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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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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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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 *** 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 *** such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before *** 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 *** 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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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 ***, 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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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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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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