Colangiocarcinoma y hepatocolangiocarcinoma combinado en pacientes con cirrosis / Cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma in cirrhotic patients

Background: Cholangiocarcinoma (CCA) is a primary hepatic tumor, frequently found in patients with liver cirrhosis and biliary tract diseases. Its varieties include isolated CCA or "combined hepatocellular-cholangiocarcinoma" (cHCC-CCA). The latter is uncommon, with poorly defined diagnostic criteria and natural history. Aim: To characterize patients with cirrhosis with a pathological diagnosis of CCA and cHCC-CCA. Material and Methods: Forty-nine liver biopsies with a pathological diagnosis of CCA were reviewed. The clinical records of patients were reviewed to fetch demographic variables, etiology of cirrhosis and clinical presentation. Results: Eight of the 49 patients had cirrhosis (16% of CCA biopsies reviewed). Their median age was 64 (27-71) years and five were females. Four patients had CCA, three patients cHCC-CCA and one had a bifocal tumor. Patients in the CCA group were more commonly symptomatic. Alpha-fetoprotein and CA 19-9 levels were elevated in one of eight and four of six patients, respectively. Within 12 months from diagnosis, five of eight patients died. Conclusions: In most of these cases, the diagnosis of cHCC-CCA and CCA was made in the liver explant study without previous imaging diagnosis. This reinforces the usefulness of the histological study, in specific cases, prior to liver transplantation and emphasizes the importance of systematic explant exploration in these cases.

Non-alcoholic steatohepatitis and risk of hepatocellular carcinoma / 中华医学杂志(英文版)

The emergence of non-alcoholic fatty liver disease (NAFLD) as the leading chronic liver disease worldwide raises some concerns. In particular, NAFLD is closely tied to sedentary lifestyle habits and associated with other metabolic diseases, such as obesity and diabetes. At the end of the disease spectrum, non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma (HCC), representing a serious health problem to modern society. Recently, an increasing number of HCC cases originating from this progressive disease spectrum have been identified, with different levels of severity and complications. Updating the current guidelines by placing a bigger focus on this emerging cause and highlighting some of its unique features is necessary. Since, the drivers of the disease are complex and multifactorial, in order to improve future outcomes, having a better understanding of NASH progression into HCC may be helpful. The risks that can promote disease progression and currently available management strategies employed to monitor and treat NASH-related HCC make up the bulk of this review.

Risco de Recorrência do Carcinoma Hepatocelular após o Uso de Antivirais de Ação Direta no Tratamento de Hepatite C: Revisão Sistemática e Metanálise / Risk of Hepatocellular Carcinoma Recurrence After the Use of Direct-Acting Antivirals in the Treatment of Hepatitis C: Systematic Review and Metanalysis / Riesgo de Recurrencia del Carcinoma Hepatocelular tras el Uso de Antivirales de Acción Directa en el Tratamiento de la Hepatitis C: Revisión Sistemática y Metanálisis

Introdução: A hepatite C está associada ao desenvolvimento do carcinoma hepatocelular (CHC). O regime terapêutico baseado em interferon vem sendo substituído pelos antivirais de ação direta (AAD) para tratamento da infecção pelo vírus da hepatite C (HCV). Contudo, estudos recentes evidenciaram um aumento inesperado da recorrência do CHC em pacientes tratados com AAD para resolução da hepatite C. Objetivo: Avaliar o risco de recorrência de hepatocarcinoma após uso de AAD em pacientes com infecção por HCV. Método: Realizou-se um levantamento nas bases de dados PubMed, MEDLINE e LILACS de acordo com os descritores DeCS/MeSH ((hepatocellular carcinoma) AND recurrence) AND Direct-acting antiviral. A revisão obedeceu ao protocolo PRISMA e está cadastrada na plataforma PROSPERO. A análise estatística dos dados foi realizada no software RStudio. Resultados: Sete artigos foram selecionados resultando em 847 pacientes. Entre os tratados com AAD, a taxa de recorrência variou entre 11,1% e 42,1% e, no grupo controle, ocorreu em 5% a 65,6% dos pacientes. O risco relativo (RR) de recorrência do CHC no grupo de pacientes que recebeu AAD foi menor do que o risco evidenciado no grupo controle, apesar de não haver significância estatística (RR 0,71 95% IC [0,55;0,93] I²=38%, p=0,14). O tempo até o diagnóstico da recorrência teve uma média de 9,35 meses no grupo exposto à terapia e 13,42 meses no grupo controle. Conclusão: Sugere-se que a terapia com AAD não aumenta o risco de recorrência do CHC em comparação com grupos controle. Nos pacientes que desenvolveram recorrência, ocorreu com maior frequência dentro do primeiro ano após introdução dos AAD.

Introduction: Hepatitis C is associated with the development of hepatocellular carcinoma (HCC). The interferon-based therapeutic regimen has been replaced by direct-acting antivirals (AAD) to treat HCV virus infection. However, recent studies have shown an unexpected increase in HCC recurrence in patients treated with AAD to resolve hepatitis C. Objective: To assess the risk of hepatocarcinoma recurrence after using AAD in patients with HCV infection. Method: A survey was carried out in PubMed, MEDLINE, and LILACS databases according to the descriptors DeCS/MeSH ((hepatocellular carcinoma) AND recurrence) AND Direct-acting antiviral. The review followed the PRISMA protocol and is registered on the PROSPERO platform. The data statistical analysis was performed through RStudio software. Results: Seven articles were selected resulting in 847 patients. Among those treated with AAD, the recurrence rate varied between 11.1% to 42.1% and, in the control group, it occurred in 5% to 65.6% of the patients. The relative risk (RR) of recurrence of HCC in the group of patients who received AAD was less than the risk evidenced in the control group, although there is no statistical significance (RR 0.71 95% CI [0.55; 0.93] I²=38%, p=0.14). The mean time until the diagnosis of recurrence was 9.35 months in the group exposed to therapy and 13.42 months in the control group. Conclusion: It is suggested that therapy with AAD does not increase the risk of HCC recurrence compared to control groups. In patients who developed recurrence, it occurred more frequently within the first year after the introduction of AAD.

Introducción: La hepatitis C está asociada con el desarrollo de carcinoma hepatocelular (CHC). El régimen terapéutico basado en interferón ha sido reemplazado por antivirales de acción directa (AAD) para tratar la infección por VHC. Sin embargo, estudios recientes han mostrado un incremento inesperado en la recurrencia del CHC en pacientes tratados con AAD para resolución de la hepatitis C. Objetivo: Evaluar el riesgo de recurrencia del hepatocarcinoma después de usar AAD en pacientes con infección por VHC. Método: Se realizó una pesquisa en las bases de datos PubMed, MEDLINE y LILACS según los descriptores DeCS/MeSH ((carcinoma hepatocelular) AND recurrencia) AND antiviral de acción directa. La revisión siguió el protocolo PRISMA y está registrada en la plataforma PROSPERO. El análisis estadístico de los datos se realizó mediante el software RStudio. Resultados: Fueron seleccionados 7 artículos resultando en 847 pacientes. Entre los tratados con AAD, la tasa de recurrencia varió entre el 11,1% y el 42,1% y, en el grupo de control, ocurrió entre el 5% y el 65,6% de los pacientes. El riesgo relativo (RR) de recurrencia del CHC en el grupo de pacientes que recibieron AAD fue inferior que el riesgo evidenciado en el grupo control, aunque no hay significación estadística (RR 0,71; IC del 95% [0,55; 0,93] I²=38%, p=0,14). El tiempo hasta el diagnóstico de recidiva fue de 9,35 meses en el grupo expuesto a terapia y de 13,42 meses en el grupo control. Conclusión: Se sugiere que la terapia con AAD no aumenta el riesgo de recurrencia del CHC en comparación con los grupos control. En los pacientes que desarrollaron recurrencia, esta ocurrió con mayor frecuencia durante el primer año después de la introducción de los AAD.

Risco de Recorrência do Carcinoma Hepatocelular após o Uso de Antivirais de Ação Direta no Tratamento de Hepatite C: Revisão Sistemática e Metanálise / Risk of Hepatocellular Carcinoma Recurrence After the Use of Direct-Acting Antivirals in the Treatment of Hepatitis C: Systematic Review and Metanalysis / Riesgo de Recurrencia del Carcinoma Hepatocelular tras el Uso de Antivirales de Acción Directa en el Tratamiento de la Hepatitis C: Revisión Sistemática y Metanálisis

Introdução: A hepatite C está associada ao desenvolvimento do carcinoma hepatocelular (CHC). O regime terapêutico baseado em interferon vem sendo substituído pelos antivirais de ação direta (AAD) para tratamento da infecção pelo vírus da hepatite C (HCV). Contudo, estudos recentes evidenciaram um aumento inesperado da recorrência do CHC em pacientes tratados com AAD para resolução da hepatite C. Objetivo: Avaliar o risco de recorrência de hepatocarcinoma após uso de AAD em pacientes com infecção por HCV. Método: Realizou-se um levantamento nas bases de dados PubMed, MEDLINE e LILACS de acordo com os descritores DeCS/MeSH ((hepatocellular carcinoma) AND recurrence) AND Direct-acting antiviral. A revisão obedeceu ao protocolo PRISMA e está cadastrada na plataforma PROSPERO. A análise estatística dos dados foi realizada no software RStudio. Resultados: Sete artigos foram selecionados resultando em 847 pacientes. Entre os tratados com AAD, a taxa de recorrência variou entre 11,1% e 42,1% e, no grupo controle, ocorreu em 5% a 65,6% dos pacientes. O risco relativo (RR) de recorrência do CHC no grupo de pacientes que recebeu AAD foi menor do que o risco evidenciado no grupo controle, apesar de não haver significância estatística (RR 0,71 95% IC [0,55;0,93] I²=38%, p=0,14). O tempo até o diagnóstico da recorrência teve uma média de 9,35 meses no grupo exposto à terapia e 13,42 meses no grupo controle. Conclusão: Sugere-se que a terapia com AAD não aumenta o risco de recorrência do CHC em comparação com grupos controle. Nos pacientes que desenvolveram recorrência, ocorreu com maior frequência dentro do primeiro ano após introdução dos AAD.

Introduction: Hepatitis C is associated with the development of hepatocellular carcinoma (HCC). The interferon-based therapeutic regimen has been replaced by direct-acting antivirals (AAD) to treat HCV virus infection. However, recent studies have shown an unexpected increase in HCC recurrence in patients treated with AAD to resolve hepatitis C. Objective: To assess the risk of hepatocarcinoma recurrence after using AAD in patients with HCV infection. Method: A survey was carried out in PubMed, MEDLINE, and LILACS databases according to the descriptors DeCS/MeSH ((hepatocellular carcinoma) AND recurrence) AND Direct-acting antiviral. The review followed the PRISMA protocol and is registered on the PROSPERO platform. The data statistical analysis was performed through RStudio software. Results: Seven articles were selected resulting in 847 patients. Among those treated with AAD, the recurrence rate varied between 11.1% to 42.1% and, in the control group, it occurred in 5% to 65.6% of the patients. The relative risk (RR) of recurrence of HCC in the group of patients who received AAD was less than the risk evidenced in the control group, although there is no statistical significance (RR 0.71 95% CI [0.55; 0.93] I²=38%, p=0.14). The mean time until the diagnosis of recurrence was 9.35 months in the group exposed to therapy and 13.42 months in the control group. Conclusion: It is suggested that therapy with AAD does not increase the risk of HCC recurrence compared to control groups. In patients who developed recurrence, it occurred more frequently within the first year after the introduction of AAD.

Introducción: La hepatitis C está asociada con el desarrollo de carcinoma hepatocelular (CHC). El régimen terapéutico basado en interferón ha sido reemplazado por antivirales de acción directa (AAD) para tratar la infección por VHC. Sin embargo, estudios recientes han mostrado un incremento inesperado en la recurrencia del CHC en pacientes tratados con AAD para resolución de la hepatitis C. Objetivo: Evaluar el riesgo de recurrencia del hepatocarcinoma después de usar AAD en pacientes con infección por VHC. Método: Se realizó una pesquisa en las bases de datos PubMed, MEDLINE y LILACS según los descriptores DeCS/MeSH ((carcinoma hepatocelular) AND recurrencia) AND antiviral de acción directa. La revisión siguió el protocolo PRISMA y está registrada en la plataforma PROSPERO. El análisis estadístico de los datos se realizó mediante el software RStudio. Resultados: Fueron seleccionados 7 artículos resultando en 847 pacientes. Entre los tratados con AAD, la tasa de recurrencia varió entre el 11,1% y el 42,1% y, en el grupo de control, ocurrió entre el 5% y el 65,6% de los pacientes. El riesgo relativo (RR) de recurrencia del CHC en el grupo de pacientes que recibieron AAD fue inferior que el riesgo evidenciado en el grupo control, aunque no hay significación estadística (RR 0,71; IC del 95% [0,55; 0,93] I²=38%, p=0,14). El tiempo hasta el diagnóstico de recidiva fue de 9,35 meses en el grupo expuesto a terapia y de 13,42 meses en el grupo control. Conclusión: Se sugiere que la terapia con AAD no aumenta el riesgo de recurrencia del CHC en comparación con los grupos control. En los pacientes que desarrollaron recurrencia, esta ocurrió con mayor frecuencia durante el primer año después de la introducción de los AAD.

Síndrome metabólico, hígado graso no alcohólico y hepatocarcinoma / Metabolic syndrome, nonalcoholic fatty liver disease and hepatocellular carcinoma

En las últimas décadas, los cambios en el estilo de vida pro-vocaron un incremento en la prevalencia del síndrome meta-bólico y que la enfermedad por hígado graso no alcohólico (nonalcoholic fatty liver disease, NAFLD sus siglas en inglés) se convierta en la enfermedad hepática crónica más fre-cuente en todo el mundo. Los componentes del síndrome metabólico no son sólo altamente prevalentes en pacientes con hígado graso no alcohólico, sino que a la vez aumentan el riesgo de desarrollarlo. Esta relación bidireccional ha sido claramente establecida. Asimismo se considera que NAFLD podría ser el componente hepático del síndrome metabólico. Aunque NAFLD se considera principalmente una enfermedad benigna, puede progresar a fibrosis hepática grave y carcino-ma hepatocelular (CHC), incluso se encontraría este último en hígados no cirróticos. El objetivo de esta revisión es determinar los procesos fisio-patológicos comunes a estas entidades, cuáles son las estra-tegias diagnósticas recomendadas y cuáles las intervenciones terapéuticas actualmente aprobadas.

Polimorfismos en los genes de la enzima alcohol deshidrogenasa (ADH1) y la citocromo P450 2E1 (CYP2E1) en pacientes con cirrosis y carcinoma hepatocelular / Polymorphisms in alcohol dehydrogenase (ADH1) and cytochrome p450 2E1 (CYP2E1) genes in patients with cirrhosis and/or hepatocellular carcinoma

Introducción. Uno de los principales factores de riesgo del carcinoma hepatocelular es el consumo crónico de alcohol. En estudios en diferentes poblaciones, se sugiere que las variantes genéticas de las enzimas que participan en el metabolismo del alcohol, como la alcohol deshidrogenasa (ADH) y la citocromo P450 (CYP2E1), estarían asociadas con riesgo de enfermedades hepáticas terminales. Objetivo. Identificar y caracterizar las variantes alélicas de los genes ADH1B, ADH1C y CYP2E1 en pacientes colombianos con diagnóstico de cirrosis y carcinoma hepatocelular. Materiales y métodos. Se incluyeron muestras de pacientes atendidos entre el 2005 y el 2007, y entre el 2014 y el 2016, en la unidad de hepatología de un hospital de Medellín. La genotipificación de las muestras se hizo mediante reacción en cadena de la polimerasa (Polymerase Chain Reaction, PCR) con análisis de los polimorfismos en la longitud de los fragmentos de restricción (Restriction Fragment Length Polymorphism, RFLP). Los resultados se compararon con los de dos grupos de control y con lo reportado en la base de datos del 1000 Genomes Project. Resultados. Se recolectaron 97 muestras de pacientes con diagnóstico de cirrosis y carcinoma hepatocelular. Los dos factores de riesgo más frecuentes fueron el consumo crónico de alcohol (18,6 %) y las colangiopatías (17,5 %). Los genotipos más frecuentes en la población de estudio fueron el ADH1B*1/1 (82 %), el ADH1C*1/1 (59 %) y el CYP2E1*C/C (84 %). Conclusiones. En este primer estudio de los polimorfismos en pacientes colombianos con diagnóstico de cirrosis y carcinoma hepatocelular, los genotipos más frecuentes fueron el ADH1B*1/1, el ADH1C*1/1 y el CYP2E1*C/C. No se observaron diferencias estadísticamente significativas en la frecuencia de los genotipos entre los casos y los controles. Se requieren estudios adicionales en población colombiana para evaluar el riesgo de la enfermedad hepática terminal por consumo crónico de alcohol y la asociación con los polimorfismos.

Introduction: One of the most important risk factors for hepatocellular carcinoma (HCC) is alcohol consumption: Studies in different populations suggest that the risk of liver disease could be associated with genetic variants of the enzymes involved in alcohol metabolism, such as alcohol dehydrogenase (ADH) and cytochrome P450 CYP2E1. Objective: To identify and characterize the allelic variants of ADH1B, ADH1C and CYP2E1 genes in Colombian patients with cirrhosis and/or HCC. Materials and methods: We included samples from patients attending the hepatology unit between 2005-2007 and 2014-2016 of a hospital in Medellin. Samples were genotyped using PCR-RFLP. We compared the results with two control groups and the 1000 Genomes Project database. Results: We collected 97 samples from patients with a diagnosis of cirrhosis and/or HCC. The two main risk factors were chronic alcohol consumption (18.6%) and cholangiopathies (17.5%). The most frequent genotypes in the study population were ADH1B*1/1 (82%), ADH1C*1/1 (59%), and CYP2E1*C/C (84%). Conclusions: This first study of polymorphisms in Colombian patients diagnosed with cirrhosis and/or HCC showed genotypes ADH1B*1/1, ADH1C*1/1 and CYP2E1*C/C as the most frequent. We found no significant differences in the genotype frequency between cases and controls. Further studies are necessary to explore the association between polymorphisms and the risk of end-stage liver disease from alcohol consumption.

Intérêt de la résection hépatique devant un carcinome hépatocellulaire à propos d'un cas au C.H.U. d'Angondjé

Le carcinome hépatocellulaire (CHC), est une affection fortement associée aux maladies chroniques du foie en particulier la cirrhose. Son incidence et sa mortalité augmentent avec une grande disparité géographique en rapport avec la répartition de ses étiologies. La morbidité augmente, bien qu'on note une meilleure prise en charge des autres complications de la cirrhose ; la mortalité reste élevée en raison du diagnostic souvent tardif du CHC. La chirurgie demeure le seul traitement curatif validé. De toutes les procédures chirurgicales, la transplantation est de loin celle qui offre la possibilité de traiter en un temps le CHC et son étiologie. Dans notre contexte, de pays en développement avec des infrastructures et du personnel qualifié limités, la transplantation est inaccessible. Pour cette raison, la résection partielle du foie reste l'approche la plus adaptée dans nos structures en Afrique. A partir d'une observation, nous discutons de sa faisabilité, de ses indications, de son efficacité et du devenir du foie restant

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.

Survival benefits of interferon-based therapy in patients with recurrent hepatitis C after orthotopic liver transplantation

Recurrent hepatitis C after orthotopic liver transplantation (OLT) is universal and can lead to graft failure and, consequently, reduced survival. Hepatitis C treatment can be used to prevent these detrimental outcomes. The aim of this study was to describe rates of hepatitis C recurrence and sustained virological response (SVR) to interferon-based treatment after OLT and its relationship to survival and progression of liver disease through retrospective analysis of medical records of 127 patients who underwent OLT due to cirrhosis or hepatocellular carcinoma secondary to chronic hepatitis C between January 2002 and December 2013. Fifty-six patients were diagnosed with recurrent disease, 42 started interferon-based therapy and 37 completed treatment. Demographic, treatment- and outcome-related variables were compared between SVR and non-responders (non-SVR). There was an overall 54.1% SVR rate with interferon-based therapies. SVR was associated with longer follow-up after treatment (median 66.5 vs 37 months for non-SVR, P=0.03) and after OLT (median 105 vs 72 months, P=0.074), and lower rates of disease progression (15 vs 64.7%, P=0.0028) and death (5 vs 35.3%, P=0.033). Regardless of the result of therapy (SVR or non-SVR), there was a significant difference between treated and untreated patients regarding the occurrence of death (P<0.001) and months of survival (P<0.001). Even with suboptimal interferon-based therapies (compared to the new direct-acting antivirals) there is a 54.1% SVR rate to treatment. SVR is associated with improved survival and reduced risks of clinical decompensation, loss of the liver graft and death.

Influence of hepatocellular carcinoma etiology in the survival after resection / Influência da causa do carcinoma hepatocelular na sobrevida de pacientes após ressecção

ABSTRACT Background: Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and its incidence is increasing around the world in the last decades, making it the third cause of death by cancer in the world. Hepatic resection is one of the most effective treatments for HCC with five-year survival rates from 50-70%, especially for patients with a single nodule and preserved liver function. Some studies have shown a worse prognosis for HCC patients whose etiology is viral. That brings us to the question about the existence of a difference between the various causes of HCC and its prognosis. Aim: To compare the prognosis (overall and disease-free survival at five years) of patients undergoing hepatectomy for the treatment of HCC with respect to various causes of liver disease. Method: Was performed a review of medical records of patients undergoing hepatectomy between 2000 and 2014 for the treatment of HCC. They were divided into groups according to the cause of liver disease, followed by overall and disease-free survival analysis for comparison. Results: There was no statistically significant difference in the outcomes of the groups of patients divided according to the etiology of HCC. Overall and disease-free survival at five years of the patients in this sample were 49.9% and 40.7%, respectively. Conclusion: From the data of this sample, was verified that there was no prognostic differences among the groups of HCC patients of the various etiologies.

RESUMO Racional: O carcinoma hepatocelular (CHC) é o mais frequente tipo de câncer primário do fígado e a sua incidência vem aumentando nas últimas décadas, tornando-o hoje a terceira causa de morte por câncer no mundo. A ressecção hepática é um dos tratamentos mais eficazes para ele com taxas de sobrevida em cinco anos de 50-70%, especialmente para pacientes com nódulo único e função hepática preservada. Alguns estudos mostraram pior prognóstico para os pacientes com CHC cuja causa é a infecção por vírus B ou C. Isso leva à questão sobre a existência de possível diferença entre as diversas causas e o prognóstico. Objetivo: Comparar o prognóstico (sobrevida global e livre de doença em cinco anos) de pacientes submetidos à hepatectomia para o tratamento do CHC com relação às diversas causas da hepatopatia. Método: Foi realizado levantamento de prontuários dos pacientes submetidos à hepatectomia entre 2000 e 2014 para tratamento de CHC. Eles foram divididos em grupos de acordo com a causa da hepatopatia, sendo feita análise de sobrevida para comparação. Resultados: Não houve diferença estatisticamente significante de prognóstico entre os grupos de pacientes divididos conforme a causa do CHC. A sobrevida global e livre de doença em cinco anos foi de 49.9% e 40.7%, respectivamente. Conclusão: Pôde-se constatar que não houve diferença em relação ao prognóstico entre os grupos de pacientes das diversas causas de CHC.

Adeno-Associated Virus 2-Mediated Hepatocellular Carcinoma is Very Rare in Korean Patients

BACKGROUND: The incidence and etiology of hepatocellular carcinoma (HCC) vary widely according to race and geographic regions. The insertional mutagenesis of adeno-associated virus 2 (AAV2) has recently been considered a new viral etiology of HCC. The aim of this study was to investigate the frequency and clinical characteristics of AAV2 in Korean patients with HCC. METHODS: A total of 289 unrelated Korean patients with HCC, including 159 Hepatitis-B-related cases, 16 Hepatitis-C-related cases, and 114 viral serology-negative cases, who underwent surgery at the Samsung Medical Center in Korea from 2009 to 2014 were enrolled in this study. The presence of AAV2 in fresh-frozen tumor tissues was investigated by DNA PCR and Sanger sequencing. The clinical and pathological characteristics of AAV2-associated HCC in these patients were compared with previous findings in French patients. RESULTS: The AAV2 detection rate in Korean patients (2/289) was very low compared with that in French patients (11/193). Similar to the French patients, the Korean patients with AAV2-related HCC showed no signs of liver cirrhosis. The Korean patients were younger than the French patients with the same AAV2-associated HCC; the ages at diagnosis of the two Korean patients were 47 and 39 yr, while the median age of the 11 French patients was 55 yr (range 43-90 yr). CONCLUSIONS: AAV2-associated HCC was very rare in Korean patients with HCC. Despite a limited number of cases, this study is the first to report the clinical characteristics of Korean patients with AAV2-associated HCC. These findings suggest epidemiologic differences in viral hepatocarcinogenesis between Korean and European patients.

The assessment of hepatocellular carcinoma risk in patients with chronic hepatitis B under antiviral therapy

Hepatocellular carcinoma (HCC) is a primary concern for patients with chronic hepatitis B (CHB). Antiviral therapy has been reasonably the focus of interest for HCC prevention, with most studies reporting on the role of the chronologically preceding agents, interferon-alfa and lamivudine. The impact of interferon-alfa on the incidence of HCC is clearer in Asian patients and those with compensated cirrhosis, as several meta-analyses have consistently shown HCC risk reduction, compared to untreated patients. Nucleos(t)ide analogues also seem to have a favorable impact on the HCC incidence when data from randomized or matched controlled studies are considered. Given that the high-genetic barrier agents, entecavir and tenofovir, are mainly used in CHB because of their favorable effects on the overall long-term outcome of such patients, the most clinically important challenge is the identification of patients who require close HCC surveillance despite on-therapy virological remission. Several risk scores have been developed for HCC prediction in CHB patients. Most of them, such as GAG-HCC, CU-HCC and REACH-B, have been developed and validated in Asian untreated and treated CHB patients, but they do not seem to offer good predictability in Caucasian CHB patients for whom a newer score, PAGE-B, has been recently developed.

Complications Requiring Hospital Admission and Causes of In-Hospital Death over Time in Alcoholic and Nonalcoholic Cirrhosis Patients

BACKGROUND/AIMS: Data on the epidemiology of alcoholic cirrhosis, especially in Asian countries, are limited. We compared the temporal evolution of patterns of alcoholic and nonalcoholic cirrhosis over the last decade. METHODS: We retrospectively examined the inpatient datasets of five referral centers during 2002 and 2011. The study included patients who were admitted due to specific complications of liver cirrhosis. We compared the causes of hospital admissions and in-hospital deaths between patients with alcoholic and nonalcoholic cirrhosis. RESULTS: Among the included 2,799 hospitalizations (2,165 patients), 1,496 (1,143 patients) were from 2002, and 1,303 (1,022 patients) were from 2011. Over time, there was a reduction in the rate of hepatic encephalopathy (HE) as a cause of hospitalization and an increase in the rate of hepatocellular carcinoma. Deaths that were attributable to HE or spontaneous bacterial peritonitis (SBP) significantly decreased, whereas those due to hepatorenal syndrome (HRS) significantly increased over time in patients with alcoholic cirrhosis. However, in patients with nonalcoholic cirrhosis, hepatic failure and HRS remained the principal causes of in-hospital death during both time periods. CONCLUSIONS: The major causes of in-hospital deaths have evolved from acute cirrhotic complications, including HE or SBP to HRS in alcoholic cirrhosis, whereas those have remained unchanged in nonalcoholic cirrhosis during the last decade.

HEPATOCELLULAR CARCINOMA IN A NON-CIRRHOTIC PATIENT WITH SUSTAINED VIROLOGICAL RESPONSE AFTER HEPATITIS C TREATMENT / Carcinoma hepatocelular em paciente não cirrótico com resposta virológica sustentada após tratamento para hepatite C

Chronic infection by hepatitis C virus (HCV) is one of the main risk factors for the development of liver cirrhosis and hepatocellular carcinoma. However, the emergence of hepatocellular carcinoma (HCC) in non-cirrhotic HCV patients, especially after sustained virological response (SVR) is an unusual event. Recently, it has been suggested that HCV genotype 3 may have a particular oncogenic mechanism, but the factors involved in these cases as well as the profile of these patients are still not fully understood. Thus, we present the case of a non-cirrhotic fifty-year-old male with HCV infection, genotype 3a, who developed HCC two years after treatment with pegylated-interferon and ribavirin, with SVR, in Brazil.

A infecção crônica pelo vírus da hepatite C é um dos principais fatores de risco para o desenvolvimento de cirrose hepática e carcinoma hepatocelular. Entretanto, o surgimento do carcinoma hepatocelular em pacientes portadores de hepatite C na ausência de cirrose, especialmente após o tratamento e a obtenção de resposta virológica sustentada, é um evento incomum. Recentemente tem sido sugerido que o genótipo 3 do vírus da hepatite C possa ter um mecanismo oncogênico particular, mas todos os fatores envolvidos nestes casos, assim como o perfil destes pacientes, ainda não estão totalmente esclarecidos. Deste modo, apresentamos o caso de um paciente masculino de 50 anos de idade, com infecção pelo vírus da hepatite C genótipo 3a, não cirrótico, que desenvolveu carcinoma hepatocelular dois anos após ter atingido resposta virológica sustentada com o tratamento com interferon peguilado e ribavirina.

Non-alcoholic steatohepatitis-related liver cirrhosis is increasing in China: A ten-year retrospective study

OBJECTIVE: Little is known about metabolic factors in cirrhotic patients in China. Therefore, we aimed to quantify the prevalence of both metabolic factors and non-alcoholic steatohepatitis-related liver cirrhosis in China. METHODS: The medical records of 1,582 patients diagnosed with liver cirrhosis from June 2003 to July 2013 at Daping Hospital (Chongqing, China) were retrospectively reviewed through a computer-generated search. RESULTS: Serum hepatitis B virus surface antigen was present in 1,083 (68.5%) patients, and hepatitis B was found to be the only etiological factor in 938 (59.3%) of all patients. Obesity, diabetes mellitus, and arterial hypertension were observed in 229 (14.5%), 159 (10.1%), and 129 (8.2%) patients, respectively. From 2012-2013, the proportion of non-alcoholic steatohepatitis-related liver cirrhosis increased to 3.2%, whereas the average proportion of non-alcoholic steatohepatitis-related liver cirrhosis in the previous ten years was 1.9%. The incidence of hepatocellular carcinoma was much higher in males than in females (6.3% vs. 3.7%, respectively, p=0.036). Obesity and diabetes mellitus did not significantly increase the incidence of hepatocellular carcinoma in the whole cirrhotic group. The presence of hepatitis B virus was the only risk factor for hepatocellular carcinoma in cirrhotic patients (p<0.001). CONCLUSIONS: Although hepatitis B virus remains the main etiology of liver cirrhosis in China, steatohepatitis-related liver cirrhosis is increasing in frequency. Hepatitis B virus was the sole significant risk factor for hepatocellular carcinoma in the whole cirrhotic group in the present study, in contrast to obesity and diabetes mellitus, for which only a trend of increased hepatocellular carcinoma was found. .

Hepatitis C virus-induced hepatocellular carcinoma

Hepatitis C virus (HCV) is a leading etiology of hepatocellular carcinoma (HCC). The interaction of HCV with its human host is complex and multilayered; stemming in part from the fact that HCV is a RNA virus with no ability to integrate in the host's genome. Direct and indirect mechanisms of HCV-induced HCC include activation of multiple host pathways such as liver fibrogenic pathways, cellular and survival pathways, interaction with the immune and metabolic systems. Host factors also play a major role in HCV-induced HCC as evidenced by genomic studies identifying polymorphisms in immune, metabolic, and growth signaling systems associated with increased risk of HCC. Despite highly effective direct-acting antiviral agents, the morbidity and incidence of liver-related complications of HCV, including HCC, is likely to persist in the near future. Clinical markers to selectively identify HCV subjects at higher risk of developing HCC have been reported however they require further validation, especially in subjects who have experienced sustained virological response. Molecular biomarkers allowing further refinement of HCC risk are starting to be implemented in clinical platforms, allowing objective stratification of risk and leading to individualized therapy and surveillance for HCV individuals. Another role for molecular biomarker-based stratification could be enrichment of HCC chemoprevention clinical trials leading to smaller sample size, shorter trial duration, and reduced costs.

Inflammation and Hepatic Fibrosis, Then Hepatocellular Carcinoma / 대한소화기학회지

Inflammation is one of the most prominent characteristic features of chronic liver disease, liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Most of HCC cases develop in patients with cirrhosis and cirrhosis develops in patients with chronic liver inflammation. Therefore, there is no doubt that there exist some strong connection among inflammation, fibrosis, and cancer. In fact, chronic unresolved inflammation is associated with persistent hepatic injury and concurrent regeneration, leading to sequential development of fibrosis, cirrhosis, and eventually HCC. This review will discuss the common mechanism of inflammation and fibrosis in chronic liver diseases, and then demonstrate why HCC develops in inflammatory and fibrotic conditions.

Exposición a aflatoxina: un problema de salud pública / Exposition to aflatoxin: A public health problem

La aflatoxina, una micotoxina producida por hongos contaminantes, es un potente tóxico hepático y un agente carcinógeno. La exposición a ella en la dieta es de particular importancia en ciertas regiones del Sureste de Asia y de África subsahariana, cuyas poblaciones presentan alta frecuencia de carcinoma hepatocelular y de la mutación en el codón 249 del gen p53; además, tienen alta prevalencia de la infección por el virus de la hepatitis B. Este factor de riesgo es muy importante si se tiene en cuenta que se ha demostrado sinergia entre la infección por dicho virus y la exposición a aflatoxina en la patogénesis del carcinoma hepatocelular. Pocos estudios han explorado la exposición a aflatoxinas en la dieta de la población latinoamericana y se desconoce el papel en ella de esta micotoxina como factor de riesgo para dicho carcinoma. En este artículo se presenta una revisión sobre diversos aspectos de las aflatoxinas, con énfasis en su relación con la infección por el virus de la hepatitis B y con el carcinoma hepatocelular.

Aflatoxin, a mycotoxin produced by pollutant molds, is a potent hepatotoxic and carcinogenic agent. Dietary exposition to it is of particular importance in certain regions of Southeast Asia and sub-Saharan Africa. Populations in these regions suffer from high incidence of hepatocellular carcinoma, and have high frequency of the mutation in the codon 249 of p53 gene; besides, prevalence of Hepatitis B virus (HBV) infection is high in those populations. Synergism between infection with HBV and the exposition to this mycotoxin in the pathogenesis of hepatocellular carcinoma has been demonstrated. Few studies have explored the exposition to aflatoxin in the diet of populations in Latin America, and the role in them of this mycotoxin as a risk factor for hepatocellular carcinoma is unknown. In this article different aspects of aflatoxin are reviewed with emphasis on its relationship with HBV infection and with such neoplasia.