Hepatitis D: advances and challenges / 中华医学杂志(英文版)

Hepatitis D virus (HDV) infection causes the most severe form of viral hepatitis with rapid progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Although discovered > 40 years ago, little attention has been paid to this pathogen from both scientific and public communities. However, effectively combating hepatitis D requires advanced scientific knowledge and joint efforts from multi-stakeholders. In this review, we emphasized the recent advances in HDV virology, epidemiology, clinical feature, treatment, and prevention. We not only highlighted the remaining challenges but also the opportunities that can move the field forward.

From MAFLD to hepatocellular carcinoma and everything in between / 中华医学杂志(英文版)

Metabolic (dysfunction) associated fatty liver disease (MAFLD), previously known as non-alcoholic fatty liver disease, is the most common cause of chronic liver disease worldwide. Many risk factors contribute to the pathogenesis of MAFLD with metabolic dysregulation being the final arbiter of its development and progression. MAFLD poses a substantial economic burden to societies, which based on current trends is expected to increase over time. Numerous studies have addressed various aspects of MAFLD from its risk associations to its economic and social burden and clinical diagnosis and management, as well as the molecular mechanisms linking MAFLD to end-stage liver disease and hepatocellular carcinoma. This review summarizes current understanding of the pathogenesis of MAFLD and related diseases, particularly liver cancer. Potential therapeutic agents for MAFLD and diagnostic biomarkers are discussed.

Hematocele y hemoperitoneo como manifestación inicial de carcinoma hepatocelular: caso clínico / Hematocele and hemoperitoneum as initial manifestation of hepatocellular carcinoma: report of one case

Hepatocellular carcinoma (HCC) rupture is a rare complication, with a higher prevalence in countries of Asia and Europe. Its clinical manifestations can be nonspecific, from abdominal pain and bloating to hemodynamic involvement. We report a 70-year-old male patient with a history of chronic liver disease, presenting with an enlargement and ecchymosis of the scrotum, associated with abdominal bloating. The initial abdominal ultrasound study showed increased liquid content in the scrotal sac and regional edema. A CT of the abdomen and pelvis showed a liver mass with characteristics of hepatocellular carcinoma, associated with extensive hemoperitoneum that drained into the scrotal sac. The patient was treated with embolization of the right hepatic artery and later with surgical resection of the tumor mass, with a good clinical evolution.

Colangiocarcinoma intrahepatico con manifestaciones clínicas atípicas: reporte de caso / Intrahepatic cholangiocarcinoma with atípical clinical manifestations, case report

El colangiocarcinoma es una neoplasia de la vía biliar, siendo el segundo cáncer hepático primario más frecuente en el mundo, con una incidencia del 2%. Predomina enhombres, la sobrevida en estados tempranos es de 40 meses con cirugíay 12 meses con quimioterapiaen estados mas avanzados.Objetivo:identificar manifestaciones clínicas no específicas, que orienten al médico a realizar un diagnóstico temprano del Colangiocarcinoma. Presentación del caso clínico: paciente masculino, en la sexta década de la vida, diabético, con historia de 18 meses de presentar fatiga y tos seca sin predominio de horario, durante el proceso diagnóstico se encontró hepatomegalia y anemia microcítica hipocrómica.La tomografía computarizada abdominal, reveló masa heterogénea en hígado. El resultado de los marcadores tumorales CA 19.9 y antígeno carcinoembrionario fueron normales.Conclusión: el colangiocarcinoma es un tipo de cáncer que se puede presentar con síntomas inespecíficos por lo que la sospecha clínica puede ser difícil y debe apoyarse en estudios complementarios...(AU)

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)

Hipertiroidismo como clave diagnóstica de un coriocarcinoma avanzado: Una asociación inusual / Hyperthyroidism as a diagnostic key to advanced choriocarcinoma. An unusual association

El hipertiroidismo es una condición relativamente frecuente con múltiples etiologías. La más común es la enfermedad de Graves, seguida del bocio multinodular y el adenoma tóxico. La asociación entre hipertiroidismo y cáncer es infrecuente en la práctica clínica. Presentamos el caso de un varón de 42 años con síntomas de hipertiroidismo de dos meses de evolución. Al examen físico se constató una marcada hepatomegalia de consistencia duro pétrea. El examen de testículos se reveló normal. Se llevó a cabo el diagnóstico de hipertiroidismo a través del dosaje hormonal. Los estudios por imágenes mostraron la presencia de múltiples lesiones sólidas compatibles con metástasis hepáticas. Luego de descartar las causas habituales de hipertiroidismo y las neoplasias primarias de la glándula tiroides, se consideró la posibilidad de mimetismo molecular a través de la producción ectópica de gonadotrofina coriónica humana. Se obtuvieron valores críticamente elevados de esta hormona y en un segundo tiempo se confirmó el diagnóstico histológico de coriocarcinoma a través de una biopsia hepática. Consideramos que el reconocimiento de este mecanismo poco frecuente de hipertiroidismo, puede ser una clave diagnóstica para arribar rápidamente al diagnóstico correcto, particularmente en los tumores extragonadales.

Hyperthyroidism is a relatively frequent condition with multiple causes. The most common cause is Graves' disease; followed by hyperthyroid multinodular goiter and toxic adenoma. Association between hyperthyroidism and cancer is infrequent in daily practice. We present the case of a 42-year-old man who developed severe symptoms of hyperthyroidism within a period of two months. Physical examination revealed significant hepatomegaly. Testicular examination proved normal. Imaging studies showed the presence of multiple hepatic solid lesions consistent with metastases. After discarding the most common causes of hyperthyroidism and primary thyroid gland neoplasm, the possibility of molecular mimicry was considered through human chorionic gonadotrophin production. Critical high values of this hormone were found and choriocarcinoma histological diagnosis was confirmed through a liver biopsy. We consider that the recognition of this rare mechanism of hyperthyroidism may be a clue permitting a faster diagnosis, particularly when extragonadal tumors are present.

Dermatomiositis asociada con carcinoma hepatocelular relacionado con el virus de la hepatitis B: un reporte de caso en Perú / Dermatomyositis associated with hepatitis B virus-related hepatocellular carcinoma: a case report in Peru

La dermatomiositis (DM) es una miopatía inflamatoria de causa desconocida caracterizada por inflamación muscular, debilidad músculo-esquelética proximal y manifestaciones cutáneas típicas. Se ha asociado a malignidades como un síndrome paraneoplásico. Reportamos el caso de un paciente varón de 33 años, diagnosticado de hepatitis B, VHB crónico inactivo, que presentó lesiones papulares, pruriginosas y descamativas en cara, manos, zona inguinal y pies. Al examen físico se evidenció pápulas de Gottron, signo del heliotropo, debilidad muscular simétrica proximal. Se realizó una biopsia de piel donde se encontraron hallazgos compatibles con DM. Tras una ecografía abdominal se encontró una tumoración hepática, cuyo resultado en biopsia fue de carcinoma hepatocelular moderadamente diferenciado. Posteriormente se le realiza segmentectomía con lo cual síntomas de DM disminuyen. Es un caso infrecuente, y de sumo interés por lo que se decide reportar.

Dermatomyositis is an idiopathic inflammatory myopathie characterized by proximal skeletal muscle weakness, typical skin manifestations and muscle inflammation. This disease has been associated with malignancies as a paraneoplastic syndrome. We present a patient of thirty-three years diagnosed with hepatitis B, chronic inactive HBV who presents papular, pruritic and desquamative lesions on the face, hands, inguinal area and feet. At the physical examination is evidentiated Gottron's papules, heliotrope sign and proximal symmetric muscular weakness. Findings compatible with DM were found in a skin biopsy. An abdominal ultrasound revealed a liver tumor whereby a biopsy was performed and the result was a moderately differentiated hepatocellular carcinoma. Subsequently, a segmentectomy has been made and consequently the DM symptoms decreased. This case is of great interest and rare reason why we decided to reported it.

Hepatectomía en 2 tiempos con técnica de ALPPS (Asociación de bipartición hepática con ligadura portal para hepatectomía en 2 tiempos): experiencia y resultados iniciales del Hospital Regional de Talca / 2 stage hepatectomy with ALPPS technique (Liver splitting association) with ligature portal for hepatectomy in 2 times): experience and initial results of the Regional Hospital of Talca

Resumen Introducción: La insuficiencia hepática posoperatoria (IHP) es una causa importante de morbimortalidad posoperatoria en cirugía hepática. Un remanente hepático futuro (RHF) insuficiente es una de las principales causas IHP La asociación de bipartición hepática con ligadura portal para hepatectomía en 2 tiempos (ALPPS) es una técnica relativamente nueva que induce una rápida hipertrofia parenquimatosa reduciendo el tiempo de espera para lograr un volumen hepático adecuado. Nuestro objetivo es comunicar la experiencia y los resultados iniciales de la hepatectomía en 2 tiempos utilizando la técnica de ALLPS. Material y Método: Se incluyeron todos los pacientes en los que se ha realizado una hepatectomía en 2 tiempos utilizando la técnica de ALPPS entre el 1 de junio de 2014 y el 31 de julio de 2016 en la Unidad de Cirugía Digestiva del Hospital Regional de Talca. Resutados: Durante el periodo de estudio, se realizaron 47 hepatectomías en el Hospital Regional de Talca. En 3 casos (6.3%), se realizó una hepatectomía en 2 tiempos utilizando la técnica de ALPPS, en todos ellos se logró una hipertrofia del remanente hepático futuro (RHF) que permitió completar el segundo tiempo sin IHP clínicamente significativa. Conclusión: En nuestra experiencia inicial, la técnica de ALPPS logró aumentar el RHF permitiendo resecar pacientes que inicialmente tenían un RHF insuficiente para ser sometidos a una hepatectomía mayor.

Introduction: Postoperative liver failure (POLF) is a relevant cause of morbimortality after liver surgery. An insufficient future liver remnant (FLR) is one of the main causes of POLF. The association of hepatic bipartition with portal ligation for 2-stage hepatectomy (ALPPS) is a relatively new technique that induces rapid parenchymal hypertrophy reducing the waiting time to achieve adequate FLR. Our aim is to communicate the experience and the initial results of the hepatectomy in 2-stages using the ALLPS technique. Material and Method: All patients in whom a 2-stage hepatectomy using ALPPS technique between June 1, 2014 and July 31, 2016 in the Digestive Surgery Unit of the Hospital Regional of Talca were included. Results: There were 47 hepatectomies performed at the Hospital Regional of Talca. In 3 cases (6.3%), a 2-stage hepatectomy was performed using the ALPPS technique, in all of which a hypertrophy of the future hepatic remnant (RHF) was achieved, which allowed completing the second stage without POLF clinically significant. Conclusion: In our initial experience, the ALPPS technique successfully allowed increase FLR in patients who initially had insufficient FLR to be submitted a major liver resection.

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.

Ressonância magnética com difusão para a avaliação da resposta terapêutica de metástases hepáticas de câncer colorretal em pacientes submetidos à quimioterapia de 1ª e 2ª linhas associada à Cetuximabe ou Bevacizumabe / Early prediction of pathological response using MR diffusion weighted imaging in patients with breast cancer submitted to neoadjuvant chemotherapy

O câncer colorretal é a terceira neoplasia maligna mais comum, sendo o fígado um órgão comumente acometido por metástases. Portanto, uma avaliação acurada do envolvimento hepático é vital para o planejamento do tratamento. O prognóstico dos. pacientes com câncer colorretal metastático mudou drasticamente nos últimos anos,. principalmente devido aos novos agentes citotóxicos e biológicos. À medida que se. caminha para melhor compreensão do uso destes medicamentos na prática clínica, observa-se a necessidade de identificar biomarcadores relacionados ao prognóstico.. A ressonância magnética (RM) com difusão é uma ferramenta promissora para o. diagnóstico e avaliação da resposta. Objetivos: Avaliar a efetividade do monitoramento da resposta terapêutica ao tratamento quimioterápico em pacientes. portadores de adenocarcinoma colorretal metastático, em tratamento de 1ª (primeira). linha ou 2ª (segunda) linha com Folfox ou Folfiri e anticorpos monoclonais. (Bevacizumabe ou Cetuximabe), utilizando-se a ressonância magnética com a técnica de difusão através da análise quantitativa do coeficiente de difusão aparente (ADC) e verificar a correlação com o método RECIST. Materiais e Métodos: Estudo prospectivo, onde foram recrutados pacientes adultos portadores de câncer colorretal metastático ao diagnóstico ou recidivado, atendidos no Departamento de Oncologia Clínica do A.C. Camargo Cancer Center no período de um ano, os quais foram submetidos ao tratamento quimioterápico de 1ª e 2ª linhas para doença metastática com Folfox ou Folfiri associado a anticorpo monoclonal (Cetuximabe ou Bevacizumabe). Foi realizado um exame de ressonância magnética do abdome superior com difusão pré-tratamento e exames adicionais ao final do 4º, 8º e 12º ciclos de quimioterapia, para avaliação de resposta das lesões hepáticas metastáticas ao tratamento proposto. Foi realizada conjuntamente a avaliação das metástases hepáticas pelo método RECIST para comparação com a avaliação quantitativa obtida pela Ressonância Magnética com difusão através do ADC. Resultados: Nove pacientes foram avaliados neste estudo. A média de idade dos pacientes foi 57,2 anos (dp=13,8), sendo a idade mínima de 34 e a máxima de 80 anos, com 5 pacientes do sexo feminino e 4 do sexo masculino. O Folfox foi utilizado em 6 pacientes e o Folfiri em 3 pacientes, sendo 6 pacientes de 1ª linha e 3 de 2ª linha de tratamento. Quanto ao Anticorpo monoclonal, 5 pacientes fizeram uso do Cetuximabe e 4 usaram o Bevacizumabe. O número de metástases hepáticas observadas em um mesmo. paciente variou de 1 até 8 lesões, com um total de 24 lesões analisadas. O tamanho. médio das lesões foi de 36,6 mm (± 21,1 mm). Seis (66,7%) dos 9 pacientes tiveram. resposta parcial (RP), 2 (22,2%) foram classificados como doença estável (DE) e 1. paciente (11,1%) apresentou progressão de doença (PD). Nenhum caso de resposta completa (RC) foi observado no follow-up. Correlação RECIST e ADC: Baseado na avaliação das lesões pelo método RECIST, as lesões foram agrupadas como respondedoras quando houve resposta completa (RC) e resposta parcial (RP) e como não respondedoras quando houve progressão de doença (PD) e doença estável (DE), para comparação com a avaliação pelo ADC. Seis pacientes responderam à quimioterapia e 3 pacientes não responderam. Em relação às lesões, 14 lesões responderam ao tratamento e 10 lesões não responderam. Na análise entre as lesões que responderam e as que não responderam ao tratamento quimioterápico de acordo com o padrão de resposta pelo RECIST não foi observada significância estatística em relação ao ADC basal (p=0,940 (após o 4º ciclo) e p=0,909 (após o 8º ciclo)). Não foi observada diferença estatística na análise das variações após o 4º ciclo de quimioterapia (p=0,245 e percentual com p=0,144), como também não observamos correlação entre a redução final do tamanho tumoral e o valor do ADC basal(p=0,869). Identificamos o melhor ponto de corte (cutoff) de ADC entre as lesões que responderam à quimioterapia e as que não responderam ao tratamento. O cutoff de ADC absoluto foi de 0,05 x 10-3 mm²/sec (AUC=0,66), e o cutoff de ADC percentual foi de 3,8% (AUC=0,70). Considerando-se o Cutoff de ADC percentual de 3,8%, não observamos significância estatística entre as lesões que responderam e as que não responderam à quimioterapia (p=0,057. Conclusões: A RM com difusão, por meio da análise quantitativa do ADC, demonstrou ser um método útil para monitorizar as lesões hepáticas de câncer colorretal metastático em tratamento com quimioterapia. A variação de ADC correlacionou-se com o RECIST, sendo que o aumento do ADC esteve associado com a redução do tamanho das lesões (resposta parcial/respondedores). No entanto, não houve significância estatística, muito provavelmente devido à amostragem limitada. Conseguimos identificar um ponto de. corte através da curva ROC que poderá ser validado em estudos posteriores com uma. maior casuística

Colorectal cancer is the third most common malignancy, and the liver is an organ commonly affected by metastases. Therefore, an accurate assessment of liver involvement is vital for treatment planning. The prognosis of patients with metastatic colorectal cancer has changed dramatically in recent years, mainly due to new cytotoxic and biological agents. In order to better understand the use of these drugs in clinical practice, there is a need to identify biomarkers related to prognosis. Magnetic resonance imaging (MRI) with diffusion is a promising tool for the diagnosis and assessment of response. Objectives: To evaluate the effectiveness of the monitoring of the therapeutic response to chemotherapy treatment in patients with metastatic colorectal adenocarcinoma, in treatment of 1st (first) line or 2nd (second) line with Folfox or Folfiri and monoclonal antibodies (Bevacizumab or Cetuximab) using magnetic resonance imaging using the technique of diffusion through of the quantitative analysis of the apparent diffusion coefficient (ADC) and verify the correlation with the RECIST method. Materials and Methods: Prospective study conducted adult patients with metastatic colorectal cancer diagnosis or relapsed, assisted in the Department of Clinical Oncology of AC Camargo Cancer Center during one year, which underwent chemotherapy 1st and 2nd lines for metastatic disease with Folfox or Folfiri associated with monoclonal antibody (Cetuximab or Bevacizumab). We performed a magnetic resonance examination of the upper abdomen pretreatment and additional exams at the end of the 4th, 8th and 12th cycles of chemotherapy, to evaluate the response of metastatic liver lesions to the proposed treatment. It was performed jointly evaluating the liver metastases by RECIST method for quantitative comparison with the evaluation obtained by MRI with diffusion through ADC. Results: Nine patients were evaluated in this study. The mean age of the patients was 57.2 years (sd = 13.8), with a minimum age of 34 and a maximum of 80 years, with 5 female patients and 4 male. The Folfox was used in 6 patients and Folfiri in 3 patients, being 6 patients of 1st line and 3 of 2nd line of treatment. Regarding the use of the monoclonal antibody, 5 patients were using Cetuximab and 4 used Bevacizumab. The number of liver metastases in the same patient observed varied from one (1) to 8 lesions with a total of 24 lesions analyzed. The average size of the lesions was 36.6 mm (± 21.1 mm). Six (66.7%) of the 9 patients had partial response (PR), 2 (22.2%) were classified as stable disease (SD) and 1 patient (11.1%) presented disease progression (PD). No case of complete response (CR) was observed at follow-up. Correlation RECIST and ADC: Based on the evaluation of the lesions by the RECIST method, the lesions were grouped as responders when there was complete response (CR) and partial response (PR) and as no responders when there was disease progression (PD) and stable disease (SD), for comparison with the evaluation by the ADC. Six patients responded to chemotherapy and 3 patients did not respond. Regarding the lesions, 14 lesions responded to the treatment and 10 lesions did not respond. In the analysis between the lesions that responded and those that did not respond to the chemotherapy treatment according to the response pattern by the RECIST, no statistical significance was observed in relation to baseline ADC (p = 0.940 (after the 4th cycle) and p = 0.909 (after the 8th cycle)). No statistical difference was observed in the analysis of the variations after the 4th cycle of chemotherapy (p = 0.245 and percentage with p = 0.144), nor did we observe a correlation between final reduction of tumor size and baseline ADC (p = 0.869). We identified the best ADC cut-off between the lesions that responded to chemotherapy and those that did not respond to treatment. The absolute ADC cut-off was 0.05 x 10-3 mm²/sec (AUC = 0.66), and the percentage ADC cut-off was 3.8% (AUC = 0.70). Considering the Cut-off of ADC percentage of 3.8%, we did not observe statistical significance between the lesions that responded and those that did not respond to chemotherapy (p = 0.057). Conclusions: MRI, with its quantitative analysis of ADC, has been shown to be a useful method to monitor hepatic changes of the metastatic in treatment with chemotherapy. The variation in ADC correlated with RECIST, and the increase in ADC was associated with the reduction of lesion size (partial response / responders). However, there was no statistical significance, most likely due to limited sampling. We were able to identify a cutoff point through the ROC curve that could be validated in later studies with a larger casuistry

Hemoperitoneo como manifestación inicial de carcinoma hepatocelular: reporte de tres casos / Hemoperitoneum as initial manifestation of hepatocellular carcinoma: report of three cases

Hepatocellular carcinoma (HCC) is the main primary liver malignancy. Its prevalence is increasing and is associated in 90% to cirrhotic patients. Hemoperitoneum secondary to spontaneous rupture of the tumor is an uncommon complication in Latin America and the Western world, being more prevalent in Asian races. However, it is associated to hemodynamic repercussion with high mortality, therefore high level of suspicion and early treatment are required. Regarding the management of the condition, in addition to hemodynamic stabilization, active hemostatic control is recommended over conservative management, transarterial chemoembolization being currently the chosen alternative. We present a series of three clinical cases of patients who debuted with clinical manifestation of hemoperitoneum during the diagnostic process of a HCC.

El carcinoma hepatocelular (CHC) corresponde a la principal neoplasia maligna primaria hepática. Su prevalencia va en aumento y se asocia en 90% a pacientes cirróticos. El hemoperitoneo secundario a rotura espontánea del tumor constituye una complicación infrecuente en Latinoamérica y Occidente, siendo más prevalente en razas asiáticas. Sin embargo, se asocia a repercusión hemodinámica con alta mortalidad, por lo que requiere un alto índice de sospecha y tratamiento oportuno precoz. En cuanto al manejo del cuadro, junto a la estabilización hemodinámica se recomienda un control hemostático activo por sobre manejo conservador, siendo la embolización transarterial la alternativa de elección actualmente. Describimos a continuación una serie de tres casos clínicos de pacientes que debutan con manifestación clínica de hemoperitoneo durante el proceso diagnóstico de un CHC.

Nonalcoholic steatohepatitis and hepatocellular carcinoma: Brazilian survey

OBJECTIVE: The majority of cases of hepatocellular carcinoma have been reported in individuals with cirrhosis due to chronic viral hepatitis and alcoholism, but recently, the prevalence has become increasingly related to nonalcoholic steatohepatitis around the world. The study aimed to evaluate the clinical and histophatological characteristics of hepatocellular carcinoma in Brazilians' patients with nonalcoholic steatohepatitis at the present time. METHODS: Members of the Brazilian Society of Hepatology were invited to complete a survey regarding patients with hepatocellular carcinoma related to nonalcoholic steatohepatitis. Patients with a history of alcohol intake (>20 g/day) and other liver diseases were excluded. Hepatocellular carcinoma diagnosis was performed by liver biopsy or imaging methods according to the American Association for the Study of Liver Diseases’ 2011 guidelines. RESULTS: The survey included 110 patients with a diagnosis of hepatocellular carcinoma and nonalcoholic fatty liver disease from nine hepatology units in six Brazilian states (Bahia, Minas Gerais, Rio de Janeiro, São Paulo, Paraná and Rio Grande do Sul). The mean age was 67±11 years old, and 65.5% were male. Obesity was observed in 52.7% of the cases; diabetes, in 73.6%; dyslipidemia, in 41.0%; arterial hypertension, in 60%; and metabolic syndrome, in 57.2%. Steatohepatitis without fibrosis was observed in 3.8% of cases; steatohepatitis with fibrosis (grades 1-3), in 27%; and cirrhosis, in 61.5%. Histological diagnosis of hepatocellular carcinoma was performed in 47.2% of the patients, with hepatocellular carcinoma without cirrhosis accounting for 7.7%. In total, 58 patients with cirrhosis had their diagnosis by ultrasound confirmed by computed tomography or magnetic resonance imaging. Of these, 55% had 1 nodule; 17%, 2 nodules; and 28%, ≥3 nodules. CONCLUSIONS: Nonalcoholic steatohepatitis is a relevant risk factor associated with hepatocellular carcinoma in patients with and without cirrhosis in Brazil. In this survey, hepatocellular carcinoma was observed in elevated numbers of patients with steatohepatitis without cirrhosis.

Comparative study on liver transplantation with and without hepatocellular carcinoma with cirrhosis: analysis of meld, waiting time and survival / Estudo comparativo em pacientes cirróticos portadores e não portadores de carcinoma hepatocelular submetidos ao transplante hepático: análise do meld, do tempo em lista de espera e da sobrevida

Background: Liver transplantation is the usual treatment for hepatocellular carcinoma. Aim : To analyze the MELD score, waiting time and three month and one year survival for liver transplantation in cirrhotic patients affected by hepatocellular carcinoma or not. Methods: This was a retrospective, observational and analytical study of 93 patients submitted to liver transplantation. Results: There were 28 hepatocellular carcinoma and 65 non-hepatocellular carcinoma patients with no differences related to age and sex distribution. The main causes of cirrhosis on hepatocellular carcinoma were hepatitis C virus (57.1%) and hepatitis B virus (28.5%), more frequent than non-hepatocellular carcinoma patients, which presented 27.7% and 4.6% respectively. The physiological and exception MELD score on hepatocellular carcinoma were 11.9 and 22.3 points. On non-hepatocellular carcinoma, it was 19.4 points, higher than the physiological MELD and lower than the exception MELD on hepatocellular carcinoma. The waiting time for transplantation was 96.2 days for neoplasia, shorter than the waiting time for non-neoplasia patients, which was 165.6 days. Three month and one year survival were 85.7% and 78.6% for neoplasia patients, similar to non-neoplasia, which were 77% and 75.4%. Conclusion : Hepatocellular carcinoma patients presented lower physiological MELD score, higher exception MELD score and shorter waiting time for transplantation when compared to non-hepatocellular carcinoma patients. Three month and one year survival were the same between the groups.

Racional : O tratamento habitual do carcinoma hepatocelular é o transplante hepático. Objetivo : Analisar o MELD, o tempo em lista de espera e a sobrevida em três meses e em um ano de pacientes submetidos ao transplante hepático cadavérico e divididos em dois grupos: portadores e não portadores de carcinoma hepatocelular. Método : Estudo analítico, observacional e retrospectivo de 93 pacientes transplantados. Resultados : Os grupos foram similares em relação ao sexo e à idade. Os 28 pacientes com a neoplasia apresentaram maior frequência de vírus da hepatite C (57,1%) e da hepatite B (28,5%) em relação aos 65 não portadores, que foi de 27,7% e 4,6% respectivamente. O MELD fisiológico e corrigido dos portadores de carcinoma hepatocelular foi de 11,9 e 22,3 pontos, enquanto que o dos pacientes sem foi de 19,4 pontos, maior do que o MELD fisiológico e menor do que o MELD corrigido dos portadores. O tempo em lista de espera dos com a neoplasia foi de 96,2 dias, menor do que a dos sem a ela que foi de 165,6 dias. A sobrevida em três meses e em um ano dos pacientes acometidos pela neoplasia foi de 85,7% e 78,6%, igual à sobrevida dos não acometidos que foi de 77% e 75,4%. Conclusão : Os portadores de carcinoma hepatocelular apresentaram menor MELD fisiológico, menor tempo em lista e maior MELD corrigido em relação aos não portadores. A sobrevida em três meses e em um ano foi igual entre os grupos.

Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Indications for Treatment / 대한소화기학회지

The landscape of treatment for HCV infection has evolved substantially with the advent of highly effective direct-acting antiviral agents (DAA). The Korean Association for the Study of the Liver updated guideline for managemnt of hepatitis C in accordance with the introduction of DAA into practice in late 2015. Due to high effectiveness and few side effects of DAA, indications for treatment has been widened to include patients who had been contraindicated for the combination treatment of peginterferon-α and ribavirin, i.e. decompensated cirrhosis and pre- and post-liver transplant setting. As succeesul treatment of HCV can reduce complications of cirrhosis, development of hepatocelluar carcinoma and liver-related mortality, and improve extrahepatic manifestions, all HCV-infected patients with no contraindication should be considered for treatment. Considering the risk for morbidity and mortality and benefit of treatment, patients with advanced fibrosis ≥F3 including compensated and decompensated cirrhosis, those in the pre- and post-tranplasnt setting, and those with severe extrahepatic manifestations including HCV-related mixed cryoglobulinemia and glomerulonephritis should be given priority for treatment.

Cyanoacrylate injection versus band ligation for bleeding from cardiac varices along the lesser curvature of the stomach

BACKGROUND/AIMS: Practice guidelines recommend endoscopic band ligation (EBL) and endoscopic variceal obturation (EVO) for bleeding from esophageal varices and fundal varices, respectively. However, the optimal treatment for bleeding from cardiac varices along the lesser curvature of the stomach (GOV1) remains undefined. This retrospective study compared the efficacy between EBL and EVO for bleeding from GOV1. METHODS: Patients treated by EBL or EVO via cyanoacrylate injection for bleeding from GOV1 were enrolled. Patients diagnosed with hepatocellular carcinoma or treated with endoscopic injection sclerotherapy were excluded. RESULTS: The study included 91 patients treated for bleeding from GOV1. The mean age was 56.3±10.9 years (mean±SD), and 78 of them (85.7%) were men. Overall, 51 and 40 patients were treated with EBL and EVO, respectively. A trend for a higher hemostasis rate was noted in the EVO group (100%) than in the EBL group (82.6%, P=0.078). Varices rebled in 15 patients during follow-up. The rebleeding rate was significantly higher in the EBL group than in the EVO group (P=0.004). During follow-up, 13 patients died (11 in the EBL group and 2 in the EVO group); the survival rate was marginally significant between two groups (P=0.050). The rebleeding-free survival rate was significantly higher in the EVO group than in the EBL group (P=0.001). CONCLUSIONS: Compared to EBL, EVO offered significantly lower rebleeding rates, significantly higher rebleeding-free survival rates, and a trend for higher hemostasis and survival rates. EVO appears to be the better therapeutic option for bleeding from GOV1.

Survival outcomes of hepatic resection compared with transarterial chemoembolization or sorafenib for hepatocellular carcinoma with portal vein tumor thrombosis

BACKGROUND/AIMS: Treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains controversial. We compared the outcomes of hepatic resection (HR), transarterial chemoembolization (TACE), and sorafenib therapy as treatments for HCC with PVTT. METHODS: Patients diagnosed as HCC with PVTT between January 2000 and December 2011 who received treatment with sorafenib, HR, or TACE were included. Patients with main PVTT, superior mesenteric vein tumor thrombosis, or Child-Turcotte-Pugh (CTP) class C were excluded. The records of 172 patients were analyzed retrospectively. HR, TACE, and sorafenib treatment were performed is 40, 80, and 52 patients respectively. PVTT was classified as either involving the segmental branch (type I) or extending to involve the right or left portal vein (type II). RESULTS: The median survival time was significantly longer in the HR group (19.9 months) than in the TACE and sorafenib groups (6.6 and 6.2 months, respectively; both p<0.001), and did not differ significantly between the latter two groups (p=0.698). Among patients with CTP class A, type I PVTT or unilobar-involved HCC, the median survival time was longer in the HR group than in the TACE and sorafenib groups (p=0.006). In univariate analyses, the initial treatment method, tumor size, PVTT type, involved lobe, CTP class, and presence of cirrhosis or ascites were correlated with overall survival. The significant prognostic factors for overall survival in Cox proportional-hazards regression analysis were initial treatment method (HR vs. TACE: hazard ratio=1.750, p=0.036; HR vs. sorafenib: hazard ratio=2.262, p=0.006), involved lobe (hazard ratio=1.705, p=0.008), PVTT type (hazard ratio=1.617, p=0.013), and CTP class (hazard ratio=1.712, p=0.012). CONCLUSIONS: Compared with TACE or sorafenib, HR may prolong the survival of patients with HCC in cases of CTP class A, type I PVTT or unilobar-involved HCC.

Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy

Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis.