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.

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.

An age-period-cohort analysis of mortality rates for stomach, colorectal, liver, and lung cancer among prefectures in Japan, 1999-2018

BACKGROUND@#Although change in the birth cohort effect on cancer mortality rates is known to be highly associated with the decreasing rates of age-standardized cancer mortality rates in Japan, the differences in the trends of cohort effect for representative cancer types among the prefectures remain unknown. This study aimed to investigate the differences in the decreasing rate of cohort effects among the prefectures for representative cancer types using age-period-cohort (APC) analysis.@*METHODS@#Data on stomach, colorectal, liver, and lung cancer mortality for each prefecture and the population data from 1999 to 2018 were obtained from the Vital Statistics in Japan. Mortality data for individuals aged 50 to 79 years grouped in 5-year increments were used, and corresponding birth cohorts born 1920-1924 through 1964-1978 were used for analysis. We estimated the effects of age, period, and cohort on each type of mortality rate for each prefecture by sex. Then, we calculated the decreasing rates of cohort effects for each prefecture. We also calculated the mortality rate ratio of each prefecture compared with all of Japan for cohorts using the estimates.@*RESULTS@#As a result of APC analysis, we found that the decreasing rates of period effects were small and that there was a little difference in the decreasing rates among prefectures for all types of cancer among both sexes. On the other hand, there was a large difference in the decreasing rates of cohort effects for stomach and liver cancer mortality rates among prefectures, particularly for men. For men, the decreasing rates of cohort effects in cohorts born between 1920-1924 and 1964-1978 varied among prefectures, ranging from 4.1 to 84.0% for stomach cancer and from 20.2 to 92.4% for liver cancers, respectively. On the other hand, the differences in the decreasing rates of cohort effects among prefectures for colorectal and lung cancer were relatively smaller.@*CONCLUSIONS@#The decreasing rates of cohort effects for stomach and liver cancer varied widely among prefectures. It is possible that this will influence cancer mortality rates in each prefecture in the future.

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.

Mortalidade por Câncer de Fígado e Vias Biliares no Brasil: Tendências e Projeções até 2030 / Mortality due to Malignant Neoplasms of the Liver and Bile Ducts in Brazil: Trends and Projections until 2030 / Mortalidad por Cáncer de Hígado y Biliar en Brasil: Tendencias y Proyecciones hasta 2030

Introdução: A neoplasia de fígado e vias biliares intra-hepáticas é a sétima mais incidente e representa a segunda maior causa de morte por câncer no mundo. Sendo assim, é crucial compreender a epidemiologia dessa doença, no que diz respeito às tendências temporais da mortalidade e da carga que essa doença apresentará no futuro. Objetivo: Analisar a tendência da mortalidade por câncer de fígado e vias biliares no Brasil e calcular as projeções de mortalidade até 2030. Método: Estudo ecológico baseado em óbitos por neoplasia maligna de fígado e vias biliares intra-hepáticas (C22) ocorridos no Brasil no período de 2001 a 2015 e registrados no Sistema de Informação sobre Mortalidade. As tendências de mortalidade foram analisadas pela regressão Joinpoint; para o cálculo das projeções, foi utilizado o programa Nordpred. Resultados: Para o sexo feminino, houve redução das taxas de mortalidade nas Regiões Centro-Oeste, Sudeste e Norte no Brasil; para o sexo masculino, essas Regiões apresentaram tendências de aumento, porém não significativo. As taxas de mortalidade para o sexo feminino apresentarão reduções no futuro, com destaque para as taxas das Regiões Norte e Nordeste, com redução de cerca de 30% até 2030. Para o sexo masculino, haverá acréscimo de 12% nas taxas de mortalidade para a Região Sul. Conclusão: A mortalidade por câncer de fígado e vias biliares no Brasil apresenta tendência de redução para o sexo feminino e estabilidade para o sexo masculino, e essa característica será mantida nas próximas décadas.

Introduction: Intrahepatic liver and biliary tract neoplasm is the seventh most incident and represents the second leading cause of cancer death in the world. Therefore, it is crucial to understand the epidemiology of this disease in relation to the temporal trends of mortality and burden that this disease will present in the future. Objective: To analyze the trend in mortality by liver and biliary cancer in Brazil and to calculate mortality projections until 2030. Method: An ecological study based in deaths from malignant liver and bile duct cancer (C22) occurred in Brazil from 2001 to 2015 and recorded in the Mortality Information System. Mortality trends were analyzed by Joinpoint regression, while for the calculation of projections, the Nordpred program was used. Results: For females, there was a reduction in mortality rates in the Midwest, Southeast and North regions in Brazil; for males, these regions showed increasing but no significant trends. Mortality rates for females will decrease in the future, with emphasis for the rates in the North and Northeast, with a reduction of about 30% by 2030. For males, there will be a 12% increase in mortality rates for the Southern Region. Conclusion: Mortality due to liver and biliary cancer in Brazil shows a tendency of reduction for females and stability for males, and this characteristic will be maintained in the coming decades.

Introducción: La neoplasia intrahepática del hígado y del tracto biliar es el séptimo cáncer más común y representa la segunda causa principal de muerte por cáncer en el mundo. Por lo tanto, es crucial comprender la epidemiología de esta enfermedad con respecto a las tendencias temporales de mortalidad y carga que esta enfermedad presentará en el futuro. Objetivo: Analizar la tendencia de la mortalidad por cáncer de hígado y biliar en Brasil y calcular las proyecciones de mortalidad para 2030. Método: Un estudio ecológico basado en las muertes por cáncer de hígado y conducto biliar (C22) en Brasil en el de 2001 a 2015 y registrado en el Sistema de Información de Mortalidad. Las tendencias de mortalidad se analizaron mediante regresión de Joinpoint, mientras que para el cálculo de las proyecciones se utilizó el programa Nordpred. Resultados: Para las mujeres, hubo una reducción en las tasas de mortalidad en las regiones del Medio Oeste, Sudeste y Norte no Brasil; para los hombres, estas regiones mostraron tendencias crecientes, pero no significativas. Las tasas de mortalidad para las mujeres disminuirán en el futuro, con énfasis en las tasas en el norte y el noreste, con una reducción de alrededor del 30% para 2030. Para los hombres, habrá un aumento del 12% en las tasas de mortalidad para las mujeres. Conclusión: La mortalidad por cáncer de hígado y biliar en Brasil muestra una tendencia a la reducción de las mujeres y la estabilidad de los hombres, y esta característica se mantendrá en las próximas décadas.

Impacto da lista de espera para AADs em pacientes cirróticos por VHC / Waiting daas list mortality impact in hcv cirrhotic patients

ABSTRACT BACKGROUND: The infection for the hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality through its evolution to liver cirrhosis, end-stage liver complications and hepatocellular carcinoma. Currently, the new drugs for the HCV infection, based on direct antiviral agents, have changed the outcomes in this setting. OBJECTIVE: To assess death incidence, during the wait for the treatment with the new drugs, and to analyze which independent variable (age, sex, ascite, HDA, albumin, α-fetoprotein, platelets and Meld score) had relation with death. METHODS: Prospective study with cirrhotic patients by HCV. Inclusion: cirrhotic patients by hepatic biopsy (METAVIR), clinic or image, detectable RNA (HCV). Exclusion: Other stages of hepatic fibrosis and hepatocellular carcinoma. Descriptive statistic in continue variables. Fisher Exact and Kaplan Meier and Cox Regression Analysis to assess the association of variables studied with death. P<0.05. RESULTS: A total of 129 patients were included. Of this, 73% were men. Mean age was 57.8±12.1, albumin of 3.5±0.6 mg/dL, platelets of 123.4±59.6 and Meld score of 10.59±3.56. The time of observation was 11.2±3.26 months, and the number of death 9/129 (6,9%). The Kaplan-Meier showed association between death with albumin lower than 2.9 (0.0006), MELD score higher than 15 (0.007) and α-fetoprotein higher than 40 ng/mL (<0.0001). Adjusted Cox Regression Analysis showed that α-fetoprotein higher than 40 ng/ml could be considered an independent risk for death. CONCLUSION: We conclude that, patients with advanced cirrhosis should be prioritized for treatment with direct antiviral agents.

RESUMO CONTEXTO: A infecção pelo vírus da hepatite C (VHC) é uma das principais causas de morbidade e mortalidade relacionada ao fígado, através de sua evolução para cirrose hepática, complicações hepáticas em estágio terminal e carcinoma hepatocelular. Atualmente, os novos fármacos para a infecção pelo VHC, baseados nos novos antivirais de ação direta (AADs), modificaram os resultados nesse cenário. OBJETIVO: Avaliar a incidência de morte, durante a espera pelo tratamento com as novas drogas, e analisar quais variáveis independentes (idade, sexo, ascite, HDA, albumina, α-fetoproteína, plaquetas e escore de MELD) tiveram relação com o óbito. MÉTODOS: Estudo prospectivo com pacientes cirróticos pelo VHC. Inclusão: pacientes cirróticos por biópsia hepática (METAVIR), clínica ou imagem, RNA detectável (VHC). Exclusão: Outras fases de fibrose hepática e carcinoma hepatocelular. Estatística descritiva em variáveis contínuas. Exato de Fisher e Kaplan Meier e Análise de Regressão de Cox para avaliar a associação das variáveis estudadas com o óbito. P<0,05. RESULTADOS: Um total de 129 pacientes foram incluídos. Destes, 73% eram homens. A idade média foi de 57,8±12,1, a albumina de 3,5±0,6 mg/dL, as plaquetas de 123,4±59,6 e o escore de MELD de 10,59±3,56. O tempo de observação foi de 11,2±3,26 meses e o número de mortes 9/129 (6,9%). O Kaplan-Meier mostrou associação entre o óbito com albumina menor que 2,9 (0,0006), escore MELD maior que 15 (0,007) e α-fetoproteína maior que 40 ng/mL (<0,0001). A análise de regressão de Cox ajustada mostrou que α-fetoproteína maior que 40 ng/mL poderia ser considerada um risco independente para morte. CONCLUSÃO: Concluímos que pacientes com cirrose avançada devem ser priorizados para tratamento com AADs.

Metástase hepática colorretal metacrônica tem melhor prognóstico - é verdade? / Metachronous colorectal liver metastases has better prognosis - is it true?

ABSTRACT BACKGROUND: Liver metastases from colorectal cancer are an important public health problem due to the increasing incidence of colorectal cancer worldwide. Synchronous colorectal liver metastasis has been associated with worse survival, but this prognosis is controversial. OBJECTIVE: The objective of this study was to evaluate the recurrence-free survival and overall survival between groups of patients with metachronous and synchronous colorectal hepatic metastasis. METHODS: This was a retrospective analysis of medical records of patients with colorectal liver metastases seen from 2013 to 2016, divided into a metachronous and a synchronous group. The Cox regression model and the Kaplan-Meier method with log-rank test were used to compare survival between groups. RESULTS: The mean recurrence-free survival was 9.75 months and 50% at 1 year in the metachronous group and 19.73 months and 63.3% at 1 year in the synchronous group. The mean overall survival was 20.00 months and 6.2% at 3 years in the metachronous group and 30.39 months and 31.6% at 3 years in the synchronous group. Patients with metachronous hepatic metastasis presented worse overall survival in multivariate analysis. The use of biological drugs combined with chemotherapy was related to the best overall survival prognosis. CONCLUSION: Metachronous colorectal hepatic metastasis was associated with a worse prognosis for overall survival. There was no difference in recurrence-free survival between metachronous and synchronous metastases.

RESUMO CONTEXTO: As metástases hepáticas de câncer colorretal representam um importante problema de saúde pública devido à incidência crescente de câncer colorretal pelo mundo. A metástase hepática colorretal sincrônica está associada a pior sobrevida, no entanto, o pior prognóstico é assunto controverso. OBJETIVO: O objetivo do estudo foi avaliar a sobrevida livre de recorrência e a sobrevida global entre os grupos de pacientes com metástase hepática colorretal metacrônica e sincrônica. MÉTODO: Análise retrospectiva através de revisão de prontuários de pacientes com metástase hepática colorretal atendidos no período de 2013 a 2016, divididos em grupos metacrônico e sincrônico. Foram utilizados o modelo de regressão de Cox e o método de Kaplan-Meier com teste de Log-rank para comparação de sobrevida entre os grupos. RESULTADOS: A média de sobrevida livre de recorrência no grupo metacrônico foi de 9,75 meses e 50% em 1 ano, e no grupo sincrônico 19,73 meses e 63,3% em 1 ano. A média de sobrevida global no grupo metacrônico foi de 20,00 meses e 6,2% em 3 anos, e no grupo sincrônico 30,39 meses e 31,6% em 3 anos. Os pacientes com metástase hepática metacrônica apresentaram pior sobrevida global em análise multivariada. O uso de drogas biológicas associadas ao tratamento quimioterápico foi relacionado ao melhor prognóstico em sobrevida global. CONCLUSÃO: A metástase hepática colorretal metacrônica foi associada a pior prognóstico na sobrevida global. Não houve diferença na sobrevida livre de recorrência entre as metástases metacrônica e sincrônica.

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.

Critical evaluation of long-term results of malignant hepatic tumors treated by means curative laparoscopic hepatectomy / Avaliação crítica dos resultados em longo prazo de tumores hepáticos malignos tratados por hepatectomia laparoscópica curativa

ABSTRACT Background: Laparoscopic hepatectomy has presented great importance for treating malignant hepatic lesions. Aim: To evaluate its impact in relation to overall survival or disease free of the patients operated due different hepatic malignant tumors. Methods: Thirty-four laparoscopic hepatectomies were performed in 31 patients with malignant neoplasm. Patients were distributed as: Group 1 - colorectal metastases (n=14); Group 2 - hepatocellular carcinoma (n=8); and Group 3 - non-colorectal metastases and intrahepatic cholangiocarcinoma (n=9). The conversion rate, morbidity, mortality and tumor recurrence were also evaluated. Results: Conversion to open surgery was 6%; morbidity 22%; postoperative mortality 3%. There was tumor recurrence in 11 cases. Medians of overall survival and disease free survival were respectively 60 and 46 m; however, there was no difference among studied groups (p>0,05). Conclusion: Long-term outcomes of laparoscopic hepatectomy for treating hepatic malignant tumors are satisfactory. There is no statistical difference in relation of both overall and disease free survival among different groups of hepatic neoplasms.

RESUMO Racional: A hepatectomia laparoscópica tem apresentado grande importância no tratamento das lesões hepáticas malignas. Objetivo: Avaliar o impacto dela realizada por uma única equipe em relação à sobrevida global e tempo livre de doença nos diferentes tumores malignos hepáticos. Métodos: Foram realizadas 34 hepatectomias laparoscópicas em 31 pacientes com neoplasia maligna. Os doentes foram distribuídos em: Grupo 1 - metástases colorretais (n=14); Grupo 2 - carcinoma hepatocelular (n=8) e Grupo 3 - metástases não-colorretais e colangiocarcinoma intra-hepático (n=9). As curvas de sobrevida e sobrevida livre de doença foram estimadas. Foram avaliadas também a taxa de conversão, morbidade, mortalidade e recorrência tumoral. Resultados: A taxa de conversão foi de 6%; a morbidade de 22%; a mortalidade pós-operatória de 3%; recorrência tumoral em 11 casos. As medianas de sobrevida global e de sobrevida livre de doença foram respectivamente de 60 e 46 m, contudo não houve diferença entre os grupos estudados (p>0,05). Conclusão: Os resultados em longo prazo da hepatectomia laparoscópica para o tratamento de tumores malignos hepáticos são satisfatórios. Não houve diferença estatisticamente significante quanto às sobrevidas global e livre de doença nos diferentes grupos de neoplasia tratada.

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.

Estado actual de la epidemiología, diagnóstico, tratamiento y control de la hepatitis C / Present status of epidemiology, diagnosis, treatment and control of hepatitis C

La hepatitis C, infección producida por el virus de la hepatitis C (VHC), que se transmite por sangre, es una causa principal de hepatitis crónica, cirrosis y cáncer del hígado a nivel mundial. La mortalidad, incidencia y prevalencia de las infecciones por VHC han ido en aumento, superando en muchos casos la de otras infecciones como el VIH. Más de 71 millones de personas en el mundo padecen hepatitis C crónica, pero el 80% desconoce que tiene la infección y solamente 1% ha recibido tratamiento, pese a que existen medicamentos que curan la infección en más del 90% de los casos y pueden disminuir el riesgo de las complicaciones que llevan a la muerte. En el 2016 los países miembros de la Organización Mundial de la Salud (OMS) acordaron la primera estrategia mundial del sector salud contra la hepatitis víricas 2016-2021, y para su implementación es necesario concienciar a todos los involucrados acerca de la magnitud de las hepatitis virales. Esta revisión aborda aspectos epidemiológicos, microbiológicos y clínicos con el propósito de presentar un panorama general de la situación actual de la hepatitis C a nivel mundial y nacional.

Hepatitis C, an infection produced by hepatitis C virus (HCV), is transmitted by blood and is a leading cause of chronic hepatitis, cirrhosis and liver cancer around the world. HCV infection mortality, incidence and prevalence have been increasing, in many cases exceeding other infections like HIV. Globally, more than 71 million people suffer from chronic hepatitis C but 80% are unaware that they are infected and only 1% have been treated even though there are medicines that can cure the infection in more than 90% of the cases and also can reduce the risk of complications that can lead to death. In 2016, countries belonging to the World Health Organization (WHO) adopted the first Global Health Sector Strategy on Viral Hepatitis 2016-2021, for its implementation, it is necessary to raise awareness among all concerning parties of the magnitude of viral hepatitis. This review addresses epidemiological, microbiological and clinical aspects with the purpose of presenting a general view of the current situation of hepatitis C at the national and global levels.

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.

Mortalidade por cirrose, câncer hepático e transtornos devidos ao uso de álcool: Carga Global de Doenças no Brasil, 1990 e 2015 / Mortality due to cirrhosis, liver cancer, and disorders attributed to alcohol use: Global Burden of Disease in Brazil, 1990 and 2015

RESUMO: Introdução: O uso de álcool é um dos principais fatores de risco preveníveis para mortalidade ou incapacidade prematuras. Objetivo: Descrever as estimativas de mortalidade e anos de vida perdidos por morte prematura (YLL) por cirrose, câncer hepático e transtornos devidos ao uso de álcool no Brasil e suas unidades da federação (UFs), em 1990 e 2015. Métodos: Estudo descritivo com dados do estudo de Carga Global de Doenças (2015) e do Sistema de Informações sobre Mortalidade (SIM). Modelos estatísticos foram empregados para obter estimativas corrigidas de mortalidade pelas causas selecionadas. As taxas de mortalidade foram padronizadas por idade (TMPI). Resultados: Em 1990, foram estimados 16.226 óbitos para as 3 condições (17,0/100 mil habitantes), enquanto em 2015 foram 28.337 (15,7/100 mil habitantes). Houve redução da mortalidade (por 100 mil habitantes) por cirrose (de 11,4 para 9,5) e estabilidade por câncer hepático (1,5 e 1,9) e transtornos devidos ao uso de álcool (4,1 e 4,3). As TMPI foram 5,1 vezes maiores entre os homens, e as 5 UFs com maiores TMPI e YLL foram da Região Nordeste: Sergipe, Ceará, Pernambuco, Paraíba e Alagoas. As taxas de mortalidade e de YLL pelas três condições estudadas ascenderam no ranking das causas de óbito, em ambos os sexos, exceto a cirrose no feminino. Conclusão: As três condições estudadas são responsáveis por importante carga de mortalidade prematura no Brasil, principalmente entre homens e residentes na região nordeste. Esses resultados reforçam a necessidade de políticas públicas para o enfrentamento ao consumo nocivo do álcool no Brasil.

ABSTRACT: Introduction: Alcohol use is one of the main preventable risk factors affecting mortality and premature disability. Objective: To describe the estimates of mortality and years of life lost as a result of premature death (YLL) due to cirrhosis, liver cancer, and disorders attributed to alcohol use in Brazil and its federated units in 1990 and 2015. Methods: Descriptive study using data from the Global Burden of Disease Study (2015) and the Mortality Information System (SIM). Statistical models were used to obtain corrected mortality estimates for selected causes. Rates were standardized by age. Results: In 1990, 16,226 deaths were estimated for the three conditions (17.0/100 thousand inhabitants), while in 2015 there were 28,337 deaths (15.7/100 thousand inhabitants). There was a reduction in mortality (per 100 thousand) due to cirrhosis (from 11.4 to 9.5), stability in mortality rates related to liver cancer (1.5 and 1.9), and stability in mortality rates caused by alcohol use disorders (4.1 and 4.3). Mortality rates were 5.1 times higher among men, and the five states with the highest mortality rates and YLL were from the Northeast Region: Sergipe, Ceará, Pernambuco, Paraíba, and Alagoas. Mortality and YLL rates for the three conditions studied increased in the ranking of causes of death in both sexes, with the exception of cirrhosis in the female population. Conclusion: The three conditions studied are responsible for a significant burden of premature mortality in Brazil, especially among men and residents of the northeast region. These results reinforce the urgent need for public policies that address harmful alcohol consumption in Brazil.