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Gaviria-Calle M, Duque-Jaramillo A, Aranzazu M, Di Filippo D, Montoya M, Roldán I, Palacio N, Jaramillo S, Restrepo JC, Hoyos S, Navas MC. Polymorphisms in alcohol dehydrogenase (ADH1) and cytochrome p450 2E1 (CYP2E1) genes in patients with cirrhosis and/or hepatocellular carcinoma. BIOMEDICA : REVISTA DEL INSTITUTO NACIONAL DE SALUD 2018; 38:555-568. [PMID: 30653870 DOI: 10.7705/biomedica.v38i4.3897] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Revised: 04/27/2018] [Indexed: 12/21/2022]
Abstract
Introduction: One of the most important risk factors for hepatocellular carcinoma (HCC) is alcohol consumption: Studies in different populations suggest that the risk of liver disease could be associated with genetic variants of the enzymes involved in alcohol metabolism, such as alcohol dehydrogenase (ADH) and cytochrome P450 CYP2E1. Objective: To identify and characterize the allelic variants of ADH1B, ADH1C and CYP2E1 genes in Colombian patients with cirrhosis and/or HCC. Materials and methods: We included samples from patients attending the hepatology unit between 2005-2007 and 2014-2016 of a hospital in Medellin. Samples were genotyped using PCR-RFLP. We compared the results with two control groups and the 1000 Genomes Project database. Results: We collected 97 samples from patients with a diagnosis of cirrhosis and/or HCC. The two main risk factors were chronic alcohol consumption (18.6%) and cholangiopathies (17.5%). The most frequent genotypes in the study population were ADH1B*1/1 (82%), ADH1C*1/1 (59%), and CYP2E1*C/C (84%). Conclusions: This first study of polymorphisms in Colombian patients diagnosed with cirrhosis and/or HCC showed genotypes ADH1B*1/1, ADH1C*1/1 and CYP2E1*C/C as the most frequent. We found no significant differences in the genotype frequency between cases and controls. Further studies are necessary to explore the association between polymorphisms and the risk of end-stage liver disease from alcohol consumption.
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Affiliation(s)
- Marcela Gaviria-Calle
- Grupo de Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
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Piñero F, Costa P, Boteon YL, Duque SH, Marciano S, Anders M, Varón A, Zerega A, Poniachik J, Soza A, Padilla Machaca M, Menéndez J, Zapata R, Vilatoba M, Muñoz L, Maraschio M, Podestá LG, McCormack L, Gadano A, Boin ISFF, García P, Silva M. A changing etiologic scenario in liver transplantation for hepatocellular carcinoma in a multicenter cohort study from Latin America. Clin Res Hepatol Gastroenterol 2018; 42:443-452. [PMID: 29773419 DOI: 10.1016/j.clinre.2018.03.014] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 02/28/2018] [Accepted: 03/12/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIM Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC) and liver transplantation (LT). Our study focused on changing trends of liver related HCC etiologies during the last years in Latin America. METHODS From a cohort of 2761 consecutive adult LT patients between 2005 and 2012 in 17 different centers, 435 with HCC were included. Different periods including years 2005-2006, 2007-2008, 2009-2010 and 2011-2012 were considered. Etiology of liver disease was confirmed in the explant. RESULTS Participating LT centers per country included 2 from Brazil (n=191), 5 transplant programs from Argentina (n=98), 2 from Colombia (n=65), 4 from Chile (n=49), 2 from Mexico (n=12), and 1 from Peru (n=11) and Uruguay (n=9). Chronic hepatitis C infection was the leading cause of HCC in the overall cohort (37%), followed by HBV (25%) and alcoholic liver disease (17%). NAFLD and cryptogenic cirrhosis accounted for 6% and 7%, respectively. While HCV decreased from 48% in 2005-06 to 26% in 2011-12, NAFLD increased from 1.8% to 12.8% during the same period, accounting for the third cause of HCC. This represented a 6-fold increase in NAFLD-HCC, whereas HCV had a 2-fold decrease. Patients with NAFLD were older, had lower pre-LT serum AFP values and similar 5-year survival and recurrence rates than non-NAFLD. CONCLUSION There might be a global changing figure regarding etiologies of HCC in Latin America. This epidemiological change on the incidence of HCC in the world, although it has been reported, should still be confirmed in prospective studies.
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Affiliation(s)
- Federico Piñero
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Austral University, School of Medicine, avenue Presidente-Perón 1500, (B1629HJ) Pilar, Buenos Aires, Argentina.
| | - Paulo Costa
- Hospital Federal University of Ceará, Ceara, Brazil
| | | | - Sergio Hoyos Duque
- Hospital Pablo Tobón Uribe and Gastroenterology group from Universidad de Antioquía, Medellín, Colombia
| | | | | | - Adriana Varón
- Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia
| | - Alina Zerega
- Sanatorio Allende from Córdoba, Córdoba, Argentina
| | - Jaime Poniachik
- Hospital Clínico Universidad de Chile, Santiago de Chile, Chile
| | - Alejandro Soza
- Hospital Universidad Católica de Chile, Santiago de Chile, Chile
| | | | | | - Rodrigo Zapata
- Clinica Alemana de Santiago, Universidad del Desarrollo, Santiago de Chile, Chile; Hospital del Salvador, Universidad de Chile, Santiago de Chile, Chile
| | | | - Linda Muñoz
- Hospital Universitario de Monterrey, Monterrey, Mexico
| | | | - Luis G Podestá
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Austral University, School of Medicine, avenue Presidente-Perón 1500, (B1629HJ) Pilar, Buenos Aires, Argentina
| | | | - Adrian Gadano
- Hospital Italiano from Buenos Aires, Buenos Aires, Argentina
| | | | | | - Marcelo Silva
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Austral University, School of Medicine, avenue Presidente-Perón 1500, (B1629HJ) Pilar, Buenos Aires, Argentina
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Sarcopenia in a mice model of chronic liver disease: role of the ubiquitin–proteasome system and oxidative stress. Pflugers Arch 2018; 470:1503-1519. [DOI: 10.1007/s00424-018-2167-3] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Revised: 06/06/2018] [Accepted: 06/11/2018] [Indexed: 02/06/2023]
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Piñero F, Pages J, Marciano S, Fernández N, Silva J, Anders M, Zerega A, Ridruejo E, Ameigeiras B, D'Amico C, Gaite L, Bermúdez C, Cobos M, Rosales C, Romero G, McCormack L, Reggiardo V, Colombato L, Gadano A, Silva M. Fatty liver disease, an emerging etiology of hepatocellular carcinoma in Argentina. World J Hepatol 2018; 10:41-50. [PMID: 29399277 PMCID: PMC5787683 DOI: 10.4254/wjh.v10.i1.41] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 12/07/2017] [Accepted: 01/15/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma (HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease (NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit. RESULTS A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers (n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC (37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLD-HCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015 (4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3% (P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups (6.6 ng/mL vs 26 ng/mL; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality. CONCLUSION The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.
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Affiliation(s)
- Federico Piñero
- Hepatology and Liver Transplantation Unit, Hospital Universitario Austral, Buenos Aires 1629, Argentina
| | - Josefina Pages
- Hepatology and Liver Transplantation Unit, Hospital Universitario Austral, Buenos Aires 1629, Argentina
| | - Sebastián Marciano
- Hepatology Section, Liver Transplant Program, Department of Academic Research, Hospital Italiano from Buenos Aires, Buenos Aires 1424, Argentina
| | - Nora Fernández
- Hepatology and Gastroenterology, Hospital Británico, Buenos Aires 1280, Argentina
| | - Jorge Silva
- Hepatobiliary Surgery, Hospital G Rawson, San Juan 5400, Argentina
| | - Margarita Anders
- Department of Hepatology and Liver Transplant Program, Hospital Aleman, Buenos Aires 1118, Argentina
| | - Alina Zerega
- Department of Hepatology and Liver Transplantation, Sanatorio Allende, Córdoba 5016, Argentina
| | - Ezequiel Ridruejo
- Hepatology Section, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC", Buenos Aires 1425, Argentina
| | - Beatriz Ameigeiras
- Department of Hepatology, Hospital Ramos Mejía, Buenos Aires 1221, Argentina
| | - Claudia D'Amico
- Department of Hepatology, Centro Especialidades Medicas Ambulatorias (CEMA), Mar del Plata 7600, Argentina
| | - Luis Gaite
- Department of Hepatology and Liver Transplantation, Clínica de Nefrología de Santa Fe, Santa Fe 3000, Argentina
| | - Carla Bermúdez
- Hepatology Section, Liver Transplant Program, Department of Academic Research, Hospital Italiano from Buenos Aires, Buenos Aires 1424, Argentina
| | - Manuel Cobos
- Department of Hepatology and Liver Transplant Program, Hospital Aleman, Buenos Aires 1118, Argentina
| | - Carlos Rosales
- Hepatobiliary Surgery, Hospital G Rawson, San Juan 5400, Argentina
| | - Gustavo Romero
- Department of Hepatology and Gastroenterology, Hospital C Bonorino Udaondo, Buenos Aires 1264, Argentina
| | - Lucas McCormack
- Department of Hepatology and Liver Transplant Program, Hospital Aleman, Buenos Aires 1118, Argentina
| | - Virginia Reggiardo
- Department of Hepatology and Gastroenterology, Hospital Centenario, Santa Fe 2002, Argentina
| | - Luis Colombato
- Hepatology and Gastroenterology, Hospital Británico, Buenos Aires 1280, Argentina
| | - Adrián Gadano
- Hepatology Section, Liver Transplant Program, Department of Academic Research, Hospital Italiano from Buenos Aires, Buenos Aires 1424, Argentina
| | - Marcelo Silva
- Hepatology and Liver Transplantation Unit, Hospital Universitario Austral, Buenos Aires 1629, Argentina
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Lei JY, Wang WT, Yan LN. Up-to-seven criteria for hepatocellular carcinoma liver transplantation: A single center analysis. World J Gastroenterol 2013; 19:6077-6083. [PMID: 24106409 PMCID: PMC3785630 DOI: 10.3748/wjg.v19.i36.6077] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2013] [Revised: 08/15/2013] [Accepted: 08/20/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To detect whether the up-to-seven should be used as inclusion criteria for liver transplantation for hepatocellular carcinoma.
METHODS: Between April 2002 and July 2008, 220 hepatocellular carcinoma (HCC) patients who were diagnosed with HCC and underwent liver transplantation (LT) at our liver transplantation center were included. These patients were divided into three groups according to the characteristics of their tumors (tumor diameter, tumor number): the Milan criteria group (Group 1), the in up-to-seven group (Group 2) and the out up-to-seven group (Group 3). Then, we compared long-term survival and tumor recurrence of these three groups.
RESULTS: The baseline characteristics of transplant recipients were comparable among these three groups, except for the type of liver graft (deceased donor liver transplant or live donor liver transplantation). There were also no significant differences in the pre-operative α-fetoprotein level. The 1-, 3-, and 5-year overall survival and tumor-free survival rate for the Milan criteria group were 94.8%, 91.4%, 89.7% and 91.4%, 86.2%, and 86.2% respectively; in the up-to-seven criteria group, these rates were 87.8%, 77.8%, and 76.6% and 85.6%, 75.6%, and 75.6% respectively (P < 0.05). However, the advanced HCC patients’ (in the group out of up-to-seven criteria) overall and tumor-free survival rates were much lower, at 75%, 53.3%, and 50% and 65.8%, 42.5%, and 41.7%, respectively (P < 0.01).
CONCLUSION: Considering that patients in the up-to-seven criteria group exhibited a considerable but lower survival rate compared with the Milan criteria group, the up-to-seven criteria should be used carefully and selectively.
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Maggs JRL, Suddle AR, Aluvihare V, Heneghan MA. Systematic review: the role of liver transplantation in the management of hepatocellular carcinoma. Aliment Pharmacol Ther 2012; 35:1113-34. [PMID: 22432733 DOI: 10.1111/j.1365-2036.2012.05072.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2011] [Revised: 09/18/2011] [Accepted: 03/02/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Liver transplantation offers a potential cure for this otherwise devastating disease. The selection of the most appropriate candidates is paramount in an era of graft shortage. AIM To review systematically the role of liver transplantation in the management of HCC in current clinical practice. METHODS An electronic literature search using PUBMED (1980-2010) was performed. Search terms included HCC, hepatoma, liver cancer, and liver transplantation. RESULTS Liver transplantation is a highly successful treatment for HCC, in patients within Milan criteria (MC), defined as a solitary tumour ≤50 mm in diameter or ≤3 tumours ≤30 mm in diameter in the absence of extra-hepatic or vascular spread. Other eligibility criteria for liver transplantation are also used in clinical practice, such as the University of California, San Francisco criteria, with outcomes comparable to MC. Loco-regional therapies have a role in the bridging treatment of HCC by minimising wait-list drop-out secondary to tumour progression. Beyond MC, encouraging results have been demonstrated for patients with down-staged tumours. Post-liver transplantation, there is no evidence to support a specific immunosuppressive regimen. In the context of an insufficient cadaveric donor pool to meet demand, the role of adult living donation may be increasingly important. CONCLUSIONS Liver transplantation offers a curative therapy for selected patients with HCC. The optimisation of eligibility criteria is paramount to ensure that maximum benefit is accrued. Although wait-list therapies have been incorporated into clinical practice, additional high quality data are required to support this strategy.
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Affiliation(s)
- J R L Maggs
- Institute of Liver Studies, King's College Hospital, London, UK
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Silva MF, Sherman M. Criteria for liver transplantation for HCC: what should the limits be? J Hepatol 2011; 55:1137-47. [PMID: 21718672 DOI: 10.1016/j.jhep.2011.05.012] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2011] [Revised: 05/17/2011] [Accepted: 05/18/2011] [Indexed: 02/07/2023]
Abstract
Liver transplantation is a well-established treatment in a subset of patients with cirrhosis and hepatocellular carcinoma. The Milan criteria (single nodule up to 5 cm, up to three nodules none larger than 3 cm, with no evidence of extrahepatic spread or macrovascular invasion) have been traditionally accepted as standard of care. However, some groups have proposed that these criteria are too restrictive, and exclude some patients from transplantation who might benefit from this procedure. Transplanting patients with tumors beyond the established criteria falls into two categories, those whose tumors are beyond the Milan criteria at presentation without the use of treatment prior to transplantation (expanded criteria), and those in whom treatment allows the Milan Criteria to be fulfilled (down-staging). Currently, however, there is no international consensus regarding these approaches in clinical practice. The purpose of this systematic review is to clarify this debate through a critical analysis of available data. Finally, some comments on predictive factors apart from morphological characteristics are also addressed.
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Affiliation(s)
- Mauricio F Silva
- Department of HBP Surgery and Transplantation, Santa Casa General Hospital, Porto Alegre, Brazil.
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Navas MC, Suarez I, Carreño A, Uribe D, Rios WA, Cortes-Mancera F, Martel G, Vieco B, Lozano D, Jimenez C, Gouas D, Osorio G, Hoyos S, Restrepo JC, Correa G, Jaramillo S, Lopez R, Bravo LE, Arbelaez MP, Scoazec JY, Abedi-Ardekani B, Santella RM, Chemin I, Hainaut P. Hepatitis B and Hepatitis C Infection Biomarkers and TP53 Mutations in Hepatocellular Carcinomas from Colombia. HEPATITIS RESEARCH AND TREATMENT 2011; 2011:582945. [PMID: 22114738 PMCID: PMC3207138 DOI: 10.1155/2011/582945] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2011] [Accepted: 08/22/2011] [Indexed: 02/07/2023]
Abstract
Hepatocellular Carcinoma (HCC) is a leading cause of cancer-related death worldwide. Globally, the most important HCC risk factors are Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV), chronic alcoholism, and dietary exposure to aflatoxins. We have described the epidemiological pattern of 202 HCC samples obtained from Colombian patients. Additionally we investigated HBV/HCV infections and TP53 mutations in 49 of these HCC cases. HBV biomarkers were detected in 58.1% of the cases; HBV genotypes F and D were characterized in three of the samples. The HCV biomarker was detected in 37% of the samples while HBV/HCV coinfection was found in 19.2%. Among TP53 mutations, 10.5% occur at the common aflatoxin mutation hotspot, codon 249. No data regarding chronic alcoholism was available from the cases. In conclusion, in this first study of HCC and biomarkers in a Colombian population, the main HCC risk factor was HBV infection.
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Affiliation(s)
- Maria-Cristina Navas
- Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
| | - Iris Suarez
- Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
| | - Andrea Carreño
- Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
| | - Diego Uribe
- Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
| | - Wilson Alfredo Rios
- Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
| | - Fabian Cortes-Mancera
- Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
| | - Ghyslaine Martel
- International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon, France
| | - Beatriz Vieco
- Departamento de Patología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
| | - Diana Lozano
- Departamento de Patología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
| | - Carlos Jimenez
- Departamento de Patología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
| | - Doriane Gouas
- International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon, France
| | - German Osorio
- Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
- Departamento de Patología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
| | - Sergio Hoyos
- Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
- Hospital Pablo Tobón Uribe, Medellín, Colombia
| | - Juan Carlos Restrepo
- Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
- Hospital Pablo Tobón Uribe, Medellín, Colombia
| | - Gonzalo Correa
- Grupo de Gastrohepatologia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
- Hospital Pablo Tobón Uribe, Medellín, Colombia
| | | | - Rocio Lopez
- Departamento de Patologia, Fundacion Santa Fe de Bogota, Bogotá D.C., Colombia
| | - Luis Eduardo Bravo
- Departamento de Patología, Facultad de Salud, Universidad del Valle, Cali, Colombia
| | - Maria Patricia Arbelaez
- Grupo de Epidemiologia, Facultad Nacional de Salud Publica, Universidad de Antioquia, Medellín, Colombia
| | - Jean-Yves Scoazec
- Service d'Anatomie Pathologique, Hôpital Edouard Herriot, 69437 Lyon, France
| | | | | | | | - Pierre Hainaut
- International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon, France
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Mazzaferro V, Bhoori S, Sposito C, Bongini M, Langer M, Miceli R, Mariani L. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience. Liver Transpl 2011; 17 Suppl 2:S44-57. [PMID: 21695773 DOI: 10.1002/lt.22365] [Citation(s) in RCA: 435] [Impact Index Per Article: 31.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Vincenzo Mazzaferro
- Units of Gastrointestinal Surgery and Liver Transplantation, National Cancer Institute of Milan, Milan, Italy.
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