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Therapeutic approaches for portal biliopathy: A systematic review

World Journal of Gastroenterology 2016年第45期22卷 9909-9920页

作者： Irene Franceschet Alberto Zanetto Alberto Ferrarese Patrizia Burra marco senzolo Gastroenterology Unit Department of Surgery Oncology and Gastroenterology University Hospital of Padua Multivisceral Transplant Unit Department of Surgery Oncology and Gastroenterology University Hospital of Padua

Portal biliopathy(PB) is defined as the presence of biliary abnormalities in patients with non-cirrhotic/nonneoplastic extrahepatic portal vein obstruction(EHPVO) and portal cavernoma(PC). The pathogenesis of PB is due to ab extrinseco compression of bile ducts by PC and/or to ischemic damage secondary to an altered biliary vascularization in EHPVO and PC. Although asymptomatic biliary abnormalities can be frequently seen by magnetic resonance cholangiopancreatography in patients with PC(77%-100%), only a part of these(5%-38%) are symptomatic. Clinical presentation includes jaundice, cholangitis, cholecystitis, abdominal pain, and cholelithiasis. In this subset of patients is required a specific treatment. Different therapeutic approaches aimed to diminish portal hypertension and treat biliary strictures are available. In order to decompress PC, surgical porto-systemic shunt or transjugular intrahepatic porto-systemic shunt can be performed, and treatment on the biliary stenosis includes endoscopic(Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy, balloon dilation, stone extraction, stent placement) and surgical(bilioenteric anastomosis, cholecystectomy) approaches. Definitive treatment of PB often requires multiple and combined interventions both on vascular and biliary system. Liver transplantation can be considered in patients with secondary biliary cirrhosis, recurrent cholangitis or unsuccessful control of portal hypertension.

关键词：门 biliopathy 门 cavernoma 磁性的回声 cholangiopancreatography 内视镜后退 cholangiopancreatography 波尔图全身的分流

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Neuropsychological alterations in hepatitis C infection:The role of inflammation

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World Journal of Gastroenterology 2011年第29期17卷 3369-3374页

作者： marco senzolo Sami Schiff Cristina Maria D’Aloiso Chiara Crivellin Evangelos Cholongitas Patrizia Burra Sara Montagnese Multivisceral Transplant Unit Department of Surgical and Gastroenterological SciencesUniversity Hospital of Padua35128 PaduaItaly Department of Clinical and Experimental Medicine University Hospital of Padua35128 PaduaItaly The Royal Free Sheila Sherlock Liver Centre and Department of Surgery UCL and Royal Free HospitalPond StreetLondon NW3 2QGUnited Kindom

About 50% of patients with hepatitis C virus(HCV)infection complain of neuropsychiatric symptoms,"brain fog",weakness,fatigue,and exhibit some degree of quality of life impairment,irrespective of the severity of liver disease.Since the first observation of HCV-related cognitive deficits,10 studies have been published that have evaluated neuropsychiatric performance in patients with HCV infection and different degrees of hepatic impairment.Unfortunately,these have often included patients with cirrhosis,patients who had acquired the infection through previous intravenous drug misuse,who had a history of relatively recent treatment with interferon,or were on psychoactive medication.In addition,different neuropsychological batteries and tests that explored different cognitive domains were used,which makes the results of the studies difficult to compare.Finally,limited information is available on the pathogenesis of HCV-related cognitive impairment.Cerebral and/or systemic inflammation may be important players but their potential role has not been substantiated by experimental data.The present review outlines the available evidence of the presence of cognitive impairment in patients with HCV infection,with a focus on the potential relationship with cerebral and/or systemic inflammation.

关键词：丙型肝炎病毒病毒感染炎症反应心理学神经认知功能障碍精神药物肝功能损害

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Invasive fungal infection before and after liver transplantation

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World Journal of Gastroenterology 2020年第47期26卷 7485-7496页

作者： Alberto Ferrarese Annamaria Cattelan Umberto Cillo Enrico Gringeri Francesco Paolo Russo Giacomo Germani Martina Gambato Patrizia Burra marco senzolo Multivisceral Transplant Unit Padua University HospitalPadua 35128Italy Tropical and Infectious Disease Unit Padua University HospitalPadua 35128Italy Padua University Hospital Hepatobiliary Surgery and Liver Transplant CenterPadua 35128Italy

Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure,who suffer from a profound state of immune dysfunction and receive intensive care management.In such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before surgery.In the post-transplant setting,the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis,even if several major issues still remain,such as duration,target population and drug type(s).Nevertheless,the development of IFD in the early phase after surgery significantly impairs graft and patient survival.This review outlines presentation,prophylactic and therapeutic strategies,and outcomes of IFD in LT candidates and recipients,providing specific considerations for clinical practice.

关键词： Acute-on-chronic liver failure Sepsis Cirrhosis Candidemia Acute liver failure Invasive fungal infection

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Hepatitis C virus related cirrhosis decreased as indication to liver transplantation since the introduction of direct-acting antivirals: A single-center study

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World Journal of Gastroenterology 2018年第38期24卷 4403-4411页

作者： Alberto Ferrarese Giacomo Germani Martina Gambato Francesco Paolo Russo marco senzolo Alberto Zanetto Sarah Shalaby Umberto Cillo Giacomo Zanus Paolo Angeli Patrizia Burra Multivisceral Transplant Unit Department of Surgery Oncology and Gastroenterology Padua University Hospital Hepatobiliary Surgery and Liver Transplant Unit Department of Surgery Oncology and Gastroenterology Padua University Hospital Internal Medicine Department of Medicine Padua University Hospital

AIM To evaluate waiting list(WL) registration and liver transplantation(LT) rates in patients with hepatitis C virus(HCV)-related cirrhosis since the introduction of direct-acting antivirals(DAAs).METHODS All adult patients with cirrhosis listed for LT at Padua University Hospital between 2006-2017 were retrospectively collected using a prospectivelyupdated database; patients with HCV-related cirrhosis were divided by indication for LT [dec-HCV vs HCV/hepatocellular carcinoma(HCC)] and into two interval times(2006-2013 and 2014-2017) according to the introduction of DAAs. For each patient, indications to LT, severity of liver dysfunction and the outcome in the WL were assessed and compared between the two different time periods. For patients receiving DAA-based regimens, the achievement of viral eradication and the outcome were also evaluated. RESULTS One thousand one hundred and ninty-four [male(M)/female(F): 925/269] patients were included. Considering the whole cohort, HCV-related cirrhosis was the main etiology at the time of WL registration(490/1194 patients, 41%). HCV-related cirrhosis significantly decreased as indication to WL registration after DAA introduction(from 43.3% in 2006-2013 to 37.2% in 2014-2017, P = 0.05), especially amongst decHCV(from 24.2% in 2006-2013 to 15.9% in 2014-2017, P = 0.007). Even HCV remained the most common indication to LT over time(289/666, 43.4%), there was a trend towards a decrease after DAAs introduction(from 46.3% in 2006-2013 to 39% in 2014-2017, P = 0.06). HCV patients(M/F: 43/11, mean age: 57.7 ± 8 years) who achieved viral eradication in the WL had better transplant-free survival(log-rank test P = 0.02) and delisting rate(P = 0.002) than untreated HCV patients. CONCLUSION Introduction of DAAs significantly reduced WL registrations for HCV related cirrhosis, especially in the setting of decompensated cirrhosis.

关键词： Liver transplantation Hepatitis C Cirrhosis Sustained virological response

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Management of bacterial infection in the liver transplant candidate

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World Journal of Hepatology 2018年第2期10卷 222-230页

作者： Alberto Ferrarese Alberto Zanetto Chiara Becchetti Salvatore Stefano Sciarrone Sarah Shalaby Giacomo Germani Martina Gambato Francesco Paolo Russo Patrizia Burra marco senzolo Multivisceral Transplant Unit Department of Surgery Oncology and Gastroenterology Padua University Hospital

Bacterial infection(BI) is a common cause of impairment of liver function in patients with cirrhosis, especially in the liver transplant candidates. These patients share an immunocompromised state and increased susceptibility to develop community and hospital-acquired infections. The changing epidemiology of BI, with an increase of multidrug resistant strains, especially in healthcareassociated settings, represents a critical issue both in the waiting list and in the post-operative management. This review focused on the role played by BI in patients awaiting liver transplantation, evaluating the risk of drop-out from the waiting list, the possibility to undergo liver transplantation after recovery from infection or during a controlled infection.

关键词： Cirrhosis Portal hypertension Bacterial infection Liver transplantation

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Perioperative thrombotic complications in liver transplantation

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世界胃肠病学杂志：英文版 2015年第26期21卷 8004-8013页

作者： Paolo Feltracco Stefania Barbieri Umberto Cillo Giacomo Zanus marco senzolo Carlo Ori Department of Medicine UO Anaesthesia and Intensive CarePadua University Hospital Hepatobiliary Surgery and Liver Transplant Unit Department of SurgeryOncology and GastroenterologyUniversity Hospital of Padua Multivisceral Transplant Unit Department of SurgeryOncology and GastroenterologyUniversity Hospital of Padua

Although the perioperative bleeding complications and the major side effects of blood transfusion have always been the primary concern in liver transplantation(OLT),the possible cohesion of an underestimated intrinsic hypercoagulative state during and after the transplant procedure may pose a major threat to both patient and graft survival.Thromboembolism during OLT is characterized not only by a complex aetiology,but also by unpredictable onset and evolution of the disease.The initiation of a procoagulant process may be triggered by various factors,such as inflammation,venous stasis,ischemia-reperfusion injury,vascular clamping,anatomical and technical abnormalities,genetic factors,deficiency of profibrinolytic activity,and platelet activation.The involvement of the arterial system,intracardiac thrombosis,pulmonary emboli,portal vein thrombosis,and deep vein thrombosis,are among the most serious thrombotic events in the perioperative period.The rapid detection of occlusive vascular events is of paramount importance as it heavily influences the prognosis,particularly when these events occur intraoperatively or early after OLT.Regardless of the lack of studies and guidelines on anticoagulant prophylaxis in this setting,many institutions recommend such an approach especially in the subset of patients at high risk.However,the decision of when,how and in what doses to use the various chemical anticoagulants is still a difficult task,since there is no common consensus,even for highrisk cases.The risk of postoperative thromboembolism causing severe hemodynamic events,or even loss of graft function,must be weighed and compared with the risk of an important bleeding.In this article we briefly review the risk factors and the possible predictors of major thrombotic complications occurringin the perioperative period,as well as their incidence and clinical features.Moreover,the indications to pharmacological prophylaxis and the current treatment strategies are also summarized.

关键词： Vascular complications Thromboembolicphenomena Liver transplantation Hepatic arteryocclusion Postoperative complications Pulmonaryemboli

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Markers of acute rejection and graft acceptance in liver transplantation

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World Journal of Gastroenterology 2015年第4期21卷 1061-1068页

作者： Giacomo Germani Kryssia Rodriguez-Castro Francesco Paolo Russo marco senzolo Alberto Zanetto Alberto Ferrarese Patrizia Burra Multivisceral Transplant Unit Department of SurgeryOncology and GastroenterologyPaduaUniversity Hospital35128 PaduaItaly

The evaluation of the immunosuppression state in liver transplanted patients is crucial for a correct posttransplant management and a major step towards the personalisation of the immunosuppressive therapy. However, current immunological monitoring after liver transplantation relies mainly on clinical judgment and on immunosuppressive drug levels, without a proper assessment of the real suppression of theimmunological system. Various markers have been studied in an attempt to identify a specific indicator of graft rejection and graft acceptance after liver transplantation. Considering acute rejection, the most studied markers are pro-inflammatory and immunoregulatory cytokines and other proteins related to inflammation. However there is considerable overlap with other conditions, and only few of them have been validated. Standard liver tests cannot be used as markers of graft rejection due to their low sensitivity and specificity and the weak correlation with the severity of histopathological findings. Several studies have been performed to identify biomarkers of tolerance in liver transplanted patients. Most of them are based on the analysis of peripheral blood samples and on the use of transcriptional profiling techniques. Amongst these, NK cell-related molecules seem to be the most valid marker of graft acceptance, whereas the role CD4+CD25+Foxp3+ T cells has still to be properly defined.

关键词： Liver transplantation Acute cellular rejection Tol

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Liver transplantation for viral hepatitis in 2015

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World Journal of Gastroenterology 2016年第4期22卷 1570-1581页

作者： alberto ferrarese alberto zanetto martina gambato ilaria bortoluzzi elena nadal giacomo germani marco senzolo patrizia burra francesco paolo russo Gastroenterology/Multivisceral Transplant Unit Department of SurgeryOncology and GastroenterologyPadua University Hospital35128 PD PaduaItaly

Liver transplantation(LT) is a life-saving treatment forpatients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus(HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus(HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.

关键词： Liver transplantation Hepatitis B virus Hepatitis C virus Recurrence post-transplantation Antiviral therapy Prophylactic therapy

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Direct-acting antivirals and hepatocellular carcinoma occurrence and recurrence in hepatitis C virus-related liver cirrhosis: fact or fiction

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Hepatoma Research 2018年第11期4卷 16-31页

作者： Alberto Zanetto Sarah Shalaby Alberto Ferrarese Chiara Becchetti Salvatore Sciarrone Giacomo Germani marco senzolo Martina Gambato Francesco Paolo Russo Patrizia Burra Multivisceral Transplant Unit Department of SurgeryOncology and GastroenterologyPadua University HospitalPadua 35128Italy

Since the widespread adoption of new direct-acting antiviral agents (DAAs), the approach to hepatitis C virus (HCV) infection has changed profoundly as almost all patients can be cured regardless of the stage of their liver disease. On the other hand, there are a few conflicting reports on the risk of hepatocellular carcinoma (HCC) occurring and recurring in patients given DAA-based therapy. The present review focuses on the latest and most relevant literature providing evidence on the occurrence and recurrence of HCC after HCV antiviral treatment with the new DAAs. Retaining the distinction between HCC occurrence and recurrence, we also discuss its patterns of presentation and speculate on the possible pathogenic mechanisms. We offer our personal viewpoints on this important issue, which has kept clinicians second-guessing in real-world clinical practice, when dealing with HCV eradication in the setting of advanced liver disease in this interferon-free era.

关键词： Hepatitis C virus direct-acting antiviral agent occurrence recurrence hepatocellular carcinoma and liver cirrhosis

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Rethinking the role of non-selective beta blockers in patients with cirrhosis and portal hypertension

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World Journal of Hepatology 2016年第24期8卷 1012-1018页

作者： Alberto Ferrarese Alberto Zanetto Giacomo Germani Patrizia Burra marco senzolo Multivisceral Transplant Unit Department of Surgery Oncology and Gastroenterology Padua University Hospital

Non-selective beta blockers(NSBB) are commonly used to prevent portal hypertensive bleeding in cirrhotics.Nevertheless, in the last years, the use of NSBB in critically decompensated patients, especially in those with refractory ascites, has been questioned, mainly for an increased risk of mortality and worsening of systemic hemodynamics. Moreover, even if NSBB have been reported to correlate with a higher risk of renal failure and severe infection in patients with advanced liver disease and hypotension, their use has been associated with a reduction of risk of spontaneous bacterial peritonitis, modification of gut permeability and reduction of bacterial translocation. This manuscript systematically reviews the published evidences about harms and benefits of the use of NSBB in patients with decompensated cirrhosis.

关键词： Beta blockers Ascites Cirrhosis Portal hypertension

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