Overall survival predictors in hepatocellular carcinoma patients treated with sorafenib

SUMMARY Malignant liver tumors are the fourth leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) accounts for 75-85% of these. Most patients are diagnosed at incurable stages. Palliative care is the appropriate treatment course in these circumstances (chemoembolization and sorafenib). There are few national studies on sorafenib. The objective is to evaluate survival predictors of HCC patients treated with sorafenib and evaluate the compliance of its indication in relation to BCLC recommendations. METHODS A total of 88 patients with an indication of sorafenib from 2010 to 2017 at the ISCMSP were retrospectively analyzed. Univariate and multivariate analyzes were performed in the search for predictors of survival. RESULTS The mean age was 61.2 years, 70.5% were men, most were classified as Child-Pugh A (69.3%), and BCLC C (94.3%). Cirrhosis was present in 84.6% and portal hypertension in 55.7%. Hepatitis C virus was the most common etiology (40.9%). Sixty-nine (78.4%) patients received the medication, with the average duration of treatment being 9.7 months. The mean overall survival was 16.8 months. Significant differences were observed in the multivariate analysis: ECOG PS (p = 0.024): Child-Pugh (p = 0.013), time of medication use (p <0.001), clinical worsening (p = 0.031) and portal thrombosis (p = 0.010). CONCLUSION Absence of portal thrombosis, Child-Pugh A, longer time of medication use, ECOG PS 0, and absence of suspension due to clinical worsening were predictors of better overall survival in the study. The drug's indication complies with BCLC guidelines in 94% of patients.

RESUMO Tumores malignos do fígado são a quarta maior causa de morte por câncer, sendo que o carcinoma hepatocelular (CHC) corresponde a 85-90% desses casos. A maioria dos doentes apresenta-se, ao diagnóstico, sem possibilidade de tratamento curativo, restando apenas as opções paliativas (quimioembolização e sorafenibe). Há poucos estudos nacionais acerca do sorafenibe. OBJETIVO Avaliar fatores preditivos de sobrevida em pacientes com CHC que tiveram indicação de tratamento com sorafenibe na Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP) e avaliação da conformidade da indicação da medicação em relação às recomendações do BCLC. MÉTODOS Foram analisados retrospectivamente os dados de 88 pacientes que tiveram indicação de tratamento com sorafenibe no período de 2010 a 2017 na ISCMSP. Análises univariada e multivariada foram realizadas na busca de preditores de sobrevida global nos pacientes que receberam a medicação. RESULTADOS Idade média de 61,2 anos, sendo 70,5% homens. A maioria (69,3%) foi classificada como Child Pugh A e BCLC C (94,3%). A cirrose esteve presente em 84,6% e a hipertensão portal em 55,7% desses. O vírus da hepatite C foi a etiologia mais comum (40,9%) do CHC. Sessenta e nove (78,4%) pacientes receberam a medicação, sendo o tempo médio de duração do tratamento 9,7 meses e a sobrevida global média, 16,8 meses. Diferenças significativas foram observadas na análise multivariada: Ecog PS (p=0,024), CP (p=0,013), tempo de uso de medicação (p<0,001), suspensão por piora clínica (p=0,031) e trombose portal (p=0,010). CONCLUSÃO Ausência de trombose portal, Child Pugh A, Ecog PS 0, tempo maior de uso de medicação e ausência de suspensão por piora clínica foram fatores preditores de melhor sobrevida global e a indicação da medicação esteve em conformidade com as orientações do BCLC em 94% dos pacientes.

Pacientes com carcinoma hepatocelular são favorecidos no atual sistema brasileiro de alocação de fígados para transplante. Análise de riscos competitivos / Hepatocellular carcinoma patients are advantaged in the current brazilian liver transplant allocation system. a competing risk analysis

ABSTRACT BACKGROUND: In Brazil, the Model for End-Stage Liver Disease (MELD) score is used to prioritize patients for deceased donor liver transplantation (DDLT). Patients with hepatocellular carcinoma (HCC) receive standardized MELD exception points to account for their cancer risk of mortality, which is not reflected by their MELD score. OBJECTIVE: To compare DDLT rates between patients with and without HCC in Rio Grande do Sul, the Southernmost state of Brazil. METHODS - We retrospectively studied 825 patients on the liver-transplant waiting list from January 1, 2007, to December 31, 2016, in a transplant center located in Porto Alegre, the capital of Rio Grande do Sul, to compare DDLT rates between those with and without HCC. The time-varying hazard of waiting list/DDLT was estimated, reporting the subhazard ratio (SHR) of waiting list/DDLT/dropout with 95% confidence intervals (CI). The final competing risk model was adjusted for age, MELD score, exception points, and ABO group. RESULTS: Patients with HCC underwent a transplant almost three times faster than patients with a calculated MELD score (SHR 2.64; 95% CI 2.10-3.31; P<0.001). The DDLT rate per 100 person-months was 11.86 for HCC patients vs 3.38 for non-HCC patients. The median time on the waiting list was 5.6 months for patients with HCC and 25 months for patients without HCC. CONCLUSION: Our results demonstrated that, in our center, patients on the waiting list with HCC have a clear advantage over candidates listed with a calculated MELD score.

RESUMO CONTEXTO: No Brasil, o escore MELD (Model for End-Stage Liver Disease) é utilizado para priorizar os pacientes para transplante hepático de doador falecido (THDF). Pacientes com carcinoma hepatocelular (CHC) recebem pontos de exceção padronizados pelo MELD para contrapesar o risco de mortalidade do seu câncer, que não é refletido pelo seu escore MELD. OBJETIVO: Comparar as taxas de THDF entre pacientes com e sem CHC no Rio Grande do Sul, o Estado mais ao sul do Brasil. MÉTODOS: Foram estudados retrospectivamente 825 pacientes em lista de espera de transplante de fígado entre 1 de janeiro de 2007 e 31 de dezembro de 2016 em um centro de transplantes localizado em Porto Alegre, capital do Rio Grande do Sul, para comparação das taxas de THDF entre aqueles com e sem CHC. Foi estimado o risco variável no tempo de lista de espera/THDF, com relato da taxa de sub-risco (SHR) de lista de espera/THDF/desistência com intervalos de confiança (IC) de 95%. O modelo final de risco competitivo foi ajustado para idade, escore MELD, pontos de exceção e grupo ABO. RESULTADOS: Os candidatos com CHC foram submetidos a um transplante quase três vezes mais rápido do que os pacientes com um escore MELD calculado (SHR 2,64; IC 95% 2,10-3,31; P<0,001). A taxa de THDF por 100 pessoas-mês foi de 11,86 para os pacientes com CHC vs 3,38 para os pacientes sem CHC. O tempo mediano de permanência em lista de espera foi de 5,6 meses para os pacientes com CHC e 25 meses para os pacientes sem CHC. CONCLUSÃO: Nossos resultados demonstraram que, em nosso centro, pacientes em lista de espera com CHC têm evidente vantagem sobre candidatos listados com um escore MELD calculado.

Mortalidade por carcinoma hepatocelular associado às hepatites virais B e C no estado de São Paulo / Hepatocellular carcinoma mortality associated with viral hepatitis B and C in the State of São Paulo

Introdução: A mortalidade por carcinoma hepatocelular associado às hepatites virais B e C representa um grave problema de saúde pública. O carcinoma hepatocelular constitui a terceira maior causa de morte de etiologia neoplásica e o quinto tumor maligno mais frequente no mundo. A infecção crônica pelo vírus da hepatite B e pelo vírus da hepatite C são as principais causas de doença hepática crônica e carcinoma hepatocelular (CHC). Objetivos: descrever os óbitos por CHC associados às hepatites virais B e C no Estado de São Paulo e analisar a distribuição espacial e temporal desses óbitos. Métodos: Estudo descritivo ecológico com análise temporal e distribuição espacial dos óbitos por CHC associados às hepatites virais B e C no Estado de São Paulo, no período de 2009 a 2017, com dados do Sistema de Informação sobre Mortalidade (SIM). Foram calculadas as taxas de mortalidade por CHC associado às hepatites virais B e C. A tendência temporal foi analisada por regressão de Prais-Winsten. Os óbitos foram descritos segundo as características sociodemográficas e comparados pelo teste de qui-quadrado de Pearson ou teste exato de Fisher. Os óbitos foram espacialmente distribuídos segundo departamento regional de saúde. Foram calculadas as taxas brutas de mortalidade e as taxas suavizadas pelo método Bayesiano Empírico Local. Resultados: No período de 2009 a 2017, 26,3% dos óbitos por CHC no estado de São Paulo foram associados ao HBV ou ao HCV. Observou-se uma maior proporção de óbitos por CHC associado ao HCV (22,2%) quando comparado ao HBV (3,9%). A taxa de mortalidade por CHC associado às hepatites B ou C apresentou tendência de queda e decréscimo de 0,41 (2009) para 0,33 (2017) óbitos por 100.000 habitantes/ano, com diminuição anual de 3,0%. A taxa de mortalidade por CHC associado à hepatite B também apresentou tendência de queda, variando de 0,07 (2009) para 0,04 (2017) óbitos por 100.000 habitantes/ano, com diminuição anual de 9,1%. No entanto, a taxa de mortalidade por CHC associado à hepatite C apresentou tendência estacionária, de 0,34 (2009) para 0,29 (2017) óbitos por 100.000 habitantes/ano. Os óbitos predominaram no sexo masculino e em indivíduos de raça branca. A faixa etária que apresentou maior número de óbitos foi de 50 a 59 anos de idade. A maioria dos óbitos tinham de 8 a 11 anos de estudo. A distribuição espacial revelou uma distribuição heterogênea dos óbitos no estado de São Paulo. Conclusões: A tendência de queda nas taxas de mortalidade por CHC associado à hepatite B evidência um importante avanço no controle do agravo devido as ações de imunização com a vacina Hepatite B. No entanto, a taxa de mortalidade por CHC associado à hepatite C vem se mantendo estável ao longo do período estudado, indicando a necessidade de ações para a redução dessas taxas. A distribuição espacial dos óbitos auxiliará os gestores e profissionais dos DRS, que poderão olhar para esses dados e levantar hipóteses para conhecimento mais aprofundado das suas regiões, a partir desses resultados.

Introduction: Mortality from hepatocellular carcinoma associated with viral hepatitis B and C represents a serious public health problem. Hepatocellular carcinoma is the third leading cause of death of neoplastic etiology and the fifth most common malignant tumor in the world. Chronic infection with hepatitis B virus and hepatitis C virus are the main causes of chronic liver disease and hepatocellular carcinoma (HCC). Objectives: describe the deaths due to HCC associated with viral hepatitis B and C in the State of São Paulo and analyze the spatial and temporal distribution of these deaths. Methods: Descriptive ecological study with temporal analysis and spatial distribution of deaths from HCC associated with viral hepatitis B and C in the State of São Paulo, from 2009 to 2017, with data from the Mortality Information System (SIM). Mortality rates for HCC associated with viral hepatitis B and C were calculated. The temporal trend was analyzed by Prais-Winsten regression. Deaths were described according to sociodemographic characteristics and compared using Pearson's chi-square test or Fisher's exact test. The deaths were spatially distributed according to the regional health department. Crude mortality rates and smoothed rates were calculated using the Local Empirical Bayesian method. Results: In the period from 2009 to 2017, 26.3% of deaths from HCC in the state of São Paulo were associated to HBV or HCV. There was a higher proportion of deaths from HCC associated to HCV (22.2%) when compared to HBV (3.9%). The mortality rate due to HCC associated with hepatitis B or C showed a downward trend and a decrease from 0.41 (2009) to 0.33 (2017) deaths per 100,000 inhabitants / year, with an annual decrease of 3.0%. The mortality rate due to HCC associated with hepatitis B also showed a downward trend, ranging from 0.07 (2009) to 0.04 (2017) deaths per 100,000 inhabitants / year, with an annual decrease of 9.1%. However, the HCC mortality rate associated with hepatitis C showed a stationary trend, from 0.34 (2009) to 0.29 (2017) deaths per 100,000 inhabitants / year. Deaths predominated in males and in white individuals. The age group with the highest number of deaths was 50 to 59 years old. Most deaths had 8 to 11 years of study. The spatial distribution revealed a heterogeneous distribution of deaths in the state of São Paulo. Conclusions: The downward trend in mortality rates due to HCC associated with hepatitis B shows an important advance in the control of the disease due to the immunization actions with the Hepatitis B vaccine. However, the mortality rate due to HCC associated with hepatitis C has been keeping stable over the study period, indicating the need for actions and measures to reduce these rates. The spatial distribution of deaths will assist the managers and professionals of the DRS, who will be able to look at this data and raise hypotheses for a deeper knowledge of their regions, based on these results.

A poor prognosis in human hepatocellular carcinoma is associated with low expression of DPP4

This study aimed to explore the prognostic role of dipeptidyl peptidase 4 (DPP4) expression in hepatocellular carcinoma (HCC). DPP4 expression was measured in formalin-fixed paraffin-embedded specimens that were gathered from 327 HCC patients. Immunohistochemistry analyses were utilized to examine DPP4 expression characteristics and prognostic values (overall survival (OS) and time to recurrence) of DDP4 in HCC tissues. In addition, a patient-derived xenograft (PDX) model was used to assess the correlation between DPP4 expression and tumor growth in vivo. DPP4 was expressed in low levels in HCC tissues in contrast to paired peritumoral tissues (38 cases were down-regulated in a total of 59 cases, 64.4%. P=0.0202). DPP4 expression was significantly correlated with TNM stage (P=0.038), tumor number (P=0.035), and vascular invasion (P=0.024), and significantly reduced in patients who were in TNM stages II and III-V, with multiple tumors, and with microvascular invasion compared to patients with TNM stage I, single tumor, and no microvascular invasion. Notably, HCC tissues with low expression of DPP4 had poor OS (P=0.016) compared with HCC tissues with high expression of DPP4, and results from PDX model showed that tumor growth was significantly faster in HCC patients that lowly expressed DPP4 compared to those with highly expressed DPP4. Our findings suggested that low levels of DPP4 could impact the aggressiveness of HCC and contribute to a poor prognosis.

Comparison of the prognostic value of platelet-based prognostic models in patients with malignant hepatic tumors after TACE therapy

Abstract Purpose: To investigate the prognostic value of 17 platelet-based prognostic scores in patients with malignant hepatic tumors after TACE therapy. Methods: In total, 92 patients were divided into death group and survival group according to long-term follow-up results. The AUC was calculated to determine the optimal cut-off values for predicting prognosis. To determine better prognostic models, platelet-based models were analyzed separately after being showed as binary according to cut-off values. Cumulative survival rates of malignant hepatic tumors were calculated using Kaplan-Meier curves and differences were analyzed by the log-rank test. Univariate and multivariate analyses were performed to identify platelet-based prognostic scores associated with overall survival. Results: Univariate analysis showed that APGA, APRI, FIB-4, FibroQ, GUCI, King's score, Lok index, PAPAS, cirrhosis, number of tumors, vascular cancer embolus, AFP, ALP and APTT were significantly related to prognosis. A multivariate analysis showed that the APGA, number of tumors, ALP and APTT were independently associated with overall survival. Conclusion: This study showed that the APGA, a platelet-based prognostic score, was an independent marker of prognosis in patients with malignant hepatic tumors after TACE and was superior to the other platelet-based prognostic scores in terms of prognostic ability.

Impacto do escore MELD na sobrevida de pacientes portadores de carcinoma hepatocelular, transplantados no Brasil: revisão sistemática / Impact of the MELD score on the survival of hepatocellular carcinoma transplantation patients in Brazil: a systematic review

RESUMO O objetivo do estudo foi o de analisar o valor preditivo do escore MELD (Model for End-Stage Liver Disease) na sobrevida de médio e longo prazo em pacientes portadores de carcinoma hepatocelular (CHC), transplantados no Brasil. O estudo foi registrado no PROSPERO (International Prospective Register of Systematic Reviews), sob o nº 152.363. Os critérios de inclusão basearam-se nas recomendações PRISMA. A pesquisa foi realizada nos bancos de dados indexados do Lilacs, SciELO, Pubmed e Cochrane Library, e utilizou como estratégia de busca os termos MeSH: ((("Meld Score") OR "Model for End-Stage Liver Disease") AND "Hepatocellular Carcinoma") AND ("Brazil"). Foram incluídos artigos com texto completo, publicados a partir de janeiro de 2006 até outubro de 2019. A busca inicial encontrou 162 artigos. Após a leitura dos resumos e textos completos disponíveis, foram excluídos 156 artigos, totalizando seis artigos para análise qualitativa. Embora o número reduzido de artigos elegíveis tenha sido um fator limitante do estudo, nossos resultados corroboraram parcialmente aos encontrados nos EUA, Reino Unido e Irlanda. Nestes países, ao contrário do Brasil, o modelo prognóstico MELD mostrou forte associação com a sobrevida pós-transplante hepático. No entanto, a baixa capacidade preditiva do modelo em médio e longo prazo, foi similar ao nosso estudo. Configura-se a premência do desenvolvimento e validação de um modelo de sobrevida pós-transplante aos portadores de CHC, aperfeiçoando o sistema de alocação de órgãos no Brasil.

ABSTRACT This study aimed to analyse the predictive value of Model For End-Stage Liver Disease (MELD) score on medium- and long-term survival in transplanted hepatocellular carcinoma (HCC) patients in Brazil. The study was registered with International Prospective Register of Systematic Reviews (PROSPERO) under N# 152,363. Inclusion criteria were based on Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. The search was performed on the indexed databases of Lilacs, SciELO, PubMed, and Cochrane Library, and used as search strategy the following Medical Subject Headings (MeSH) terms: ((("MELD Score") OR "Model For End-Stage Liver Disease") AND "Hepatocellular Carcinoma") AND ("Brazil"). We included full-text articles published from January 2006 to October 2019. The initial search found 162 articles. After reading the available abstracts and full texts, 156 articles were excluded, totaling six articles for qualitative analysis. Although the small number of eligible articles was a limiting factor of the study, our results partially corroborated those found in the United States, United Kingdom, and Ireland. In these countries, unlike Brazil, MELD prognostic model has shown a strong association with post-liver transplant (LT) survival. However, the low predictive capacity of the model in medium- and long-term has been similar to the one of our study. The urgency of the development and validation of a post-transplant survival model for patients with HCC is set, improving the organ allocation system in Brazil.

Combinación poco habitual de hepatocarcinoma con síndrome de Sjögren / Uncommon combination of hepatocarcinoma with Sjögren's syndrome

El síndrome de Sjögren es una enfermedad reumática que aumenta el riesgo de padecer enfermedades malignas. Dentro de estas se identifican a los linfomas como las que con mayor frecuencia se presentan. El hepatocarcinoma es una de las enfermedades más agresivas y su incidencia ha ido en aumento asociado al alto consumo de alcohol. Se presenta el caso de una paciente de 56 años de edad con diagnóstico de un síndrome de Sjögren, con manifestaciones clínicas y anátomopatológicas que permiten llegar al diagnóstico de un hepatocarcinoma, asociación muy infrecuente. El hepatocarcinoma provoca un deterioro progresivo del estado de salud de los pacientes. Conocer sus síntomas y signos es de vital importancia con el fin de llegar al diagnóstico precoz de la enfermedad y evitar así las complicaciones que de él se derivan. No se encuentra relación etiopatogénica entre estas dos afecciones(AU)

Sjögren's syndrome is a rheumatic disease that increases the risk of suffering from malignant diseases. Lymphomas are identified among them as most frequent. Hepatocarcinoma is one of the most aggressive conditions and the incidence has been increasing associated with high alcohol consumption. We present the case of a 56-year-old patient with diagnosis of Sjögren's syndrome that presents clinical and anatomo-pathological manifestations allowing the diagnosis of a very rare hepatocarcinoma. This entity causes a progressive deterioration of the patient health status. It is of vital importance knowing the symptoms and signs in order to reach early diagnosis, thus avoid complications. There is no etiopathogenic relationship between these two conditions(AU)

HAP score as prognostic factor of hepatocellular carcinoma treated with transarterial chemoembolization in a Latin American center / HAP score como factor pronóstico del carcinoma hepatocelular tratado con quimioembolización transarterial en un centro de Latinoamérica

Introduction: Hepatocellular carcinoma (HCC) in cirrhosis is diagnosed, most of times, when it is not susceptible to curative treatment. Transarterial chemoembolization (TACE) is a palliative therapeutic option with heterogeneous results. The HAP score stratifies patients who will benefit from the first TACE. Objective: To evaluate if the HAP score is a prognostic factor of HCC treated with TACE. Materials and methods: Retrospective cohort study in cirrhotic patients with HCC and first TACE at the Edgardo Rebagliati Martins National Hospital, Lima-Peru, from June 2011 to June 20139. The HAP score was applied, mortality and survival were observed with a follow-up of 36 months. Results: We included 54 patients with age of 67.7±9.9 years, 59.3% Child-Pugh A and 40.7% Child-Pugh B, MELD score of 11±2.7; 51.9 and 40.7% were BCLC A and B, respectively; 66.7% had a single tumor and 70.4% had a predominant tumor <5cm. The HAP score classified 8, 14, 26 and 6 patients as HAP A, B, C and D, respectively. The overall survival was 19.5±11.2 months and 32.8±6.5 months for HAP A, 24.9±14.8 months for HAP B, 13.9±5.2 months for HAP C and 14±6.6 months for HAP D. There were no deaths at 12 months in HAP A. At 24 months, mortality for HAP C and D was 100%. At 36 months, the survival rate for HAP A and B was 75 and 42.9%, respectively. Conclusions: The HAP score is a useful tool to guide the management decisions of cirrhotic patients with HCC requiring TACE due to its value in predicting mortality and survival.

Introducción: El carcinoma hepatocelular (CHC) en cirrosis es diagnosticado, la mayoría de veces, cuando no es susceptible de tratamiento curativo. La quimioembolizacón transarterial (QETA) es una opción terapéutica paliativa con resultados heterogéneos. El HAP score estratifica a los pacientes que se beneficiarán con la primera QETA. Objetivo: Demostrar si el HAP score es un factor pronóstico del CHC tratado con QETA. Materiales y métodos: Estudio de cohortes retrospectivo en pacientes cirróticos con CHC y primera QETA en el Hospital Nacional Edgardo Rebagliati Martins, Lima-Perú, junio-2011 a junio-2013. Se aplicó el HAP score, y se observó la mortalidad y sobrevida con un seguimiento de 36 meses. Resultados: Se incluyeron 54 pacientes con edad de 67,7±9,9 años, 59,3% Child-Pugh A y 40,7% Child-Pugh B, MELD de 11±2,7; 51,9 y 40,7% fueron BCLC A y B, respectivamente; 66,7% tuvo tumor único y el 70,4% tumor predominante menor a 5 cm. Se clasificó como HAP A, B, C y D a 8, 14, 26 y 6 pacientes, respectivamente. La sobrevida general fue 19,5±11,2 meses; y 32,8±6,5 meses para HAP A, 24,9±14,8 meses para HAP B, 13,9±5,2 meses para HAP C y 14±6,6 meses para HAP D. A los 24 meses, la mortalidad para HAP C y D fue 100%. A los 36 meses, la sobrevida para HAP A y B fue 75 y 42,9%, respectivamente. Conclusiones: El HAP score es una herramienta útil que orienta al manejo del CHC tributario de QETA por su valor pronóstico de mortalidad y sobrevida.

Transplante hepático na hepatite delta: experiência da América do Sul / Liver transplantation in hepatitis delta: south america experience

ABSTRACT BACKGROUND: The Amazon region is one of the main endemic areas of hepatitis delta in the world and the only one related to the presence of genotype 3 of the delta virus. OBJECTIVE: To analyze the profile, mortality and survival of cirrhotic patients submitted to liver transplantation for chronic hepatitis delta virus and compare with those transplanted by hepatitis B virus monoinfection. METHODS: Retrospective, observational and descriptive study. From May 2002 to December 2011, 629 liver transplants were performed at the Walter Cantídio University Hospital, of which 29 patients were transplanted due to cirrhosis caused by chronic delta virus infection and 40 by hepatitis B chronic monoinfection. The variables analyzed were: age, sex, MELD score, Child-Pugh score, upper gastrointestinal bleeding and hepatocellular carcinoma occurrence before the transplantation, perioperative platelet count, mortality and survival. RESULTS: The Delta Group was younger and all came from the Brazilian Amazon Region. Group B presented a higher proportion of male patients (92.5%) compared to Group D (58.6%). The occurrence of upper gastrointestinal bleeding before transplantation, MELD score, and Child-Pugh score did not show statistical differences between groups. The occurrence of hepatocellular carcinoma and mortality were higher in the hepatitis B Group. The survival in 4 years was 95% in the Delta Group and 75% in the B Group, with a statistically significant difference (P=0.034). Patients with hepatitis delta presented more evident thrombocytopenia in the pre-transplantation and in the immediate postoperative period. CONCLUSION: The hepatitis by delta virus patients who underwent liver transplantation were predominantly male, coming from the Brazilian Amazon region and with similar liver function to the hepatitis B virus patients. They had a lower incidence of hepatocellular carcinoma, more marked perioperative thrombocytopenia levels and frequent episodes of upper gastrointestinal bleeding. Patients with hepatitis by delta virus had lower mortality and higher survival than patients with hepatitis B virus.

RESUMO CONTEXTO: A região Amazônica é uma das principais áreas endêmicas da hepatite delta no mundo e a única relacionada com a presença do genótipo 3 do vírus delta. OBJETIVO: Analisar o perfil, mortalidade e sobrevida dos pacientes cirróticos submetidos a transplante hepático por hepatite crônica pelo vírus delta e comparar com os transplantados pela monoinfecção do vírus da hepatite B. MÉTODOS: Estudo retrospectivo, observacional e descritivo. Entre maio de 2002 a dezembro de 2011, foram realizados 629 transplantes de fígado no Hospital Universitário Walter Cantídio, dos quais 29 pacientes foram transplantados por cirrose causada pela infecção crônica do vírus delta e 40 pela monoinfecção crônica da hepatite B. As variáveis analisadas foram: origem, idade, sexo, escore de MELD, classificação de Child-Pugh, ocorrência de hemorragia digestiva alta e carcinoma hepatocelular antes do transplante, número de plaquetas perioperatória, mortalidade e sobrevida. RESULTADOS: O Grupo Delta foi mais jovem e todos oriundos da região Amazônica Brasileira. O Grupo B apresentou maior proporção de pacientes do sexo masculino (92,5%) em relação ao Grupo D (58,6%). A ocorrência de hemorragia digestiva alta antes do transplante, escore de MELD e classificação de Child-Pugh não obtiveram diferenças estatísticas entre os grupos. A ocorrência de carcinoma hepatocelular e a mortalidade foram maiores no grupo com hepatite B. A sobrevida em 4 anos foi de 95% no Grupo delta e 75% no Grupo B com diferença estatisticamente significante (P=0,034). Pacientes com hepatite delta, apresentaram mais acentuada plaquetopenia no pré-transplante e no pós-operatório imediato. CONCLUSÃO: Os pacientes com hepatite por vírus delta submetidos ao transplante hepático eram predominantemente homens, vindos da região da Amazônia brasileira e com função hepática semelhante a dos pacientes com vírus da hepatite B. Apresentavam menor incidência de carcinoma hepatocelular, níveis de trombocitopenia perioperatória mais acentuados e episódios frequentes de hemorragia digestiva alta. Os pacientes com hepatite por vírus delta apresentaram menor mortalidade e maior sobrevida que os pacientes com vírus da hepatite B.

Higher values in liver elastography and meld score are mortality predictors on liver transplant waiting list / Valores mais altos na elastografia do fígado e pontuação meld são preditores de mortalidade na lista de espera do transplante de fígado

ABSTRACT Background: 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.

RESUMO Racional: A elastografia hepática tem sido relatada nos carcinomas hepatocelulares (CHC); porém, não é claro identificar o risco de morbimortalidade na lista de transplante hepático. Objetivo: Avaliar a morbimortalidade com elastografia transitória e escore MELD. Método: Pacientes adultos com cirrose na triagem para transplante de fígado foram incluídos no estudo. Resultados: Foram incluídos 103 pacientes (sem CHC n=58 (66%), CHC n=45 (44%). O escore MELD médio foi de 14,7±6,4, a hipertensão portal foi de 83,9% e o valor médio de elastografia transitória foi de 32,73±22,5 kPa. O valor médio de ARFI (Impulsão de Força de Radiação Acústica) do parênquima hepático foi de 1,98 (0,65-3,2) m/s e 2,16 (0,59-2,8) m/s no grupo CHC. O grupo CHC foi significativamente associado à infecção por vírus da hepatite C (OR 26,84, p<0,0001), níveis mais altos de alfa-feto proteína sérica (OR 5,51; p=0,015), hipertensão portal clínica (OR 0,25; p=0,032) e pontuação MELD semelhante (p=0,693). Os valores de AUROCs (Area Under the Receiver Operating Characteristics) mostraram sensibilidade e especificidade para a alfa-feto proteína sérica (limite de 9,1 ng/ml), valor elastografia transitória (valor de corte 9 kPa) e valor ARFI (valor de corte 2,56 m/s) de 50% e 86%, 92% e 17% e 21% e 92%, respectivamente. O grupo de sobrevivência apresentou valor elastografia transitória médio de 31,65±22,2 kPa vs. 50,87±20,9 kPa (p=0,098) e valores mais elevados de MELD (p=0,035). Conclusão: Valores mais elevados na elastografia do fígado e nos escores MELD predizem a mortalidade.

Adherence to BCLC recommendations for the treatment of hepatocellular carcinoma: impact on survival according to stage

OBJECTIVES: This study sought to assess the adherence of newly diagnosed hepatocellular carcinoma patients to the Barcelona Clinic Liver Cancer system treatment guidelines and to examine the impact of adherence on the survival of patients in different stages of the disease. METHODS: This study included all patients referred for the treatment of hepatocellular carcinoma between 2010 and 2012. Patients (n=364) were classified according to the Barcelona Clinic Liver Cancer guidelines. Deviations from the recommended guidelines were discussed, and treatment was determined by a multidisciplinary team. The overall survival curves were estimated with the Kaplan-Meier method and were compared using the log-rank test. RESULTS: The overall rate of adherence to the guidelines was 52%. The rate of adherence of patients in each scoring group varied as follows: stage 0, 33%; stage A, 45%; stage B, 78%; stage C, 35%; and stage D, 67%. In stage 0/A, adherent patients had a significantly better overall survival than non-adherent patients (hazard ratio=0.19, 95% confidence interval (CI): 0.09-0.42; p<0.001). Among the stage D patients, the overall survival rate was worse in adherent patients than in non-adherent patients (hazard ratio=4.0, 95% CI: 1.67-9.88; p<0.001), whereas no differences were observed in patients in stages B or C. CONCLUSIONS: The rate of adherence to the Barcelona Clinic Liver Cancer staging system in clinical practice varies according to clinical disease stage. Adherence to the recommended guidelines positively impacts survival, especially in patients with early-stage disease.

Avaliação do tratamento dos nódulos do hepatocarcinoma nos pacientes em lista de espera para transplante hepático / Evaluation of the treatment of the hepatocarcinoma nodules in the patients in waiting list for liver transplant

RESUMO Objetivo: comparar o resultado do transplante de fígado por hepatocarcinoma em pacientes submetidos ou não ao tratamento loco-regional e downstaging, em relação à sobrevida e risco de recidiva na fila de transplante. Métodos: estudo retrospectivo dos pacientes portadores de hepatocarcinoma submetidos a transplante hepático na região metropolitana de São Paulo, entre janeiro de 2007 e dezembro de 2011, a partir de doador falecido. A amostra foi constituída de 414 pacientes. Destes, 29 foram incluídos na lista por downstaging. Os demais 385 foram submetidos ou não ao tratamento loco-regional. Resultados: as análises dos 414 prontuários demonstraram um predomínio de pacientes do sexo masculino (79,5%) e com média de idade de 56 anos. O tratamento dos nódulos foi realizado em 56,4% dos pacientes em fila de espera para o transplante. O método mais utilizado foi a quimio-embolização (79%). Os pacientes submetidos ao tratamento loco-regional tiveram redução significativa no tamanho do maior nódulo (p<0,001). Não houve diferença estatística entre grupos com e sem tratamento loco-regional (p=0,744) e em relação à mortalidade entre pacientes incluídos no Critério de Milão ou ao downstaging (p=0,494). Conclusões: não houve diferença na sobrevida e ocorrência de recidiva associadas ao tratamento loco-regional. Os pacientes incluídos através do processo de downstaging apresentaram resultados de sobrevida comparáveis àqueles previamente classificados como Critério de Milão/Brasil.

ABSTRACT Objective: to compare the outcome of liver transplantation for hepatocarcinoma in submitted or not to locoregional treatment and downstaging regarding survival and risk of recurrence in transplant waiting list patients. Methods: retrospective study of patients with hepatocarcinoma undergoing liver transplantation in the metropolitan region of São Paulo, between January 2007 and December 2011, from a deceased donor. The sample consisted of 414 patients. Of these, 29 patients were included in the list by downstaging. The other 385 were submitted or not to locoregional treatment. Results: the analysis of 414 medical records showed a predominance of male patients (79.5%) with average age of 56 years. Treatment of the lesions was performed in 56.4% of patients on the waiting list for transplant. The most commonly used method was chemoembolization (79%). The locoregional patients undergoing treatment had a significant reduction in nodule size greater (p<0.001). There was no statistical difference between groups with and without locoregional treatment (p=0.744) and on mortality among patients enrolled in the Milan criteria or downstaging (p=0.494). Conclusion: there was no difference in survival and recurrence rate associated with locoregional treatment. Patients included by downstaging process had comparable survival results to those previously classified as Milan/Brazil criteria.

Retrospective analysis of hepatitis B virus chronic infection in 247 patients: clinical stages, response to treatment and poor prognostic factors

Abstract Background: Chronic hepatitis B is a major cause of cirrhosis, and the natural history of the disease has several clinical stages that should be thoroughly understood for the implementation of proper treatment. Nonetheless, curing the disease with antiviral treatment remains a challenge. Aims: To describe the clinical course, response to treatment, and poor prognostic factors in 247 hepatitis B virus chronic infection patients treated in a tertiary hospital in Brazil. Methods: This was a retrospective and observational study, by analyzing the medical records of HBV infected patients between January 2000 and January 2015. Results: Most patients were male (67.2%) and 74.1% were HBeAg negative. Approximately 41% had cirrhosis and 8.5% were hepatitis C virus coinfected. The viral load was negative after two years on lamivudine, entecavir and tenofovir in 86%, 90.6%, and 92.9% of the patients, respectively. The five-year resistance rates for lamivudine, adefovir, entecavir, and tenofovir were 57.5%, 51.8%, 1.9%, and 0%, respectively. The overall seroconversion rates were 31.2% for HBeAg and 9.4% for HBsAg. Hepatocellular carcinoma was diagnosed in 9.7% of patients, liver transplantation was performed in 9.7%, and overall mortality was 10.5%. Elevations of serum alanine aminotransferase (p = 0.0059) and viral load (p < 0.0001) were associated with progression to liver cirrhosis. High viral load was associated with progression to hepatocellular carcinoma (p < 0.0001). Significant risk factors associated with death were elevated alanine aminotransferase (p = 0.0039), liver cirrhosis (p < 0.0001), high viral load (p = 0.007), and hepatocellular carcinoma (p = 0.0008). HBeAg positive status was not associated with worse outcomes, and treatment may have been largely responsible. Conclusions: Elevations of viral load and serum alanine aminotransferase may select patients with worse prognosis, especially progression to cirrhosis and hepatocellular carcinoma, which were strongly association with death.

Surveillance for Hepatocellular Carcinoma Reduces Mortality: an Inverse Probability of Treatment Weighted Analysis

ABSTRACT Background. Evidence supporting benefit of hepatocellular carcinoma (HCC) surveillance in reducing mortality is not well-established. The effect of HCC surveillance in reducing mortality was assessed by an inverse probability of treatment weighting (IPTW)- based analysis controlled for inherent bias and confounders in observational studies. Material and methods. This retrospective cohort study was conducted on 446 patients diagnosed with HCC between 2007 and 2013 at a major referral center. Surveillance was defined as having at least 1 ultrasound test within a year before HCC diagnosis. Primary outcome was survival estimated using the Kaplan-Meier method with lead-time bias adjustment and compared using the log-rank test. Hazard ratio (HR) and 95% confidence interval (Cl) were computed using conventional Cox and weighted Cox proportional hazards analysis with IPTW adjustment. Results. Of the 446 patients, 103 (23.1%) were diagnosed with HCC through surveillance. The surveillance group had more patients with the Barcelona-Clinic Liver Cancer stage A (80.6% vs. 33.8%, P < 0.0001), more patients eligible for potentially curative treatment (73.8% vs. 44.9%, P < 0.0001), and longer median survival (49.6 vs. 15.9 months, P < 0.0001). By conventional multivariate Cox analysis, HR (95% Cl) of surveillance was 0.63 (0.45-0.87), P = 0.005. The estimated effect of surveillance remained similar in the IPTW-adjusted Cox analysis (HR: 0.57; 95% Cl: 0.43-0.76, P < 0.001). Conclusions. HCC surveillance by ultrasound is associated with a 37% reduction in mortality. Even though surveillance is recommended in all guidelines, but in practice, it is underutilized. Interventions are needed to increase surveillance rate for improving HCC outcome.

Liver Transplantation for Hepatocellular Carcinoma: Impact of Wait Time at a Single Center

ABSTRACT Introduction and aim. Liver transplantation (LT) provides durable survival for hepatocellular carcinoma (HCC). However, there is continuing debate concerning the impact of wait time and acceptable tumor burden on outcomes after LT. We sought to review outcomes of LT for HCC at a single, large U.S. center, examining the influence of wait time on post-LT outcomes. Material and methods. We reviewed LT for HCC at Mayo Clinic in Florida from 1/1/2003 until 6/30/2014. Follow up was updated through 8/1/ 2015. Results. From 2003-2014,978 patients were referred for management of HCC. 376 patients were transplanted for presumed HCC within Milan criteria, and the results of these 376 cases were analyzed. The median diagnosis to LT time was 183 days (8 - 4,337), and median transplant list wait time was 62 days (0 -1815). There was no statistical difference in recurrence-free or overall survival for those with wait time of less than or greater than 180 days from diagnosis of HCC to LT. The most important predictor of long term survival after LT was HCC recurrence (HR: 18.61, p < 0.001). Recurrences of HCC as well as survival were predicted by factors related to tumor biology, including histopathological grade, vascular invasion, and pre-LT serum alpha-fetoprotein levels. Disease recurrence occurred in 13%. The overall 5-year patient survival was 65.8%, while the probability of 5-year recurrence-free survival was 62.2%. Conclusions. In this large, single-center experience with long-term data, factors of tumor biology, but not a longer wait time, were associated with recurrence-free and overall survival.

The Impact of Early Dermatologic Events in the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib

ABSTRACT Background 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 evaluated 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.

Practical Considerations of Real Life of Hepatocellular Carcinoma in a Tertiary Center of Brazil

ABSTRACT Background. Hepatocellular carcinoma (HCC) is the most common malignancy that develops in cirrhotic livers. Its clinical and epidemiological characteristics and mortality rates vary according to geographical region. The objective of this study was to evaluate the clinical profile, epidemiological characteristics, laboratory parameters, treatment and survival of patients with HCC. Material and methods. Patients with HCC seen between 2000 and 2012 were studied. The Kaplan-Meier method was used for survival analysis according to variables in question. Results. The study included 247 patients with a mean age of 60 ± 10 years. There was a predominance of males (74%). The main etiologies of HCC were HCV infection (55%), excessive alcohol consumption (12%), and HBV infection (8%). Liver cirrhosis was present in 92% of cases. The mean tumor number and diameter were 2 and 5 cm, respectively. Patients meeting the Milan criteria corresponded to 43% of the sample. Liver transplantation was performed in 22.4% of patients of the Milan subset and in 10% of the whole sample. The overall mean survival was 60 months, with a 1-, 3- and 5-year survival probability of 74%, 40% and 29%, respectively. Lower survival was observed among patients with alcoholic etiology. Survival was higher among patients submitted to liver transplantation (P < 0.001), TACE (P < 0.001), or any kind of treatment (P < 0.001). However, no difference was found for surgical resection (P = 0.1) or sorafenib (P = 0.1). Conclusion. Patients with HCC were mainly older men diagnosed at an advanced stage. Treatment was associated with better overall survival, but few patients survived to be treated.

Combination of TACE and Sorafenib Improves Outcomes in BCLC Stages B/C of Hepatocellular Carcinoma: A Single Centre Experience

ABSTRACT Background & Aim. Transarterial chemoembolization (TACE) or sorafenib is recommended for hepatocellular carcinoma BCLC stages B and C respectively. We studied the role of combination of TACE and sorafenib in BCLC stages B/C. Material and methods. We undertook an observational study on a cohort of cirrhotics with HCC from August 2010 through October 2014. Patients in BCLC stages B/C who had received TACE and/or sorafenib were included. mRECIST criteria were used to assess tumor response. The primary end point was overall survival. Results. Out of 124 patients, 47.6% were in BCLC-B and 52.4% in BCLCC. Baseline characteristics were comparable. The predominant etiology was cryptogenic (37.2% and 38.5%, p = NS). 49.1% in BCLC-B and 56.9% in BCLC-C had received TACE+sorafenib. In BCLC-B, the overall survival improved from 9 months (95% CI 6.3-11.7) using TACE only to 16 months (95% CI 12.9-19.1) using TACE+sorafenib (p < 0.05). In BCLC-C, addition of TACE to sorafenib improved the overall survival from 4 months (95%CI 3-5) to 9 months (95%CI 6.8-11.2) (p < 0.0001). As per mRECIST criteria, patients on TACE+sorafenib had reduced progressive disease (37.8% vs. 83.3%), improved partial response (43.2% vs. 3.3%) and one had complete response compared to those on sorafenib alone (p < 0.0001) in BCLC-C but not in BCLC-B group. Hand foot syndrome was noted in 27.7% patients on sorafenib and post TACE syndrome in 80.2% patients, but both were reversible. No major adverse events were noted. Conclusion. TACE+sorafenib was more effective than TACE or sorafenib alone in HCC BCLC stages B or C with a significant survival benefit and improved tumour regression especially in BCLC-C patients.

Sarcopenia Predicts Reduced Survival in Patients with Hepatocellular Carcinoma at First Diagnosis

Abstract: Background. Sarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis. Aim. To assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center. Material and methods. Abdominal computed tomography of 92 consecutive hepatocellular carcinoma cirrhotic patients, enrolled and followed from 2004 to 2014, were retrospectively studied with a software analyzing the cross-sectional areas of muscles at third lumbar vertebra level. Data was normalized for height, skeletal muscle index (SMI) calculated and presence of Sarcopenia measured. Sarcopenia was defined by SMI ≤ 41 cm2/m2 for women and ≤ 53 cm2/m2 for men with body mass index (BMI) ≥ 25, and ≤ 43 cm2/m2 for men and women with BMI < 25, respectively. Results. Median age at diagnosis was 71.9 years (30.7-86.4) and BMI 24.7 (17.5-36.7), comparable in women 23.1, (17.5-36.7) and men 24.7 (18.4-36.7). A class of CHILD score and BCLC A prevailed (55.4% and 41.3%, respectively); metastatic disease was found in 12% of cases. Sarcopenia was present in 40.2% of cases, mostly in females (62.9%; p = 0.005). Mean overall survival was reduced in sarcopenic patients, 66 (95% CI 47 to 84) vs. 123 (95% CI 98 to 150) weeks (p = 0.001). At multivariate analysis, sarcopenia was a predictor of reduced overall survival, independent of age (p = 0.0027). Conclusions. This retrospective study shows high prevalence of sarcopenia among cirrhotic patients with hepatocellular carcinoma. Presence of sarcopenia was identified as independent predictor of reduced overall survival. As easily measurable by CT, sarcopenia should be determined for prognostic purposes in this patient population.

Liver transplantation for carcinoma hepatocellular in Aão Paulo: 414 cases by the Milan/Brazil criteria / O transplante hepático por hepatocarcinoma na era meld em São Paulo: análise de 414 casos transplantados pelo critério de Milão/Brasil

ABSTRACT Background: The criterion of Milan (CM) has been used as standard for indication of liver transplantation (LTx) for hepatocellular carcinoma (HCC) worldwide for nearly 20 years. Several centers have adopted criteria expanded in order to increase the number of patients eligible to liver transplantation, while maintaining good survival rates. In Brazil, since 2006, the criterion of Milan/Brazil (CMB), which disregards nodules <2 cm, is adopted, including patients with a higher number of small nodules. Aim: To evaluate the outcome of liver transplantation within the CMB. Methods: The medical records of patients with HCC undergoing liver transplantation in relation to recurrence and survival by comparing CM and CMB, were analyzed. Results: 414 LTx for HCC, the survival at 1 and 5 years was 84.1 and 72.7%. Of these, 7% reached the CMB through downstaging, with survival at 1 and 5 years of 93.1 and 71.9%. The CMB patient group that exceeded the CM (8.6%) had a survival rate of 58.1% at five years. There was no statistical difference in survival between the groups CM, CMB and downstaging. Vascular invasion (p<0.001), higher nodule size (p=0.001) and number of nodules >2 cm (p=0.028) were associated with relapse. The age (p=0.001), female (p<0.001), real MELD (p<0.001), vascular invasion (p=0.045) and number of nodes >2 cm (p<0.014) were associated with worse survival. Conclusions: CMB increased by 8.6% indications of liver transplantation, and showed survival rates similar to CM.

RESUMO Racional: O critério de Milão (CM) vem sendo utilizado como padrão para indicação do transplante hepático (TxH) por hepatocarcinoma (HCC) em todo mundo há quase 20 anos. Diversos centros têm adotado critérios expandidos com intuito de aumentar o número de pacientes candidatos ao transplante, mantendo bons índices de sobrevida. No Brasil, desde 2006, o critério de Milão/Brasil (CMB), que desconsidera nódulos <2 cm, é adotado, incluindo pacientes com maior número de nódulos pequenos. Objetivo: Avaliar o resultado do transplante hepático dentro do CMB. Métodos: Foram analisados os prontuários dos pacientes com HCC submetidos ao TxH em relação à recidiva e sobrevida através da comparação entre CM e CMB. Resultados: Em 414 TxH por HCC, a sobrevida em 1 e 5 anos foi de 84,1 e 72,7%. Destes, 7% atingiram o CMB através de downstaging, com sobrevida em 1 e 5 anos de 93,1 e 71,9%. O grupo de pacientes do CMB que excederam o CM (8,6%) teve sobrevida de 58,1% em cinco anos. Não houve diferença estatística na sobrevida entre os grupos CM, CMB e downstaging. A invasão vascular (p<0,001), tamanho do maior nódulo (p=0,001) e número de nódulos >2 cm (p=0,028) associaram-se com recidiva. A idade (p=0,001), sexo feminino (p<0,001), MELD real (p<0,001), invasão vascular (p=0,045) e o número de nódulos >2 cm (p<0,014) estiveram associados com a piora na sobrevida. Conclusões: O CMB aumentou em 8,6% as indicações de TxH e apresentou índices de sobrevida semelhantes ao CM.