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1.
Braz. j. biol ; 84: e252676, 2024. ilus, graf, tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1364501

RESUMO

Hepatitis C virus infection (HCV) is the foremost reason of progressive hepatic fibrosis and cirrhosis, with an elevated risk of hepatocellular carcinoma (HCC) development. Medicinal plants have been used for human health benefits for several years, but their therapeutic potential needs to be explored. The main objective of this study was to figure out the in vitro antiviral and anticancer characteristics of total crude protein of Iberis gibraltarica against HCV and HCC. Total crude protein of Iberis gibraltarica was isolated and quantified. The level of cytotoxicity was measured against the HepG2 cell line and it shows no significant cytotoxicity at the concentration of 504µg/ml. The anti-HCV effect was determined by absolute quantification via real time RT-PCR method and viral titer was reduced up to 66% in a dose dependent manner against the total protein of Iberis gibraltarica. The anticancer potential of Iberis gibraltarica was also examined through mRNA expression studies of AFP and GPC3 genes against the total protein of Iberis gibraltarica-treated HepG2 cells. The results show up to 90% of the down-regulation expression of AFP and GPC3. The obtained results indicate the therapeutic potential of total protein of Iberis gibraltarica against HCV and hepatocellular carcinoma in vitro.


A infecção pelo vírus da hepatite C (HCV) é a principal causa de fibrose hepática progressiva e cirrose, com risco elevado de desenvolvimento de carcinoma hepatocelular (HCC). As plantas medicinais vêm sendo utilizadas para benefícios à saúde humana há vários anos, mas seu potencial terapêutico precisa ser explorado. O principal objetivo deste estudo foi descobrir as características antivirais e anticancerígenas in vitro da proteína bruta total de Iberis gibraltarica contra HCV e HCC. A proteína bruta total de Iberis gibraltarica foi isolada e quantificada. O nível de citotoxicidade foi medido contra a linha celular HepG2 e não apresenta citotoxicidade significativa na concentração de 504µg/ml. O efeito anti-HCV foi determinado por quantificação absoluta através do método RT-PCR em tempo real e o título viral foi reduzido em até 66% de forma dose-dependente contra a proteína total de Iberis gibraltarica. O potencial anticancerígeno de Iberis gibraltarica também foi examinado através de estudos de expressão de mRNA dos genes AFP e GPC3 contra a proteína total de células HepG2 tratadas com Iberis gibraltarica. Os resultados mostram até 90% da expressão de regulação negativa de AFP e GPC3. Os resultados obtidos indicam o potencial terapêutico da proteína total de Iberis gibraltarica contra HCV e carcinoma hepatocelular in vitro.


Assuntos
Plantas Medicinais , Terapêutica , Carcinoma Hepatocelular/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico
2.
Hepatología ; 4(2): 103-115, 2023. tab, fig
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1428989

RESUMO

Introducción. El acceso al trasplante hepático (TH) en pacientes con carcinoma hepatocelular (CHC) se basa en la aplicación de criterios morfológicos rigurosos estipulados desde 1996, co-nocidos como criterios de Milán. Una de las estrategias descritas para expandir estos criterios se conoce como downstaging (reducción del estadiaje tumoral mediante terapias locorregionales). El objetivo de este estudio fue describir el comportamiento postrasplante de pacientes con CHC que ingresaron dentro de los parámetros de Milán, comparado con el de aquellos pacientes llevados a terapia de downstaging en un centro colombiano. Metodología. Se incluyeron pacientes adultos con cirrosis hepática (CH) y CHC que fueron llevados a TH en el Hospital Pablo Tobón Uribe, entre julio de 2012 a septiembre de 2021. Como desenlace principal se definió recurrencia y tiempo de recurrencia de la enfermedad tumoral, muerte por todas las causas y tiempo al fallecimiento. Se evaluaron las características sociodemográficas y clínicas de cada grupo. Se incluyeron scores pronósticos de recurrencia de la enfermedad tumoral. Resultados. Se trasplantaron 68 pacientes con CH y CHC, 50 (73,5 %) eran hombres y la edad promedio fue 59 años; 51 pacientes (75 %) cumplían con los criterios de Milán y 17 (25 %) fueron llevados a terapia de downstaging previo al TH. No hubo diferencias significativas en la supervivencia global y supervivencia libre de trasplante entre los dos grupos evaluados, p=0,479 y p=0,385, respectivamente. Tampoco hubo diferencia significativa en la recurrencia de la enfermedad tumoral entre ambos grupos (p=0,81). En total hubo 7 casos de recurrencia tumoral (10,2 %) y 11 casos de muerte (16,2 %). Conclusiones. No se encontraron diferencias significativas en recurrencia y mortalidad entre los pacientes que cumplían los criterios de Milán y los trasplantados luego de la terapia de downstaging, en un tiempo de se-guimiento de 53 meses hasta el último control posterior al trasplante hepático. Esta sería la primera evaluación prospectiva de un protocolo de downstaging para CHC en Colombia.


Introduction. Access to liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is based on the application of rigorous morphological criteria stipulated since 1996, known as the Milan criteria. One of the strategies described to expand these criteria is known as downstaging (tu-mor staging reduction through locoregional therapies). The objective of this study was to describe the post-transplant performance of patients with HCC who were admitted within the Milan parameters, compared with those of patients taken to downstaging therapy, in a Colombian center. Methodolo-gy. Adult patients with cirrhosis and HCC that received LT between July 2012 and September 2021 at the Pablo Tobón Uribe Hospital were included. The main outcome was defined as recurrence and time to recurrence of the tumor disease, death from all causes, and time to death. The socio-demographic and clinical characteristics of each group were evaluated. Tumor disease recurrence prognostic scores were included. Results. Sixty-eight patients with cirrhosis and HCC received LT in the time frame, 50 (73.5%) were men and the mean age was 59 years. Fifty-one patients were trans-planted (75%) fulfilling Milan criteria, and 17 (25%) patients received downstaging therapies before LT. There were no significant differences in overall survival and transplant-free survival between the two groups, p=0.479 and p=0.385, respectively. There was also no significant difference in the recurrence of the tumor disease between both groups (p=0.81). In total there were 7 tumoral recurrences (10.2%) and 11 deaths (16.2%). Conclusions. There were no differences in recurrence and survival between patients transplanted fulfilling Milan criteria and those receiving downstaging therapies, following a mean time of 53 months after LT. This is the first prospective evaluation of the downstaging protocol in Colombia.


Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Sobrevida , Transplante de Fígado , Carcinoma Hepatocelular , Sobrevivência , Terapêutica , Fibrose , Cirrose Hepática
3.
São Paulo; s.n; s.n; 2023. 93 p. graf, tab.
Tese em Português | LILACS | ID: biblio-1437666

RESUMO

A quimioprevenção do câncer refere-se ao uso de compostos naturais ou sintéticos para prevenir o desenvolvimento das neoplasias antes do estabelecimento da malignidade. O ácido butirico (AB) atua como um potente quimiopreventivo na hepatocarcinogênese, reduzindo o número e o tamanho de lesões pré neoplásicas persistentes (pLPN), induzindo a apoptose e modulando mecanismos epigenéticos. Já o ácido caprílico (AC), além da sua atuação como potencializador de absorção, vem sendo investigado na área da prevenção do câncer. Neste cenário, o objetivo do trabalho visa avaliar a atividade quimiopreventiva de lipídios estruturados (EST) obtidos por interesterificação enzimática da tributirina com a tricaprilina, na fase de promoção da hepatocarcinogênese experimental. Após o processo de interesterificação, o produto final apresentou novos triacilgliceróis com composição de duas moléculas de ácido butírico para uma de ácido caprilíco. Ratos machos isogênicos da linhagem Fischer 344 foram submetidos ao modelo do hepatócito resistente, sendo distribuídos em dois grupos e tratados diariamente por via intragástrica com lipídios estruturados (EST) ou com o seu controle isocalórico, a maltodextrina (MD), durante a fase de promoção. Como esperado, não houve diferença estatística (p>0,05) em relação ao peso inicial e final dos animais dos grupos MD e EST, o que indica ausência de toxicidade dos compostos administrados. Na análise macroscópica do fígado, foi observada uma redução de 33,3% no grupo EST em relação ao número médio de nódulos macroscópicos em comparação ao grupo MD, porém essa redução não atingiu diferença estatística (p>0,05). Para a avaliação das lesões pré neoplásicas (LPN) foi utilizada a marcação imunoistoquímica para glutationa-S-transferase (GST-P). O grupo EST apresentou uma redução no número de lesões em remodelação e total GSTP-P+, quando comparado com o grupo MD (p<0,05). Quando avaliada a % de corpúsculos apoptóticos e índice de proliferação celular, não houve diferença estatística entre os grupos (p>0,05). Animais tratados com lipídios estruturados apresentaram maiores (p<0,05) concentrações de AC e AB por grama de tecido hepático em relação ao tratamento com maltodextrina. Em relação aos danos no DNA, o grupo EST resultou em cometas de comprimentos menores (p<0,05), menores níveis de γ-H2AX (p<0,05) e maiores concentrações de p53 nuclear, quando comparados aos animais que receberam maltodextrina, sugerindo uma proteção contra danos no DNA no grupo tratado com EST. Os resultados mostraram que o tratamento com EST resultou em ações efetivas na fase de promoção da hepatocarcinogênese experimental


Cancer chemoprevention refers to the use of natural or synthetic compounds to prevent the development of neoplasms before the establishment of malignancy. Butyric acid (AB) acts as a potent chemopreventive in hepatocarcinogenesis, reducing the number and size of persistent preneoplastic lesions (pLPN), inducing apoptosis and modulating epigenetic mechanisms. Caprylic acid (CA), in addition to its role as an absorption enhancer, has been investigated in the area of cancer prevention. In this scenario, the objective of this work was to evaluate the chemopreventive activity of structured lipids (EST) obtained by enzymatic interesterification of tributyrin with tricaprylin, in the phase of promotion experimental hepatocarcinogenesis. After the interesterification process, the final product presented new triacylglycerols with a composition of two molecules of butyric acid to one of caprylic acid. Isogenic male Fischer 344 rats were submitted to the resistant hepatocyte model, divided into two groups and treated daily intragastrically with structured lipids (EST) or with its isocaloric control, maltodextrin (MD), during the promotion phase. As expected, there was no statistical difference (p>0.05) in relation to the initial and final weight of the animals in the MD and EST groups, which indicates the absence of toxicity of the administered compounds. In the macroscopic analysis of the liver, a reduction of 33.3% was observed in the EST group in relation to the mean number of macroscopic nodules compared to the MD group, but this reduction did not reach a statistical difference (p>0.05). For the evaluation of pre-neoplastic lesions (PNL) immunohistochemical staining for glutathione-Stransferase (GST-P) was used. The EST group showed a reduction in the number of remodeling lesions and total GSTP-P+, when compared to the MD group (p<0.05). Animals treated with structured lipids had higher (p<0.05) concentrations of AC and AB per gram of liver tissue compared to treatment with maltodextrin. Regarding DNA damage, the EST group resulted in comets of shorter lengths (p<0.05), lower levels of γ-H2AX (p<0.05) and high concentration of nuclear p53, when compared to animals that received maltodextrin, suggesting protection against DNA damage in the EST treated group. The results showed that EST treatment resulted in effective actions in the promotion phase of experimental hepatocarcinogenesis


Assuntos
Animais , Masculino , Ratos , Quimioprevenção , Lipase/análise , Neoplasias/patologia , Ferimentos e Lesões/complicações , Biotecnologia/classificação , Carcinoma Hepatocelular/patologia , Absenteísmo
4.
Rev. méd. Chile ; 150(11): 1431-1437, nov. 2022. tab
Artigo em Espanhol | LILACS | ID: biblio-1442049

RESUMO

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


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/complicações , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patologia , Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/diagnóstico , Ductos Biliares Intra-Hepáticos/patologia , Estudos Retrospectivos , Cirrose Hepática/complicações
5.
Rev. colomb. gastroenterol ; 37(2): 163-172, Jan.-June 2022. tab, graf
Artigo em Inglês, Espanhol | LILACS | ID: biblio-1394945

RESUMO

Abstract Introduction: Hepatocellular carcinoma (HCC) is the most frequent malignant primary liver tumor globally. In 2018, it ranked sixth and represented the fourth cause of death from cancer; the five-year overall survival is 18 %. Most cases of HCC develop in patients with cirrhosis of any etiology, especially because of hepatitis B and C viruses, alcohol, and recently nonalcoholic steatohepatitis (NASH). Aim: To analyze the clinical characteristics, diagnostic methods, treatments, prognostic variables, and survival. Materials and methods: This retrospective descriptive study was conducted on a cohort of patients diagnosed with cirrhosis and treated between January 2011 and December 2020 at a health care center in Bogotá. The diagnosis of HCC was confirmed radiologically or by biopsy. We analyzed the information descriptively with absolute frequency measures in the case of categorical variables. For continuous variables, the information was summarized with measures of central tendency (mean or median) and their relevant measures of dispersion. Results: We included 152 patients diagnosed with HCC, with a mean age of 69.4 years; 51.3 % were men. The leading cause of HCC was nonalcoholic fatty liver disease (NAFLD), which accounted for almost a third of cases (32 %); other causes were alcohol (15 %) and hepatitis C virus (14 %). The median manifestation of the tumor was two nodules with a size close to 4 cm. Besides, 35 % of patients had a BCLC (Barcelona Clinic Liver Cancer) stage with curative options, and 25 % received curative treatment options. The first-line systemic therapy used in this cohort was sorafenib®, used in 35 patients (33.7 %). Survival curves showed that women, Child-Pugh class A, and BCLC stage 0 had higher median survival. Multivariate analysis showed a higher risk of death for males (hazard ratio [HR]: 2.16; confidence interval [CI]: 1.24-3.76), Child-Pugh class B (HR: 2.14; CI 1.16-3.95), and Child-Pugh class C (HR: 7.52; CI 2.88-19.57). Conclusions: NAFLD is the leading cause of HCC in this cohort. A third of patients are diagnosed in early BCLC stages with a curative treatment option, and 25 % are treated with curative therapies. Sorafenib was the first-line therapy in advanced HCC. Overall survival after diagnosis of HCC remains low, being necessary to join forces in the follow-up of patients with cirrhosis to improve these outcomes.


Resumen Introducción: el hepatocarcinoma (HCC) es el tumor hepático primario maligno más frecuente en el mundo: en 2018 ocupó la sexta posición y representó la cuarta causa de muerte por cáncer; la supervivencia global a 5 años es del 18 %. La mayoría de los casos de HCC se desarrolla en pacientes con cirrosis de cualquier etiología, especialmente por virus de la hepatitis B y C, alcohol y, recientemente, por la esteatohepatitis no alcohólica (NASH). Objetivo: analizar las características clínicas, métodos de diagnóstico, tratamientos, variables pronósticas y supervivencia. Metodología: estudio descriptivo retrospectivo de una cohorte de pacientes con diagnóstico de cirrosis atendidos entre enero de 2011 y diciembre de 2020 en un centro de atención médica de Bogotá, con diagnóstico de HCC confirmado radiológicamente o por biopsia. La información se analizó de forma descriptiva con medidas de frecuencia absoluta en el caso de las variables categóricas; para las variables continuas se resumió la información con medidas de tendencia central (media o medianas) y su respectiva medida de dispersión. Resultados: se incluyeron 152 pacientes diagnosticados con HCC, con edad promedio de 69,4 años, 51,3 % eran hombres. La principal causa de HCC fue el hígado graso no alcohólico (NAFLD), que representó casi una tercera parte de los casos (32 %); otras causas fueron el alcohol (15 %) y el virus de la hepatitis C (14 %). La mediana de presentación del tumor fue de 2 nódulos con un tamaño cercano a 4 cm. El 35 % de los pacientes tenía un estadio BCLC (Barcelona Clinic Liver Cancer) con opciones curativas y el 25 % de los pacientes recibió opciones curativas de tratamiento. La terapia sistémica de primera línea utilizada en esta cohorte fue el sorafenib®, que se utilizó en 35 pacientes (33,7 %). Las curvas de supervivencia mostraron que las mujeres, el estadio Child-Pugh A y el estadio BCLC 0 presentaron mayores medianas de supervivencia. El análisis multivariado evidenció un mayor riesgo de muerte al ser hombre (Hazard ratio [HR]: 2,16; intervalo de confianza [IC]: 1,24 a 3,76), estar en los estadios Child-Pugh B (HR: 2,14; IC: 1,16 a 3,95) y Child-Pugh C (HR: 7,52; IC: 2,88 a 19,57). Conclusiones: el NAFLD es la principal causa de HCC en la presente cohorte, una tercera parte de los pacientes se diagnostica en estadios BCLC tempranos con opción curativa de tratamiento, y un 25 % se trata con terapias curativas. El sorafenib fue la terapia de primera línea en HCC avanzado. La supervivencia global luego del diagnóstico de HCC sigue siendo baja, y es necesario aunar esfuerzos en el seguimiento de los pacientes con cirrosis para mejorar estos resultados.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Terapêutica , Vírus da Hepatite B , Carcinoma Hepatocelular , Diagnóstico , Hepatopatia Gordurosa não Alcoólica , Sorafenibe , Hepatite B , Neoplasias Hepáticas , Pacientes , Sobrevida , Intervalos de Confiança , Causalidade , Análise Multivariada , Medidas de Tendência Central , Neoplasias
6.
Braz. J. Pharm. Sci. (Online) ; 58: e201148, 2022. graf
Artigo em Inglês | LILACS | ID: biblio-1420444

RESUMO

Abstract Hepatocellular carcinoma (HCC) is a common cause of cancer-related death. Sorafenib is the first approved drug for the treatment of advanced HCC. Depression is frequent in cancer patients. Moreover, sorafenib might exert depression as an adverse drug reaction and paroxetine, a selective serotonin reuptake inhibitor, is a recommended pharmacotherapy. This study aimed to investigate the potential synergistic effects of paroxetine and sorafenib on HepG2 cell proliferation and death. Paroxetine and sorafenib were administered to HepG2 cells as single-agents or in combination. Cell viability was determined with XTT cell viability assay. Cellular apoptosis and DNA content were assessed by flow cytometry. The expression of anti-apoptotic Bcl-2 was examined by immunofluorescence confocal microscopy. A lower dose of sorafenib was found to be required to inhibit cell proliferation when in combination with paroxetine. Similarly, the coadministration enhanced cellular apoptosis and resulted in cell cycle arrest. Confocal imaging revealed a remarkably lower cell density and increased expression of Bcl-2 following combined treatment of paroxetine with sorafenib. To our knowledge, this is the first study demonstrating the synergistic effect of paroxetine and sorafenib in HCC and might provide a potentially promising therapeutic strategy.


Assuntos
Paroxetina/efeitos adversos , Células Hep G2/classificação , Sorafenibe/agonistas , Preparações Farmacêuticas/análise , Carcinoma Hepatocelular/patologia , Tratamento Farmacológico/instrumentação , Citometria de Fluxo/métodos
7.
Rev. argent. radiol ; 86(3): 166-178, 2022. graf
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1407206

RESUMO

Resumen La apariencia en imágenes típicas del carcinoma hepatocelular (HCC) es ampliamente reconocida y consiste en hiperrealce en fase arterial con lavado en las fases venosa portal y tardía, tanto en tomografía computada como en resonancia magnética. Este patrón se observa en el 60% de los casos y se ha incorporado en las directrices diagnósticas de las diferentes organizaciones que participan en el estudio de las enfermedades hepáticas y su presencia evita la necesidad de una biopsia. Además, son signos auxiliares útiles en el diagnóstico del HCC la hiperintensidad en secuencias ponderadas en T2, la presencia de grasa, la trombosis tumoral venosa y el crecimiento entre intervalos en los estudios de seguimiento. Sin embargo, no todos los pacientes con HCC presentan estas características y en el 40% de los casos las presentaciones atípicas plantean un reto diagnóstico y de manejo de los pacientes.


Abstract The typical imaging appearance of hepatocellular carcinoma (HCC) is widely recognized and consists in hyper enhancement in the arterial phase with lavage in the portal and late venous phases, as on computed tomography (CT) as on magnetic resonance imaging (MRI). This pattern is observed in 60% of cases and has been incorporated into the diagnostics directives of the different organizations which participates in the hepatic diseases studies and its presence avoid the necessity of a biopsy. Besides, are auxiliar signs useful on the HCC diagnostic, T2 hyperintensity, presence of grease, venous tumor thrombosis and the growth between intervals in follow up studies. However, not all HCC patients harbor these characteristics and in 40% of cases the atypical introduction proposes a diagnostic and handling challenge of patients.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Carcinoma/diagnóstico por imagem , Carcinoma Hepatocelular/diagnóstico por imagem , Fibrose , Neoplasias
9.
Hepatología ; 3(2): 143-154, 2022. ilus, tab
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1396059

RESUMO

La enfermedad COVID-19, causada por el coronavirus tipo 2 (SARS-CoV-2), ha tenido un gran impacto en la salud a nivel mundial. A pesar de considerarse una enfermedad principalmente respiratoria, el virus SARS-CoV-2 también es responsable de otro tipo de manifestaciones extrapulmonares, como son las enfermedades hepatobiliares. En esta revisión se describen los posibles mecanismos de patogénesis implicados en la lesión hepática causada por el SARS-CoV-2. Adicionalmente, se analiza la relación entre COVID-19 y la enfermedad hepática crónica, las implicaciones que tiene en el carcinoma hepatocelular y en el trasplante hepático, así como las recomendaciones para la vacunación contra el SARS-CoV-2 en los pacientes afectados por enfermedad hepática. Por último, se proponen algunas estrategias para superar el reto al que se enfrenta el médico en el manejo delos pacientes con enfermedades hepatobiliares y COVID-19.


COVID-19, caused by the type 2 coronavirus (SARS-CoV-2), has had a major impact on health worldwide. Despite being mainly a respiratory disease, the SARS-CoV-2 virus is also responsible for other types of extrapulmonary manifestations, such as hepatobiliary diseases. This review describes the possible mechanisms of pathogenesis involved in liver injury caused by SARS-CoV-2, the relationship between COVID-19 and chronic liver disease, the effects that it has on hepatocellular carcinoma and liver transplantation, as well as the recommendations for vaccination against SARS-CoV-2 in patients affected by liver disease. Finally, some strategies are suggested to overcome the challenge faced by the clinician in the management of patients with hepatobiliary disease and COVID-19.


Assuntos
Humanos , SARS-CoV-2 , COVID-19 , Hepatopatias , Vacinação , Carcinoma Hepatocelular , Doenças do Sistema Digestório , Fígado
10.
Hepatología ; 3(1): 40-56, 2022. ilus, tab
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1396216

RESUMO

El trasplante de hígado es el último recurso para el tratamiento de hepatopatías. Para evitar el rechazo del injerto se requieren esquemas de inmunosupresión que han ido evolucionando a lo largo de los años. Se realizó una revisión bibliográfica en la base de datos PubMed sobre las terapias inmunosupresoras disponibles para evitar el rechazo del injerto en el trasplante hepático, los esquemas utilizados, efectos adversos, interacciones y sus modificaciones desde la fase de inducción hasta el seguimiento posterior. Se encontró que la inducción habitual es con esteroides o terapia inmunológica clonal. En el mantenimiento, los inhibidores de la calcineurina son los más utilizados, las dosis se deben ajustar según sus niveles séricos y la presencia de efectos adversos como nefrotoxicidad o diabetes. Por otra parte, los inhibidores del mTOR han sido considerados como agentes reductores del riesgo de recidiva de cáncer hepatocelular. Las características del paciente y sus comorbilidades (embarazo, insuficiencia renal, diabetes, sepsis, carcinoma hepatocelular) requieren modificar el tratamiento e individualizarlo


Liver transplantation is the last option for the treatment of liver disease. Immunosuppression schemes are required to avoid graft rejection, which have evolved over the years. A literature review was carried out in PubMed on the immunosuppressive therapies available to avoid graft rejection in liver transplantation, as well as on the schemes used, adverse effects, interactions and their modifications from the induction phase to subsequent follow-up. The usual induction was found to be with steroids or clonal immune therapy. In maintenance, calcineurin inhibitors are the most widely used, and their doses should be adjusted according to their serum levels and the presence of adverse effects such as nephrotoxicity or diabetes. On the other hand, mTOR inhibitors have been considered to reduce the risk of hepatocellular cancer recurrence. The characteristics of the patient and their comorbidities (pregnancy, kidney failure, diabetes, sepsis, hepatocellular carcinoma) require modification and individualization of the treatment.


Assuntos
Humanos , Terapia de Imunossupressão , Transplante de Fígado , Carcinoma Hepatocelular , Inibidores de Calcineurina , Rejeição de Enxerto , Hepatopatias , Neoplasias Hepáticas
11.
Hepatología ; 3(1): 57-71, 2022. ilus, tab
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1396218

RESUMO

El carcinoma hepatocelular (CHC) es una de las principales causas de morbilidad y mortalidad relacionada con el cáncer en todo el mundo. La mayoría de los casos ocurren en un contexto de cirrosis o hepatitis crónica. Los pacientes con CHC avanzado no disponían de terapias efectivas hasta el 2008, cuando el sorafenib, un inhibidor de la tirosina quinasa multi-target, demostró un beneficio en comparación con el placebo, en términos de supervivencia y tiempo a progresión de la enfermedad. Desde el 2016, diferentes tratamientos de primera y segunda línea con mecanismos de acción similares (lenvatinib, regorafenib, cabozantinib, ramucirumab) demostraron eficacia. Sin embargo, la investigación de fármacos que inhiben otras vías tumorales seguía siendo de máxima prioridad y los inhibidores de puntos de control inmunitario (ICI) mostraron resultados prometedores en el ámbito clínico para el tratamiento del CHC, revolucionando el manejo en estos pacientes. Recientemente, el anticuerpo contra la proteína de muerte programada-1 (PD-1), atezolizumab combinado con bevacizumab, demostró superioridad sobre el sorafenib en un ensayo clínico aleatorizado de fase III, convirtiéndose en la terapia de elección en primera línea. Actualmente están emergiendo resultados de múltiples estudios de fase III, que continuarán modificando el tratamiento del CHC. En este artículo se revisa la evolución y los cambios recientes de las terapias sistémicas para CHC, mostrando la secuencia actual de estos tratamientos, una vez iniciados.


Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related morbidity and mortality worldwide. Most cases occur in the context of cirrhosis or chronic liver inflammation. Patients with advanced HCC had no effective therapies until 2008, when sorafenib, a multi-target tyrosine kinase inhibitor, showed beneficial results when compared to placebo in terms of survival and time to progression. Since 2016, different first and second line treatments with similar mechanisms of action (lenvatinib, regorafenib, cabozantinib, ramucirumab) have shown efficacy. However, researchstudies with drugs that inhibit other tumor pathways remained a top priority, and immune checkpoint inhibitors (ICIs) showed promising results in the clinical setting of HCC management. Recently, antibodies against the programmed death protein-1 (PD-1), atezolizumab combined with bevacizumab, have shown superiority over sorafenib in a randomized phase III clinical trial, becoming the first-line therapy of choice. Results from multiple phase III studies are currently emerging, which will continue to modify HCC treatment. This article reviews recent developments and changes in systemic therapies for HCC, showing the current sequencing of these treatments once they begin.


Assuntos
Humanos , Carcinoma Hepatocelular , Proteínas Tirosina Quinases , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Imunoterapia
12.
Braz. J. Pharm. Sci. (Online) ; 58: e18984, 2022. graf
Artigo em Inglês | LILACS | ID: biblio-1364429

RESUMO

Interferon-ß-1a (INF-ß-1a) has gained significant attention due to its emerging applications in the treatment of different human diseases. Therefore, many researchers have attempted to produce it in large quantities and also in a biologically active form using different expression systems. In the present study, we aimed to improve the expression level of INF-ß-1a by Pichia pastoris using optimization of culture conditions. The codon-optimized INF-ß- 1a gene was cloned into pPICZαA plasmid under the control of alcohol oxidase I (AOX1) promoter. The protein expression was induced using different concentrations of methanol at different pHs and temperatures. The biological activity of produced protein was evaluated by anti-proliferative assay. The ideal culture conditions for the expression of INF-ß-1a by P. pastoris were found to be induction with 2% methanol at pH 7.0 culture medium at 30 C which yielded a concentration of 15.5 mg/L INF-ß-1a in a shake flask. Our results indicate that differences in glycosylation pattern could result in different biological activities as INF- ß-1a produced by P. pastoris could significantly more reduce the cell viability of HepG-2 cells, a hepatocellular carcinoma cell line, than a commercially available form of this protein produced by CHO


Assuntos
Pichia/classificação , Interferon beta/agonistas , Carcinoma Hepatocelular/patologia , Otimização de Processos , Códon , Células , Carcinoma Hepatocelular , Concentração de Íons de Hidrogênio
13.
Rev. bras. epidemiol ; 25: e220004, 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1360903

RESUMO

ABSTRACT: Objective: This study aimed to describe and analyze the temporal and spatial distribution of deaths due to hepatocellular carcinoma (HCC) associated with hepatitis B (HBV) and C viruses (HCV) in the state of São Paulo. Methods: This is an ecological study of HCC deaths associated with HBV and HCV in the state of São Paulo, from 2009 to 2017, with data from the Mortality Information System (SIM). The temporal trend was analyzed by linear regression with Prais-Winsten estimation. Deaths were described according to sociodemographic characteristics by means of absolute and relative frequencies and were spatially distributed according to the regional health department. Results: It is found that 26.3% of deaths due to HCC were associated with HBV or HCV. A higher proportion of deaths due to HCC associated with HCV was observed (22.2%) when compared to HBV (3.9%). The mortality rate due to HCC associated with HBV showed a downward trend, and the mortality rate due to HCC associated with HCV showed a steady trend. Deaths of males, white individuals, those who aged from 50 to 59 years, and those who had 8-11 years of schooling predominated. Spatial analysis revealed a heterogeneous distribution of deaths in the state of São Paulo. Conclusions: The downward trend in mortality rates due to HCC associated with HBV shows an important advance in the disease control. However, the mortality rate due to HCC associated with HCV has remained stable throughout the study period. The spatial distribution of deaths may contribute to raise hypotheses for deeper knowledge of these diseases in the regions.


RESUMO: Objetivos: Este estudo tem como objetivo descrever e analisar a distribuição temporal e espacial dos óbitos por carcinoma hepatocelular associados às hepatites virais B e C no estado de São Paulo. Métodos: Estudo ecológico dos óbitos por carcinoma hepatocelular associados a hepatites virais B e hepatites virais C no estado de São Paulo, de 2009 a 2017, com dados do Sistema de Informação sobre Mortalidade. A tendência temporal foi analisada por regressão linear, com método de Prais-Winsten. Os óbitos foram descritos segundo as características sociodemográficas, por meio de frequências absolutas e relativas, e foram espacialmente distribuídos segundo departamento regional de saúde. Resultados: Dos óbitos por carcinoma hepatocelular, 26,3% foram associados a hepatites virais B ou hepatites virais C. Observou-se maior proporção de óbitos por carcinoma hepatocelular associado a hepatites virais C (22,2%) quando comparada àquela associada a hepatites virais B (3,9%). A taxa de mortalidade por carcinoma hepatocelular associado a hepatites virais B apresentou tendência de queda, no entanto a taxa de mortalidade por carcinoma hepatocelular associado a hepatites virais C apresentou tendência estacionária. Predominaram óbitos de pacientes do sexo masculino, de cor branca, de 50-59 anos e com oito a 11 anos de estudo. A análise espacial revelou distribuição heterogênea dos óbitos no estado de São Paulo. Conclusão: A tendência de queda nas taxas de mortalidade por carcinoma hepatocelular associado a hepatites virais B revela um importante avanço no controle do agravo. Entretanto, a taxa de mortalidade por carcinoma hepatocelular associado a hepatites virais C vem-se mantendo estável ao longo do período estudado. A distribuição espacial dos óbitos pode contribuir para levantar hipóteses com vistas ao conhecimento mais aprofundado desses agravos nas regiões.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Vírus , Carcinoma Hepatocelular/complicações , Hepatite B/complicações , Neoplasias Hepáticas , Brasil/epidemiologia
14.
Rev. colomb. cir ; 37(1): 96-105, 20211217. fig, tab
Artigo em Espanhol | LILACS | ID: biblio-1357579

RESUMO

Introducción. La resección quirúrgica es el tratamiento de elección de las neoplasias primarias y secundarias del hígado. Los pacientes con hepatocarcinoma de los segmentos centrales representan un reto, siendo la hepatectomía extendida la técnica más usada, sin embargo, el riesgo postquirúrgico de falla hepática es alto, dado que la resección puede comprometer entre el 65 % y el 80 % del volumen hepático. La mesohepatectomía es una alternativa que permite dejar un volumen hepático residual suficiente. El objetivo de este trabajo es presentar nuestra experiencia en el tratamiento de pacientes con hepatocarcinomas en segmentos centrales a quienes se les realizó mesohepatectomía. Serie de casos. Se presentan tres pacientes no cirróticos, con hepatocarcinoma en los segmentos 4, 5 y 8, que fueron atendidos en el Hospital San Vicente Fundación, en las sedes de Medellín y de Rionegro, entre 2018 y 2020. Resultados. La mesohepatectomía se realizó mediante ligadura selectiva de los pedículos del segmento 4 y del sector anterior derecho. Se utilizó aspirador ultrasónico y endograpadora para la transección hepática. La duración de la maniobra de Pringle varió entre 16 y 43 minutos. El sangrado promedio fue de 1000 ml. Solo un paciente presentó fuga biliar tipo B. No hubo mortalidad a 30 días. Conclusiones. La mesohepatectomía es una alternativa segura para pacientes con tumores en los segmentos centrales, que permite disminuir el riesgo de falla hepática luego de la resección.


Introduction. Surgical resection is the treatment of choice for primary and secondary neoplasms of the liver. Patients with central segment hepatocarcinoma represent a challenge, with extended hepatectomy being the most widely used technique. However, the postsurgical risk of liver failure is high since resection can compromise between 65% and 80% of liver volume. Mesohepatectomy is an alternative that allows a sufficient residual liver volume to be left. The objective of this work is to present treatment of patients with central segment hepatocarcinoma.Clinical cases. Three non-cirrhotic patients are presented, with hepatocarcinoma in segments 4, 5 and 8, who were treated at the San Vicente Fundación Hospital in Medellín and Rionegro, between 2018 and 2020.Results. Mesohepatectomy was performed by selective ligation of the pedicles of segment 4 and the right anterior sector. An ultrasonic aspirator and endostapler were used for liver transection. The duration of the Pringle ma-neuver ranged from 16 to 43 minutes. The average bleeding was 1000 cc. Only one patient had type B bile leakage. There was no 30-day mortality.Conclusions. Mesohepatectomy is a safe alternative for patients with tumors in the central segments, which reduces the risk of liver failure after resection.


Assuntos
Humanos , Falência Hepática , Carcinoma Hepatocelular , Cirrose Hepática , Hepatectomia
15.
Rev. cuba. med. mil ; 50(3): e1095, 2021. graf
Artigo em Espanhol | CUMED, LILACS | ID: biblio-1357318

RESUMO

Introducción: El carcinoma hepatocelular es un tumor hipervascular compuesto por vasos sanguíneos anormales, constituye la forma más frecuente de cáncer primario del hígado. Alrededor del 90 por ciento de estos tumores se desarrollan sobre una enfermedad hepática previa. Un aumento en la carga vascular debido a la hipertensión portal conlleva a sangrado. Objetivo: Presentar un paciente a quien se le practicó laparotomía exploradora de urgencia por hemoperitoneo de gran cuantía secundario a una rotura intratumoral sobre un hígado cirrótico. Caso clínico: Paciente de 66 años de edad, con antecedentes patológicos de diabetes mellitus tipo 2, hiperplasia benigna de próstata, alcoholismo crónico y cirrosis hepática. Acudió al cuerpo de guardia por dolor abdominal difuso y signos de hipovolemia aguda. Se realizó laparotomía de urgencia y se constata hemoperitoneo de gran cuantía, secundario a una rotura intratumoral. Se le realizó aspiración de contenido hemático, electrocoagulación y compresión por empaquetamiento. Se controló el sangrado. El paciente tuvo una evolución tórpida y falleció 24 horas posteriores a la laparotomía. Conclusiones: El hemoperitoneo secundario a rotura de un carcinoma hepatocelular, es una complicación poco frecuente, pero fatal; por lo que se hace necesario su estudio para lograr un diagnóstico y tratamiento oportuno(AU)


Introduction: Hepatocellular carcinoma is a hypervascular tumor made up of abnormal blood vessels. It is the most frequent form of primary liver cancer. About 90 percent of these tumors develop over a previous liver disease. An increase in vascular load due to portal hypertension leads to bleeding. Objective: To present a patient who underwent emergency exploratory laparotomy due to large hemoperitoneum secondary to an intratumoral rupture of a cirrhotic liver. Clinical case: A 66-year-old male patient with a pathological history of type 2 diabetes mellitus, benign prostatic hyperplasia, chronic alcoholism and liver cirrhosis. He came to emergency due to diffuse abdominal pain, as well as signs of acute hypovolemia. An emergency laparotomy was performed, confirming a large hemoperitoneum secondary to an intratumoral rupture. Blood content aspiration, electrocoagulation and compression by packing were performed, managing to control bleeding. He had a torpid evolution, dying 24 hours after the laparotomy. Conclusions: Hemoperitoneum secondary to rupture of a hepatocellular carcinoma is a rare, but fatal complication; therefore, its study is necessary to achieve a timely diagnosis and treatment(AU)


Assuntos
Humanos , Masculino , Idoso , Hiperplasia Prostática , Carcinoma Hepatocelular , Hipovolemia , Hemoperitônio , Cirrose Hepática , Neoplasias Hepáticas
16.
Electron. j. biotechnol ; 52: 21-29, July. 2021. ilus, tab, graf
Artigo em Inglês | LILACS | ID: biblio-1283484

RESUMO

BACKGROUND: Super-paramagnetic iron oxide nanoparticles (SPION) contain a chemotherapeutic drug and are regarded as a promising technique for improving targeted delivery into cancer cells. RESULTS: In this study, the fabrication of 5-fluorouracil (5-FU) was investigated with loaded Dextran (DEXSPION) using the co-precipitation technique and conjugated by folate (FA). These nanoparticles (NPs) were employed as carriers and anticancer compounds against liver cancer cells in vitro. Structural, magnetic, morphological characterization, size, and drug loading activities of the obtained FA-DEX-5-FUSPION NPs were checked using FTIR, VSM, FESEM, TEM, DLS, and zeta potential techniques. The cellular toxicity effect of FA-DEX-5-FU-SPION NPs was evaluated using the MTT test on liver cancer (SNU-423) and healthy cells (LO2). Furthermore, the apoptosis measurement and the expression levels of NF-1, Her-2/neu, c-Raf-1, and Wnt-1 genes were evaluated post-treatment using flow cytometry and RT-PCR, respectively. The obtained NPs were spherical with a suitable dispersity without noticeable aggregation. The size of the NPs, polydispersity, and zeta were 74 ± 13 nm, 0.080 and 45 mV, respectively. The results of the encapsulation efficiency of the nano-compound showed highly colloidal stability and proper drug maintenance. The results indicated that FA-DEX-5-FU-SPION demonstrated a sustained release profile of 5-FU in both phosphate and citrate buffer solutions separately, with higher cytotoxicity against SNU-423 cells than against other cells types. These findings suggest that FA-DEX-SPION NPs exert synergistic effects for targeting intracellular delivery of 5-FU, apoptosis induction, and gene expression stimulation. CONCLUSIONS: The findings proved that FA-DEX-5-FU-SPION presented remarkable antitumor properties; no adverse subsequences were revealed against normal cells.


Assuntos
Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Fluoruracila/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Polímeros , Expressão Gênica/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Apoptose/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Preparações de Ação Retardada , Nanopartículas/administração & dosagem , Nanopartículas de Magnetita , Citometria de Fluxo
17.
Int. j. med. surg. sci. (Print) ; 8(2): 1-12, jun. 2021. graf, ilus
Artigo em Inglês | LILACS | ID: biblio-1284445

RESUMO

Background/aim: Autophagic cell death and apoptosis of tumor cells has become one of the main objectives in cancer treatment, whereas tumor cell lines are mainly used in studies for providing important data for the evaluation of potential anti cancer substances. In this study, our objective was to evaluate morphological and biochemical changes including rate of apoptosis and Alpha Fetoprotein (AFP) levels at different concentrations of Carnosic Acid (CA) on Human Hepatocellular Carcinoma HepG2 Cells.Materials and methods: Human Hepatocellular Carcinoma (7th passage HepG2 cells) Cell lines were cultured on 11 µM D263M schott glass coverslips placed in 12-well plates and were treated with DMSO, 1, 2.5, 5 and 10 µM concentrations of CA for 24, 48 and 72 hours. Morphological and biochemical data were recorded daily including apoptosis rates demonstrated by Caspase 3, Annexin V expressions under inverted light and Immunofluorescence microscopy, then data were analyzed for statistical significance. AFP, albumin and total protein levels were analyzed spectrophotometricaly for biochemical evaluation.Results: Our results showed that CA significantly inhibited HepG2 cell proliferation in a dose and time dependant manner and significantly caused the formation of autophagic vacuoles starting from 5µM and reaching significance at 10 µM concentrations. Significant decrease was observed in AFP when 48 and 72 hours expressions were examined, with the lowest level reached at 72 hours in the 10 µM CA group. Additionally, increase in albumin levels reached significance only in the 48 h group whereas non-significant increases were also observed in 24 h and 72 h groups.Conclusion: Our current study demonstrates significant increase in apoptosis rates by Carnosic Acid mainly at 10µM concentrations, supporting its anticancer effect on HepG2 cells. These findings are also supported by changes in biochemical analyses of Albumin and AFP levels at 10 µM concentrations.


Antecedentes / objetivos: La muerte celular autofágica y la apoptosis de células tumorales se ha convertido en uno de los principales objetivos en el tratamiento del cáncer, mientras que las líneas celulares tumorales se utilizan principalmente en estudios para proporcionar datos importantes para la evaluación de posibles sustancias anticancerígenas. En este estudio, nuestro objetivo fue evaluar los cambios morfológicos y bioquímicos, incluida la tasa de apoptosis y los niveles de alfa fetoproteína (AFP) a diferentes concentraciones de ácido carnósico (CA) en células de carcinoma hepatocelular humano HepG2.Materiales y métodos: Carcinoma hepatocelular humano (HepG2).Las líneas celulares se cultivaron en cubreobjetos de vidrio Schott D263M de 11 µM colocados en placas de 12 pocillos y se trataron con DMSO, concentraciones de CA 1, 2,5, 5 y 10 µM durante 24, 48 y 72 horas. Los datos morfológicos y bioquímicos se registraron diariamente, incluidas las tasas de apoptosis demostradas por Caspasa 3, las expresiones de Anexina V bajo luz invertida y microscopía de inmunofluorescencia, luego se analizaron los datos para determinar la significación estadística. Los niveles de AFP, albúmina y proteínas totales se analizaron espectrofotométricamente para evaluación bioquímica.Resultados: Nuestros resultados mostraron que CA inhibió significativamente la proliferación de células HepG2 de una manera dependiente de la dosis y el tiempo y causó significativamente la formación de vacuolas autofágicas comenzando desde 5 µM y alcanzando significancia a concentraciones de 10 µM. Se observó una disminución significativa en la AFP cuando se examinaron las expresiones de 48 y 72 horas, alcanzando el nivel más bajo a las 72 horas en el grupo de CA 10 µM. Además, el aumento en los niveles de albúmina alcanzó significación solo en el grupo de 48 h, mientras que también se observaron aumentos no significativos en los grupos de 24 hy 72 h.Conclusión: Nuestro estudio demuestra un aumento significativo en las tasas de apoptosis por el ácido carnósico principalmente a concentraciones de 10 µM, lo que respalda su efecto anticancerígeno en las células HepG2. Estos hallazgos también están respaldados por cambios en los análisis bioquímicos de los niveles de albúmina y AFP a concentraciones de 10 µM.


Assuntos
Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Abietanos/administração & dosagem , Células Hep G2/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Sobrevivência Celular , Células Cultivadas , Apoptose/efeitos dos fármacos , Microscopia de Fluorescência
18.
Rev. Assoc. Méd. Rio Gd. do Sul ; 65(2): 01022105, Abr. - Jun. 2021.
Artigo em Português | LILACS | ID: biblio-1367471

RESUMO

RESUMO A hemocromatose hereditária (HH) é uma doença genética autossômica recessiva, a mais comum encontrada em caucasianos, causada pelo acúmulo de ferro em diferentes órgãos, predominantemente no fígado, causando sua disfunção. As mutações hereditárias relacionadas ao gene HFE representam quase 90% dos casos de hemocromatose entre as populações de descendência europeia. A absorção excessiva do ferro ocasiona acúmulo em órgãos como coração, pâncreas e fígado ocasionando diversas manifestações clínicas. Além dos sintomas gerais, a progressiva sobrecarga de ferro causa uma das principais complicações, a cirrose hepática. A regressão da fibrose pode ser alcançada após o tratamento, promovendo a remoção do estímulo e restaurando a função do fígado. Caso a HH não seja tratada ou o tratamento não tenha sido efetivo, o paciente pode evoluir para um estado fibrótico de cirrose irreversível, que pode culminar com o carcinoma hepatocelular (CHC), complicação responsável por 45% das mortes em pacientes com HH. Nesse sentido, nota-se a importância de compreender os métodos diagnósticos, rastreamento e tratamento, de maneira a possibilitar manejos precoces e evitar complicações potencialmente fatais. Além disso, o fato da população dos estados do sul do Brasil ser composta em sua maioria por descendentes norte-europeus - os mais acometidos pela HH - justifica a importância de literaturas e estudos clínicos mais recentes e realizados nessa região com o objetivo de compreender a evolução clínica da doença e estabelecer medidas preventivas para a manifestação de lesões hepáticas. PALAVRAS-CHAVE: Hemocromatose, HFE, diagnóstico, cirrose hepática, carcinoma hepatocelular


ABSTRACT Hereditary hemochromatosis (HH) is an autosomal recessive genetic disease, the most common found in Caucasians, caused by the accumulation of iron in different organs, predominantly in the liver, causing its dysfunction. Inherited mutations related to the HFE gene represent almost 90% of cases of hemochromatosis among populations of European descent. Excessive iron absorption causes accumulation in organs such as the heart, pancreas and liver, causing several clinical manifestations. In addition to the general symptoms, progressive iron overload causes one of the main complications, liver cirrhosis. Regression of fibrosis can be achieved after treatment, promoting stimulus removal and restoring liver function. If HH is not treated or the treatment has not been effective, the patient may progress to a fibrotic state of irreversible cirrhosis, which can culminate in hepatocellular carcinoma (HCC), a complication responsible for 45% of deaths in patients with HH. In this sense, the importance of understanding diagnostic methods, screening and treatment is noted, in order to enable early management and avoid potentially fatal complications. In addition, the fact that the population of the southern states of Brazil is composed mostly of North European descendants ­ the most affected by HH ­ justifies the importance of more recent literature and clinical studies carried out in this region in order to understand the clinical course of the disease and establish preventive measures for the manifestation of liver damage. KEYWORDS: Hemochromatosis, HFE, diagnosis, liver cirrhosis, hepatocellular carcinoma


Assuntos
Humanos , Diagnóstico , Proteína da Hemocromatose , Hemocromatose , Cirrose Hepática , Carcinoma Hepatocelular
19.
Medicina (B.Aires) ; 81(3): 346-358, jun. 2021. graf
Artigo em Inglês | LILACS | ID: biblio-1346469

RESUMO

Abstract Hepatocellular carcinoma (HCC) is the most common primary liver tumor. Hexachlorobenzene (HCB) is an endocrine disruptor and a liver tumor promoter. Deregulation of thyroid hormone (TH) homeostasis may play a significant role in early neoplastic transformation. The aim of this study was to evaluate the relation between TH metabolism and the regulation of cell growth in an in vivo and in vitro model. We examined the role of transforming growth factor-β1 (TGF-β1) on TH deiodinase expression and hepatocyte proliferation. An initiation (DEN)/promotion (HCB) tumor model from rat liver and HepG2 cells were used. We evaluated PCNA, p21, p27, SMAD2/3, TGF-β1, deiodinase 1 (D1), D3, protein expression levels; D1 and D3 mRNA expression; TH and TGF-β1, D1, D3, and GST-P protein levels in focal/non-focal areas. In vivo, HCB decreased triiodothyronine (T3) and D1 mRNA levels and increased thyroxine (T4) and D3 mRNA levels in liver from DEN+HCB vs. DEN group. HCB increased protein levels from D3, TGF-β1, and PCNA and decreased D1 in focal-areas. In vitro, HCB increased PCNA, pSMAD 2/3, and TGF-β1 protein levels and mRNA expression and decreased p21 and p27 protein levels. Exogenous T3 treatment prevent HCB induced molecular alterations related to hepatocyte proliferation whereas T4 did not have any effect. These effects were prevented by using a TGF-β1 receptor II inhibitor. Results suggest that alteration of TH homeostasis, through D1 function, play a key role in hepatocyte proliferation and that TGF-β1-SMAD pathway is involved in this process confirming their role in early neoplastic transformation in HCC.


Resumen El hepatocarcinoma (HCC) es un tumor hepático primario. El hexaclorobenceno (HCB) es un disruptor endocrino y un promotor de tumores hepáticos. La desregulación de la homeostasis de las hormonas tiroideas (HT) puede ser un proceso importante para la transformación neoplásica temprana. Nuestro objetivo fue evaluar la relación entre el metabolismo de las HT y la regulación de la prolifera ción celular. Se utilizó un modelo tumoral de iniciación (DEN)/promoción (HCB) de hígado de rata (in vivo) (DEN/ HCB) y células HepG2 (in vitro). Evaluamos los niveles de PCNA, p21, p27, SMAD2/3, TGF-β1, D1, D3, ARNm de D1 y D3, HT y los niveles de TGF-β1, D1, D3 y GST-P en áreas focales/no focales. In vivo, HCB disminuyó los niveles de T3 y ARNm de la D1 y aumentó los niveles de T4 y ARNm de D3 del grupo DEN + HCB frente al grupo DEN. El HCB aumentó los niveles de D3, TGF-β1 y PCNA y disminuyó el D1 en las áreas focales. In vitro, HCB aumentó los niveles de PCNA, pSMAD 2/3 y TGF-β1 y la expresión de ARNm mientras que disminuyó los niveles de p21 y p27. El tratamiento con T3 exógeno previno las alteraciones moleculares relacionadas con la proliferación hepatocitaria. Estos efectos se evitaron utilizando un inhibidor del receptor II de TGF-β1. Los resultados sugieren que la alteración de la homeostasis de HT, a través de la D1 y la vía TGF-β1-SMAD, juega un papel clave en la proliferación celular y en las transformaciones neoplásicas tempranas en el HCC.


Assuntos
Animais , Ratos , Carcinoma Hepatocelular , Fator de Crescimento Transformador beta1 , Iodeto Peroxidase/genética , Neoplasias Hepáticas , Proliferação de Células
20.
Rev. méd. Chile ; 149(4): 635-640, abr. 2021. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1389484

RESUMO

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.


Assuntos
Humanos , Masculino , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/complicações , Ruptura Espontânea/diagnóstico por imagem , Hematocele , Hemoperitônio/etiologia , Hemoperitônio/diagnóstico por imagem
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