 2,677 patients received a LT: 1,216 (45.4%) for decompensated cirrhosis. Of these, 234 (19.2%) had ACLF at LT: 58 (4.8%) had ACLF-1, 78 (6.4%) had ACLF-2, and 98 (8.1%) had ACLF-3. Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and the Netherlands had medium rates (9-15%); and the United Kingdom and Spain had low rates (3-5%) (p <0.0001). The 1-year probability of survival after LT for patients with ACLF was 81% (95% CI 74-87). Pre-LT arterial lactate levels >4 mmol/L (hazard ratio [HR] 3.14; 95% CI 1.37-7.19), recent infection from multidrug resistant organisms (HR 3.67; 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74; 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the waiting list. In an intention-to-treat analysis, 1-year survival of patients with ACLF on the LT waiting list was 73% for ACLF-1 or -2 and 50% for ACLF-3.

Conclusion: The results reveal wide variations in the listing of patients with ACLF in Europe despite favourable post-LT survival. Risk factors for mortality were identified, enabling a more precise prognostic assessment of patients with ACLF.

Lay Summary: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonised to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified to help select patients with favourable outcomes.
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http://dx.doi.org/10.1016/j.jhep.2021.03.030DOI Listing
May 2021

Liver Fibrosis and Steatosis in Alström Syndrome: A Genetic Model for Metabolic Syndrome.

Diagnostics (Basel) 2021 Apr 28;11(5). Epub 2021 Apr 28.

Internal Medicine 3, Department of Medicine, DIMED, University of Padua, 35128 Padua, Italy.

Alström syndrome (ALMS) is an ultra-rare monogenic disease characterized by insulin resistance, multi-organ fibrosis, obesity, type 2 diabetes mellitus (T2DM), and hypertriglyceridemia with high and early incidence of non-alcoholic fatty liver disease (NAFLD). We evaluated liver fibrosis quantifying liver stiffness (LS) by shear wave elastography (SWE) and steatosis using ultrasound sonographic (US) liver/kidney ratios (L/K) in 18 patients with ALMS and 25 controls, and analyzed the contribution of metabolic and genetic alterations in NAFLD progression. We also genetically characterized patients. LS and L/K values were significantly higher in patients compared with in controls ( < 0.001 versus = 0.013). In patients, LS correlated with the Fibrosis-4 Index and age, while L/K was associated with triglyceride levels. LS showed an increasing trend in patients with metabolic comorbidities and displayed a significant correlation with waist circumference, the homeostasis model assessment, and glycated hemoglobin A1c. SWE and US represent promising tools to accurately evaluate early liver fibrosis and steatosis in adults and children with ALMS during follow-up. We described a new pathogenic variant of exon 8 in . Patients with ALMS displayed enhanced steatosis, an early increased age-dependent LS that is associated with obesity and T2DM but also linked to genetic alterations, suggesting that could be involved in liver fibrogenesis.
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http://dx.doi.org/10.3390/diagnostics11050797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170882PMC
April 2021

Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI).

Intern Emerg Med 2021 Jun 24;16(4):1005-1015. Epub 2021 Apr 24.

Internal Medicine Department, San Carlo Hospital, Paderno Dugnano, Milan, Italy.

During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managed in Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO/FiO ratio at admission was strongly inversely associated with survival. The use of conventional oxygen supplementation increased with the number of pre-existing comorbidities, but it did not associate with better survival in patients with PaO/FiO ratio < 100. The latter, significantly benefited by the early use of non-invasive mechanical ventilation. Our study identified PaO/FiO ratio at admission and comorbidity as the main alert signs to inform clinical decisions and resource allocation in non-critically ill COVID-19 patients admitted to IMU.
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http://dx.doi.org/10.1007/s11739-021-02742-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065333PMC
June 2021

Bacterial Infections in Cirrhosis as a Cause or Consequence of Decompensation?

Clin Liver Dis 2021 05 10;25(2):357-372. Epub 2021 Mar 10.

Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University and Hospital of Padova, Via Giustiniani 2, Padova 35100, Italy.

Bacterial infections are ominous events in liver cirrhosis. Cirrhosis-associated immune dysfunction and pathologic bacterial translocation are responsible for the increased risk of infections. Bacteria induce systemic inflammation, which worsens circulatory dysfunction and induces oxidative stress and mitochondrial dysfunction. Bacterial infections, frequently associated with decompensation, are the most common precipitating event of acute-on-chronic liver failure (ACLF). After decompensation, patients with cirrhosis have an increased risk of developing infections. Bacterial infections should be ruled out in these patients and strategies to prevent infections should be implemented to prevent further decompensation. We review infections as a cause and consequence of decompensation in cirrhosis.
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http://dx.doi.org/10.1016/j.cld.2021.01.006DOI Listing
May 2021

Liver Transplantation for T2 Hepatocellular Carcinoma during the COVID-19 Pandemic: A Novel Model Balancing Individual Benefit against Healthcare Resources.

Cancers (Basel) 2021 Mar 19;13(6). Epub 2021 Mar 19.

Italian National Transplant Center, Italian National Institute of Health, 00118 Rome, Italy.

The COVID-19 pandemic caused temporary drops in the supply of organs for transplantation, leading to renewed debate about whether T2 hepatocellular carcinoma (HCC) patients should receive priority during these times. The aim of this study was to provide a quantitative model to aid decision-making in liver transplantation for T2 HCC. We proposed a novel ethical framework where the individual transplant benefit for a T2 HCC patient should outweigh the harm to others on the waiting list, determining a "net benefit", to define appropriate organ allocation. This ethical framework was then translated into a quantitative Markov model including Italian averages for waiting list characteristics, donor resources, mortality, and transplant rates obtained from a national prospective database (n = 8567 patients). The net benefit of transplantation in a T2 HCC patient in a usual situation varied from 0 life months with a model for end-stage liver disease (MELD) score of 15, to 34 life months with a MELD score of 40, while it progressively decreased with acute organ shortage during a pandemic (i.e., with a 50% decrease in organs, the net benefit varied from 0 life months with MELD 30, to 12 life months with MELD 40). Our study supports the continuation of transplantation for T2 HCC patients during crises such as COVID-19; however, the focus needs to be on those T2 HCC patients with the highest net survival benefit.
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http://dx.doi.org/10.3390/cancers13061416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003429PMC
March 2021

Expectancy to Eat Modulates Cognitive Control and Attention Toward Irrelevant Food and Non-food Images in Healthy Starving Individuals. A Behavioral Study.

Front Psychol 2020 13;11:569867. Epub 2021 Jan 13.

Department of General Psychology, University of Padova, Padua, Italy.

It is thought that just as hunger itself, the expectancy to eat impacts attention and cognitive control toward food stimuli, but this theory has not been extensively explored at a behavioral level. In order to study the effect of expectancy to eat on attentional and cognitive control mechanisms, 63 healthy fasting participants were presented with an affective priming spatial compatibility Simon task that included both food and object (non-food) distracters. The participants ( = 63) were randomly assigned to two groups: an "immediate expectancy" group made up of participants who expected to eat immediately after the task ( = 31; females = 21; age = 26.8 ± 9.6) and a "delayed expectancy" cohort made up of individuals who expected to eat a few hours later ( = 32; females = 21; age = 25.0 ± 8.0). Slower reaction times (RTs) toward the food and non-food distracters and a more pronounced effect on the RTs in the incompatible condition [i.e., the Simon effect (SE)] were noted in both groups. The effect of the food and non-food distracters on the RTs was more pronounced in the immediate with respect to the delayed expectancy group. The magnitude of the SE for the food and the non-food distracters was also greater in the immediate with respect to the delayed expectancy group. These results seem to indicate that when the expectancy to eat is short, the RTs are delayed, and the SE is more pronounced when food and non-food distracters are presented. Instead, when the expectancy to eat is more distant, the distracters have less of an effect on the RTs and the correspondence effect is smaller. Our results suggest that the expectancy to eat can modulate both attention orienting and cognitive control mechanisms in healthy fasting individuals when distracting details are competing with information processing during goal directed behavior.
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http://dx.doi.org/10.3389/fpsyg.2020.569867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838084PMC
January 2021

Changes in the epidemiology and management of bacterial infections in cirrhosis.

Clin Mol Hepatol 2021 Jul 28;27(3):437-445. Epub 2021 Jan 28.

Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy.

Patients with cirrhosis are susceptible to develop infections because of immune dysfunction, changes in microbiome and increase in bacterial translocation from the gut to systemic circulation. Bacterial infections can worse the clinical course of the disease, triggering the development of complications such as acute kidney injury, hepatic encephalopathy, organ failures and acute on chronic liver failure. In recent years, the spread of multi drug resistant bacteria made more challenging the management of infections in patients with cirrhosis. Hence, the mortality rate associated to sepsis is increasing in these patients. Therefore, the optimization of the management of infections has a high priority in cirrhosis. Herein we reviewed the recent changes in the epidemiology and the management of bacterial infections in patients with liver cirrhosis.
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http://dx.doi.org/10.3350/cmh.2020.0329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273641PMC
July 2021

Effects of a reorganization of cirrhosis care during the lockdown for SARS-CoV-2 outbreak.

JHEP Rep 2021 Apr 19;3(2):100229. Epub 2021 Jan 19.

Department of Medicine - DIMED, University and Hospital of Padova, Padova, Italy.

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http://dx.doi.org/10.1016/j.jhepr.2021.100229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816870PMC
April 2021

The Use of Rifaximin in Patients With Cirrhosis.

Hepatology 2021 Jan 9. Epub 2021 Jan 9.

Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, CIBEReHD, Barcelona, Catalonia, Spain.

Rifaximin is an oral nonsystemic antibiotic with minimal gastrointestinal absorption and broad-spectrum antibacterial activity covering both gram-positive and gram-negative organisms. Rifaximin is currently used worldwide in patients with cirrhosis for preventing recurrent HE because its efficacy and safety have been proven by large randomized clinical trials. In the last decade, experimental and clinical evidence suggest that rifaximin could have other beneficial effects on the course of cirrhosis by modulating the gut microbiome and affecting the gut-liver axis, which in turn can interfere with major events of the pathophysiological cascade underlying decompensated cirrhosis, such as systemic inflammatory syndrome, portal hypertension, and bacterial infections. However, the use of rifaximin for prevention or treatment of other complications, including spontaneous bacterial peritonitis or other bacterial infections, is not accepted because evidence by clinical trials is still very weak. The present review deals in the first part with the potential impact of rifaximin on pathogenic mechanisms in liver diseases, whereas in the second part, its clinical effects are critically discussed. It clearly emerges that, because of its potential activity on multiple pathogenic events, the efficacy of rifaximin in the prevention or management of complications other than HE deserves to be investigated extensively. The results of double-blinded, adequately powered randomized clinical trials assessing the effect of rifaximin, alone or in combination with other drugs, on hard clinical endpoints, such as decompensation of cirrhosis, acute-on-chronic liver failure, and mortality, are therefore eagerly awaited.
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http://dx.doi.org/10.1002/hep.31708DOI Listing
January 2021

Spontaneous portosystemic shunts in cirrhosis: Detection, implications, and clinical associations.

Dig Liver Dis 2020 Dec 16. Epub 2020 Dec 16.

Department of Medicine-DIMED(,) University of Padova, Padova, Italy. Electronic address:

Background: Spontaneous portosystemic shunts (SPSS) are common in cirrhosis. Their characterization and clinical implications remain unclear.

Aims: To devise a system of assessment of these shunts, and assess their clinical implications METHODS: We retrospectively studied patients with cirrhosis who underwent imaging in a liver transplant program. A novel index was computed to assess total SPSS -the diameter of a circle having an area equivalent to the sum of the areas of all the existing shunts. This 'SPSS equivalent diameter' was compared with the clinical variables.

Results: Among 127 patients, 70% (CI 62-77) had SPSS, and 57% (CI 62-77) had multiple SPSS. The risk for SPSS was related to the severity of cirrhosis (Child-Pugh B/C vs. A: OR 2.4 CI 1.1-5.4) and alcoholic aetiology (OR 2.9 CI 1.2-7.1). The SPSS equivalent diameter was related to a history of HE, cognitive impairment (EEG/PHES) and ammonia(p<0.05). The diameter of the inferior cava vein >19.5 mm was a predictor of large SPSS (AUC 0.77, CI:0.68-0.87, p ≤ 0.001).

Conclusions: The SPSS equivalent diameter, a comprehensive assessment of portosystemic shunting, was associated with severity of liver disease, hyperammonemia, and cognitive dysfunction. The diameter of the inferior vena cava was a good predictor of SPSS.
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http://dx.doi.org/10.1016/j.dld.2020.11.020DOI Listing
December 2020
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