LUCAS SOUTO NACIF
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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conferenceObject Acute-on-chronic liver failure (ALCF) and liver transplantation(2018) NACIF, L.; AQUINO, F.; TANIGAWA, R.; ANDRAUS, W.; HADDAD, L.; PINHEIRO, R.; MARTINO, R.; ROCHA-SANTOS, V.; FARIAS, A.; D'ALBUQUERQUE, L. Carneiro; ALVES, V.- Translational medical research and liver transplantation: systematic review(2018) NACIF, Lucas Souto; KIM, Vera; GALVAO, Flavio; ONO, Suzane Kioko; PINHEIRO, Rafael Soares; CARRILHO, Flair Jose; D'ALBUQUERQUE, Luiz CarneiroTranslational medicine has become a priority, but there is still a big difference between the arrival of new treatments and investment. Basic science should not be neglected because the translation from basic research is not sustained in the absence of basic research. The purpose of this literature review was to analyze the translational medicine in the liver transplant field: liver ischemia-reperfusion injury (IRI), immunosuppression, clinical and surgical complications, small-for-size syndrome (SFSS), rejection, and ongoing innovations (liver machine, liver preservation, artificial livers, and regenerative medicine). We performed a systematic literature review that were updated in October 2016. The searches were performed in the Cochrane Central Register of Controlled Trials and Review, PubMed/Medline, Embase, and LILACS databases. All the selected studies on the management of translational medical research in liver transplantation (LT) were analyzed. Initially the search found 773 articles. Methodological viewing and analysis of the articles, followed by the application of scientific models, including translational medicine in the liver transplant field. In conclusions, this review demonstrates the application of scientific research with translation medical benefits regarding the LT. The literature has a great tendency, improvements and investments in the study of translational medicine in LT. Innovative studies and technologies from basic science help to clarify clinical doubts. Moreover, evidence increases the importance of scientific research in quality of clinical practice care.
- Imatinib-induced fulminant liver failure in chronic myeloid leukemia: Role of liver transplant and second-generation tyrosine kinase inhibitors: A case report(2018) NACIF, L. S.; WAISBERG, D. R.; PINHEIRO, R. S.; LIMA, F. R.; ROCHA-SANTOS, V.; ANDRAUS, W.; D'ALBUQUERQUE, L. C.Background: There is a worldwide problem of acute liver failure and mortality associated with remaining on the waiting for a liver transplant. In this study, we highlight results published in recent years by leading transplant centers in evaluating imatinib-induced acute liver failure in chronic myeloid leukemia and follow-up in liver transplantation. Case presentation: A 36-year-old brown-skinned woman (mixed Brazilian race) diagnosed 1 year earlier with chronic myeloid leukemia was started after delivery of a baby and continued for 6 months with imatinib mesylate (selective inhibitor of Bcr-Abl tyrosine kinase), which induced liver failure. We conducted a literature review using the PubMed database for articles published through September 2017, and we demonstrate a role of liver transplant in this situation for imatinib-induced liver failure. We report previously published results and a successful liver transplant after acute liver failure due to imatinib-induced in chronic myeloid leukemia treatment. Conclusions: We report a case of a successful liver transplant after acute liver failure resulting from imatinib-induced chronic myeloid leukemia treatment. The literature reveals the importance of prompt acute liver failure diagnosis and treatment with liver transplant in selected cases. © 2018 The Author(s).
- Access to Liver Transplantation in Different ABO-Blood Groups and ""Exceptions Points"" in a Model for End-Stage Liver Disease Allocation System: A Brazilian Single-Center Study(2018) MARTINO, R. B.; WAISBERG, D. R.; DIAS, A. P. M.; INOUE, V. B. S.; ARANTES, R. M.; HADDAD, L. B. P.; ROCHA-SANTOS, V.; PINHEIRO, R. S. N.; NACIF, L. S.; D'ALBUQUERQUE, L. A. C.Background. In the Model for End-Stage Liver Disease (MELD) system, patients with ""MELD exceptions"" points may have unfair privilege in the competition for liver grafts. Furthermore, organ distribution following identical ABO blood types may also result in unjust organ allocation. The aim of this study was to investigate access to liver transplantation in a tertiary Brazilian center, regarding ""MELD exceptions"" situations and among ABO-blood groups. Methods. A total of 465 adult patients on the liver waitlist from August 2015 to August 2016 were followed up until August 2017. Patients were divided into groups according to ABO-blood type and presence of ""exceptions points."" Results. No differences in outcomes were observed among ABO-blood groups. However, patients from B and AB blood types spent less time on the list than patients from A and O groups (median, 46, 176, 415, and 401 days, respectively; P=.03). ""Exceptions points"" were granted for 141 patients (30.1%), hepatocellular carcinoma being the most common reason (52.4%). Patients with ""exceptions points"" showed higher transplantation rate, lower mortality on the list, and lower delta-MELD than non-exceptions patients (56.7% vs 19.1% [P<.01]; 18.4% vs 38.5% [P<.01], and 2.0 +/- 2.6 vs 6.9 +/- 7.0 [P<.01], respectively). Patients with refractory ascites had a higher mortality rate than those with other ""exceptions"" or without (48%). Conclusions. The MELD system provides equal access to liver transplantation among ABO-blood types, despite shorter time on the waitlist for AB and B groups. The current MELD exception system provides advantages for candidates with ""exception points,"" resulting in superior outcomes compared with those without exceptions.
- Transient Elastography in Acute Cellular Rejection Following Liver Transplantation: Systematic Review(2018) NACIF, L. S.; GOMES, C. D. C.; MISCHIATTI, M. N.; KIM, V.; PARANAGUA-VEZOZZO, D.; REINOSO, G. L.; CARRILHO, F. J.; D'ALBUQUERQUE, L. C.Background. Transient elastography (TE) is a noninvasive technique that measures liver stiffness. When an inflammatory process is present, this is shown by elevated levels of stiffness. Acute cellular rejection (ACR) is a consequence of an inflammatory response directed at endothelial and bile epithelial cells, and it is diagnosed through liver biopsy. This is a systematic review of the viability of TE in ACR following liver transplantation. Methods. The Cochrane Library, Embase, and Medline PubMed databases were searched and updated to November 2016. The MESH terms used were ""Liver Transplantation,"" ""Graft Rejection,"" ""Elasticity Imaging Techniques"" (PubMed), and ""Elastography"" (Cochrane and Embase). Results. Seventy studies were retrieved and selected using the PICO (patient, intervention, comparison or control, outcome) criteria. Three prospective studies were selected to meta-analysis and evaluation. A total of 33 patients with ACR were assessed with TE. One study showed a cutoff point of >7.9 kPa to define graft damage and <5.3 kPa to exclude graft damage (receiver operating characteristic 0.93; P<.001). Another study showed elevated levels of liver stiffness in ACR patients. However, in this study, no cutoff point for ACR was suggested. The final prospective study included 27 patients with ACR at liver biopsy. Cutoff points were defined as TE > 8.5 kPa, moderate to severe ACR, with a specificity of 100% and receiver operating characteristic curve of 0.924. The measurement of TE < 4.2 kPa excludes the possibility of any ACR (P=.02). Conclusions. TE may be an important tool for the severity of ACR in patients following liver transplantation. Further studies should be performed to better define the cutoff points and applicability of the exam.
- Intraoperative Surgical Portosystemic Shunt in Liver Transplantation: Systematic Review and Meta-Analysis(2018) NACIF, Lucas Souto; ZANINI, Leonardo Yuri; SARTORI, Vinicius Farina; KIM, Vera; ROCHA-SANTOS, Vinicius; ANDRAUS, Wellington; D'ALBUQUERQUE, Luiz CarneiroBackground: Expanded clinical and surgical techniques in liver transplantation can markedly improve patient and graft survival. The main purpose of this study was to evaluate the efficacy of intraoperative portocaval shunts in liver transplantation. Material/Methods: Searches were conducted in Cochrane, MEDLINE, and EMBASE databases, and updated in January 2018. The following specific outcomes of interest were defined and evaluated separated using 2 different reviews and meta-analyses for 1) hemi-portocaval shunt (HPCS) and 2) temporary portocaval shunt (TPCS). Comparative studies were analyzed separately for both surgical portocaval shunt modalities. Results: Only 1 well-designed randomized controlled trial was found. Most studies were retrospective or prospective. Initially, we found 1479 articles. Of those selected, 853 were from PubMed/MEDLINE, 32 were from Cochrane and 594 were from EMBASE. Our meta-analysis included a total of 3232 patients for all the included studies. Results found that 41 patients with HPCS experienced increased 1-year patient survival (OR 16.33; P=0.02) and increased 1-year graft survival (OR 17.67; P=0.01). The TPCS analysis with 1633 patients found patients had significantly shorter intensive care unit length of stay (days) (P=0.006) and hospital length of stay (P=0.02) and had decreased primary nonfunction (PNF) (OR 0.30, P=0.02) and mortality rates (OR 0.52, P=0.01). Conclusions: Intraoperative surgical portosystemic shunt in relation to liver transplantation with TPCS was able to prevent PNF, decrease hospital length of stay and unit care length of stay. Furthermore, in analyzing data for patients with HPCS, we observed increases in the 1-year graft and patient survival rates. More prospective randomized trials are needed to arrive at a more precise conclusion.
- Better Selection Criteria With Prognostic Factors for Liver Transplantation(2018) NACIF, L. S.; PINHEIRO, R. S.; ROCHA-SANTOS, V.; BARBOSA, V. M.; DIAS, A. P. de Moura; MARTINO, R. B.; MACEDO, R. A.; DUCATTI, L.; HADDAD, L.; GALVAO, F.; ANDRAUS, W.; D'ALBUQUERQUE, L. CarneiroBackground. Liver transplantation has evolved significantly in recent years, with each advancement part of the effort toward increasing patient and graft survival as well as quality of life. The objective of this study was to evaluate the prognostic factors and selection criteria for liver transplantation. Methods. Our study was a statistical analysis, logistic regression, and survival evaluation of a total of 80 liver transplants that were performed between June 1, 2016 and September 24, 2016. Recipient factors evaluated included age, retransplantation, hemodialysis, cardiac risk, portal vein thrombosis, hospitalization, fulminant hepatitis, previous surgery, renal failure, and Model for End-stage Liver Disease (MELD) score. Donor factors included age, cardiac arrest, acidosis, days in the intensive care unit, steatosis, and vasoactive drug use. Results. Of the 80 patients transplanted, 65 deceased donor liver transplants (DDLTs) and 15 living donor liver transplants (LDLTs) were performed. LDLT overall 1-year patient survival was 77.5% and graft survival 75%, and DDLT overall patient survival was 89.23% and graft survival was 86.15%. On evaluated score criteria analyzed we observed a significant score on recipient (P=.01) and not significant on donor (P=.45). Isolated factors evaluated included recipient age (relative risk [RR] 3.15, 95% confidence interval [CI] 0.89 to 11.09; P=.074), retransplant (RR 4.22, 95% CI 1.36 to 13.1; P=.013), and hemodialysis (RR 4.23, 95% CI 1.45 to 12.31, P=.008). On donor evaluation, we observed moderate and severe steatosis (RR 3.8, 95% CI 0.86 to 16.62; P=.06). Conclusion. In conclusion, we demonstrate a relevant model of criteria selection of liver transplant patients that is able to make a better match between the donor and recipient allocation for a better graft and patient survival.
- HIGHER VALUES IN LIVER ELASTOGRAPHY AND MELD SCORE ARE MORTALITY PREDICTORS ON LIVER TRANSPLANT WAITING LIST(2018) NACIF, Lucas Souto; PARANAGUA-VEZOZZO, Denise C.; MATSUDA, Alina; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair J.; FARIAS, Alberto Queiroz; D'ALBUQUERQUE, Luiz Carneiro; ANDRAUS, WellingtonBackground: Liver elastography have been reported in hepatocellular carcinoma (HCC) with higher values; however, it is unclear to identify morbimortality risk on liver transplantation waiting list. Aim: To assess liver stiffness, ultrasound and clinical findings in cirrhotic patients with and without HCC on screening for liver transplant and compare the morbimortality risk with elastography and MELD score. Method: Patients with cirrhosis and HCC on screening for liver transplant were enrolled with clinical, radiological and laboratory assessments, and transient elastography. Results: 103 patients were included (without HCC n=58 (66%); HCC n=45 (44%). The mean MELD score was 14.7 +/- 6.4, the portal hypertension present on 83.9% and the mean transient elastography value was 32.73 +/- 22.5 kPa. The median acoustic radiation force impulse value of liver parenchyma was 1.98 (0.65-3.2) m/s and 2.16 (0.59-2.8) m/s in HCC group. The HCC group was significantly associated with HCV infection (OR 26.84; p<0.0001), higher levels of serum alpha-fetoprotein (OR 5.51; p=0.015), clinical portal hypertension (OR 0.25; p=0.032) and similar MELD score (p=0.693). The area under the receiver operating characteristics (AUROC) showed sensitivity and specificity for serum alpha-fetoprotein (cutoff 9.1 ng/ml), transient elastography value (cutoff value 9 kPa), and acoustic radiation force impulse value (cutoff value 2.56 m/s) of 50% and 86%, 92% and 17% and 21% and 92%, respectively. The survival group had a mean transient elastography value of 31.65 +/- 22.2 kPa vs. 50.87 +/- 20.9 kPa (p=0.098) and higher MELD scores (p=0.035). Conclusion: Elastography, ultrasound and clinical findings are important non-invasive tools for cirrhosis and HCC on screening for liver transplant. Higher values in liver elastography and MELD scores predict mortality.
conferenceObject Surgical Porto-Caval Shunt and liver transplantation: systematic review(2018) NACIF, L.; ZANINI, L.; SARTORI, V.; PINHEIRO, R.; ARANTES, R.; DUCATTI, L.; GALVAO, F.; ANDRAUS, W.; DALBUQUERQUE, L. Carneiro- Liver biopsy may facilitate pancreatic graft evaluation: Positive association between liver steatosis and pancreatic graft adipose infiltration(2018) NACIF, Lucas S.; ROCHA-SANTOS, Vinicius; CLARO, Laura C. L.; VINTIMILLA, Agustin; FERREIRA, Leandro A.; ARANTES, Rubens M.; PINHEIRO, Rafael S.; ANDRAUS, Wellington; ALVES, Venancio A. F.; D'ALBUQUERQUE, Luiz CarneiroOBJECTIVES: The number of pancreatic transplants has decreased in recent years. Pancreatic grafts have been underutilized compared to other solid grafts. One cause of discard is the macroscopic appearance of the pancreas, especially the presence of fatty infiltration. The current research is aimed at understanding any graft related association between fatty tissue infiltration of the pancreas and liver steatosis. METHODS: From August 2013 to August 2014, a prospective cross-sectional clinical study using data from 54 multiple deceased donor organs was performed. RESULTS: Micro-and macroscopic liver steatosis were significantly correlated with the donor body mass index ([BMI]; p=0.029 and p=0.006, respectively). Positive gamma associations between pancreatic and liver macroscopic and microscopic findings (0.98; confidence interval [CI]: 0.95-1 and 0.52; CI 0.04-1, respectively) were observed. Furthermore, comparisons of liver microscopy findings showed significant differences between severe versus absent (p<0.001), severe versus mild (p<0.001), and severe versus moderate classifications (p<0.001). The area under the receiver operating curve was 0.94 for the diagnosis of steatosis by BMI evaluation using a cut-off BMI of 27.5 kg/m(2), which yielded 100% sensitivity, 87% specificity, and 100% negative predictive value. CONCLUSIONS: We observed a positive association of macroscopic and microscopic histopathological findings in steatotic livers with adipose infiltration of pancreatic grafts.