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COVID-19 in a pregnant kidney transplant recipient-what we need to know:A case report

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World Journal of Transplantation 2022年第10期12卷 325-330页

作者： roberta angelico Maria Luisa Framarino-dei-Malatesta Giuseppe Iaria Department of Surgical Sciences HPB and Transplant UnitUniversity of Rome Tor VergataRome 00100Italy Department of Gynecologic-Obstetrical and Urologic Sciences Policlinico Umbero ISapienza University of RomeRome 00100Italy Kidney Transplant Unit San Camillo ForlaniniRome 00100Italy

BACKGROUND In the era of the coronavirus disease 2019(COVID-19)pandemic,kidney transplant recipients are more susceptible to severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection,developing severe morbidity and graft *** women are also more likely to develop severe COVID-19 disease,causing pregnancy complications such as preterm births and acute kidney *** SUMMARY Herein,we report the case of a pregnant woman with a third kidney transplantation who developed COVID-19 *** reduction of immunosuppressive drugs and strict monitoring of trough blood levels were needed to avoid severe SARS-CoV-2-related complications,and permitted to continue a healthy pregnancy and maintain good graft *** such a complex scenario,the concomitance of COVID-19-related morbidity,the risk of acute rejection in the hyperimmune recipient,graft dysfunction and pregnancy complications make the management of immunosuppression a very difficult task and clinicians must be *** Tailoring the immunosuppressive regimen is a key factor affecting both the graft outcome and pregnancy safety.

关键词： Kidney transplantation Pregnancy SARS-CoV-2 infection COVID-19 disease Immunosuppression Complications Case report

Hepatitis B virus recurrence after liver transplantation: An old tale or a clear and present danger?

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World Journal of Gastroenterology 2020年第18期26卷 2166-2176页

作者： Ilaria Lenci Martina Milana Giuseppe Grassi Tommaso M Manzia Carlo Gazia Giuseppe Tisone roberta angelico Leonardo Baiocchi Hepatology and Liver Transplant Unit University of Tor VergataRome 00133Italy Hepato-Pancreato-Biliary and Transplant Department of SurgeryUniversity of Rome Tor VergataRome 00133Italy

Hepatitis B virus(HBV) recurrence after liver transplantation(LT) has been described more than 50 years ago. Similarly, to other clinical conditions, in which impairment of host immune defense favors viral replication, early reports described in details recurrence and reactivation of HBV in liver transplant recipients. The evidence of a possible, severe, clinical evolution of HBV reappearance in a significant percentage of these patients, allowed to consider,for some years, HBV positivity a contraindication for LT. Moving from the old to the new millennium this picture has changed dramatically. Several studies contributed to establish efficient prophylactic protocols for HBV recurrence and with the advent of more potent anti-viral drugs an increased control of infection was achieved in transplanted patients as well as in the general immunecompetent HBV population. Success obtained in the last decade led some authors to the conclusion that HBV is now to consider just as a "mere nuisance".However, with regard to HBV and LT, outstanding issues are still on the table:(1)A standard HBV prophylaxis protocol after transplant has not yet been clearly defined;(2) The evidence of HBV resistant strains to the most potent antiviral agents is claiming for a new generation of drugs;and(3) The possibility of prophylaxis withdrawal in some patients has been demonstrated, but reliable methods for their selection are still lacking. The evolution of LT for HBV is examined in detail in this review together with the description of the strategies adopted to prevent HBV recurrence and their pros and cons.

关键词： Liver transplant Hepatitis B virus Viral recurrence Prophylaxis Minimization Antiviral drug

Chronic rejection after liver transplantation:Opening the Pandora’s box

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World Journal of Gastroenterology 2021年第45期27卷 7771-7783页

作者： roberta angelico Bruno Sensi Tommaso M Manzia Giuseppe Tisone Giuseppe Grassi Alessandro Signorello Martina Milana Ilaria Lenci Leonardo Baiocchi Department of Surgery Sciences HPB and Transplant UnitUniversity of Tor VergataRome 00100Italy Hepatology Unit University of Tor VergataRome 00100Italy

Chronic rejection(CR)of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver *** its prevalence has declined steadily with the introduction of potent immunosuppressive therapy,CR still represents an important cause of graft injury,which might be irreversible,leading to graft loss requiring *** date,we still do not fully appreciate the mechanisms underlying this *** addition to T cell-mediated CR,which was initially the only recognized type of CR,recently a new form of liver allograft CR,antibody-mediated CR,has been *** has indeed opened an era of thriving research and renewed interest in the *** biopsy is needed for a definitive diagnosis of CR,but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver ***,the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury,which should not be *** for CR may only be effective in the“early”phases,and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver ***,we provide an overview of the current knowledge and research on CR,focusing on early detection,identification of non-invasive biomarkers,immunosuppressive management,re-transplantation and future perspectives of CR.

关键词： Liver transplantation Chronic rejection Immunosuppression T cell-mediated rejection Antibody-mediated rejection Donor-specific antibody Re-transplantation Graft loss Complications Outcomes

Moving forward in the treatment of cholangiocarcinoma

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World Journal of Gastrointestinal Oncology 2021年第12期13卷 1939-1955页

作者： Tommaso M Manzia Alessandro Parente Ilaria Lenci Bruno Sensi Martina Milana Carlo Gazia Alessandro Signorello roberta angelico Giuseppe Grassi Giuseppe Tisone Leonardo Baiocchi Hepato-Pancreato-Biliary and Transplant Department of SurgeryUniversity of Rome Tor VergataRome 00133Italy The Liver Unit Queen Elizabeth Hospital BirminghamBirmingham B152THUnited Kingdom Hepatology Unit University of Tor VergataRome 00133Italy

Despite being the second most frequent primary liver tumor in humans,early diagnosis and treatment of cholangiocarcinoma(CCA)are still *** fact,survival after 5 years is expected in less than one fourth of patients diagnosed with this *** incidence,late appearance of symptoms and heterogeneous biology are all factors contributing to our limited knowledge of this cancer and determining its poor prognosis in the clinical *** efforts have been made in the last decades in order to achieve an improved classification/understanding with regard to the diverse CCA *** within the biliary tree has helped to distinguish between intrahepatic,perihilar and distal CCA *** analysis contributed to identifying several characteristic genetic aberrations in CCA that may also serve as possible targets for *** findings are expected to significantly improve the management of this malignancy in the near *** this changing scenario our review focuses on the current and future strategies for CCA *** systemic and surgical treatments are discussed in *** results of the main studies in this field are reported,together with the ongoing *** current findings suggest that an integrated multidisciplinary approach to this malignancy would be helpful to improve its outcome.

关键词： Cholangiocarcinoma Treatment Genetic aberration Immunotherapy Liver resection Liver transplantation

De novo malignancies after liver transplantation: The effect of immunosuppression-personal data and review of literature

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World Journal of Gastroenterology 2019年第35期25卷 5356-5375页

作者： Tommaso Maria Manzia roberta angelico Carlo Gazia Ilaria Lenci Martina Milana Oludamilola T Ademoyero Domiziana Pedini Luca Toti Marco Spada Giuseppe Tisone Leonardo Baiocchi HPB and Transplant Unit Department of Surgery University of Rome Tor Vergata Rome 00133 Italy Division of Abdominal Transplantation and HPB Surgery Bambino Gesù Children's Hospital IRCCS Rome 00165 Italy Wake Forest Institute for Regenerative Medicine Winston-Salem NC 27101 United States Hepatology and Liver Transplant Unit University of Tor Vergata Rome 00133 Italy

BACKGROUND Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients. AIM To study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients. METHODS A systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood *** Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences

关键词： Pediatric liver transplant Immunosuppression weaning Clinical operational tolerance Adult liver transplant Graft rejection Immune system De novo malignancies Immunosuppression minimization Cancer

Combined endovascular-surgical treatment for complex congenital intrahepatic arterioportal fistula: A case report and review of the literature

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World Journal of Hepatology 2020年第4期12卷 160-169页

作者： roberta angelico Guglielmo Paolantonio Monica Paoletti Chiara Grimaldi Maria Cristina Saffioti Lidia Monti Manila Candusso Massimo Rollo Marco Spada Department of Abdominal Transplantation and Hepatobiliary and Pancreatic Surgery Bambino GesùChildren’s Hospital IRCCSRome 00165Italy Department of Surgery Hepato-bilio-pancreatic Surgery and Transplant UnitUniversity of Rome Tor VergataFondazione PVTRome 00133Italy Interventional Radiology Unit Department of ImagingBambino GesùChildren’s Hospital IRCCSRome 00165Italy Department of Imaging Bambino GesùChildren’s Hospital IRCCSRome 00165Italy Division of Hepatogastroenterology Bambino GesùChildren’s Hospital IRCCSRome 00165Italy

BACKGROUND Congenital intrahepatic arterioportal fistula(IAPF) is a rare vascular malformation in infants that causes severe portal hypertension(PH) with poor prognosis if untreated. Currently, radiological embolisation is considered the first-line therapy for simple IAPF; however, it might be not resolutive for complex hepatic vascular lesions. When endovascular embolization is not sufficient to completely obliterate the IAPF, surgical intervention is needed, but it has been associated with severe morbidity and mortality in small ***, indications are not *** SUMMARY We present the first case of a 6-month-old girl with trisomy 21 affected by a complex congenital IAFP, which caused severe PH, successfully treated with an endovascular-surgical hybrid procedure. The novel technique comprised a multistep endovascular embolisation, including a superselective transarterial embolisation of the afferent vessels and a direct transhepatic embolisation of the dilated portal vein segment, combined with selective surgical ligation of the arterial branches that supply the fistula, which were too small to be *** complex IAPF was also associated with severe cholestasis and intra/extrahepatic biliary tree dilatation, which was successfully treated by a temporary biliary drainage. At 24-mo follow-up, the hybrid endovascularsurgical procedure achieved complete occlusion of the complex IAPF and resolution of the PH. A comprehensive review of the literature on congenital IAPF management, focussed on alternative treatment strategies, is also *** The combined radiological-surgical approach is a safe and effective treatment option for complex IAPF and avoids major invasive surgery.

关键词： Liver Intrahepatic arterioportal fistula Congenital malformation Portal hypertension Radiological embolization Hepatic surgery Case report

Impact of immunosuppression minimization and withdrawal in long-term hepatitis C virus liver transplant recipients

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World Journal of Gastroenterology 2014年第34期20卷 12217-12225页

作者： Tommaso Maria Manzia roberta angelico Paolo Ciano Jon Mugweru Kofi Owusu Daniele Sforza Luca Toti Giuseppe Tisone Department of Experimental Medicine and Surgery Section of TransplantationTor Vergata University of Rome00133 RomeItaly Wake Forest School of Medicine Winston-SalemNC 27106United States

AIM:To investigate the effects of different immunosuppressive regimens and avoidance on fibrosis progression in hepatitis C virus(HCV)liver transplant(LT)***:We retrospectively compared the liver biopsies of well-matched HCV LT recipients under calcineurin inhibitors(CNI group,n=21)and mycophenolate(MMF group,n=15)monotherapy,with those patients who successfully withdrawn immunosuppression(IS)therapy from at least 3 years(TOL group,n=10).To perform the well-matched analysis,all HCV transplanted patients from December 1993 were *** those HCV patients who reached the following criteria were considered for the analysis:(1)at least3 years of post-operative follow-up;(2)patients with normal liver graft function under low dose CNI monotherapy(CNI group);(3)patients with normal liver graft function under antimetabolite(Micophenolate Mofetil or coated mycophenolate sodium)monotherapy(MMF group);and(4)recipients with normal liver function without any *** excluded from the analysis recipients who were IS free or under monotherapy for<36 mo,recipients with cirrhosis or with unstable liver function ***:Thirty six recipients were enrolled in the ***,clinical data,time after LT and baseline liver biopsies were comparable in the three *** six years of follow-up,there was no worsening of hepatic fibrosis in the MMF group(2.5±1.5Ishak Units vs 2.9±1.7 Ishak Units,P=0.5)and TOL group(2.7±10.7 vs 2.5±1.2,P=0.2).In contrast,a significant increase in the fibrosis score was observed in the CNI group(2.2±1.7 vs 3.9±1.6,P=0.008).The yearly fibrosis progression rate was significantly worse in the CNI group(0.32±0.35)vs MMF group(0.03±0.31,P=0.03),and TOL group(-0.02±0.27,P=0.02).No differences have been reported in grading scores for CNI group(2.79±1.9,P=0.7),MMF group(3.2±1.5,P=0.9)and TOL group(3.1±1.4,P=0.2).Twenty four patients were treated with low dose ribavirin(8TOL,7 MMF,9 CNI).The hepatitis C titers were comparable in the

关键词： Liver transplantation Hepatitis C virus recurrence