Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis / 医学前沿

Hepatocellular carcinoma (HCC), which makes up the majority of liver cancer, is induced by the infection of hepatitis B/C virus. Biomarkers are needed to facilitate the early detection of HCC, which is often diagnosed too late for effective therapy. The tRNA-derived small RNAs (tsRNAs) play vital roles in tumorigenesis and are stable in circulation. However, the diagnostic values and biological functions of circulating tsRNAs, especially for HCC, are still unknown. In this study, we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum. We identified tRF-Gln-TTG-006, which was remarkably upregulated in HCC serum (training cohort: 24 HCC patients vs. 24 healthy controls). In the validation stage, we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity (80.4%) and specificity (79.4%) even in the early stage (Stage I: sensitivity, 79.0%; specificity, 74.8%; 155 healthy controls vs. 153 HCC patients from two cohorts). Moreover, in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells, and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays. In summary, our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.

Papel da imunohistoquímica no diagnóstico diferencial do carcinoma hepatocelular precoce e dos nódulos com displasia de alto grau em pacientes com cirrose / Results of immunohistochemistry in the differential diagnosis of early hepatocellular carcinoma and nodules with high-grade dysplasia in patients with cirrhosis

ABSTRACT BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary cancer of the liver and cirrhosis is considered a pre-malignant disease. In this context, the evolutionary sequence from low grade dysplastic nodule and high grade dysplastic nodule (HGDN) to early HCC and advanced HCC has been studied. The differential diagnosis between HGDN and early HCC is still a challenge, especially in needle biopsies OBJECTIVE: To evaluate an immunohistochemistry panel to differentiate dysplastic nodules and HCC. METHODS: Patients with cirrhosis who underwent surgical resection or liver transplantation were included. The sensitivity, specificity and accuracy for the diagnosis of neoplasia were analyzed by evaluating five markers: heat shock protein 70, glypican 3, glutamine synthetase, clathrin heavy chain and beta-catenin. P≤0.05 was considered statistically significant. RESULTS: One hundred and fifty-six nodules were included; of these, 57 were HCC, 14 HGDN, 18 low grade dysplastic nodules and 67 regenerative macronodules. Sensitivity of HCC diagnosis was 64.9% for glypican 3 and 77.2% for glutamine syntetase, while specificity was 96.0% and 96.0% respectively. When the panel of four markers was considered (excluding beta catenin), the specificity ranged from 87.9% for one positive marker to 100% for at least three markers. The best accuracy for HCC diagnosis was obtained with at least two positive markers, which was associated with a sensitivity of 82.5% and specificity of 99%. CONCLUSION: Differential diagnosis of dysplastic nodules and HCC by morphological criteria can be challenging. Immunomarkers are useful and should be used for the differential diagnosis between HCC and HGDN.

RESUMO CONTEXTO: O carcinoma hepatocelular (CHC) é o câncer primário do fígado mais frequente e a cirrose é considerada uma doença pré-maligna. Nesse contexto, a sequência evolutiva do nódulo displásico de baixo grau e nódulo displásico de alto grau (NDAG) para CHC precoce e CHC avançado tem sido estudada. O diagnóstico diferencial entre NDAG e CHC precoce ainda é um desafio, principalmente em biópsias por agulha. OBJETIVO: Avaliar um painel de imunohistoquímica para diferenciar nódulos displásicos de CHC. MÉTODOS: Foram incluídos pacientes com cirrose submetidos à ressecção cirúrgica ou transplante de fígado. A sensibilidade, especificidade e acurácia para o diagnóstico da neoplasia foram analisadas avaliando cinco marcadores: proteína de choque térmico 70kDa, glipican 3, glutamina sintetase, clatrina de cadeia pesada e beta-catenina. P≤0,05 foi considerado estatisticamente significativo. RESULTADOS: Cento e cinquenta e seis nódulos foram incluídos; destes, 57 eram CHC, 14 NDAG, 18 nódulos displásicos de baixo grau e 67 macronódulos regenerativos. A sensibilidade do diagnóstico de CHC foi de 64,9% para glipican 3 e 77,2% para glutamina sintetase, enquanto a especificidade foi de 96,0% e 96,0%, respectivamente. Quando o painel de quatro marcadores foi considerado (excluindo beta catenina), a especificidade variou de 87,9% para um marcador positivo a 100% para pelo menos três marcadores. A melhor acurácia para o diagnóstico de CHC foi obtida com pelo menos dois marcadores positivos, o que foi associado a uma sensibilidade de 82,5% e especificidade de 99%. CONCLUSÃO: O diagnóstico diferencial de nódulos displásicos e CHC por critérios morfológicos pode ser desafiador. Imunomarcadores são úteis e devem ser usados para o diagnóstico diferencial entre CHC e NDAG.

Serum LAPTM4B-35 protein as a novel diagnostic marker for hepatocellular carcinoma / 北京大学学报(医学版)

OBJECTIVE@#LAPTM4B-35 protein is one of the isoforms that are encoded by a cancer driver gene, LAPTM4B. This gene was primarily found and identified in our lab of Peking University School of Basic Medical Sciences. The LAPTM4B-35 protein and its encoded mRNA are significantly over-expressed in a variety of cancers, such as hepatocellular carcinoma (HCC), lung cancers (including non small-cell lung cancer and small-cell lung cancer), stomach cancer, colorectal carcinoma, pancreatic cancer, gallbladder cancer, cholangiocarcinoma, breast cancer, prostate cancer, ovarian cancer, cervical cancer, endometrial cancer, and so on. It has firmly demonstrated through lab experiments either in vivo or in vitro, as well as clinical studies that the over-expression of LAPTM4B-35 can promote cancer growth, metastasis, and multidrug resistance. Specially, the expressive level of LAPTM4B-35 is associa-ted with recurrence of HCC. The aim of this study is to identify the release of LAPTM4B-35 protein from hepatocellular carcinoma into blood of HCC patients and into the medium of cultured HCC cells, and to identify its possible form of LAPTM4B-35 protein existed in blood and cell culture medium, as well as to explore the possibility of LAPTM4B-35 protein as a novel HCC biomarker for diagnosis of HCC and prognosis of HCC patients.@*METHODS@#Immunobloting (Western blot) and enzyme-linked immunosorbent assay (ELISA) were used for identification of LAPTM4B-35 protein in the blood of HCC patients and normal individuals. Ultrafiltration and ultracentrifugation were used to isolate and purify exosomes from the culture medium of HCC cells.@*RESULTS@#LAPTM4B-35 protein existed in the blood from HCC patients and normal donors that were demonstrated through Western blot and ELISA. LAPTM4B-35 was also released into the culture medium of HCC cells in the form of exosomes. Preliminary experiments showed that the average and the median of LAPTM4B-35 protein level in the blood of HCC patients (n=43) were both significantly higher than that in the blood of normal donors (n=33) through sandwich ELISA.@*CONCLUSION@#It is promising that the LAPTM4B-35 protein which is released from HCC cells in the form of exosomes into their extraenvironment may be exploited as a novel cancer biomarker for HCC serological diagnosis.

Hepatocarcinoma fibrolamelar. Presentación de un caso clínico / Fibrolamellar hepatocarcinoma. Presentation of a clinical case / Hepatocarcinoma fibrolamelar. Relato de um caso clínico

Resumen: El hepatocarcinoma fibrolamelar es una entidad poco frecuente cuya incidencia varía entre 1% y 5% en el porcentaje de todos los hepatocarcinomas. Afecta principalmente a pacientes jóvenes con hígado sano, y en el 50% de los casos su diagnóstico se realiza en etapas avanzadas de la enfermedad. Se presenta el caso de un paciente de 15 años de edad, sano, que consulta por tumoración abdominal de tres meses de evolución, dolor en epigastrio y adelgazamiento. Los estudios de imagen informan tumoración que sustituye el lóbulo izquierdo del hígado con realce heterogéneo en la fase arterial, que infiltra la vena suprahepática izquierda. Además, informa lesiones en los segmentos V y VIII, extensas adenopatías en el hilio hepático, y nódulos a nivel peritoneal y subpleural. Se realizó punción biópsica hepática que confirmó el diagnóstico de hepatocarcinoma fibrolamelar, iniciándose tratamiento oncoespecífico.

Summary: Fibrolamellar hepatocellular carcinoma is a rare entity that represent between 1% to 5% of all hepatocarcinomas. Tipically affects younger patients (10 to 30 year of age) of both sexes, without underlying liver disease. In 50% of the cases the diagnosis is made in advanced stages of the disease. We present the case of a male patient of 15 years of age, healthy, who consulted due to an abdominal tumor of 3 months evolution, epigastric pain and weight loss. The imaging studies report a tumor that replaces the left lobe with heterogeneous enhancement in the arterial phase that infiltrates the left suprahepatic vein. Injuries in segment V and VIII. Extensive lymphadenopathy in the liver liver. Peritoneal and subpleural nodule. Hepatic biopsy puncture was performed confirming fibrolaminar hepatocarcinoma. Start once specific treatment.

Resumo: Entidade pouco frequente cuja incidência varia entre 1% e 5% de todos os hepatocarcinomas. Acomete principalmente pacientes jovens com fígado saudável e em quase 50% dos casos o diagnóstico é feito em estágios avançados da doença. Apresentamos o caso de um paciente do sexo masculino, de 15 anos de idade, saudável, que consultou devido a um tumor abdominal de 3 meses de evolução, dor epigástrica e perda de peso. Os estudos de imagem relatam um tumor que substitui o lobo esquerdo com realce heterogêneo na fase arterial que infiltra a veia supra-hepática esquerda. Lesões do segmento V e VIII. Linfadenopatia extensa no fígado do fígado. Nódulo peritoneal e subpleural. A punção da biópsia hepática foi realizada confirmando o hepatocarcinoma fibrolaminar. Iniciar um tratamento específico.

Atualização das recomendações da Sociedade Brasileira de Hepatologia para o diagnóstico e tratamento do carcinoma hepatocellular / Brazilian society of hepatology updated recommendations for diagnosis and treatment of hepatocellular carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.

RESUMO O carcinoma hepatocelular (CHC) é uma das principais causas de mortalidade relacionada a câncer no Brasil e no mundo. A Sociedade Brasileira de Hepatologia (SBH) publicou em 2015 suas primeiras recomendações sobre a abordagem do CHC. Desde então, novas evidências sobre o diagnóstico e tratamento do CHC foram relatadas na literatura médica, levando a diretoria da SBH a promover uma reunião monotemática sobre câncer primário de fígado em agosto de 2018 com o intuito de atualizar as recomendações sobre o manejo da neoplasia. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização baseada em evidências científicas visando que pudesse nortear a prática clínica multidisciplinar do CHC. O texto resultante foi submetido a avaliação e aprovação de todos membros da SBH através de sua homepage. O documento atual é a versão final que contêm as recomendações atualizadas e revisadas da SBH.

Carcinoma hepatocelular y embarazo: reporte de caso, Hospital Escuela universitario, Honduras / Hepatocellular carcinoma and pregnancy: case report, Hospital Escuela Universitario, Honduras

El carcinoma hepatocelular es uno de los tumores más frecuentes del hígado, a nivel global se ubica entre la cuarta y quinta malignidad más frecuente, con incidencia calculada en 600 000 casos al año, y el 3.5% de todas las malignidades en mujeres, la tasa de incidencia global es 5.5/100 000 mujeres. Objetivo:describir un caso de carcinoma hepatocelular en el embarazo en Honduras, confirmado por histopatología. Presentación del caso clínico:gestante de 35 años, atendida en el Hospital Escuela Universitario, con 39.4 semanas de gestación por fecha de última menstruación, quien se presenta con fiebre no cuantificada de dos días de evolución; niega vómitos, diarrea, pérdida de peso, dolor tipo obstétrico, salida de líquido o sangrado transvaginal y afirma movimientos fetales activos. Refiere masa en hipocondrio derecho de dos meses de evolución, que ha crecido de forma insidiosa, dolorosa, dificulta la respiración y deambulación. Al examen físico abdomen distendido, doloroso, en cuadrante superior derecho, se palpa masa sólida de aproximadamente 20 centímetros, bordes irregulares, no móvil, adherida a planos profundos y dolorosa a la palpación. Frecuencia cardiaca fetal 137/minuto; altura de fondo uterino 34 centímetros; actividad uterina 3/10++; movimientos fetales positivos; encajado y cefálico por maniobras de Leopold. Se realiza diagnóstico histopatológico y por imagen de carcinoma hepatocelular. Conclusión: carcinoma hepatocelular en el embarazo, evoluciona con buen resultado perinatal, además sin evidencia de metástasis materno-fetal; esto posiblemente se deba a la identificación y manejo temprano de esta rara patología...(AU)

Diagnostic d'un carcinome hépatocellulaire à l'échographie à Bangui

Objectif : Décrire les aspects échographiques des tumeurs hépatiques évocatrices de carcinome hépatocellulaire (CHC) en Centrafrique. Matériels et méthodes : C'était une étude descriptive de 12 mois concernant tous les patients ayant présenté des tumeurs hépatiques à l'échographie. Le dosage du taux d'alpha-foeto-protéine et la recherche sérologique de hépatite virale B et C étaient réalisés chez certains. Résultats : trente-six (36) CHC ont été évoqués sur 119 tumeurs, soit une fréquence de 30,3%. L'âge moyen était de 46,3 ans (+/-15,8), avec une prédominance masculine (n=25). Les principaux motifs de consultation étaient l'altération de l'état général (7), le ballonnement abdominal (n=6) et la douleur abdominale (n=5). La majorité des tumeurs étaient multiples (n=31), mesuraient plus de 3cm (n=27), étaient hétérogènes (n=19). Vingt-trois (23) cas étaient en faveur d'un CHC sur cirrhose. L'antigène HBS (Ag HBS) était positif dans 8 cas. L'alpha foeto-protéine(AFP) était significatif dans 11 cas. Conclusion : Le diagnostic du CHC est tardif en Centrafrique et repose principalement sur l'échographie. Il faut déjà envisager l'examen anatomopathologique écho guidé et encourager aussi une politique de prévention contre les virus de l'hépatite B et C et l'éthylisme chronique

Diagnostic value of serum heat shock protein 70 in hepatocellular carcinoma patients

Background and study aim: Hepato-cellular carcinoma (HCC) is the commonest essential hepatic threat among adult. Nowadays, the HCC determination without obsessive relationship is done by imaging methods. To elucidate the role of heat shock protein 70(HSP70) in the diagnosis of HCC. Subjects and Methods: This case control study was achieved in Internal Medicine and Clinical Pathology Departments, Zagazig University, Egypt. It involved 99 participants divided into three groups; control group, cirrhotic patients and cirrhotic patients with HCC. Participants underwent complete history taking, comprehensive clinical examination, laboratory investigations including viral markers and alpha-fetoprotein. HSP 70 level was calculated via the enzyme-linked immunosorbent assay (ELISA) technique. Radiological investigations including abdominal ultrasonography and triphasic CT scan were done. Results: There was a non-significant difference between the studied groups concerning demographic characteristics. There was a significant difference between them regarding hemoglobin, platelet count, liver and kidney function tests and coagulation profile(p<0.05). Also, there was a significant difference between them as regards HSP 70, and AFP with the maximum values in HCC group. HSP 70 at cutoff ≥120 ng/ml can diagnose HCC at sensitivity 85%, specificity 50%, and accuracy 84% (p<0.05). AFP at cutoff ≥20 ng/ml can recognize HCC with sensitivity 87.5%, specificity 75.8% and accuracy 89%. Combined HSP 70 and AFP increase the sensitivity of diagnosis at 91.5% and accuracy to 93%. Conclusion: HSP 70 as a serum biomarker can be used with AFP to increase the accuracy of HCC diagnosis

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.

Mujer joven con hepatocarcinoma fibrolamelar metastásico; citorreducción y HIPEC: a propósito de un caso / Young woman with metastatic fibrolamellar hepatocarcinoma; cytoreductive surgery and HIPEC: a case report

Objetivo: Reportar un caso clínico de hepatocarcinoma fibrolamelar metastásico y su manejo multidisciplinario. Caso clínico: Paciente de 24 años de edad con dolor abdominal, distensión abdominal y fiebre. Se le realizó tomografía computarizada de abdomen donde se encontró tumoración hepática irregular. Se realizó laparotomía con evidencia de múltiples implantes en cavidad abdominal y se diagnosticó mediante estudio histopatológico hepatocarcinoma fibrolamelar metastásico. Se decidió realizar citorreducción más quimioterapia hipertérmica intraperitoneal (HIPEC). La sobrevida de la paciente fue de 11 meses. Discusión: El hepatocarcinoma fibrolamelar es un tumor raro. Aún no hay consenso sobre el mejor tratamiento en pacientes con metástasis que tengan buena funcionalidad. El manejo actual se basa en la quimioterapia sistémica y la resección quirúrgica en casos localizados. En el caso de nuestra paciente, la cirugía citorreductora más HIPEC se realizó con la intención de mejorar la supervivencia. Se necesita más evidencia para definir esta estrategia como tratamiento estándar.

Aim: To report a clinical case of metastatic fibrolamellar hepatocarcinoma and its multidisciplinary management. Case report: 24 year-old patient with abdominal pain, bloating and fever. A computed tomography of the abdomen was performed; an irregular hepatic tumor was found. A laparotomy was performed with evidence of multiple implants in the abdominal cavity and the histopathology report was metastatic fibrolamellar hepatocarcinoma. It was decided to perform cytoreductive surgery plus HIPEC. The patient's survival was 11 months. Discussion: Fibrolamellar hepatocarcinoma is a rare tumor. There is still no consensus on the treatment of choice in patients with metastases with good functionality status. Current management is based on systemic chemotherapy and surgical resection in localized cases. In the case of our patient, cytoreductive surgery plus HIPEC was performed with the intention of improving survival. More evidence is needed to define this strategy as standard treatment.

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

Hepatocellular carcinoma: diagnosis and operative management / Carcinoma hepatocelular: diagnóstico e manejo cirúrgico

ABSTRACT Introduction: Hepatocellular carcinoma is an aggressive malignant tumor with high lethality. Aim: To review diagnosis and management of hepatocellular carcinoma. Methods: Literature review using web databases Medline/PubMed. Results: Hepatocellular carcinoma is a common complication of hepatic cirrhosis. Chronic viral hepatitis B and C also constitute as risk factors for its development. In patients with cirrhosis, hepatocelular carcinoma usually rises upon malignant transformation of a dysplastic regenerative nodule. Differential diagnosis with other liver tumors is obtained through computed tomography scan with intravenous contrast. Magnetic resonance may be helpful in some instances. The only potentially curative treatment for hepatocellular carcinoma is tumor resection, which may be performed through partial liver resection or liver transplantation. Only 15% of all hepatocellular carcinomas are amenable to operative treatment. Patients with Child C liver cirrhosis are not amenable to partial liver resections. The only curative treatment for hepatocellular carcinomas in patients with Child C cirrhosis is liver transplantation. In most countries, only patients with hepatocellular carcinoma under Milan Criteria are considered candidates to a liver transplant. Conclusion: Hepatocellular carcinoma is potentially curable if discovered in its initial stages. Medical staff should be familiar with strategies for early diagnosis and treatment of hepatocellular carcinoma as a way to decrease mortality associated with this malignant neoplasm.

RESUMO Introdução: O carcinoma hepatocelular é neoplasia maligna agressiva com elevada morbidade e mortalidade. Objetivo: Revisão sobre a fisiopatologia, o diagnóstico e o manejo do carcinoma hepatocelular nos vários estágios da doença. Método: Revisão da literatura utilizando a base Medline/PubMed e literatura adicional. Resultados: O carcinoma hepatocelular é geralmente complicação da cirrose hepática. As hepatites virais crônicas B e C também são fatores de risco para o surgimento do carcinoma hepatocelular. Quando associado à cirrose hepática, ele geralmente surge a partir da evolução de um nódulo regenerativo hepatocitário que sofre degeneração maligna. O diagnóstico é efetuado através de tomografia computadorizada de abdome com contraste endovenoso, e a ressonância magnética pode auxiliar nos casos que não possam ser definidos pela tomografia. O único tratamento potencialmente curativo para o carcinoma hepatocelular é a ressecção do tumor, seja ela realizada através de hepatectomia parcial ou de transplante. Infelizmente, apenas cerca de 15% dos carcinomas hepatocelulares são passíveis de tratamento cirúrgico. Pacientes portadores de cirrose hepática estágio Child B e C não devem ser submetidos à ressecção hepática parcial. Para esses pacientes, as opções terapêuticas curativas restringem-se ao transplante de fígado, desde que selecionáveis para esse procedimento, o que na maioria dos países dá-se através dos Critérios de Milão. Conclusão: Quando diagnosticado em seus estágios iniciais, o carcinoma hepatocelular é potencialmente curável. O melhor conhecimento das estratégias de diagnóstico e tratamento propiciam sua identificação precoce e a indicação de tratamento apropriado.

Risk Factors for Prognosis of Hepatocellular Carcinoma After Curative Resection In Patients with Low Hepatitis B Viral Load

ABSTRACT Background. A retrospective cohort study was conducted to investigate the effect of hepatitis B surface antigen (HBsAg) level on prognosis in low viral load (< 2000 lU/mL) patients with hepatitis B-related hepatocellular carcinoma (HCC) after curative resection. Material and methods. A total of 192 patients with low viral load who had received curative resection of pathologically confirmed HCC were analyzed to determine the factors affecting prognosis. The risk factors for survival, early and late recurrence (2 years as a cut-off) were studied. Results. The median follow-up time was 38.5 months. The overall survival rates at 1-, 3-, and 5-year after curative resection were 94.2%, 64.0%, and 45.2%, respectively. The cumulative recurrence rates at 1-, 3-, and 5-year after curative resection were 22.4%, 46.5%, and 67.0%, respectively. Patients with high serum HBsAg levels (> 250 lU/mL) had significantly lower survival rates than those with low HBsAg levels (HR: 1.517,95% Cl: 1.005-2.292, P = 0.047). Stratified analysis showed that patients with high HBsAg levels had a significantly higher late recurrence incidence than those with low HBsAg levels (HR: 2.155, 95% Cl: 1.094-4.248, P = 0.026), but did not have a significantly higher risk of early recurrence postoperatively (HR: 1.320,95% Cl: 0. 837-2.082, P = 0.233). Multivariate analysis revealed that HBsAg > 250 lU/mL was an independent risk factor associated with late recurrence (HR: 2.109, 95% Cl: 1.068-4.165, P = 0.032). Conclusions. HBsAg > 250 lU/mL at the time of tumor resection was an independent risk factor for late recurrence in low viral load HCC patients.

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.

La ponction biopsie hépatique écho-guidée en ambulatoire à Ouagadougou : indications, apport diagnostique et complications

Objectif : Déterminer l'apport diagnostique de la ponction biopsie hépatique par voie per cutanée sous guidage échographique.Matériel et méthodes : étude rétrospective descriptive réalisée de mars 2013 à mars 2017. Ont été inclus tous les patients ayant bénéficié d'une biopsie hépatique sous guidage échographique. Les variables recueillies ont été le sexe, l'âge, l'indication, le nombre de carottes biopsiques, les complications et le diagnostic anatomopathologique.Résultats. 53 patients ont été colligés. Il y avait 37 hommes (69,81%) et 16 femmes (30,18 %) soit un sex ratio de 2,31. L'âge moyen était de 45,79 ans avec des extrêmes de 15 et de 82 ans. Les indications étaient principalement représentées par l'exploration des nodules dans 49 cas (92,24%) et des hépatopathies chroniques dans 4 cas (7,76%). Le diagnostic anatomopathologique était essentiellement dominé par le CHC dans 33 cas (63,46%). Une douleur modérée passagère, était notée chez 37,73% des patients au passage de la capsule. Aucune complication majeure n'était retrouvée.Conclusion. La réalisation des PBH sous guidage échographique était fiable et réalisable en ambulatoire, pour peu que le bilan d'hémostase, l'utilisation d'une prémédication et d'une aiguille fine avec un système coaxial soit respecté

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

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

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

Análise retrospectiva da infecção crônica pelo vírus da hepatite B em 247 pacientes: fases evolutivas, resposta ao tratamento e fatores de pior prognóstico / Retrospective analysis of hepatitis B virus chronic infection in 247 patients clinical stages, response to treatment and poor prognostic factors

Introdução. A hepatite B crônica é uma importante causa de cirrose hepática e a história natural da doença tem várias fases clínicas que devem ser bem entendidas para se realizar o tratamento adequado. Objetivos. Descrever o comportamento clínico, a resposta ao tratamento e os fatores de pior prognóstico em 247 pacientes com infecção crônica pelo vírus da hepatite B. Métodos. Estudo retrospectivo observacional, realizado através da análise dos prontuários dos pacientes entre janeiro de 2000 e janeiro de 2015. Resultados. A maioria dos pacientes eram do gênero masculino (67,2%) e 74,1% eram HBeAg negativo. Cerca de 41% tinham cirrose hepática e 8,5% eram coinfectados pelo vírus da hepatite C. A negativação da carga viral em um ano com lamivudina, entecavir e tenofovir foi respectivamente de 56%, 75% e 75%; efeitos adversos foram mais comuns com tenofovir. A resistência virológica em cinco anos a lamivudina, adefovir e entecavir foi respectivamente de 57,5%, 51,8% e 1,9%. A taxa geral de soroconversão do HBeAg foi de 31,2% e do HBsAg foi de 9,7%. Carcinoma hepatocelular foi diagnosticado em 9,7%, transplante hepático foi realizado em 9,7% e a mortalidade geral foi de 10,5%. Elevações de alanina aminotransferase (p=0,0194) e carga viral (p<0,0001) foram associadas à evolução para cirrose hepática. Carga viral elevada foi associada à evolução para carcinoma hepatocelular (p=0,0019). Os fatores de risco significativos relacionados ao óbito foram elevação de alanina aminotransferase (p=0,0118), cirrose hepática (p<0,0001) e carcinoma hepatocelular (p=0,0008). Positividade para o HBeAg não foi associada a piores desfechos. Conclusões. Cirrose hepática e carcinoma hepatocelular foram associados a um pior prognóstico e novos estudos devem ser direcionados para prevenir estes fatores com a finalidade de diminuir o óbito relacionado a esse vírus. (AU)

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. Aim. To describe the clinical course, response to treatment and poor prognostic factors in 247 hepatitis B virus chronic infection patients. Methods. We carried out a retrospective and observational study, by analyzing the medical records of patients between January 2000 and January 2015. Results. Most patients were male (67.2%) and 74.1% were HBeAg negative. Approximately 41% had liver cirrhosis and 8.5% were hepatitis C virus coinfected. The viral load was negative in one year with lamivudine, entecavir and tenofovir in 56%, 75% and 75% of patients, respectively; adverse effects were more frequent with tenofovir. Virological resistance in five years for lamivudine, adefovir and entecavir was 57.5%, 51.8% and 1.9%, respectively. The overall rate of seroconversion was 31.2% for HBeAg and 9.7% 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 = 0.0194) and viral load (p <0.0001) were associated with progression to liver cirrhosis. High viral load was associated with progression to hepatocellular carcinoma (p = 0.0019). Significant risk factors associated with death were elevated alanine aminotransferase (p = 0.0118), liver cirrhosis (p <0.0001) and hepatocellular carcinoma (p = 0.0008). HBeAg positive state was not associated with worse outcomes. Conclusions. Liver cirrhosis and hepatocellular carcinoma were associated with a worse prognosis and further studies should concentrate on prevention of these factors in order to reduce mortality.(AU)

Socioeconomic disparities in access to a hepatocellular carcinoma screening program in Brazil

OBJECTIVES: Cirrhotic patients must receive an abdominal ultrasound every 6 months as part of hepatocellular carcinoma (HCC) screening. The aim of this study was to assess if HCC screening was performed as recommended by the literature and to observe the differences between the private and public services in Brazil. METHODS: We analyzed data from the HCC screenings of 253 cirrhotic patients from the University Hospital (n=177) and private sector (n=76) in Vitória, ES, Brazil. RESULTS: Ultrasound screening was performed every 13.1 months on average (SD 9.02). In 37 out of 253 patients, the screenings were performed close to the recommended frequency; 16 were performed every 6 months, and 21 were mostly performed during the follow-up period every 6 months. In the remaining 216 cases, ultrasounds were not performed according to the guidelines; for 106 patients, less than 50% of all ultrasounds were performed every 6 months and 110 patients showed an interval greater than one year. Patients from the private sector received ultrasound screenings near the ideal in 28.9% of cases, while patients from the University Hospital received ultrasounds in only 8.4% of cases (p<0.0001). HCC was diagnosed in 30 patients (11.8%). For these 30 patients, 11 screenings were properly performed within 6 months (36.6%) and only 1 out of the 11 (9%) met the criteria for transplant. In the remaining 19 patients who did not receive the screening within 6 months, 6 (31.5%) did not meet the criteria for transplant. CONCLUSION: HCC screening in our environment was irregularly performed, mainly in the public service setting, which prevented early diagnosis in a large number of patients.

Noninvasive Diagnosis of Hepatocellular Carcinoma: Elaboration on Korean Liver Cancer Study Group-National Cancer Center Korea Practice Guidelines Compared with Other Guidelines and Remaining Issues

Hepatocellular carcinoma (HCC) can be diagnosed based on characteristic findings of arterial-phase enhancement and portal/delayed "washout" in cirrhotic patients. Several countries and major academic societies have proposed varying specific diagnostic criteria for HCC, largely reflecting the variable HCC prevalence in different regions and ethnic groups, as well as different practice patterns. In 2014, a new version of Korean practice guidelines for management of HCC was released by the Korean Liver Cancer Study Group (KLCSG) and the National Cancer Center (NCC). According to the KLCSG-NCC Korea practice guidelines, if the typical hallmark of HCC (i.e., hypervascularity in the arterial phase with washout in the portal or 3 min-delayed phases) is identified in a nodule > or = 1 cm in diameter on either dynamic CT, dynamic MRI, or MRI using hepatocyte-specific contrast agent in high-risk groups, a diagnosis of HCC is established. In addition, the KLCSG-NCC Korea practice guidelines provide criteria to diagnose HCC for subcentimeter hepatic nodules according to imaging findings and tumor marker, which has not been addressed in other guidelines such as Association for the Study of Liver Diseases and European Association for the Study of the Liver. In this review, we briefly review the new HCC diagnostic criteria endorsed by the 2014 KLCSG-NCC Korea practice guidelines, in comparison with other recent guidelines; we furthermore address several remaining issues in noninvasive diagnosis of HCC, including prerequisite of sonographic demonstration of nodules, discrepancy between transitional phase and delayed phase, and implementation of ancillary features for HCC diagnosis.