LUCIANA BERTOCCO DE PAIVA HADDAD
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/37 - Laboratório de Transplante e Cirurgia de Fígado, Hospital das Clínicas, Faculdade de Medicina
LIM/37 - Laboratório de Transplante e Cirurgia de Fígado, Hospital das Clínicas, Faculdade de Medicina
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- COST EFFECTIVENESS OF USING TERLIPRESSIN TO TREAT HEPATORENAL SYNDROME(2022) FERREIRA, Luciana Marcondes; TERRABUIO, Débora Raquel; FERREIRA, Caroline Marcondes; MAZO, Daniel Ferraz de Campos; HADDAD, Luciana Bertocco de PaivaABSTRACT Background Hepatorenal syndrome (HRS) is the most severe form of acute kidney injury in patients with advanced cirrhosis, and it is associated with high mortality. It is usually diagnosed according to criteria defined by the International Ascites Club. Currently, the most frequently indicated pharmacological therapy for the treatment of HRS is a combination of splanchnic vasoconstrictors (terlipressin or norepinephrine) in combination with albumin. With the progressive increase in healthcare spending, it is important to conduct a cost-effectiveness analysis of pharmacological treatment in patients who are diagnosed with HRS. Objective: To perform a cost-effectiveness assessment for the use of terlipressin in combination with albumin to treat HRS in patients with cirrhosis. Methods: Economic evaluation of cost-effectiveness based on secondary data from studies showed the efficacy of terlipressin therapy compared with norepinephrine combined with albumin or albumin alone. The cost-effectiveness analysis was calculated using an incremental cost-effectiveness ratio (ICER), and a sensitivity analysis was developed by varying the values of therapies and probabilities. The Brazilian real was the currency used in the analysis, and the results were converted to US dollars. Results: After selection, eligibility, and evaluation of the quality of publications, the results demonstrated that administration of terlipressin or norepinephrine in combination with albumin in patients diagnosed with HRS type 1 was efficacious. The cost of treatment with terlipressin in combination with albumin was USD $1,644.06, administration of albumin alone was USD $912.02, and norepinephrine plus albumin was USD $2,310.78. Considering that the combination therapies demonstrated effectiveness, the incremental cost of terlipressin and norepinephrine in combination with albumin was USD $666.73, and an effectiveness of 0.570 was found for terlipressin in combination with albumin and 0.200 for norepinephrine in combination with albumin. The incremental effectiveness was 0.370, and the ICER was USD $1,801.97. Thus, the parameters of increasing cost per therapy and ICER indicated that the combined therapy of terlipressin plus albumin was cost effective compared to albumin alone or norepinephrine plus albumin in a public single-payer healthcare system. Conclusion: A cost-effectiveness analysis showed that terlipressin in combination with albumin when administered concomitantly to patients who were diagnosed with type 1 HRS is cost-effective compared to norepinephrine in combination with albumin administered in a controlled environment.
conferenceObject COVID-19 Infection in Liver Transplant Recipients: Results From a Brazillian Multicentric Historical Cohort(2022) BOIN, Ilka F. S. F.; RICCETTO, Eduardo; GENZINI, Tercio; MOREIRA, Lucio F. P.; STUCCHI, Raquel S. B.; SILVA, Renato F.; HADDAD, Luciana; ALMEIDA, Marcio D.; WATANABE, Andre; PEIXOTO, Gustavo S.; MELO, Claudio M. L.; TEFFILI, Nertan L.; HALPERN, Marcia; GODOY, Maira C.; MANCERO, Jorge M. P.; GARCIA, Jose Huygens P.; ATAIDE, Elaine C.- COVID-19 Pandemic Impact on Liver Donation in the Largest Brazilian Transplantation Center(2022) FORTUNATO, Allana C.; PINHEIRO, Rafael S.; FERNANDES, Michel Ribeiro; NACIF, Lucas Souto; ARANTES, Rubens Macedo; ROCHA-SANTOS, Vinicius; WAISBERG, Daniel Reis; MARTINO, Rodrigo Bronze De; DUCATTI, Liliana; HADDAD, Luciana Bertocco; SONG, Alice Tung; ABDALA, Edson; ANDRAUS, Wellington; CARNEIRO-D'ALBUQUERQUE, Luiz AugustoBackground. COVID-19 has spread worldwide and has become a public health emergency and a pandemic of international concern. The solid organ donation system was no different. This study aimed to investigate the effect of COVID-19 on the liver transplant (LT) system in Brazilian territory. Methods. We retrospectively reviewed all liver donor records allocated in Sao Paulo State, Brazil, 1 year before and 1 year during the COVID-19 pandemic. We defined the pre-COVID-19 (PRE) period as between April 2019 and April 2020 and the post-COVID-19 (POST) period as between April 2020 and April 2021. Moreover, we compared LT performed in our institution during these periods. To evaluate outcomes, we compared 30-day survival after LT. Results. In the PRE period, 1452 livers were offered for donation in Sao Paulo State and other Brazilian territories. Of these, 592 were used in LT. In the POST period, 1314 livers were offered for donation, but only 477 were used in LT. Organ refusal was higher in the POST period (P < .05). Our center performed 127 and 156 LTs in these periods, respectively, and an increase above 20% was significant (P = .039). There was no difference in 30-day survival between the periods (87.2% vs 87.9%, P > .5, respectively). Conclusions. The COVID-19 pandemic harmed potential and allocated donors and LTs per-formed. However, it is possible to maintain the LT volume of a transplant center without compromising survival outcomes through preventive strategies against COVID-19 propagation.
- Incidence of Donor Hepatic Artery Thrombosis in Liver Grafts Recognized During Organ Procurement and Backtable: A Rare but Treacherous Pitfall In Liver Transplantation(2022) SILVA, Natalie Almeida; WAISBERG, Daniel Reis; FERNANDES, Michel Ribeiro; PINHEIRO, Rafael Soares; SANTOS, Joao Paulo Costa; LIMA, Marisa Rafaela Damasceno; ALVAREZ, Paola Sofia Espinoza; ERNANI, Lucas; LINS-ALBUQUERQUE, Marcos Vinicius; NACIF, Lucas Souto; ROCHA-SANTOS, Vinicius; MARTINO, Rodrigo Bronze; DUCATTI, Liliana; ARANTES, Rubens Macedo; SONG, Alice Tung; LEE, Andre Dong; HADDAD, Luciana Bertocco; RIVA, Daniel Fernandes Dala; SILVA, Amanda Maria; GALVAO, Flavio Henrique; ANDRAUS, Wellington; CARNEIRO-D'ALBUQUERQUE, Luiz AugustoIntroduction. Donor hepatic artery thrombosis (dHAT) identified during liver procurement and backtable is a rare and little-reported event that can make liver transplants unfeasible.Methods. This is a retrospective study of dHAT identified during liver grafts procurements or backtable procedures. All grafts were recovered from brain-dead donors. The demographic characteristics of the donors and the incidence of dHAT were analyzed. The data were also compared to a cohort of donors without dHAT.Results. There was a total of 486 donors during the study period. The incidence of dHAT was 1.85% (n = 9). The diagnosis of dHAT was made during procurement in 5 cases (55.5%) and during the backtable in 4 (44.4%). Most donors were female (n = 5), with an average BMI of 28.14 6.9 kg/m2, hypertensive (n = 5), and with stroke as cause of brain death (n = 8). The most prevalent site of dHAT was a left hepatic artery originating from the left gastric artery (n = 4). Of the 9 cases reported, 2 livers were used for transplantation, and 7 were discarded. Comparing those cases to a cohort of 260 donors without dHAT, we found a higher incidence of anatomic variations in the hepatic artery (P = .01) and of stroke as cause of brain death (P = .05).Conclusion. The occurrence of dHAT before liver procurement is a rare event, however it may become a treacherous pitfall if the diagnosis is late. Grafts with anatomic variations recovered from women with brain death due to stroke and with past history of hypertension seem to be at a higher risk of presenting dHAT.
- Experimental Clinical Model of Liver Transplantation in Large White Pigs Without Venovenous Bypass: Pre-, Intra-, and Maintenance Care(2022) NACIF, Lucas Souto; ALVAREZ, Paola Sofia Espinoza; PINHEIRO, Rafael Soares; NETO, Amadeo Batista Da Silva; FONSECA, Giovana De Maria Rocha; FERNANDES, Michel Ribeiro; SANTOS, Joao Paulo Costas; ERNANI, Lucas; ROCHA-SANTOS, Vinicius; MARTINO, Rodrigo Bronze De; WAISBERG, Daniel Reis; MACEDO, Rubens Arantes; DUCATTI, Liliana; HADDAD, Luciana; GALVAO, Flavio Henrique Ferreira; ANDRAUS, Wellington; CARNEIRO-DALBUQUERQUE, LuizBackground. Liver transplantation in an animal model is challenging due to hemodynamics and intraoperative anesthetic care. Several models are described in the literature employing different techniques such as venovenous bypass or aortic cross-clamping to maintain hemodynamic stability, although few groups keep the animal alive in the postoperative period. This study aims to evaluate a liver transplantation clinical model in pigs without venovenous bypass or aortic cross-clamping. Methods. Male pigs weighing 20 to 35 kg underwent liver transplantation surgery without using venovenous bypass or aorta cross-clamping. Protocols were approved by the Animal Care and Use Committee of the University of Sao Paulo, Brazil. Results. Ten LTs were performed. Cold ischemia and warm ischemia were 119 +/- 33.28 minutes and 26 +/- 9.6 minutes, respectively. Hemodynamic changes were significantly higher after the postrevasculazation phase: heart rate (P < .001), medium arterial pressure (P < .001), and cardiac output (P = .03). Hypotension was treated with intravenous fluids and, in some cases, with vasoactive drugs especially during the post-reperfusion period. No animals died during the procedure and almost survival until the first postoperative day. Serum aspartate aminotransferase and lactate increased their values in the post-reperfusion phase. Conclusions. Practice-based on laboratory animals improves surgical skills and the development of experimental models aimed at new advances in this field. Perfecting our technique on the swine model, we could move forward to create a small-for-size model, test new therapeutic strategies, and define the boundaries for safely performing an enlarged liver resection or a partial liver graft transplant.
- Prognostic Factors Evaluation for Liver Transplant Mismatching: A New Way of Selecting and Allocating Organs(2022) NACIF, Lucas Souto; ZANINI, Leonardo Yuri Kasputis; FERNANDES, Michel Ribeiro; PINHEIRO, Rafael Soares; ROCHA-SANTOS, Vinicius; MARTINO, Rodrigo Bronze De; WAISBERG, Daniel Reis; MACEDO, Rubens Arantes; DUCATTI, Liliana; HADDAD, Luciana; GALVAO, Flavio Henrique Ferreira; ANDRAUS, Wellington; CARNEIRO-D'ALBUQUERQUE, LuizBackground. Liver transplant (LT) is the standard therapy for end-stage liver disease. Advances in surgical techniques and immunosuppression protocols improved the results of LT by increasing long-term survival. Nevertheless, an adequate match between the donor and recipient is paramount for avoiding futile liver transplants. We aimed to identify the prognostic factors in donor-recipient LT matching. Methods. Retrospective analysis of adult LT was conducted from January 2006 to December 2018, which included the following transplant modalities: deceased donor LT (DDLT), living donor LT (LDLT), combined liver-kidney transplant (CLKT), and domino LT (DLT). Results. Among 1101 patients who underwent LT, 958 patients underwent DDLT, 92 patients underwent LDLT, 45 patients underwent CLKT, and 6 patients underwent DLT. The overall survival (OS) in 1, 5, and 10 years were 89%, 83%, and 82%, respectively. For DDLT, OS in 1, 5, and 10 years were 91%, 84%, and 82%, respectively. For LDLT, OS in 1, 5, and 10 years were 89%, 72%, and 69%, respectively. For CKLT, OS in 1, 5, and 10 years were 90%, 71%, and 71%, respectively. None of the DLT patients died. For DDLT, the factors that affected OS were the presence of fulminant liver failure (odds ratio [OR], 2.23; 95% CI, 1.18-4.18; P = .001), hemodialysis before LT (OR, 2.12; 95% CI, 1.27-3.5; P = .004), retransplant (OR, 4.74; 95% CI, 2.75-8.17; P = .000), and recipient age > 60 years (OR, 1.86; 95% CI, 1.27-2.73; P = .001). For hospitalization before LT (due to an acute-on-chronic liver failure), the OR was 2.10 (95% CI, 1.29-3.42; P = .003). Donor intensive care unit time > 7 days (OR, 1.46; 95% CI, 1.04-2.06; P = .02) was also associated with overall mortality. Conclusions. We identified prognostic factors in donor-recipient LT matching. Furthermore, we demonstrated that an adequate organ allocation with donor-recipient selection might increase graft survival and reduce waiting list mortality.
- Septuagenarian Donors and Recipients in Deceased Donor Liver Transplantation: A Brazilian Single Center Experience and Literature Review(2022) FERNANDES, Michel Ribeiro; WAISBERG, Daniel Reis; LIMA, Marisa Rafaela Damasceno; ROCHA-SANTOS, Vinicius; MARTINO, Rodrigo Bronze; PINHEIRO, Rafael Soares; NACIF, Lucas Souto; DUCATTI, Liliana; ARANTES, Rubens Macedo; SANTOS, Joao Paulo Costa; ALVAREZ, Paola Sofia Espinoza; SILVA, Natalie Almeida; RIVA, Daniel Fernandes Dala; SILVA, Amanda Maria; SONG, Alice Tung; LEE, Andre Dong; HADDAD, Luciana Bertocco; GALVAO, Flavio Henrique; ANDRAUS, Wellington; CARNEIRO-D'ALBUQUERQUE, LuizBackground: The number of elderly patients who have end-stage liver disease and require liver transplantation has dramatically increased. On the other hand, liver grafts from elderly donors have been offered more frequently for transplantation. The present study aims to analyze the results of liver transplants performed with donors and recipients aged >= 70 years. Methods: We performed a single-center retrospective study of deceased donors liver transplants that involved recipients aged >= 7070 years or recipients who received grafts from donors aged >= 70 years from 2011 to 2021. A literature review on the results of liver transplantation in elderly recipients was also performed. Results: Thirty septuagenarian recipients were included; their overall 1- and 5-years survival was 80% and 76.6%, respectively. The prevalence of recipients aged >= 70 years in our department was 2.65%. Twenty recipients received grafts form septuagenarian donors; their overall 1- and 5-years survival was 75%. The prevalence of donors aged >= 70 years in our department was 1%. In the literature review, 17 articles were analyzed. The 5-years survival of recipients aged >= 70 years ranged from 47.1% to 78.5%. Conclusions: Septuagenarian recipients and patients who received grafts from elderly brain-dead donors present adequate overall survival after liver transplantation. Optimized donor-recipient matching is paramount for achieving good outcomes. The combination of high-risk donors with septuagenarian recipients should be avoided as well as using grafts of elderly donors that present others risk factors. Thus, the age of the donor or recipient alone cannot be considered an absolute contraindication for liver transplantation.
- Model for establishing a new liver transplantation center through mentorship from a university with transplantation expertise(2022) PINHEIRO, Rafael Soares; ANDRAUS, Wellington; ROMEIRO, Fernando Gomes; MARTINO, Rodrigo Bronze de; DUCATTI, Liliana; ARANTES, Rubens Macedo; PELAFSKY, Leonardo; HASIMOTO, Claudia Nishida; YAMASHIRO, Fabio da Silva; NACIF, Lucas Souto; HADDAD, Luciana Bertocco de Paiva; SANTOS, Vinicius Rocha; WAISBERG, Daniel Reis; VANE, Matheus Fachini; ROCHA-FILHO, Joel Avancini; OLIVEIRA, Walmar Kerche de; CARNEIRO-D'ALBUQUERQUE, Luiz AugustoBackgroundSetting up new liver transplant (LT) centers is essential for countries with organ shortages. However, good outcomes require experience, because LT learning depends on a high number of surgeries. This study aims to describe how a new center was set up from a partnership between the new center and an experienced one. The step-by-step preparation process, the time needed and the results of the new center are depicted. Material and methodsThe mentoring process lasted 40 months, in which half of the 52 patients included on the transplant list received LT. After the mentorship, a 22-month period was also analyzed, in which 46 new patients were added to the waiting list and nine were operated on. ResultsThe 30-day survival rates during (92.3%) and after (66.7%) the partnership were similar to the other LT centers in the same region, as well as the rates of longer periods. The waiting time on the LT list, the characteristics of the donors and the ischemia times did not differ during or after the mentorship. ConclusionThe partnership between universities is a suitable way to set up LT centers, achieving good results for the institutions and the patients involved.
- Hepatic Venous Outflow Obstruction in Adult Deceased Donor Liver Transplantation: Classic Piggyback Implantation Versus a Modified Technique that Widens the Ostium of the Recipient's Left and Middle Hepatic Veins(2022) SILVA, Amanda Maria; WAISBERG, Daniel Reis; FERNANDES, Michel Ribeiro; MARTINO, Rodrigo Bronze; ROCHA-SANTOS, Vinicius; PINHEIRO, Rafael Soares; NACIF, Lucas Souto; ARANTES, Rubens Macedo; DUCATTI, Liliana; GALVAO, Flavio Henrique; LEE, Andre Dong; HADDAD, Luciana Bertocco; SILVA, Natalie Almeida; RIVA, Daniel Fernandes Dala; MOREIRA, Airton Mota; OLIVEIRA, Ricardo Abdala; CARNEVALE, Francisco Cesar; ANDRAUS, Wellington; CARNEIRO-D'ALBUQUERQUE, Luiz AugustoBackground. The classic piggyback technique uses the union of the 3 hepatic veins to perform the cavo-caval anastomosis. However, due to the lateral localization of the right hepatic vein, the partial clamping of the vena cava in this technique significantly reduces the venous return to the right atrium. To avoid this, we adopted in 2015 a modified piggyback technique, in which we use the common trunk of the middle and left hepatic veins and also perform a lateral incision toward the right in the anterior wall of the vena cava in order to widen the final ostium of the cavo-caval anastomosis. The aim of the study was to analyze the incidence of hepatic venous out-flow obstruction between those 2 techniques. Methods. Retrospective study of liver transplant recipients undergoing venography for sus-pected hepatic venous outflow obstruction from January 2009 to June 2021. Patients undergoing transplantation with living donors or split grafts and pediatric cases were excluded from the study. Results. From January 2009 to December 2014 and from January 2015 to June 2021, 587 (group 1) and 730 (group 2) deceased-donor liver transplants were performed with the classic and the modified piggyback techniques, respectively. The incidence of cases with suspected hepatic venous outflow obstruction in groups 1 and 2 were 1.87% (n = 11) and 0.95% (n = 7), respectively (P = 0,15). The number of confirmed patients with outflow blockage that required endovascular treatment during venography in groups 1 and 2 were 4 (0.68%) and 5 (0.68%), respectively (P = 0,31). Conclusions. This modified piggyback technique did not increase the incidence of hepatic venous outflow obstruction at our service.
- Small-for-Size Syndrome: Systemic Review in a Porcine Experimental Model(2022) FERNANDES, Michel Ribeiro; NACIF, Lucas Souto; ALVAREZ, Espinoza; PINHEIRO, Rafael Soares; ROCHA-SANTOS, Vinicius; MARTINO, Rodrigo Bronze de; WAISBERG, Daniel Reis; MACEDO, Rubens Arantes; DUCATTI, Liliana; HADDAD, Luciana Bertocco de Paiva; GALVAO, Flavio Henrique Ferreira; ANDRAUS, Wellington; CARNEIRO-D'ALBUQUERQUE, LuizBackground. The small-for-size syndrome (SFSS) is characterized by prolonged hyperbilirubinemia, coagulopathy, and/or encephalopathy caused by a small liver graft that cannot sustain the metabolic demands of the recipient after a partial liver transplant (PLT). Models of PLT in pigs are excellent for studying this syndrome. This review aimed to identify the different porcine models of SFSS in the literature and compare their technical aspects and therapeutics methods focused on portal inflow modulation (PIM). Methods. We performed a systematic review of the porcine experimental model and SFSS. The MEDLINE-PubMed, EMBASE, Cochrane Library, LILACS, and SciELO databases were electronically searched and updated until June 20, 2021. The MeSH terms used were ""ORGAN SIZE ""AND ""LIVER TRANSPLANTATION "". Results. Thirteen SFSS porcine models were reported. Four were performed with portocaval shunt to PIM and 3 with mesocaval shunt to PIM. A few studies focused on clinical therapeutics to PIM; a study described somatostatin infusion to avoid SFSS. Initially, studies on PIM showed its potentially beneficial effects without mentioning the minimum portal flow that permits liver regeneration. However, an excessive portal diversion could be detrimental to this process. Conclusions. The use of porcine models on SFSS resulted in a better understanding of its pathophysiology and led to the establishment of various types of portal modulation, surgical techniques with different complexities, and pharmaceutical strategies such as somatostatin, making clear that without reducing the portal vein pressure the outcomes are poor. With the improvement of these techniques, SFSS can be avoided.