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

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

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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 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.

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

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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 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 toleran

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

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