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| 1 | Liver transplantation for hepatocellular carcinoma: Where do we stand?显示文摘Hepatocellular carcinoma represents an important cause of morbidity and mortality worldwide. It is the sixth most common cancer and the fourth leading cause of cancer death. Liver transplantation is a key tool for the treatment of this disease in human therefore hepatocellular carcinoma is increasing as primary indication for grafting. Although liver transplantation represents an outstanding therapy for hepatocellular carcinoma, due to organ shortage, the careful selection and management of patients who may have a major survival benefit after grafting remains a fundamental question. In fact, only some stages of the disease seem amenable of this therapeutic option, stimulating the debate on the appropriate criteria to select candidates. In this review we focused on current criteria to select patients with hepatocellular carcinoma for liver transplantation as well as on the strategies (bridging) to avoid disease progression and exclusion from grafting during the stay on wait list. The treatments used to bring patients within acceptable criteria (down-staging), when their tumor burden exceeds the standard criteria for transplant, are also reported. Finally, we examined tumor reappearance following liver transplantation. This occurrence is estimated to be approximately 8%-20% in different studies. The possible approaches to prevent this outcome after transplant are reported with the corresponding results. | Francesco Santopaolo Ilaria Lenci Martina Milana Tommaso Maria Manzia Leonardo Baiocchi | 2019 | World Journal of Gastroenterology2019，25，21： | 15 |
| 2 | Moving forward in the treatment of cholangiocarcinoma显示文摘Despite being the second most frequent primary liver tumor in humans,early diagnosis and treatment of cholangiocarcinoma(CCA)are still unsatisfactory.In fact,survival after 5 years is expected in less than one fourth of patients diagnosed with this disease.Rare 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 setting.Several efforts have been made in the last decades in order to achieve an improved classification/understanding with regard to the diverse CCA forms.Location within the biliary tree has helped to distinguish between intrahepatic,perihilar and distal CCA types.Sequence analysis contributed to identifying several characteristic genetic aberrations in CCA that may also serve as possible targets for therapy.Novel findings are expected to significantly improve the management of this malignancy in the near future.In this changing scenario our review focuses on the current and future strategies for CCA treatment.Both systemic and surgical treatments are discussed in detail.The results of the main studies in this field are reported,together with the ongoing trials.The current findings suggest that an integrated multidisciplinary approach to this malignancy would be helpful to improve its outcome. | Tommaso M Manzia Alessandro Parente Ilaria Lenci Bruno Sensi Martina Milana Carlo Gazia Alessandro Signorello Roberta Angelico Giuseppe Grassi Giuseppe Tisone Leonardo Baiocchi | 2021 | World Journal of Gastrointestinal Oncology2021，13，12： | 6 |
| 3 | De novo malignancies after liver transplantation: The effect of immunosuppression-personal data and review of literature显示文摘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 malignancy.RESULTS 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. CONCLUSION The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer. | Tommaso Maria Manzia Roberta Angelico Carlo Gazia Ilaria Lenci Martina Milana Oludamilola T Ademoyero Domiziana Pedini Luca Toti Marco Spada Giuseppe Tisone Leonardo Baiocchi | 2019 | World Journal of Gastroenterology2019，25，35： | 3 |
| 4 | Impact of immunosuppression minimization and withdrawal in long-term hepatitis C virus liver transplant recipients显示文摘AIM:To investigate the effects of different immunosuppressive regimens and avoidance on fibrosis progression in hepatitis C virus(HCV)liver transplant(LT)recipients.METHODS: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 screened.Only 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 IS.We excluded from the analysis recipients who were IS free or under monotherapy for<36 mo,recipients with cirrhosis or with unstable liver function tests.RESULTS:Thirty six recipients were enrolled in the study.Demographics,clinical data,time after LT and baseline liver biopsies were comparable in the three groups.After 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 three groups.No episodes of rejection have been reported despite differences of liver function test in the three groups during the observational period.CONCLUSION:IS withdrawal and MMF monotherapy is safe and seems to be associated with the slowest fibrosis progression in HCV LT recipients. | Tommaso Maria Manzia Roberta Angelico Paolo Ciano Jon Mugweru Kofi Owusu Daniele Sforza Luca Toti Giuseppe Tisone | 2014 | World Journal of Gastroenterology2014，20，34： | 3 |
| 5 | Chronic rejection after liver transplantation:Opening the Pandora’s box显示文摘Chronic rejection(CR)of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation.Although 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 re-transplantation.To date,we still do not fully appreciate the mechanisms underlying this process.In 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 identified.This has indeed opened an era of thriving research and renewed interest in the field.Liver 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 transplantation.Moreover,the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury,which should not be disregarded.Therapies for CR may only be effective in the“early”phases,and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage.Herein,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. | Roberta Angelico Bruno Sensi Tommaso M Manzia Giuseppe Tisone Giuseppe Grassi Alessandro Signorello Martina Milana Ilaria Lenci Leonardo Baiocchi | 2021 | World Journal of Gastroenterology2021，27，45： | 2 |
| 6 | The Tor Vergata weaning off immunosuppression protocol in stable HCV liver transplant patients: The updated follow up at 78 months显示文摘 | Giuseppe Orlando Tommaso Manzia Leonardo Baiocchi Alberto Sanchez-Fueyo Mario Angelico Giuseppe Tisone | 2008 | Transplant Immunology2008，，1： | 2 |
| 7 | Glycogen storage dis- ease type Ia and VI associated with hepatocellular carcinoma: two case reports显示文摘 | Manzia TM Angelico R Toti Cilis A | 2011 | Transplant Proc2011，43，4： | 1 |
| 8 | Saline contrast echocardiography in patients with hepatopulmonary syndrome awaiting liver transplantation 显示文摘 | Lenci I Alvior A Manzia TM | 2009 | J Am Soc Echocardiogr2009，22，1： | 1 |
| 9 | Saline contrast echocardiography in patients with hepatopulmonary syndrome awaiting fiver lransplantation显示文摘 | Lenci I Alvior A Manzia TM | 2009 | J Am Soc Echocardiogr2009，22，1： | 1 |
| 10 | Management of spermatic cord liposarcoma in renal transplant Recipients:case report显示文摘 | Manzia TM Gravante G Toti L | | 0，，04： | 1 |
| 11 | Marginal donors in liver transplantation显示文摘 | Tisone G Manzia T M Zazza S | 2004 | Transplant Proc2004，36，3： | 1 |
| 12 | Steroid-free immuno-suppression after liver transplantation does not increase the risk of graft fthroais显示文摘 | MANZIA TM TOTI L ANGELICO R | 2010 | Transplant Proc2010，42，4： | 1 |
| 13 | Hepatitis B virus recurrence after liver transplantation: An old tale or a clear and present danger?显示文摘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. | Ilaria Lenci Martina Milana Giuseppe Grassi Tommaso M Manzia Carlo Gazia Giuseppe Tisone Roberta Angelico Leonardo Baiocchi | 2020 | World Journal of Gastroenterology2020，26，18： | 1 |
| 14 | Saline contrast echocardiography in patients with hepatopulmonary syn- drome awaiting liver transplantation 显示文摘 | Lenei I Alvior A Manzia TM | 2009 | J Am Soc Echocardiogr2009，22，1： | 1 |
| 15 | Reduction in bile leaks following adult split liver transplant using a fibrin-collagen sponge: A pilot study 显示文摘 | Toti L Atria M Maria Manzia T | 2010 | Digest Liver Disease2010，42，3： | 1 |
| 16 | Intra-graft expression of genes involved in iron homeostasis pre- dicts the development of operational tolerance in human liver trans- plantation显示文摘 | Bohne F Martlnez-Llordella M Lozano J J Miquel R Benttez C Londo no M C Manzia T M Angelico R Swinkels D W Tjalsma H | 2012 | The Journal of clinical investigation2012，122，1： | 1 |
| 17 | Marginal donors in liver transplantation 显示文摘 | Tisone G Manzia TM Zazza S | 2004 | Transplant Proc2004，36，3： | 1 |
| 18 | Saline contrast echocardiography in patients with hepatopulmonary syndrome awaiting Liver transplantation显示文摘 | Lenci I Alvior A Manzia TM | 2009 | J Am Soc Echocardiogr2009，22，1： | 1 |
| 19 | Liver transplantation for the treatment of nodular regenerative hyperplasia显示文摘 | Tommaso Maria Manzia Gianpiero Gravante Daniele Di Paolo Giuseppe Orlando Luca Toti Maria Irene Bellini Paolo Ciano Mario Angelico Giuseppe Tisone | 2011 | Digestive and Liver Disease2011，，12： | 1 |
| 20 | Complete weaning off immunosuppression in HCV liver transplant recipients is feasible and favourably impacts on the progression of disease recurrence显示文摘 | Giuseppe Tisone Giuseppe Orlando Andrea Cardillo Giampiero Palmieri Tommaso Maria Manzia Leonardo Baiocchi Raffaella Lionetti Alessandro Anselmo Luca Toti Mario Angelico | 2006 | Journal of Hepatology2006，，4： | 1 |
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