Publications by authors named "Patrizia Burra"

262 Publications

The application of artificial intelligence in hepatology: A systematic review.

Dig Liver Dis 2021 Jul 12. Epub 2021 Jul 12.

Division of Internal Medicine, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy.

The integration of human and artificial intelligence (AI) in medicine has only recently begun but it has already become obvious that intelligent systems can dramatically improve the management of liver diseases. Big data made it possible to envisage transformative developments of the use of AI for diagnosing, predicting prognosis and treating liver diseases, but there is still a lot of work to do. If we want to achieve the 21 century digital revolution, there is an urgent need for specific national and international rules, and to adhere to bioethical parameters when collecting data. Avoiding misleading results is essential for the effective use of AI. A crucial question is whether it is possible to sustain, technically and morally, the process of integration between man and machine. We present a systematic review on the applications of AI to hepatology, highlighting the current challenges and crucial issues related to the use of such technologies.
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http://dx.doi.org/10.1016/j.dld.2021.06.011DOI Listing
July 2021

A Global Survey of Physicians Knowledge About Non-alcoholic Fatty Liver Disease.

Clin Gastroenterol Hepatol 2021 Jul 3. Epub 2021 Jul 3.

Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, USA; Inova Medicine, Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, USA.

Background & Aims: Despite rapidly increasing NAFLD prevalence, providers' knowledge may be limited. We assessed NAFLD knowledge and associated factors among physicians of different specialties globally.

Approach & Results: NAFLD knowledge surveys containing 54 and 59 questions covering three domains (Epidemiology/Pathogenesis, Diagnostics, and Treatment) were completed electronically by hepatologists, gastroenterologists (GEs), endocrinologists (ENDOs) and primary care physicians (PCPs) from 40 countries comprising 5 Global Burden of Disease (GBD) super-regions. Over 24 months, 2202 surveys were completed (488 hepatologists, 758 GEs, 148 ENDOs, and 808 PCPs; 50% High-Income GBD super-region, 27% from North Africa and Middle East, 12% Southeast Asia, and 5% South Asian and Latin America). Hepatologists saw the greatest number of NAFLD patients annually: median (IQR) 150 (60-300) vs. 100 (35-200) for GEs, 100 (30-200) for ENDOs, and 10 (4-50) for PCPs (all p<0.0001). The primary sources of NAFLD knowledge acquisition for hepatologists were international conferences (33% vs. 8-26%) and practice guidelines for others (39-44%). Internet was the second most common source of NAFLD knowledge for PCPs (28%). NAFLD knowledge scores were higher for hepatologists than GEs: Epidemiology 62% vs. 53%, Diagnostics 80% vs. 73%, Treatment 61% vs. 58% (p<0.0001) and ENDOs scores were higher than PCPs: Epidemiology 70% vs. 60%, Diagnostics 71% vs. 64%, Treatment 79% vs. 68% (p<0.0001). Being a hepatologist or ENDO was associated with higher knowledge scores than GE or PCP, respectively (p<0.05). Higher NAFLD knowledge scores were independently associated with greater number of NAFLD patients seen (p<0.05).

Conclusion: Despite the growing burden of NAFLD, significant knowledge gap remains for identification, diagnosis and management of NAFLD.
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http://dx.doi.org/10.1016/j.cgh.2021.06.048DOI 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

Solid Organ Transplantation During COVID-19 Pandemic: An International Web-based Survey on Resources' Allocation.

Transplant Direct 2021 Mar 11;7(3):e669. Epub 2021 Feb 11.

Department of Surgery, Oncology and Gastroenterology, Azienda Ospedaliera Universitaria, Padua, Italy.

Solid organ transplants (SOTs) are life-saving interventions, recently challenged by coronavirus disease 2019 (COVID-19). SOTs require a multistep process, which can be affected by COVID-19 at several phases.

Methods: SOT-specialists, COVID-19-specialists, and medical ethicists designed an international survey according to CHERRIES guidelines. Personal opinions about continuing SOTs, safe managing of donors and recipients, as well as equity of resources' allocation were investigated. The survey was sent by e-mail. Multiple approaches were used (corresponding authors from Scopus, websites of scientific societies, COVID-19 webinars). After the descriptive analysis, univariate and multivariate ordinal regression analysis was performed.

Results: There were 1819 complete answers from 71 countries. The response rate was 49%. Data were stratified according to region, macrospecialty, and organ of interest. Answers were analyzed using univariate-multivariate ordinal regression analysis and thematic analysis. Overall, 20% of the responders thought SOTs should not stop (continue transplant without restriction); over 70% suggested SOTs should selectively stop, and almost 10% indicated they should completely stop. Furthermore, 82% agreed to shift resources from transplant to COVID-19 temporarily. Briefly, main reason for not stopping was that if the transplant will not proceed, the organ will be wasted. Focusing on SOT from living donors, 61% stated that activity should be restricted only to "urgent" cases. At the multivariate analysis, factors identified in favor of continuing transplant were Italy, ethicist, partially disagreeing on the equity question, a high number of COVID-19-related deaths on the day of the answer, a high IHDI country. Factors predicting to stop SOTs were Europe except-Italy, public university hospital, and strongly agreeing on the equity question.

Conclusions: In conclusion, the majority of responders suggested that transplant activity should be continued through the implementation of isolation measures and the adoption of the COVID-19-free pathways. Differences between professional categories are less strong than supposed.
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http://dx.doi.org/10.1097/TXD.0000000000001115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184017PMC
March 2021

Position paper on liver and kidney diseases from the Italian Association for the Study of Liver (AISF), in collaboration with the Italian Society of Nephrology (SIN).

Dig Liver Dis 2021 Jun;53 Suppl 2:S49-S86

Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Via Giustiniani 2, 35128, Padua, Italy. Electronic address:

Liver and kidney are strictly connected in a reciprocal manner, in both the physiological and pathological condition. The Italian Association for the Study of Liver, in collaboration with the Italian Society of Nephrology, with this position paper aims to provide an up-to-date overview on the principal relationships between these two important organs. A panel of well-recognized international expert hepatologists and nephrologists identified five relevant topics: 1) The diagnosis of kidney damage in patients with chronic liver disease; 2) Acute kidney injury in liver cirrhosis; 3) Association between chronic liver disease and chronic kidney disease; 4) Kidney damage according to different etiology of liver disease; 5) Polycystic kidney and liver disease. The discussion process started with a review of the literature relating to each of the five major topics and clinical questions and related statements were subsequently formulated. The quality of evidence and strength of recommendations were graded according to the GRADE system. The statements presented here highlight the importance of strong collaboration between hepatologists and nephrologists for the management of critically ill patients, such as those with combined liver and kidney impairment.
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http://dx.doi.org/10.1016/j.dld.2021.03.035DOI 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

Limitations of current liver donor allocation systems and the impact of newer indications for liver transplantation.

J Hepatol 2021 Jul;75 Suppl 1:S178-S190

Liver Failure Group, Institute for Liver and Digestive Health, University College London, London and European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain.

Liver transplantation represents a life-saving treatment for patients with decompensated cirrhosis, a severe condition associated with a high risk of waiting list mortality. When decompensation occurs rapidly in the presence of extrahepatic organ failures, the condition is called acute-on-chronic liver failure, which is associated with an even higher risk of death, though liver transplantation can also markedly improve survival in affected patients. However, there are still gaps in our understanding of how to optimise prioritisation and organ allocation, as well as survival among patients with acute-on-chronic liver failure (both before and after transplant). Moreover, it is urgent to address inequalities in access to liver transplantation in patients with severe alcoholic hepatitis and non-alcoholic steatohepatitis. Several controversies still exist regarding gender and regional disparities, as well as the use of suboptimal donor grafts. In this review, we aim to provide a critical perspective on the role of liver transplantation in patients with decompensated cirrhosis and address areas of ongoing uncertainty.
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http://dx.doi.org/10.1016/j.jhep.2021.01.007DOI Listing
July 2021

Clinical impact of sexual dimorphism in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

Liver Int 2021 Aug 8;41(8):1713-1733. Epub 2021 Jun 8.

Gastroenterology Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy.

NAFLD/NASH is a sex-dimorphic disease, with a general higher prevalence in men. Women are at reduced risk of NAFLD compared to men in fertile age, whereas after menopause women have a comparable prevalence of NAFLD as men. Indeed, sexual category, sex hormones and gender habits interact with numerous NAFLD factors including cytokines, stress and environmental factors and alter the risk profiles and phenotypes of NAFLD. In the present review, we summarized the last findings about the influence of sex on epidemiology, pathogenesis, progression in cirrhosis, indication for liver transplantation and alternative therapies, including lifestyle modification and pharmacological strategies. We are confident that an appropriate consideration of sex, age, hormonal status and sociocultural gender differences will lead to a better understanding of sex differences in NAFLD risk, therapeutic targets and treatment responses and will aid in achieving sex-specific personalized therapies.
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http://dx.doi.org/10.1111/liv.14943DOI Listing
August 2021

Italian association for the study of the liver position statement on SARS-CoV2 vaccination.

Dig Liver Dis 2021 06 30;53(6):677-681. Epub 2021 Apr 30.

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Humanitas Research Hospital IRCCS, Rozzano, Italy.

The vaccination campaign against Sars-CoV-2 commenced in Italy at the end of December 2020. The first ones to receive the immunization against the virus were the health workers and the residents of nursing homes, following which the vaccine would be available for the entire population, beginning with the most vulnerable individuals. SARS-CoV2 vaccines have been demonstrated to be safe for the general population, although no data for patients with liver diseases or those having undergone liver transplantation are available so far. The present position statement AISF is an attempt to suggest, based on the published data on the impact of Sars-Cov-2 infection in patients with chronic liver disease, a possible priority for vaccination for this category of patients.
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http://dx.doi.org/10.1016/j.dld.2021.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086184PMC
June 2021

Determinants of increased thrombotic tendency in NASH cirrhosis: not there yet!

Transpl Int 2021 Jul 21;34(7):1325-1327. Epub 2021 May 21.

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

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http://dx.doi.org/10.1111/tri.13895DOI Listing
July 2021

The Current Management of Hepatorenal Syndrome-Acute Kidney Injury in the United States and the Potential of Terlipressin.

Liver Transpl 2021 Apr 13. Epub 2021 Apr 13.

Department of Internal Medicine and Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA.

Acute kidney injury (AKI) in the setting of cirrhosis (hepatorenal syndrome [HRS]-AKI) is a severe and often fatal complication of end-stage liver disease. The goals of treatment are to reverse renal failure and prolong survival in patients who are critically ill. However, interventions have limited efficacy, and mortality rates remain high. In the United States, the mainstay of pharmacologic therapy consists of the off-label use of vasoconstrictive agents in combination with plasma expanders, a strategy that produces modest effects. Liver transplantation is the ultimate solution but is only an option in a minority of patients because contraindications to transplantation are common and organ availability is limited. Renal replacement therapy is a temporary option but is known to confer an extremely poor short-term prognosis in patients with HRS-AKI and at best serves as a bridge to liver transplantation for the minority of patients who are transplantation candidates. The high mortality rate associated with HRS-AKI in the United States is a reflection of the suboptimal standard of care. Improved therapeutic options to treat HRS-AKI are sought. Terlipressin is a drug approved in Europe for treatment of HRS-AKI and supported by recommendations for first-line therapy by some liver societies and experts around the world. This review article will discuss the substantial unmet medical need associated with HRS-AKI and the potential benefits if terlipressin was approved in the United States.
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http://dx.doi.org/10.1002/lt.26072DOI Listing
April 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

Influence of Hepatocellular Carcinoma on Platelet Aggregation in Cirrhosis.

Cancers (Basel) 2021 Mar 8;13(5). Epub 2021 Mar 8.

Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy.

Hyper-functional platelets are being proposed as a potential therapeutic target in multiple cancers. Whether this can be considered in patients with cirrhosis and hepatocellular carcinoma (HCC) is unknown as their platelet function has not yet been investigated. We evaluated platelet function in cirrhosis patients with HCC. Patients with cirrhosis with and without HCC were prospectively recruited. Platelet aggregation, a marker of platelet function, was assessed by impedance aggregometry with adenosine diphosphate (ADP), arachidonic acid (ASPI), and thrombin (TRAP) stimulation. Plasmatic levels of Von Willebrand factor antigen (VWF) were also determined. One-hundred patients were recruited (50 cirrhotics with and 50 without HCC). Cirrhosis severity by Child class and platelet count were comparable between cirrhotics with and without HCC. Cirrhotics with HCC had higher ADP- (45 vs. 28; < 0.001), ASPI- (47 vs. 28; < 0.001), and TRAP- (85 vs. 75; = 0.01) induced platelet aggregation than cirrhotics without HCC, all indicative of platelet hyper-function. The relatively increased platelet aggregation in patients with HCC was confirmed after adjusting the analysis for platelet count/severity of thrombocytopenia. Levels of VWF were higher in patients with vs. without HCC (348 vs. 267; = 0.006), particularly in compensated cirrhosis. In patients with cirrhosis, HCC is associated with increased platelet aggregation and higher VWF. The clinical implications of these findings deserve further investigation.
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http://dx.doi.org/10.3390/cancers13051150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962527PMC
March 2021

Malnourished cirrhotic patient: what should we do?

Minerva Gastroenterol (Torino) 2021 Mar;67(1):11-22

Unit of Multivisceral Trasplants, Department of Surgery Oncology and Gastroenterology, Padua University Hospital, Padua, Italy -

Malnutrition and sarcopenia have a high prevalence in cirrhotic patients. Frailty generally overlaps with malnutrition and sarcopenia in cirrhosis, leading to increased morbidity and mortality. Rapid nutritional screening assessment should be performed in all patients with cirrhosis, and more specific tests for sarcopenia should be performed in those at high risk. The pathogenesis of malnutrition in cirrhosis is complex and multifactorial and it is not just due to reduction in protein and calorie intake. Nutritional management in malnourished patients with cirrhosis should be undertaken by a multidisciplinary team to achieve adequate protein/calorie intake. While the role of branched-chained amino acids remains somewhat contentious in achieving a global benefit of decreasing mortality- and liver-related events, these latter and vitamin supplements, are recommended for those with advanced liver disease. Novel strategies to reverse sarcopenia such as hormone supplementation, long-term ammonia-lowering agents and myostatin antagonists, are currently under investigation. Malnutrition, sarcopenia and frailty are unique, inter-related and multidimensional problems in cirrhosis which require special attention, prompt assessment and appropriate management as they significantly impact morbidity and mortality.
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http://dx.doi.org/10.23736/S2724-5985.20.02776-2DOI Listing
March 2021

Management of complex liver diseases.

Authors:
Patrizia Burra

Minerva Gastroenterol (Torino) 2021 03;67(1):2-3

Unit of Multivisceral Transplant, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy -

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http://dx.doi.org/10.23736/S2724-5985.20.02803-2DOI Listing
March 2021

Breakthrough invasive fungal infection after liver transplantation in patients on targeted antifungal prophylaxis: A prospective multicentre study.

Transpl Infect Dis 2021 Mar 26:e13608. Epub 2021 Mar 26.

Division of Infectious Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Objective: To investigate the rate of and the risk factors for breakthrough-IFI (b-IFI) after orthotopic liver transplantation (OLT) according to the new definition proposed by Mycoses-Study-Group-Education-and-Research-Consortium (MSG-ERC) and the European-Confederation-of-Medical-Mycology (ECMM).

Methods: Multicenter prospective study of adult patients who underwent OLT at three Italian hospitals, from January 2015 to December 2018. Targeted antifungal prophylaxis (TAP) protocol was developed and shared among participating centers. Follow-up was 1-year after OLT. B-IFI was defined as infection occurring during exposure to antifungal prophylaxis. Risk factors for b-IFI were analyzed among patients exposed to prophylaxis by univariable analysis.

Results: We enrolled 485 OLT patients. Overall compliance to TAP protocol was 64.3%, 220 patients received antifungal prophylaxis, 172 according to TAP protocol. Twenty-nine patients were diagnosed of IFI within 1 year after OLT. Of them, 11 presented with b-IFI within 17 (IQR 11-33) and 16 (IQR 4-30) days from OLT and from antifungal onset, respectively. Then out of 11 patients with b-IFI were classified as having high risk of IFI and were receiving anti-mould prophylaxis, nine with echinocandins and one with polyenes. Comparison of patients with and without b-IFI showed significant differences for prior Candida colonization, need of renal replacement therapy after OLT, re-operation, and CMV infection (whole blood CMV-DNA >100 000 copies/mL). Although non-significant, a higher rate of b-IFI in patients on echinocandins was observed (8.2% vs 1.8%, P = .06).

Conclusions: We observed 5% of b-IFI among OLT patients exposed to antifungal prophylaxis. The impact of echinocandins on b-IFI risk in this setting should be further explored.
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http://dx.doi.org/10.1111/tid.13608DOI Listing
March 2021

The Need for Consensus About Liver Transplantation For Patients With Neuropsychiatric Wilson's Disease.

Prog Transplant 2021 Jun 11;31(2):168-170. Epub 2021 Mar 11.

Multivisceral Transplant Unit, Gastroenterology, Padua University Hospital, Padua, Italy.

Liver transplantation is considered an effective therapeutic option for Wilson's disease (WD) patients with hepatic phenotype, since it removes the inherited defects of copper metabolism, and is associated with excellent graft and patient outcomes. The role of liver transplantation in WD patients with mixed hepatic and neuropsychiatric phenotype has remained controversial over time, mainly because of high post-operative complications, reduced survival and a variable, unpredictable rate of neurological improvement. This article critically discusses the recently published data in this field, focussing in more detail on isolated neuropsychiatric phenotype as a potential indication for liver transplantation in WD patients.
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http://dx.doi.org/10.1177/15269248211002806DOI Listing
June 2021

Development of a Risk Prediction Model for Carbapenem-Resistant Enterobacteriaceae Infection after Liver Transplantation: A Multinational Cohort Study.

Clin Infect Dis 2021 Feb 10. Epub 2021 Feb 10.

Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.

Background: Patients colonized with carbapenem resistant Enterobacteriaceae (CRE) are at higher risk of developing CRE infection after liver transplantation (LT) with associated high morbidity and mortality. Prediction model for CRE infection after LT among carriers could be useful to target preventive strategies.

Methods: Multinational multicenter cohort study of consecutive adult patients underwent LT and colonized with CRE before or after LT, from January 2010 to December 2017. Risk factors for CRE infection were analyzed by univariate analysis and by Fine-Gray sub-distribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created.

Results: 840 LT recipients found to be colonized with CRE before (n=203) or after (n=637) LT were enrolled. CRE infection was diagnosed in 250 (29.7%) patients within 19 (IQR 9-42) days after LT. Pre-and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical re-intervention were retained in the prediction model. Median 30 and 60-day predicted risk was 15% (IQR 11-24%) and 21% (IQR 15-33%), respectively. Discrimination and prediction accuracy for CRE infection was acceptable on derivation (AUC 74.6, Brier index 16.3) and bootstrapped validation dataset (AUC 73.9, Brier index 16.6). Decision-curve analysis suggested net benefit of model-directed intervention over default strategies (treat all, treat none) when CRE infection probability exceeded 10%. The risk prediction model is freely available as mobile application at https://idbologna.shinyapps.io/CREPostOLTPredictionModel/.

Conclusions: Our clinical prediction tool could enable better targeting interventions for CRE infection after transplant.
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http://dx.doi.org/10.1093/cid/ciab109DOI Listing
February 2021

A challenging liver transplantation for decompensated alcoholic liver disease after recovery from SARS-CoV-2 infection.

Transpl Int 2021 04 27;34(4):756-757. Epub 2021 Feb 27.

Multivisceral Transplant Unit and Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.

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http://dx.doi.org/10.1111/tri.13842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013652PMC
April 2021

Hepatocellular carcinoma and the risk of de novo malignancies after liver transplantation - a multicenter cohort study.

Transpl Int 2021 04 26;34(4):743-753. Epub 2021 Feb 26.

Department of Epidemiology, National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.

Patients with hepatocellular carcinoma (HCC) are at high risk of second primary malignancies. As HCC has become the leading indication of liver transplant (LT), the aim of this study was to investigate whether the presence of HCC before LT could influence the onset of de novo malignancies (DNM). A cohort study was conducted on 2653 LT recipients. Hazard ratios (HR) of DNM development for patients transplanted for HCC (HCC patients) were compared with those of patients without any previous malignancy (non-HCC patients). All models were adjusted for sex, age, calendar year at transplant, and liver disease etiology. Throughout 17 903 person-years, 6.6% of HCC patients and 7.4% of non-HCC patients developed DNM (202 cases). The median time from LT to first DNM diagnosis was shorter for solid tumors in HCC patients (2.7 vs 4.5 years for HCC and non-HCC patients, respectively, P < 0.01). HCC patients were at a higher risk of bladder cancer and skin melanoma. There were no differences in cumulative DNM-specific mortality by HCC status. This study suggests that primary HCC could be a risk factor for DNM in LT recipients, allowing for risk stratification and screening individualization.
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http://dx.doi.org/10.1111/tri.13831DOI Listing
April 2021

Presepsin as a biomarker of inflammation and prognosis in decompensated liver disease.

J Hepatol 2021 Jul 21;75(1):232-234. Epub 2021 Jan 21.

Multivisceral Transplant Unit, Gastroenterology, Padova University Hospital, Padova, Italy.

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http://dx.doi.org/10.1016/j.jhep.2021.01.016DOI Listing
July 2021