Renato Ferreira 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.

Impact of Cerebral Cardiopulmonary Resuscitation Maneuvers in a General Hospital. Prognostic Factors and Outcomes

OBJECTIVE To assess survival of patients undergoing cerebral cardiopulmonary resuscitation maneuvers and to identify prognostic factors for short-term survival. METHODS Prospective study with patients undergoing cardiopulmonary resuscitation maneuvers. RESULTS The study included 150 patients. Spontaneous circulation was re-established in 88 (58%) patients, and 42 (28%) were discharged from the hospital. The necessary number of patients treated to save 1 life in 12 months was 3.4. The presence of ventricular fibrillation or tachycardia (VF/VT) as the initial rhythm, shorter times of cardiopulmonary resuscitation maneuvers and cardiopulmonary arrest, and greater values of mean blood pressure (BP) prior to cardiopulmonary arrest were independent variables for re-establishment of spontaneous circulation and hospital discharge. The odds ratios for hospital discharge were as follows: 6.1 (95% confidence interval [CI] = 2.7-13.6), when the initial rhythm was VF/VT; 9.4 (95% CI = 4.1-21.3), when the time of cerebral cardiopulmonary resuscitation was < 15 min; 9.2 (95% CI = 3.9-21.3), when the time of cardiopulmonary arrest was < 20 min; and 5.7 (95% CI = 2.4-13.7), when BP was > 70 mmHg. CONCLUSION The presence of VF/VT as the initial rhythm, shorter times of cerebral cardiopulmonary resuscitation and of cardiopulmonary arrest, and a greater value of BP prior to cardiopulmonary arrest were independent variables of better prognosis.

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.

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.