Multiple factors affect the regeneration of liver

SUMMARY OBJECTIVE To study factors affecting the liver regeneration after hepatectomy METHODS With 3D reconstitution technology, liver regeneration ability of 117 patients was analysed, and relative factors were studied. RESULTS There was no statistically difference between the volume of simulated liver resection and the actual liver resection. All livers had different degrees of regeneration after surgery. Age, gender and blood indicators had no impact on liver regeneration, while surgery time, intraoperative blood loss, blood flow blocking time and different ways of liver resection had a significant impact on liver regeneration; In addition, the patients' own pathological status, including, hepatitis and liver fibrosis all had a significant impact on liver regeneration. CONCLUSION 3D reconstitution model is a good model to calculate liver volume. Age, gender, blood indicators and biochemistry indicators have no impact on liver regeneration, but surgery indicators and patients' own pathological status have influence on liver regeneration.

RESUMO OBJETIVO Estudar os fatores que afetam a regeneração hepática após hepatectomia. MÉTODOS A capacidade de regeneração hepática de 117 pacientes foi analisada com a tecnologia de reconstituição 3D e foram estudados os fatores relacionados. RESULTADOS Não houve diferença estatística significante entre o volume de ressecção hepática simulada e a ressecção atual. Todos os fígados apresentaram diferentes graus de regeneração após cirurgia. Idade, gênero e indicadores sanguíneos não tiveram impacto na regeneração hepática, enquanto que tempo de cirurgia, perda sanguínea intraoperatória, tempo de bloqueio do fluxo sanguíneo e diferentes formas de ressecção mostraram impacto significante na regeneração do órgão. Além disso, condições patológicas dos pacientes, incluindo hepatite e fibrose hepática, tiveram impacto significante na regeneração hepática. CONCLUSÃO O modelo de reconstituição 3D é um bom modelo para calcular o volume do fígado. Idade, gênero, indicadores sanguíneos e bioquímicos não tiveram impacto na regeneração hepática, mas indicadores operatórios e condição patológica dos pacientes mostraram influência na regeneração do órgão.

Schistosomal liver fibrosis and hepatocellular carcinoma - case series of patients submitted to liver transplantation

ABSTRACT Schistosomiasis affects approximately 207 million people in 76 countries. The association between hepatocellular carcinoma and Schistosoma mansoni infection has been investigated. Studies using animal models suggest that the parasite may accelerate the oncogenic process when combined with other factors, such as hepatitis C virus infection or exposure to a carcinogen. Herein, we report a case series of six hepatocellular carcinoma patients from Northeast Brazil, with negative serology for both hepatitis B and C virus, submitted to liver transplantation, whose explant showed evidence of schistosomal liver fibrosis. Since all patients enrolled in this study were submitted to liver transplantation, we were able to access the whole explanted liver and perform histopathological analysis, which is often not possible in other situations. Although 50% of them showed signs of liver failure, no cirrhosis or any liver disease other than schistosomal fibrosis had been detected. These uncommon findings suggest that Schistosoma mansoni infection might predispose to hepatocellular carcinoma development, regardless of the absence of other risk factors.

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

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

Serum microRNA-30c levels are correlated with disease progression in Xinjiang Uygur patients with chronic hepatitis B

We aimed to investigate the potential role and mechanism of microRNA-30c (miR-30c) in the pathological development of chronic hepatitis B (CHB). The serum levels of miR-30c in hepatitis B virus (HBV) carrier Xinjiang Uygur patients with inactive, low-replicative, high-replicative and HBe antigen-positive CHB were investigated. HepG2 cells were co-transfected with pHBV1.3 and miR-30c mimic or inhibitor or scramble RNA. The effects of miR-30c dysregulation on HBV replication and gene expression, cell proliferation and cell cycle were then investigated. miR-30c was down-regulated in Xinjiang Uygur patients with CHB compared to healthy controls and its expression level discriminated HBV carrier patients with inactive, low-replicative, high-replicative and HBe antigen-positive risk for disease progression. Overexpression of miR-30c significantly inhibited HBV replication and the expressions of HBV pgRNA, capsid-associated virus DNA and Hbx in hepatoma cells. Moreover, overexpression of miR-30c significantly inhibited cell proliferation and delayed G1/S phase transition in hepatoma cells. Opposite effects were obtained after suppression of miR-30c. Our results indicate that miR-30c was down-regulated in Xinjiang Uygur patients with CHB, and miR-30c levels could serve as a marker for risk stratification of HBV infection. Down-regulation of miR-30c may result in the progression of CHB via promoting HBV replication and cell proliferation.

Is resection of hepatocellular carcinoma in the era of liver transplantation worthwile? A single center experience / Ressecção de carcinoma hepatocelular na era do transplante de fígado: vale a pena? Experiência de um único centro

ABSTRACT Background - Liver resection for hepatocellular carcinoma is a potentially curative therapeutic procedure that can be performed readily after its indication, without the need of a long waiting time and lower costs when compared to liver transplantation, being a good alternative in patients with preserved/good liver function. Objective - Evaluate long-term results of liver resection from a high volume single center for selected patients with hepatocellular carcinoma in a context of a long waiting list for liver transplant. Methods - One hundred and one patients with hepatocellular carcinoma, with a mean age of 63.1 years, and preserved liver function were submitted to liver resection. Clinical and pathological data were evaluated as prognostic factors. Mean follow-up was 39.3 months. Results - All patients had a single nodule and 57 (58.2%) patients were within the Milan criteria. The size of the nodule ranged from 1 to 24 cm in diameter. In 74 patients, liver resection was performed with the open approach and in 27 (26.7%) was done laparoscopically. Postoperative morbidity was 55.3% being 75.5% of the complications classified as Dindo-Clavien I and II and operative mortality was 6.9%. Five-year overall and disease free survival rates were 49.9% and 40.7%, respectively.After a log-rank univariate analysis, the levels of preoperative alpha-fetoprotein (P=0.043), CA19-9 (P=0.028), capsule invasion (P=0.03), positive margin (R1-R2) (P=0.004) and Dindo-Claviens' morbidity classification IV (P=0.001) were the only parameters that had a significant negative impact on overall survival. On the odds-ratio evaluation, the only significant factors for survival were high levels of alpha-fetoprotein (P=0.037), and absence of free margins (P=0.008). Conclusion - Resection, for selected cases, is a potentially curative treatment with acceptable morbidity and mortality and, in a context of a long waiting list for transplant, plays an important role for the treatment of hepatocellular carcinoma.

RESUMO Contexto - A ressecção do carcinoma hepatocelular é um procedimento terapêutico potencialmente curativo que pode ser realizado imediatamente após sua indicação, sem a necessidade de longo tempo de espera e com custos mais baixos quando comparado com o transplante hepático, sendo uma boa alternativa em pacientes com função hepática preservada. Objetivo - Avaliar os resultados a longo prazo da ressecção hepática em centro de alto volume cirúrgico para pacientes selecionados com carcinoma hepatocelular em um contexto de uma longa lista de espera para transplante de fígado. Métodos - Cento e um pacientes com carcinoma hepatocelular, com idade média de 63,1 anos, e função hepática preservada foram submetidos à ressecção hepática. Os dados clínicos e patológicos foram avaliados como fatores prognósticos. O seguimento médio foi de 39,3 meses. Resultados - Todos os pacientes apresentavam um único nódulo e 57 (58,2%) estavam dentro dos critérios de Milão. O tamanho do nódulo variou de 1 a 24 cm de diâmetro. Em 74 pacientes, a ressecção hepática foi realizada com a abordagem aberta e em 27 (26,7%) através de laparoscopia.A morbidade pós-operatória foi de 55,3%, sendo 75,5% das complicações classificadas como Dindo-Clavien I e II e a mortalidade operatória foi de 6,9%. As sobrevida global e livre de doença em 5 anos foram 49,9% e 40,7%, respectivamente. Depois de análise univariada log-rank, os níveis de alfa-fetoproteína no pré-operatório (P=0,043), CA19-9 (P=0,028), invasão de cápsula (P=0,03), margem positiva (R1-R2) (P=0,004) e classificação de morbidade de Dindo-Claviens tipo IV (P=0,001) foram os únicos parâmetros que tiveram um impacto negativo significativo na sobrevida global. Na avaliação de risco relativo (odds-ratio), os únicos fatores importantes para a sobrevivência foram altos níveis de alfa-fetoproteína (P=0,037), e ausência de margens livres (P=0,008). Conclusão - A ressecção hepática em casos seleccionados, é um tratamento potencialmente curativo com morbilidade e mortalidade aceitáveis e, num contexto de uma longa lista de espera para transplante, tem um papel importante para o tratamento do carcinoma hepatocelular.

Association between microRNA single nucleotide polymorphisms and the risk of hepatocellular carcinoma / Asociación entre polimorfismos de un nucleótido en microRNA circulante y riesgo de carcinoma hepatocelular

Background: Hepatocellular carcinoma (HCC) has a high morbidity and mortality. Single nucleotide polymorphisms (SNPs) of microRNA (miRNA) may be associated with the susceptibility to develop certain malignant tumors. Aim: To study the association between SNPs of miRNA and hepatocellular carcinoma in peripheral blood samples. Material and Methods: Three SNPs in miRNA were studied in peripheral blood samples of 498 patients with HCC and 520 controls. Results: A significant association was observed between rs13299349 in miRNA3152 and HCC. AA genotype or A allele were significantly associated with increased risk of HCC. A allele was associated with the size and number of tumor foci. There was also a relationship between rs10061133 in miRNA449b and HCC. The G allele was significantly associated with increased risk of HCC compared with A allele. Conclusions: This study links rs13299349 in miRNA3152 and rs10061133 in miRNA449b with the risk of developing HCC.

Antecedentes: El carcinoma hepatocelular (CHC) tiene una alta morbilidad y mortalidad. Polimorfismos de un nucleótido (SNP) presentes en el microRNA (miRNA) circulante pueden asociarse a ciertos tumores. Objetivo: Estudiar la asociación entre la presencia de SNPs en miRNA circulante y la presencia de carcinoma hepatocelular. Material y Métodos: Se determinó la presencia de tres SNP en microRNA de sangre periférica en 498 pacientes con CHC y 520 controles. Resultados: El SNP rs13299349 en el miRNA3152 se asoció con CHC. El genotipo AA o el alelo A se asociaron con un riesgo mayor de presentar un CHC. El alelo A se asoció además con el tamaño y número de focos del tumor. Se observó también una relación entre el SNP rs10061133 en el miRNA449b y HCC. En este caso, el alelo G se relacionó con un mayor riesgo de CHC. Conclusiones: Los SNP rs13299349 en el miRNA3152 y rs10061133 en el miRNA449b se asocian al riesgo de desarrollar CHC.

Liver-specific magnetic resonance contrast medium in the evaluation of chronic liver disease / Aplicações do contraste hepato-específico de ressonância magnética nas hepatopatias crônicas

ABSTRACT The hepatobiliary-specific contrast medium (gadoxetic acid – Primovist®) is primarily used to improve detection and characterization of focal hepatic lesions, such as in chronic liver disease patients with suspected hepatocellular carcinoma. Since the contrast medium is selectively taken up by functioning hepatocytes in the late hepatobiliary phase, it helps to detect typical hepatocellular carcinoma, which show low signal intensity on this phase. This imaging feature also assists in differentiating regenerative/dysplastic nodules from early hepatocellular carcinomas (with over 90% accuracy), as well as hypervascular hepatocellular carcinomas from arterial pseudo-enhancement foci. Future perspectives include its use in quantification of hepatic function and fibrosis.

RESUMO O contraste hepato-específico (ácido gadoxético – Primovist®) tem como utilidade principal melhorar a detecção e a caracterização de lesões hepáticas focais, por exemplo, em hepatopatas crônicos com suspeita de hepatocarcinoma. Por apresentar captação seletiva por hepatócitos funcionantes na fase hepatobiliar tardia, auxilia na detecção de hepatocarcinomas típicos – a maioria dos quais apresentando hipossinal nessa fase. Essa característica de imagem também auxilia na diferenciação entre nódulos regenerativos/ displásicos e hepatocarcinomas precoces (com mais de 90% de acurácia), e entre hepatocarcinomas hipervascularizados e focos de pseudorrealce arterial. Perspectivas futuras promissoras incluem sua utilização na quantificação de função e de fibrose hepáticas.

Role of complementary therapies in the understanding of primary healthcare professionals: a systematic review / Papel de prácticas complementarias en la comprensión de los profesionales de atención primaria: una revisión sistemática / Papel das práticas complementares na compreensão dos profissionais da Atenção Básica: uma revisão sistemática

Objective To identify the understanding of the healthcare professionals in relation to the role of complementary therapies in primary health care. Method Systematic review by way of the following information sources: PubMed, CINAHL, PeriEnf, AMED, EMBASE, Web of Science, Psicoinfo and Psicodoc, using the keyword Primary Health Care alone, and associated with the following keywords: Medicinal Plants, Herbal Medicine, Homeopathy, Traditional Chinese Medicine, Acupuncture, Anthroposophical Medicine. Results Twenty-two studies from 1986 to 2011 were included. We identified three styles of practice: conventional medicine, complementary therapies and integrative medicine. Positioning professional practices within these three styles may facilitate discussion of concepts of health care, enhancing the health care provided as a result. Conclusion The work process in primary care presents difficulties for conducting integrative and holistic health care, but this practice has been introduced over time by professionals who integrate conventional medicine and complementary therapies, concerned with the care and well-being of patients.
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Objetivo Identificar la comprensión de los profesionales sobre el papel de las prácticas complementarias en la atención primaria. Método Revisión sistemática. Fuentes de datos: PubMed, CINAHL, PeriEnf, AMED, EMBASE, Web of Science, Psicodoc y PysicoInfo. Descriptor Atención Primaria se asoció solo a los siguientes descriptores: plantas medicinales, fitoterapia, homeopatía, acupuntura, medicina tradicional china, medicina antroposófica. Resultados Se incluyeron 22 pesquisas entre 1986-2011. Tres estilos de práctica se identificaron: medicina convencional, medicina integrativa y Terapias Complementarias. Identificar la práctica profesional dentro de estos tres estilos puede facilitar la discusión de los conceptos de salud y la atención, mejorar la atención. Conclusión El proceso de trabajo en atención primaria presenta dificultades para realización de integración y atención integral, pero esta práctica se ha introducido con profesionales que integran medicina convencional y complementaria, ocupados con la atención y bienestar del paciente.


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Objetivo Identificar a compreensão dos profissionais de saúde quanto ao papel das práticas complementares na Atenção Básica. Método Revisão sistemática cujas fontes de informação foram: PubMed, CINAHL, PeriEnf, AMED, EMBASE, Web of Science, PysicoInfo e PsicoDoc, utilizando o descritor Atenção Básica associado, isoladamente, aos seguintes descritores: Plantas Medicinais, Fitoterapia, Homeopatia, Medicina Tradicional Chinesa, Acupuntura, Medicina Antroposófica. Resultados Incluíram-se 22 estudos entre 1986-2011. Identificaram-se três estilos de prática: medicina convencional, práticas integrativas e medicina integrativa. Posicionar a prática profissional dentro desses três estilos pode facilitar a discussão de concepções de saúde e cuidado, ampliando o cuidado. Conclusão O processo de trabalho na Atenção Básica apresenta dificuldades para a realização de cuidado integrativo e holístico, mas essa prática vem sendo introduzida com profissionais que integram medicina convencional e práticas complementares, preocupados com o cuidado e o bem-estar do paciente.

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Quimioembolización hepática en el manejo terapéutico del hepatocarcinoma: Reporte de dos casos / Chemoembolization of hepatocarcinoma: Report of two cases

Chemoembolization is a therapeutic alternative for those patients with hepatocarcinoma that cannot be excised surgically or that are waiting a liver allograft. We report two patients with hepatocarcinoma who were subjected to chemoembolization. A 65 years old male with a chronic liver disease and right lobe hepatocarcinoma, waiting for a liver transplantation, was subjected to two sessions, of chemoembolization four weeks apart. A magnetic resonance showed a 80 percent reduction of tumor volume one month later. A 72 years old diabetic male with an alcoholic liver disease with two hepatocarcinoma in the right lobe was subjected to two sessions of chemoembolization, separated by four weeks. A magnetic resonance one month later showed the absence of blood flow in both lesions, suggesting complete necrosis.

Resultados do transplante hepático em pacientes com diagnóstico pré-operatório de hepatocarcinoma / Results of liver transplantation in patients with preoperative diagnosis of hepatocellular carcinoma

RACIONAL: O hepatocarcinoma é o tumor hepático maligno mais freqüente em humanos e sua forte associação com a cirrose torna a abordagem terapêutica ainda um desafio. O transplante hepático é o tratamento de escolha para os pacientes cirróticos com hepatocarcinoma irressecável em estágio precoce OBJETIVO: Avaliar a evolução pós-transplante de 15 pacientes cirróticos com diagnóstico pré-operatório de hepatocarcinoma precoce irressecável que preenchiam os Critérios de Milão e foram submetidos a transplante hepático entre setembro de 1991 e dezembro de 2003 no Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, PR MÉTODOS: Foram analisados retrospectivamente os dados clínicos dos 15 receptores de transplante hepático tendo como parâmetros principais a sobrevida do paciente e a ocorrência de recidiva tumoral após o transplante RESULTADOS: A idade média dos pacientes foi 49,2 ± 14,3 anos, sendo a hepatite crônica C a causa implicada em 60 por cento dos casos. Em 80 por cento dos pacientes realizou-se terapia adjuvante pré-transplante (quimioembolização ou alcoolização). Na análise dos explantes hepáticos constatou-se que 5 dos 12 pacientes (38,5 por cento) submetidos a terapia adjuvante apresentavam necrose completa do tumor, enquanto os demais apresentavam alguma extensão de tecido tumoral viável. Em apenas 4 dos 15 explantes (26,6 por cento) constatou-se invasão microvascular. A mediana do seguimento pós-transplante foi de 33 meses (8_71 meses), tendo ocorrido apenas um óbito precoce, não relacionado à recidiva tumoral (sepse biliar). A sobrevida pós-transplante livre de recurrência em 1 e 3 anos no grupo foi de 93 por cento CONCLUSÕES: O transplante hepático é uma excelente alternativa de tratamento em pacientes cirróticos com hepatocarcinoma irressecável em fase precoce, alcançando elevados índices de sobrevida livre de recurrência tumoral.

BACKGROUD: Hepatocellular carcinoma is the most frequent malignant hepatic tumor in humans, and its association with cirrhosis makes the therapeutic approach still a challenge. Liver transplantation is the treatment of choice for cirrhotic patients with unresectable early hepatocellular carcinoma AIM: To evaluate the post-transplant outcome of a cohort of 15 cirrhotic patients with preoperative diagnosis of unresectable early hepatocellular carcinoma according the Milan criteria who underwent liver transplantation between September 1991 and December 2003 METHODS: We retrospectively reviewed the clinical data from 15 liver transplant recipients and the explanted livers were assessed for the efficacy of preoperative therapy. Patient survival and tumor recurrence were evaluated as primary outcome measures RESULTS: The mean age of the patients was 49.2 ± 14.3 years and hepatitis C was the etiology of the underlying liver disease in 60 percent. Preoperative therapy, either chemoembolization or percutaneous ethanol injection, was performed in 12 (86 percent) patients. Complete necrosis of all tumoral lesions were observed in 5 of 12 patients (44,66 percent); all others had variable amounts of viable tumor in the explanted liver. Only 4 of the 15 (26.6 percent) explanted livers had microscopic vascular invasion. The median post-transplant follow-up was 33 months (range: 8-71months) and no tumor recurrence was detected during this period. The only death was an early event not related to the tumor. The recurrence-free survival rates at 1 and 3 years were 93 percent CONCLUSION: Liver transplantation has emerged as a good alternative for cirrhotic patients with early hepatocellular carcinoma not amenable to curative resection, offering excellent recurrence-free survival rates.

Carcinoma hepatocelular (CHC): 2ª parte / Hepatocellular carcinoma (CHCC): 2ª part

Invariavelmente no Brasil o diagnóstico do carcinoma hepatocelular (CHC) é realizado em fase avançada da doença. Fundamentos neste aspecto os autores deste trabalho, estabelecem consideraçöes sobre condiçöes pré-neoplásicas, aspectos clínicos, laboratorias, de imagem e anatompatológico relativos a este tipo de neoplasia. Propöem um esquema de seguimento dos portadores de hepatopatia crônica depende dos vírus B e näo B, enfatizando sobre a possibilidade de detecçäo de pequenos CHC, as quais poderiam se instalar sobre fígado previamente lesado