FLAIR JOSE CARRILHO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Gastroenterologia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
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conferenceObject Dynamic survival analysis of the data from the national survey of hepatocellular carcinoma and liver transplantation in Brazil(2018) FELGA, G.; CHAGAS, A.; ALMEIDA, M. D.; ALVES, V. A. F.; CARRILHO, F. J.- Clinical and pathological evaluation of fibrolamellar hepatocellular carcinoma: a single center study of 21 cases(2015) CHAGAS, Aline Lopes; KIKUCHI, Luciana; HERMAN, Paulo; ALENCAR, Regiane S. S. M.; TANI, Claudia M.; DINIZ, Marcio Augusto; PUGLIESE, Vincenzo; ROCHA, Manoel de Souza; D'ALBUQUERQUE, Luiz Augusto Carneiro; CARRILHO, Flair Jose; ALVES, Venancio A. F.OBJECTIVES: Fibrolamellar hepatocellular carcinoma is a rare primary malignant liver tumor that differs from conventional hepatocellular carcinoma in several aspects. The aim of this study was to describe the clinical, surgical and histopathological features of fibrolamellar hepatocellular carcinoma and to analyze the factors associated with survival. METHODS: We identified 21 patients with histopathologically diagnosed fibrolamellar hepatocellular carcinoma over a 22-year period. Clinical information was collected from medical records and biopsies, and surgical specimens were reviewed. RESULTS: The median age at diagnosis was 20 years. Most patients were female (67%) and did not have associated chronic liver disease. Most patients had a single nodule, and the median tumor size was 120 mm. Vascular invasion was present in 31% of patients, and extra-hepatic metastases were present in 53%. Fourteen patients underwent surgery as the first-line therapy, three received chemotherapy, and four received palliative care. Eighteen patients had ""pure fibrolamellar hepatocellular carcinoma,'' whereas three had a distinct area of conventional hepatocellular carcinoma and were classified as having ""mixed fibrolamellar hepatocellular carcinoma.'' The median overall survival was 36 months. The presence of ""mixed fibrolamellar hepatocellular carcinoma'' and macrovascular invasion were predictors of poor survival. Vascular invasion was associated with an increased risk of recurrence in patients who underwent surgery. CONCLUSION: Fibrolamellar hepatocellular carcinoma was more common in young female patients without chronic liver disease. Surgery was the first therapeutic option to achieve disease control, even in advanced cases. Vascular invasion was a risk factor for tumor recurrence. The presence of macrovascular invasion and areas of conventional hepatocellular carcinoma were directly related to poor survival.
- Early variation of inflammatory indexes refines prognostic prediction in patients with hepatocellular carcinoma under systemic treatment(2023) FONSECA, Leonardo G. Da; URATANI, Lucas Fernando; SOARES, Gabriella Fernandes; AMARAL, Paulo Siqueira Do; ALENCAR, Regiane Saraiva De Souza Melo; CHAGAS, Aline Lopes; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair JosePrognostic markers in advanced hepatocellular carcinoma (HCC) are relevant for clinical decisions. Variations in inflammatory indexes, such as neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR), may correlate with outcomes. In the present study, it was aimed to assess the prognostic role of inflammation indexes in patients with HCC and the evolutionary behavior of these variables within the first month of treatment in a cohort of patients treated with sorafenib from 2009-2021. Subgroups were divided based on the median of each variable ('low' or 'high)'. Survival was estimated using the Kaplan-Meier method. Hazard Ratio (HR) with 95% confidence interval (CI) were estimated using Cox regression models. A total of 373 patients were included, most Child-Pugh-A (83.1%) and BCLC-C (74%). Child-Pugh-A (P=0.011), performance status 0 (P<0.001), no ascites (P<0.001) and NLR<2.6 (P<0.001) were independently associated with improved survival. Baseline PLR was not correlated with survival (P=0.137). Patients who maintained low NLR at baseline and at 1 month (reference subgroup) had improved survival (18.6 months, 95% CI:15.4-22.0) compared with the subgroup that maintained high NLR at baseline and at 1 month (4.2 months, 95% CI:3.6-5.9), with HR: 3.80 (95% CI: 2.89-4.96). The subgroup with low NLR at baseline and high NLR at 1 month had a worse prognosis compared with the reference group (HR:1.4, 95% CI: 1.1-2.0), whereas the subgroup with high NLR at baseline and low at 1 month had similar outcome (HR:1.2, 95% CI: 0.8-1.6). It was concluded that evolutionary variation of NLR has a prognostic role in HCC patients under systemic therapy. This finding suggested that systemic inflammation and early modulation of the immune environment during treatment may correlate with outcomes.
- Serum lipidomic profiling as a useful tool for screening potential biomarkers of hepatitis B-related hepatocellular carcinoma by ultraperformance liquid chromatography-mass spectrometry(2015) PASSOS-CASTILHO, Ana Maria; CARVALHO, Valdemir Melechco; CARDOZO, Karina Helena Morais; KIKUCHI, Luciana; CHAGAS, Aline Lopes; GOMES-GOUVEA, Michele Soares; MALTA, Fernanda; NASTRI, Ana Catharina de Seixas-Santos; PINHO, Joao Renato Rebello; CARRILHO, Flair Jose; GRANATO, Celso Francisco HernandesBackground: Chronic hepatitis B (CHB) virus infection is a major cause of hepatocellular carcinoma (HCC), as late diagnosis is the main factor for the poor survival of patients. There is an urgent need for accurate biomarkers for early diagnosis of HCC. The aim of the study was to explore the serum lipidome profiles of hepatitis B-related HCC to identify potential diagnostic biomarkers. Methods: An ultraperformance liquid chromatography mass spectrometry (UPLC-MS) lipidomic method was used to characterize serum profiles from HCC (n = 32), liver cirrhosis (LC) (n = 30), CHB (n = 25), and healthy subjects (n = 34). Patients were diagnosed by clinical laboratory and imaging evidence and all presented with CHB while healthy controls had normal liver function and no infectious diseases. Results: The UPLC-MS-based serum lipidomic profile provided more accurate diagnosis for LC patients than conventional alpha-fetoprotein (AFP) detection. HCC patients were discriminated from LC with 78 % sensitivity and 64 % specificity. In comparison, AFP showed sensitivity and specificity of 38 % and 93 %, respectively. HCC was differentiated from CHB with 100 % sensitivity and specificity using the UPLC-MS approach. Identified lipids comprised glycerophosphocolines, glycerophosphoserines and glycerophosphoinositols. Conclusions: UPLC-MS lipid profiling proved to be an efficient and convenient tool for diagnosis and screening of HCC in a high-risk population.
- Performance of pre-transplant criteria in prediction of hepatocellular carcinoma progression and waitlist dropout(2022) PINERO, Federico; THOMPSON, Marcos; BOIN, Ilka; CHAGAS, Aline; QUINONEZ, Emilio; BERMUDEZ, Carla; VILATOBA, Mario; SANTOS, Luisa; ANDERS, Margarita; DUQUE, Sergio Hoyos; LIMA, Agnaldo Soares; MENENDEZ, Josemaria; PADILLA, Martin; PONIACHIK, Jaime; ZAPATA, Rodrigo; MARASCHIO, Martin; MENENDEZ, Ricardo Chong; MUNOZ, Linda; ARUFE, Diego; FIGUEROA, Rodrigo; PERALES, Simone R.; MACCALI, Claudia; SANDOVAL, Rodrigo Vergara; MCCORMACK, Lucas; VARON, Adriana; MARCIANO, Sebastian; MATTERA, Juan; CARRILHO, Flair; SILVA, MarceloBackground & aim Liver transplantation (LT) selection models for hepatocellular carcinoma (HCC) have not been proposed to predict waitlist dropout because of tumour progression. The aim of this study was to compare the alpha-foetoprotein (AFP) model and other pre-LT models in their prediction of HCC dropout. Methods A multicentre cohort study was conducted in 20 Latin American transplant centres, including 994 listed patients for LT with HCC from 2012 to 2018. Longitudinal tumour characteristics, and patterns of progression were recorded at time of listing, after treatments and at last follow-up over the waitlist period. Competing risk regression models were performed, and model's discrimination was compared estimating Harrell's adapted c-statistics. Results HCC dropout rate was significantly higher in patients beyond (24% [95% CI 16-28]) compared to those within Milan criteria (8% [95% IC 5%-12%]; p < .0001), with a SHR of 3.01 [95% CI 2.03-4.47]), adjusted for waiting list time and bridging therapies (c-index 0.63 [95% CI 0.57; 0.69). HCC dropout rates were higher in patients with AFP scores >2 (adjusted SHR of 3.17 [CI 2.13-4.71]), c-index of 0.71 (95% CI 0.65-0.77; p = .09 vs Milan). Similar discrimination power for HCC dropout was observed between the AFP score and the Metroticket 2.0 model. In patients within Milan, an AFP score >2 points discriminated two populations with a higher risk of HCC dropout (SHR 1.68 [95% CI 1.08-2.61]). Conclusions Pre-transplant selection models similarly predicted HCC dropout. However, the AFP model can discriminate a higher risk of dropout among patients within Milan criteria.
conferenceObject Serum Lipidomic Profiling for Screening Potential Biomarkers of Liver Cirrhosis among Patients with Chronic Hepatitis C(2015) PASSOS-CASTILHO, Ana Maria; FERRAZ, Maria Lucia; CARVALHO, Valdemir M.; CARDOZO, Karina H.; KIKUCHI, Luciana; CHAGAS, Aline; PINHO, Joao Renato R.; GOMES-GOUVEA, Michele S.; MALTA, Fernanda; CARRILHO, Flair J.; GRANATO, Celso- Percutaneous radiofrequency ablation for early hepatocellular carcinoma: Risk factors for survival(2014) KIKUCHI, Luciana; MENEZES, Marcos; CHAGAS, Aline L.; TANI, Claudia M.; ALENCAR, Regiane S. S. M.; DINIZ, Marcio A.; ALVES, Venancio A. F.; D'ALBUQUERQUE, Luiz Augusto Carneiro; CARRILHO, Flair JoseAIM: To evaluate outcomes of radiofrequency ablation (RFA) therapy for early hepatocellular carcinoma (HCC) and identify survival-and recurrence-related factors. METHODS: Consecutive patients diagnosed with early HCC by computed tomography (CT) or magnetic resonance imaging (MRI) (single nodule of <= 5 cm, or multi-(up to 3) nodules of <= 3 cm each) and who underwent RFA treatment with curative intent between January 2010 and August 2011 at the Instituto do Cancer do Estado de Sao Paulo, Brazil were enrolled in the study. RFA of the liver tumors (with 1.0 cm ablative margin) was carried out under CT-fluoro scan and ultrasonic image guidance of the percutaneous ablation probes. Procedure-related complications were recorded. At 1-mo post-RFA and 3-mo intervals thereafter, CT and MRI were performed to assess outcomes of complete response (absence of enhancing tissue at the tumor site) or incomplete response (enhancing tissue remaining at the tumor site). Overall survival and disease-free survival rates were estimated by the Kaplan-Meier method and compared by the log rank test or simple Cox regression. The effect of risk factors on survival was assessed by the Cox proportional hazard model. RESULTS: A total of 38 RFA sessions were performed during the study period on 34 patients (age in years: mean, 63 and range, 49-84). The mean follow-up time was 22 mo (range, 1-33). The study population showed predominance of male sex (76%), less severe liver disease (Child-Pugh A, n = 26; Child-Pugh B, n = 8), and single tumor (65%). The maximum tumor diameters ranged from 10 to 50 mm (median, 26 mm). The initial (immediately post-procedure) rate of RFA-induced complete tumor necrosis was 90%. The probability of achieving complete response was significantly greater in patients with a single nodule (vs patients with multi-nodules, P = 0.04). Two patients experienced major complications, including acute pulmonary edema (resolved with intervention) and intestinal perforation (led to death). The 1- and 2-year overall survival rates were 82% and 71%, respectively. Sex, tumor size, initial response, and recurrence status influenced survival, but did not reach the threshold of statistical significance. Child-Pugh class and the model for end-stage liver disease score were identified as predictors of survival by simple Cox regression, but only Child-Pugh class showed a statistically significant association to survival in multiple Cox regression analysis (HR = 15; 95% CI: 3-76 mo; P = 0.001). The 1- and 2-year cumulative disease-free survival rates were 65% and 36%, respectively. CONCLUSION: RFA is an effective therapy for local tumor control of early HCC, and patients with preserved liver function are the best candidates.
- Liver transplantation for hepatocellular carcinoma: impact of expansion criteria in a multicenter cohort study from a high waitlist mortality region(2021) PINERO, Federico; ANDERS, Margarita; BOIN, Ilka F.; CHAGAS, Aline; QUINONEZ, Emilio; MARCIANO, Sebastian; VILATOBA, Mario; SANTOS, Luisa; DUQUE, Sergio Hoyos; LIMA, Agnaldo Soares; MENENDEZ, Josemaria; PADILLA, Martin; PONIACHIK, Jaime; ZAPATA, Rodrigo; SOZA, Alejandro; MARASCHIO, Martin; MENENDEZ, Ricardo Chong; MUNOZ, Linda; ARUFE, Diego; FIGUEROA, Rodrigo; ATAIDE, Elaine Cristina de; MACCALI, Claudia; SANDOVAL, Rodrigo Vergara; BERMUDEZ, Carla; PODESTA, Luis G.; MCCORMACK, Lucas; VARON, Adriana; GADANO, Adrian; MATTERA, Juan; VILLAMIL, Federico; RUBINSTEIN, Fernando; CARRILHO, Flair; SILVA, MarceloThis study aimed to compare liver transplantation (LT) outcomes and evaluate the potential rise in numbers of LT candidates with hepatocellular carcinoma (HCC) of different allocation policies in a high waitlist mortality region. Three policies were applied in two Latin American cohorts (1085 HCC transplanted patients and 917 listed patients for HCC): (i) Milan criteria with expansion according to UCSF downstaging (UCSF-DS), (ii) the AFP score, and (iii) restrictive policy or Double Eligibility Criteria (DEC; within Milan + AFP score <= 2). Increase in HCC patient numbers was evaluated in an Argentinian prospective validation set (INCUCAI; NCT03775863). Expansion criteria in policy A showed that UCSF-DS [28.4% (CI 12.8-56.2)] or ""all-comers"" [32.9% (CI 11.9-71.3)] had higher 5-year recurrence rates compared to Milan, with 10.9% increase in HCC patients for LT. The policy B showed lower recurrence rates for AFP scores <= 2 points, even expanding beyond Milan criteria, with a 3.3% increase. Patients within DEC had lower 5-year recurrence rates compared with those beyond DEC [13.3% (CI 10.1-17.3) vs 24.2% (CI 17.4-33.1; P = 0.0006], without significant HCC expansion. In conclusion, although the application of a stricter policy may optimize the selection process, this restrictive policy may lead to ethical concerns in organ allocation (NCT03775863).
- The Impact of Early Dermatologic Events in the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib(2017) BRANCO, Fernanda; ALENCAR, Regiane S. M.; VOLT, Fernanda; SARTORI, Giovana; DODE, Andressa; KIKUCHI, Luciana; TANI, Claudia M.; CHAGAS, Aline L.; PFIFFER, Tulio; HOFF, Paulo; CARRILHO, Flair J.; MATTOS, Angelo Alves deBackground and Aims. The presence of dermatologic reaction as an adverse event to sorafenib treatment in patients with unresectable hepatocellular carcinoma has been indicated as a prognostic factor for survival in a recent prospective analysis. To date, this is the only clinical predictor of treatment response , which can be eavaluated earlier in the treatment and, therefore, contribute to a better and more individualized patient management. Material and methods. This retrospective study included 127 patients treated with sorafenib under real-life practice conditions in two hepatology reference centers in Brazil, Demographic data, disease/medical history and time of sorafenib administration as well as adverse events related to the medication were recorded in a database Results. Cirrhosis was present in 94% of patients, 85.6% were child-pugh A, 80.3%BCLC-C,81% had vascular invasion and/or extrahepatic spread and 95% had a performance status 0 to 1. The median duration of treatment was 10.1 months (range: 0.1-47 months). The most common adverse event within the first 60 days of treatment were diarrhea (62.2%) and dermatological reaction (42%). The median overall survival for the cohort was 20 months, and it was higher for patients who developed dermatological reactions within the first 60 days compared to those who did not present this adverse event. Conclusion. This retrospective analysis showed the use of sorafenib in patients selected according to BCLC staging, and it is the first external validation of early dermatologic adverse events as a predictor of overall survival in patients with advanced hepatocellular carcinoma.
- Interferon lambda and hepatitis C virus core protein polymorphisms associated with liver cancer(2016) MOREIRA, Joao Paulo; MALTA, Fernanda de Mello; DINIZ, Marcio Augusto; KIKUCHI, Luciana; CHAGAS, Aline Lopes; LIMA, Livia de Souza Botelho; GOMES-GOUVEA, Michele Soares; CASTRO, Vanessa Fusco Duarte de; SANTANA, Rubia Anita Ferraz; SUMITA, Nairo Massakazu; VEZOZZO, Denise Cerqueira Paranagua; CARRILHO, Flair Jose; PINHO, Joao Renato RebelloBackground: Hepatitis C virus (HCV) infection is often persistent and gradually advances from chronic hepatitis to liver cirrhosis and hepatocellular carcinoma (HCC). Worldwide, hepatocellular carcinoma is the fifth most common neoplasm. Method of study: the Interferon lambda (IFNL) polymorphisms genotypes (rs8099917, rs12979860 and rs12980275) and the presence of mutations in HCV core protein were analyzed in 59 patients with HCC, and also in 50 cirrhotic patients (without HCC). Results: the rs12980275-AG genotype was associated with HCC on age-adjusted analysis (OR 2.42, 95% CI 1.03-5.69, P=0.043). Core substitutions R70Q and L91M were mainly found in genotype 1b isolates. Furthermore, a borderline level of statistical significance association was found among the presence of amino acid Glutamine (Q) in the position 70 and IFNL3 genotype AG (P=0.054). Conclusions: the screening of these polymorphisms and functional studies would be useful in clinical practice for identifying groups at high risk of HCC development.