Rita de Cássia Martins Alves da Silva

Hepatocellular Carcinoma: a Comprehensive Review of Biomarkers, Clinical Aspects, and Therapy

Hepatocellular carcinoma (HCC) is a cause of several deaths related to cancer worldwidely. In early stage, curative treatments such as surgical resection, liver transplant and local ablation can improve the patient ´s survival. However, the disease is detected in advanced stage; moreover some available therapies are restricted to palliative care and local treatment. Early detections of HCC and adequate therapy are crucial to increase survival as well as to improve the patient´s quality of life. Therefore, researchers have been investigating molecular biomarkers with high sensibility and reliability as Golgi 73 protein (GP73), Glypican-3 (GPC3), Osteopontin (OPN), microRNAs and others. MicroRNAs can regulate important pathways on carcinogenesis, as tumor angiogenesis and progression. So, they can be considered as possible markers of prognosis in HCC, and therapeutic target for this tumor type. In this review, we discuss the recent advances related to the cause (highlighting the main risk factors), treatment, biomarkers, clinic aspects, and outcome in hepatocellular carcinoma.

Uso do subgalato de bismuto para hemostasia local em hepatectomias parciais em ratos

BACKGROUND: This study aimed to observe the effects of bismuth subgallate used on bleeding surfaces after hepatectomy, in relation to bleeding, adhesions and histological study. METHODS: A total of 30 rats divided in 2 equal groups were studied. Partial hepatectomy was performed in both groups. In group 1 (G-1) an electric scalpel was used and in group 2 (G-2) bismuth subgallate for hemostasis of the bloody surface was aplied. On the 7th post-operative day, rats were sacrificed and the abdominal cavity was investigated with respect to bleeding and adhesions. A total hepatectomy with the adhesions was performed for histological study. In the histological study, microcirculation thrombosis, granulomatosis reaction, necrosis, fibrosis, degree of inflammation and adhesions were analyzed. RESULTS: There was no post-operative bleeding in both groups. Adhesions were observed on all rats in both groups. G-1 presented omentum adhesions to the liver, here denominated physiological in 80% of the rats and the G-2 presented adhesions of other organs, here named pathological in all cases. The histological study showed that all rats presented a granulomatosis reaction and adhesions. G-1 presented a greater intensity of thrombosis and necrosis. There was no significant difference between the two groups in relation to fibrosis or the degree of inflammation. CONCLUSION: This study demonstrated that both methods were efficient to prevent hemorrhage. G-2 presented pathological adhesions suggesting its use is unfeasible in human beings. G-1 presented more thrombosis and also more necrosis. The granulomatosis reaction, fibrosis, degree of inflammation and microscopic adhesions were similar in between groups.

Non-alcoholic fatty liver disease (NAFLD) in different populations: A clinical and epidemiological study - sample of São José do Rio Preto.

INTRODUCTION NAFLD is an heterogeneous condition that includes steatosis and non-alcoholic steatohepatitis (NASH), in the absence of significant alcohol consumption, reaching 30% of the population. The most common risk factors are: age, gender, ethnicity, diabetes mellitus (DM), obesity, predisposition, metabolic syndrome (MS), insulin resistance (IR), drugs, and polycystic ovary syndrome. OBJECTIVE To describe the profile of patients with NAFLD seen at Hospital de Base of Rio Preto, in the state of São Paulo. METHOD Patients with NAFLD were assessed, with medical and epidemiological data collected after informed consent. RESULTS Of the 62 patients evaluated, 76% were women, 73% Caucasians, and 71% were aged between 50 and 69 years and had no symptoms. Ultrasonography results showed steatosis in 84%. NASH was diagnosed in 61% of the sample. 21 patients underwent liver biopsy, of which 36% had cirrhosis, 1 had liver cancer, and 1 pure steatosis (5% each). Risk factors were found in 70% of patients with metabolic syndrome, 87% with increased waist circumference, 63% with dyslipidemia, 61% (n=38) with high blood pressure (HBP), 28% with DM, 52% physically inactive, and 44% with insulin resistance (IR) (HOMA> 3.5). There was an association between IR and NASH (p=0.013), IR and obesity (p=0.027), IR and MS (p=0.006), and MS and steatosis on medical ultrasound (USG) (p=0.014). CONCLUSION The most frequent risk factors were MS and its variables: increased waist circumference, dyslipidemia and HBP. This underscores the importance of metabolic control in NAFLD and confirms its role as the hepatic component of metabolic syndrome.

Doença coronária obstrutiva em hepatopatas crônicos que aguardam transplante hepático

BACKGROUND Advanced liver failure (ALF) usually presents hypocholesterolemia. Nevertheless, some patients with ALF develops major coronary obstructive diseases with consequent increased risk or contraindication to liver transplantation. OBJECTIVE To analyze the contribution of classical risk factors for coronary artery disease (CAD) in patients with ALF with and without obstructive coronary disease. METHODS Evaluation of risk factors for CAD in 119 patients in a referral center for liver transplantation, with the following characteristics: patients older than 40 years of age with ALV who underwent coronary angiography. RESULTS Obstructive coronary disease was detected in 21 (17.6%) of the cases. These patients had really low cholesterol levels, of which 129.0 ± 53.5 mg/dl averaging 117.0 mg/dl in liver disease patients with normal coronary arteries and 135.4 ± 51.7 mg/dl averaging 122.0 mg/dl in liver disease patients with obstructive coronary artery disease (P = 0.8215). In multivariate logistic regression, age, sex, body mass index and the presence of diabetes, smoking and alcohol consumption were not statistically significant in distinguishing groups. Nor was there an association with the etiology of the ALF. In turn, hypertension was proven to be relevant in association with CAD (P = 0.0474). CONCLUSION Only hypertension was a risk factor with statistical significance for the development of CAD in patients with ALF awaiting liver transplantation. Because it is a modifiable risk factor, this finding guides the practice of therapeutic attitudes in an attempt to prevent or delay the development of CAD in these patients.FUNDAMENTO: La insuficiencia hepatica avanzada (IHA) generalmente cursa con hipocolesterolemia. A pesar de eso, una parcela de los pacientes con IHA desarrolla coronariopatia obstructiva de grado importante con consecuente aumento de riesgo o incluso contraindicacion para trasplante hepatico. OBJETIVOS: Analizar la contribucion de los factores de riesgo clasicos para la enfermedad arterial coronaria (EAC) en pacientes portadores de IHA con y sin coronariopatia obstructiva. METODOS: Evaluacion de los factores de riesgo para EAC en 119 pacientes, en un servicio de referencia para trasplante hepatico, con las siguientes caracteristicas: mas de 40 anos de edad, portadores de IHA y sometidos a cinecoronariografia. RESULTADOS: Coronariopatia obstructiva fue detectada en 21 (17,6%) de los casos. Estos pacientes presentaban realmente niveles bajos de colesterol, siendo de 129,0±53,5mg/dL con mediana de 117,0mg/dL en los hepatopatas con coronarias normales y 135,4±51,7mg/dL con mediana de 122,0mg/dL en los hepatopatas con coronariopatia obstructiva (P=0,8215). En la regresion logistica multivariada, la edad, el sexo, el indice de masa corporal, asi como las presencias de diabetes, de tabaquismo y de etilismo no tuvieron significancia estadistica aislada en la diferenciacion entre los grupos. Tambien no hubo asociacion con la etiologia de la IHA. A su vez, la hipertension arterial se mostro relevante en la asociacion con EAC (P=0,0474). CONCLUSION: Solo la hipertension arterial fue factor de riesgo con significancia estadistica para el desarrollo de EAC en pacientes con IHA aguardando trasplante hepatico. Por ser un factor de riesgo cambiable, este hallazgo orienta hacia una practica de actitudes terapeuticas en la tentativa de evitarse o retardar el desarrollo de la EAC en estos pacientes.

Obstructive coronary disease in patients with chronic liver disease awaiting liver transplantation

BACKGROUND Advanced liver failure (ALF) usually presents hypocholesterolemia. Nevertheless, some patients with ALF develops major coronary obstructive diseases with consequent increased risk or contraindication to liver transplantation. OBJECTIVE To analyze the contribution of classical risk factors for coronary artery disease (CAD) in patients with ALF with and without obstructive coronary disease. METHODS Evaluation of risk factors for CAD in 119 patients in a referral center for liver transplantation, with the following characteristics: patients older than 40 years of age with ALV who underwent coronary angiography. RESULTS Obstructive coronary disease was detected in 21 (17.6%) of the cases. These patients had really low cholesterol levels, of which 129.0 ± 53.5 mg/dl averaging 117.0 mg/dl in liver disease patients with normal coronary arteries and 135.4 ± 51.7 mg/dl averaging 122.0 mg/dl in liver disease patients with obstructive coronary artery disease (P = 0.8215). In multivariate logistic regression, age, sex, body mass index and the presence of diabetes, smoking and alcohol consumption were not statistically significant in distinguishing groups. Nor was there an association with the etiology of the ALF. In turn, hypertension was proven to be relevant in association with CAD (P = 0.0474). CONCLUSION Only hypertension was a risk factor with statistical significance for the development of CAD in patients with ALF awaiting liver transplantation. Because it is a modifiable risk factor, this finding guides the practice of therapeutic attitudes in an attempt to prevent or delay the development of CAD in these patients.FUNDAMENTO: La insuficiencia hepatica avanzada (IHA) generalmente cursa con hipocolesterolemia. A pesar de eso, una parcela de los pacientes con IHA desarrolla coronariopatia obstructiva de grado importante con consecuente aumento de riesgo o incluso contraindicacion para trasplante hepatico. OBJETIVOS: Analizar la contribucion de los factores de riesgo clasicos para la enfermedad arterial coronaria (EAC) en pacientes portadores de IHA con y sin coronariopatia obstructiva. METODOS: Evaluacion de los factores de riesgo para EAC en 119 pacientes, en un servicio de referencia para trasplante hepatico, con las siguientes caracteristicas: mas de 40 anos de edad, portadores de IHA y sometidos a cinecoronariografia. RESULTADOS: Coronariopatia obstructiva fue detectada en 21 (17,6%) de los casos. Estos pacientes presentaban realmente niveles bajos de colesterol, siendo de 129,0±53,5mg/dL con mediana de 117,0mg/dL en los hepatopatas con coronarias normales y 135,4±51,7mg/dL con mediana de 122,0mg/dL en los hepatopatas con coronariopatia obstructiva (P=0,8215). En la regresion logistica multivariada, la edad, el sexo, el indice de masa corporal, asi como las presencias de diabetes, de tabaquismo y de etilismo no tuvieron significancia estadistica aislada en la diferenciacion entre los grupos. Tambien no hubo asociacion con la etiologia de la IHA. A su vez, la hipertension arterial se mostro relevante en la asociacion con EAC (P=0,0474). CONCLUSION: Solo la hipertension arterial fue factor de riesgo con significancia estadistica para el desarrollo de EAC en pacientes con IHA aguardando trasplante hepatico. Por ser un factor de riesgo cambiable, este hallazgo orienta hacia una practica de actitudes terapeuticas en la tentativa de evitarse o retardar el desarrollo de la EAC en estos pacientes.

Mueller-Hillis maneuver and angle of progression: Are they correlated?

Objective: Mueller-Hillis maneuver (MHM) and angle of progression (AOP) measured by transperineal ultrasound have been used to assess fetal head descent during the second stage of labor. We aimed to assess whether AOP correlates with MHM in the second stage of labor. Method: A prospective observational study including women with singleton pregnancy in the second stage of labor was performed. The AOP was measured immediately after the Mueller-Hillis maneuver. A receiver-operating characteristics (ROC) curve analysis was performed to determine the best discriminatory AOP cut-off for the identification of a positive MHM. A p-value less than 0.05 was considered statistically significant. Results: One hundred and sixty-six (166) women were enrolled in the study and 81.3% (n=135) had a positive MHM. The median AOP was 143º (106º to 210º). The area under the curve for the prediction of a positive maneuver was 0.619 (p=0.040). Derived from the ROC curve, an AOP of 138.5º had the best diagnostic performance for the identification of a positive MHM (specificity of 65% and a sensitivity of 67%). Conclusion: An AOP of 138º seems to be associated with a positive MHM in the second stage of labor.

VEGF Polymorphisms Related to Higher Serum Levels of Protein Identify Patients with Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver. Major risk factors for hepatocellular carcinoma include chronic liver diseases, carcinogenic agents, and genetic alterations as well as vascular endothelial growth factor (VEGF) involved in angiogenesis process. The aim of this study was to evaluate the association of VEGF-A (C936T and A1154G) with HCC and cirrhosis, in addition to serum levels of VEGF, clinical profile, lifestyle habits, and comorbidities. A total of 346 individuals were studied: 102 with HCC (G1), 117 with cirrhosis (G2), and 127 controls (G3). Polymorphisms were analysed by PCR/RFLP and serum levels of VEGF by ELISA. Alpha error was set at 5%. The wild-type genotype of both polymorphisms prevailed (P > 0.05). In G1, 23% of the patients died, with no relation to genetic profile (P > 0.05). Increased VEGF level was observed in G1 and G3, related to the mutant allele of VEGF-C936T and VEGF-A1154G, respectively, and compared with the wild-type genotype (P = 0.0285; P = 0.0284, resp.) as well as G1 versus G2 and G3 for VEGF-C936T and G1 versus G2 for VEGF-A1154G (P < 0.05 for both). In conclusion, there is a relationship between mutant alleles of VEGF-C936T and VEGF-A1154G polymorphisms and higher VEGF level, making them potential markers for HCC.

Enfermedad coronaria obstructiva en hepatópatas crónicos que aguardan trasplante hepático

BACKGROUND Advanced liver failure (ALF) usually presents hypocholesterolemia. Nevertheless, some patients with ALF develops major coronary obstructive diseases with consequent increased risk or contraindication to liver transplantation. OBJECTIVE To analyze the contribution of classical risk factors for coronary artery disease (CAD) in patients with ALF with and without obstructive coronary disease. METHODS Evaluation of risk factors for CAD in 119 patients in a referral center for liver transplantation, with the following characteristics: patients older than 40 years of age with ALV who underwent coronary angiography. RESULTS Obstructive coronary disease was detected in 21 (17.6%) of the cases. These patients had really low cholesterol levels, of which 129.0 ± 53.5 mg/dl averaging 117.0 mg/dl in liver disease patients with normal coronary arteries and 135.4 ± 51.7 mg/dl averaging 122.0 mg/dl in liver disease patients with obstructive coronary artery disease (P = 0.8215). In multivariate logistic regression, age, sex, body mass index and the presence of diabetes, smoking and alcohol consumption were not statistically significant in distinguishing groups. Nor was there an association with the etiology of the ALF. In turn, hypertension was proven to be relevant in association with CAD (P = 0.0474). CONCLUSION Only hypertension was a risk factor with statistical significance for the development of CAD in patients with ALF awaiting liver transplantation. Because it is a modifiable risk factor, this finding guides the practice of therapeutic attitudes in an attempt to prevent or delay the development of CAD in these patients.FUNDAMENTO: La insuficiencia hepatica avanzada (IHA) generalmente cursa con hipocolesterolemia. A pesar de eso, una parcela de los pacientes con IHA desarrolla coronariopatia obstructiva de grado importante con consecuente aumento de riesgo o incluso contraindicacion para trasplante hepatico. OBJETIVOS: Analizar la contribucion de los factores de riesgo clasicos para la enfermedad arterial coronaria (EAC) en pacientes portadores de IHA con y sin coronariopatia obstructiva. METODOS: Evaluacion de los factores de riesgo para EAC en 119 pacientes, en un servicio de referencia para trasplante hepatico, con las siguientes caracteristicas: mas de 40 anos de edad, portadores de IHA y sometidos a cinecoronariografia. RESULTADOS: Coronariopatia obstructiva fue detectada en 21 (17,6%) de los casos. Estos pacientes presentaban realmente niveles bajos de colesterol, siendo de 129,0±53,5mg/dL con mediana de 117,0mg/dL en los hepatopatas con coronarias normales y 135,4±51,7mg/dL con mediana de 122,0mg/dL en los hepatopatas con coronariopatia obstructiva (P=0,8215). En la regresion logistica multivariada, la edad, el sexo, el indice de masa corporal, asi como las presencias de diabetes, de tabaquismo y de etilismo no tuvieron significancia estadistica aislada en la diferenciacion entre los grupos. Tambien no hubo asociacion con la etiologia de la IHA. A su vez, la hipertension arterial se mostro relevante en la asociacion con EAC (P=0,0474). CONCLUSION: Solo la hipertension arterial fue factor de riesgo con significancia estadistica para el desarrollo de EAC en pacientes con IHA aguardando trasplante hepatico. Por ser un factor de riesgo cambiable, este hallazgo orienta hacia una practica de actitudes terapeuticas en la tentativa de evitarse o retardar el desarrollo de la EAC en estos pacientes.

Comportamento do fator de necrose tumoral e da proteína C reativa em hepatectomia simultânea com colectomia em ratos

BACKGROUND: The aim of this experimental study was to observe the behavior of Tumor Necrosis Factor and C-Reative Protein in simultaneous colectomy plus hepatectomy. METHODS: In this experimental model, 40 Wistar rats underwent surgery. They were divided into four groups: the control group; group 1, rats submitted to hepatectomy to 70%; group 2, rats submitted to colectomy; and group 3, rats submitted simultaneously to both procedures: hepatectomy plus colectomy. In all groups, TNF and PCR were collected one hour after the surgical procedure. The animals were killed afterwards. RESULTS: The dosage of these elements showed values with some alterations in all groups. Group three showed a significant increase of TNFa and decrease of PCR. CONCLUSION: The more complex became the surgical act the blood levels of TFNa have increased and the levels of the PCR decreased significantly.