RESUMEN
The HFE molecule controls iron uptake from gut, and defects in the molecule have been associated with iron overload, particularly in hereditary hemochromatosis. The HFE gene including both coding and boundary intronic regions were sequenced in 304 Brazilian individuals, encompassing healthy individuals and patients exhibiting hereditary or acquired iron overload. Six sites of variation were detected: (1) H63D C>G in exon 2, (2) IVS2 (+4) T>C in intron 2, (3) a C>G transversion in intron 3, (4) C282Y G>A in exon 4, (5) IVS4 (-44) T>C in intron 4, and (6) a new guanine deletion (G>del) in intron 5, which were used for haplotype inference. Nine HFE alleles were detected and six of these were officially named on the basis of the HLA Nomenclature, defined by the World Health Organization (WHO) Nomenclature Committee for Factors of the HLA System, and published via the IPD-IMGT/HLA website. Four alleles, HFE*001, *002, *003, and *004 exhibited variation within their exon sequences.
Asunto(s)
Haplotipos , Proteína de la Hemocromatosis/genética , Hemocromatosis/genética , Sobrecarga de Hierro/genética , Polimorfismo Genético , Alelos , Secuencia de Bases , Brasil , Estudios de Cohortes , Exones , Femenino , Expresión Génica , Frecuencia de los Genes , Humanos , Intrones , Masculino , Persona de Mediana Edad , Terminología como AsuntoRESUMEN
Subjects with chronic liver disease are susceptible to hypovitaminosis A due to several factors. Therefore, identifying patients with vitamin deficiency and a requirement for vitamin supplementation is important. Most studies assessing vitamin A in the context of hepatic disorders are conducted using cirrhotic patients. A cross-sectional study was conducted in 43 non-cirrhotic patients with chronic hepatitis C to evaluate markers of vitamin A status represented by serum retinol, liver retinol, and serum retinol-binding protein levels. We also performed the relative dose-response test, which provides an indirect estimate of hepatic vitamin A reserves. These vitamin A indicators were assessed according to the stage of liver fibrosis using the METAVIR score and the body mass index. The sample study was predominantly composed of male subjects (63%) with mild liver fibrosis (F1). The relative dose-response test was <20% in all subjects, indicating vitamin A sufficiency. Overweight or obese patients had higher serum retinol levels than those with a normal body mass index (2.6 and 1.9 µmol/L, respectively; P<0.01). Subjects with moderate liver fibrosis (F2) showed lower levels of serum retinol (1.9 vs 2.5 µmol/L, P=0.01) and retinol-binding protein levels compared with those with mild fibrosis (F1) (46.3 vs 67.7 µg/mL, P<0.01). These results suggested an effect of being overweight on serum retinol levels. Furthermore, more advanced stages of liver fibrosis were related to a decrease in serum vitamin A levels.
Asunto(s)
Hepatitis C Crónica/complicaciones , Deficiencia de Vitamina A/diagnóstico , Vitamina A/análisis , Adulto , Anciano , Biomarcadores/análisis , Biopsia , Índice de Masa Corporal , Estudios Transversales , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hígado/química , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Sobrepeso/sangre , Proteínas de Unión al Retinol/análisis , Deficiencia de Vitamina A/complicaciones , Adulto JovenRESUMEN
Subjects with chronic liver disease are susceptible to hypovitaminosis A due to several factors. Therefore, identifying patients with vitamin deficiency and a requirement for vitamin supplementation is important. Most studies assessing vitamin A in the context of hepatic disorders are conducted using cirrhotic patients. A cross-sectional study was conducted in 43 non-cirrhotic patients with chronic hepatitis C to evaluate markers of vitamin A status represented by serum retinol, liver retinol, and serum retinol-binding protein levels. We also performed the relative dose-response test, which provides an indirect estimate of hepatic vitamin A reserves. These vitamin A indicators were assessed according to the stage of liver fibrosis using the METAVIR score and the body mass index. The sample study was predominantly composed of male subjects (63%) with mild liver fibrosis (F1). The relative dose-response test was <20% in all subjects, indicating vitamin A sufficiency. Overweight or obese patients had higher serum retinol levels than those with a normal body mass index (2.6 and 1.9 µmol/L, respectively; P<0.01). Subjects with moderate liver fibrosis (F2) showed lower levels of serum retinol (1.9 vs 2.5 µmol/L, P=0.01) and retinol-binding protein levels compared with those with mild fibrosis (F1) (46.3 vs 67.7 µg/mL, P<0.01). These results suggested an effect of being overweight on serum retinol levels. Furthermore, more advanced stages of liver fibrosis were related to a decrease in serum vitamin A levels.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Hepatitis C Crónica/complicaciones , Deficiencia de Vitamina A/diagnóstico , Vitamina A/análisis , Biopsia , Índice de Masa Corporal , Biomarcadores/análisis , Estudios Transversales , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Cirrosis Hepática/patología , Hígado/química , Puntuaciones en la Disfunción de Órganos , Sobrepeso/sangre , Proteínas de Unión al Retinol/análisis , Deficiencia de Vitamina A/complicacionesRESUMEN
Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver. We evaluated the association of alleles and genotypes of polymorphisms of IL-18 (-607C/A and -137G/C), IFN-γ (+874T/A) and TNF-α (-238G/A and -308G/A) with the risk and severity of HCC. One-hundred-and-twelve patients with HCC and 202 healthy controls were studied. Single nucleotide polymorphisms (SNPs) were amplified by PCR with specific primers and the products were submitted to polyacrylamide gel electrophoresis and stained with silver. We evaluated tumor presentation, tumor size and presence of metastasis. Significant higher risk of HCC was associated with: alleles IL-18 -607(*)A (P=0.0235; OR=1.48; 95%CI=1.06-2.08); TNF-α -238(*)A (P=0.0025; OR=2.12; 95%CI=1.32-3.40) and TNF-α -308(*)A (P=0.0351; OR=1.82; 95%CI=1.07-3.08); and genotypes IL-18-607AA (P=0.0048; OR=3.03; 95%CI=1.40-6.55); TNF-α -238GA (P=0.0011; OR=2.44; 95%CI=1.45-4.12); and TNF-α -308GA (P=0.0031; OR=2.51; 95%CI=1.39-4.51). Significant association was found between multinodular HCC and IL-18 -607(*)C allele (P=0.029; OR=2.40, 95%CI: 1.09-5.28), and IL-18 -607CC genotype (P=0.028; OR=3.5, 95%CI: 1.24-9.86). Diffuse HCC was significantly associated with IFN-γ +874TA genotype (P=0.044; OR=3.6, 95%CI: 1.03-12.47). The IL-18 -137(∗)C allele showed a significant association with the presence of metastasis. Thus, IL-18 -607(*)A and TNF-α (-238(*)A and -308(*)A) alleles may confer susceptibility to HCC, while IL-18 -607(*)C and -137(*)C alleles more severe disease.
Asunto(s)
Carcinoma Hepatocelular/genética , Interferón gamma/genética , Interleucina-18/genética , Neoplasias Hepáticas/genética , Polimorfismo de Nucleótido Simple , Factor de Necrosis Tumoral alfa/genética , Adolescente , Adulto , Anciano , Alelos , Brasil , Estudios de Casos y Controles , Estudios Transversales , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Retrospectivos , Riesgo , Adulto JovenRESUMEN
Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule involved in tumor escape mechanisms. Considering that the HLA-G 14bp insertion/deletion polymorphism is located at the 3' untranslated region (3'UTR) in exon 8, and since it has been associated with the magnitude of HLA-G production, we studied the association of 14bp insertion/deletion polymorphism with the risk of developing hepatocellular carcinoma (HCC). A total of 109 HCC patients followed at the University Hospital, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil, and 202 healthy controls from the same geographic area were genotyped for the 14bp insertion/deletion polymorphism using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis. Compared to controls, the frequency of the 14bp deletion allele was overrepresented in HCC patients (65% versus 56%, respectively, P = 0.0326). The 14bp deletion conferred an odds ratio (OR) of 1.46 [95% confidence interval (CI): 1.04-2.05]. Similarly, the deletion/deletion genotype was marginally overrepresented in HCC patients (45% versus 35% in controls, P = 0.0871), conferring an OR of 1.54 (95% CI: 0.96-2.48). The frequencies of the deletion/insertion or insertion/insertion genotypes observed in patients were not statistically different from those observed in controls (P > 0.05). Our results suggest that the 14bp-deletion allele in HLA-G gene is associated with HCC susceptibility in a Brazilian population.
Asunto(s)
Carcinoma Hepatocelular/genética , Predisposición Genética a la Enfermedad , Antígenos HLA-G/genética , Neoplasias Hepáticas/genética , Regiones no Traducidas 3'/genética , Anciano , Alelos , Brasil , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Eliminación de Secuencia/genética , Escape del TumorRESUMEN
As the mechanisms leading to the persistence of hepatitis B virus (HBV) infection are poorly understood and as the histocompatibility leucocyte antigen (HLA)-G is well described as a tolerogenic molecule, we evaluated HLA-G expression in 74 specimens of HBV liver biopsies and in 10 specimens obtained from previously healthy cadaver liver donors. HBV specimens were reviewed and classified by the METAVIR score, and HLA-G expression was assessed by immunohistochemistry. No HLA-G expression was observed in control hepatocytes. In contrast, 57 (77%) of 74 HBV specimens showed soluble and membrane-bound HLA-G expression in hepatocytes, biliary epithelial cells or both. No associations between the intensity of HLA-G expression and patient age or gender, HBeAg status, severity of liver fibrosis, and grade of histological findings were observed. Although significance was not reached (P = 0.180), patients exhibiting HLA-G expression presented a higher median HBV DNA viral load (105 copies/mL) than those who did not express HLA-G (10(3.7) copies/mL). These results indicate that HLA-G is expressed in most cases of chronic HBV infection in all stages and may play a role in the persistency of HBV infection.
Asunto(s)
Antígenos HLA/biosíntesis , Antígenos HLA/inmunología , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/patología , Antígenos de Histocompatibilidad Clase I/biosíntesis , Antígenos de Histocompatibilidad Clase I/inmunología , Hígado/inmunología , Hígado/patología , Adolescente , Adulto , Biopsia , Células Epiteliales/química , Femenino , Expresión Génica , Antígenos HLA-G , Hepatocitos/química , Humanos , Inmunohistoquímica , Masculino , Microscopía , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
INTRODUCTION: Orthotopic liver transplantation (OLT) is the treatment of choice of hepatocellular carcinoma (HCC) for patients with cirrhosis, mainly those with early HCC. Herein we have present the clinical characteristics and outcomes of cirrhotic patients with HCC who underwent OLT from cadaveric donors in our institution. METHODS: From May 2001 to May 2009, we performed 121 OLT including 24 patients (19.8%) with cirrhosis and HCC within the Milan criteria. In 4 cases, HCC was an incidental finding in the explants. RESULTS: The patients' average age was 55 +/- 10 years, including 82% men. Fifty percent of patients were Child class B or C. The average Model for End Stage Liver Disease for Child A, B, and C categories were 11, 15, and 18, respectively. The HCC diagnosis was made by 2 dynamic images in 16 cases; 1 dynamic image plus alphafetoprotein >400 ng/mL in 4; and 4 by histologic confirmation. Twenty patients received a locoregional treatment before OLT: 6 percutaneous ethanol injection, 9 transarterial chemoembolization, 1 transarterial embolization, and 4 a combination of these modalities. The median follow-up after OLT was 19.7 months (range, 1-51). A vascular invasion was observed in the explant of 1 patient, who developed an HCC recurrence and succumbed at 8 months after OLT. Two further patients, without vascular invasion or satellite tumor displayed tumor recurrences at 7 and 3 months after OLT, and death at 2 and 1 month after the diagnosis. The remaining 25 patients have not shown a tumor recurrence. CONCLUSION: In the present evaluation, OLT patients with early HCC and no vascular invasion showed satisfactory results and good disease-free survival. Strictly following the Milan criteria for liver transplantation in patients with HCC greatly reduces but does not completely avoid, the chances of tumor recurrence.
Asunto(s)
Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/fisiología , Adulto , Anciano , Alcoholismo/complicaciones , Brasil , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/terapia , Embolización Terapéutica/estadística & datos numéricos , Femenino , Hepatitis B/complicaciones , Hepatitis C/complicaciones , Hepatitis Autoinmune/complicaciones , Humanos , Fallo Hepático/etiología , Fallo Hepático/cirugía , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , alfa-Fetoproteínas/análisisRESUMEN
In transplant centers, few topics are more controversial than communication between organ donor families (ODF) and recipients (RE). The Organ Procurement Organizations and transplant centers have felt obliged to protect the confidentiality and interests of ODF and RE. However, some authors have reported favorable effects of contact between ODF and RE. This study sought to investigate the current situation of the communication between ODF and RE from the viewpoint of transplanted patients (n = 50) and waiting transplant patients (n = 50) at a Brazilian University Hospital, ODF (n = 10), physicians from transplant centers (n = 50), as well as the opinion of the general population of a Brazilian city (n = 100). This work was developed as a survey whose questions related to the issue of communication between ODF and RE. The results showed that the majority of transplanted patients (82%) and patients awaiting transplant (60%) wanted to meet ODF to express their gratitude for receiving the organ. Likewise, ODF (67%) wanted to have a meeting with recipients, which allowed them to confirm the benefit of their donation. The general population was also favorable (66%) to ODF and RE communication. In contrast, the physicians (74%) were opposed to the ODF and RE contact. They affirmed that direct contact could lead to serious emotional conflicts or attempts of material involvement. One believes that decisions concerning the contact between ODF and RE would have to be determined by the involved parties. The transplant team could analyze the requests case by case, but ODF and RE must have the right to make the final decision.
Asunto(s)
Familia , Relaciones Interpersonales , Trasplante de Riñón/psicología , Donantes de Tejidos/psicología , Adulto , Anciano , Comunicación , Femenino , Humanos , Renta , Masculino , Persona de Mediana Edad , Listas de EsperaRESUMEN
The objective of the present study was to analyze hepatic mitochondrial function in patients with familial amyloidotic polyneuropathy (FAP) undergoing cadaveric donor orthotopic liver transplantation. From February 2005 to May 2007, eight patients with FAP, ranging in age from 34 to 41 years and with Model for End-Stage Liver Disease scores ranging from 24 to 29. Underwent orthotopic transplantation using a liver from a deceased donor by the piggyback method. Immediately before beginning the recipient hepatectomy in a patient with FAP, a biopsy was obtained for analysis of mitochondrial function (FAP group). The control group consisted of 15 patients undergoing hepatic surgery to treat small tumors of the liver. Mitochondrial respiration was determined on the basis of oxygen consumption by energized mitochondria using a polarographic method. The membrane potential of the mitochondria was determined spectrofluorometrically. Data were analyzed statistically by the Mann-Whitney test, with the level of significance set at 5%. State 3 and 4 values, respiratory control ratio, and membrane potential were 47 +/- 8 versus 28 +/- 10 natoms O/min/mg protein (P < .05); 14 +/- 3 vs 17 +/- 7 nat.O/min/mg.prot.mit. (P > .05); 3.6 +/- .5 vs 1.7 +/- 0.7 (P < .05); and 135 +/- 5.2 vs 135 +/- 6 mV (P > .05) for control versus FAP patients, respectively, demonstrating a decreased energy status of the liver in FAP.
Asunto(s)
Neuropatías Amiloides Familiares/metabolismo , Neuropatías Amiloides Familiares/cirugía , Trasplante de Hígado , Mitocondrias Hepáticas/metabolismo , Adulto , Femenino , Hepatectomía , Humanos , Masculino , Potenciales de la Membrana , Consumo de OxígenoRESUMEN
The purpose of the present article was to present the series operated by a Liver Transplant Group of the interior of the State of Sao Paulo, Brazil. Sixty patients were transplanted from May 2001 to May 2007. Thirty percent of the patients had alcoholic cirrhosis. 18.3% had C virus-induced cirrhosis, 10% had C virus- and alcohol-induced cirrhosis, 6% had B virus-induced cirrhosis, 13.3% had cryptogenic cirrhosis, 8.3% autoimmune cirrhosis, 13.3% had familial amyloidotic polyneuropathy (FAP), and 13.3% had hepatocellular carcinomas. The series was divided by a chronological criterion into two periods: A (n = 42) and B (n = 18) with the latter group operated based upon the Model for End-stage Liver Disease (MELD) criterion. Sixty-nine percent were men. Age ranged from 14 to 66 years. Period A included 12% Child A: 59.2%, Child B; 24%, Child C; and 4.8%, FAP. Period B comprises 22.2% Child A: 11.1%, Child B: 33.3%, Child C: and 33.3%, FAP. MELD scores ranged from 8 to 35 for period A and from 14 to 31 for period B. Intraoperative mortality was 2/42 patients for period A and 0/18 for period B, overall postoperative mortality was 40% including for period A, 35% among Child B and C patients, and 5% among FAP and Child A patients (P < .05) and 16.6% for period B among 11.1% Child B patients and 5.5% FAP patients; 3.3% of patients required retransplantation due to hepatic artery thrombosis. Real postoperative survival was 60% during period A and 83.3% during period B, with an overall survival rate of 67% for the two periods. The present results show levels of postoperative mortality, (especially during period B), and survival rates similar to those reported by several other centers in Brazil.
Asunto(s)
Trasplante de Hígado/fisiología , Adolescente , Adulto , Anciano , Brasil , Hepatitis Viral Humana/cirugía , Hospitales Universitarios , Humanos , Cirrosis Hepática/cirugía , Hepatopatías/clasificación , Hepatopatías/cirugía , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. Chagas disease following solid-organ transplantation has occurred in Latin America. This report presents the occurrence of Chagas disease despite negative serological tests in both the donor and the recipient, as well as the effectiveness of treatment. A 21-year-old woman from the state of Sao Paulo (Brazil) underwent cadaveric donor liver transplantation in November 2005, due to cirrhosis of autoimmune etiology. Ten months after liver transplantation, she developed signs and symptoms of congestive heart failure (New York Heart Association functional class IV). The echocardiogram, which was normal preoperatively, showed dilated cardiac chambers, depressed left ventricular systolic function (ejection fraction = 35%) and moderate pulmonary hypertension. Clinical investigation discarded ischemic heart disease and autoimmune and other causes for heart failure. Immuno fluorescence (immunoglobulin M and immunoglobulin G) and hemagglutination tests for T cruzi were positive, and abundant T cruzi amastigotes were readily identified in myocardial biopsy specimens. Treatment with benznidazole for 2 months yielded an excellent clinical response. At the moment of submission, the patient remains in functional class I. This case highlighted that more appropriate screening for T cruzi infection is mandatory in potential donors and recipients of solid-organ transplants in regions where Chagas disease is prevalent. Moreover, it stressed that this diagnosis should always be considered in recipients who develop cardiac complications, since negative serological tests do not completely discard the possibility of disease transmission and since good results can be achieved with prompt trypanocidal therapy.
Asunto(s)
Cardiomiopatía Chagásica/diagnóstico , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/parasitología , Trypanosoma cruzi/aislamiento & purificación , Adulto , Animales , Cardiomiopatía Chagásica/tratamiento farmacológico , Ecocardiografía , Resultado Fatal , Corazón/parasitología , Humanos , Masculino , Nitroimidazoles/uso terapéutico , Trasplante de Páncreas , Tripanocidas/uso terapéutico , Disfunción Ventricular IzquierdaRESUMEN
Liver transplantation represents the most effective therapy for patients suffering from chronic end-stage liver disease. Until recently, in Brazil liver allocation was based on the Child-Turcotte-Pugh score and the waiting list followed a chronological criterion. The aim of this study was to show the clinical and laboratory patterns of our patients awaiting a liver transplantation. Seventy-nine medical records were reviewed in January 2005 to classify patients according to their age, sex, cause of cirrhosis, and Child and Model for End Stage Liver Disease (MELD) scores. The mean age of patients was 47 years; 70% were men. The main diagnosis was liver cirrhosis (97%): 27% alcoholic, 26% viral hepatitis, 20% alcoholic plus viral hepatitis, 13% cryptogenic, and 11% other causes. Sixty-three patients (80%) were Child B or C. The average MELD, scores for Child A, B, and C were 10 +/- 5, 13 +/- 3.4, and 21 +/- 4.3, respectively. Nine deaths (11%) on the waiting list occurred in 2005. Among these, 1 patient was Child B with MELD 10, while the others were Child C, with mean MELD scores of 21 +/- 3.8. Twelve patients (15%) received cadaveric orthotopic liver transplantation. Thus, in this small series, the higher MELD scores corresponded to Child C class and mortality on the waiting list.
Asunto(s)
Fallo Hepático/cirugía , Trasplante de Hígado/estadística & datos numéricos , Selección de Paciente , Listas de Espera , Brasil , Humanos , Cirrosis Hepática/cirugía , Fallo Hepático/clasificación , Trasplante de Hígado/mortalidad , Asignación de Recursos/métodos , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Among the postoperative complications, hepatic artery thrombosis can occur in up to 10% of adult orthotopic liver transplants and intervention is indicated when this occurs within 30 days by retransplantation. Primary graft dysfunction, which can occur in up to 30% of the cases and is another potential complication, although reversible, has a relatively high mortality rate. Hyperbaric therapy, an efficient mode of tissue oxygenation, is being used in an increasing number of clinical situations. We report here two cases where hyperbaric oxygen therapy greatly benefited patients with complications after orthotopic liver transplantation: one with hepatic artery thrombosis and the other with primary graft dysfunction. Both patients showed rapid clinical recovery with gradual reduction of liver and canalicular enzymes soon after commencing hyperbaric oxygen therapy.
Asunto(s)
Arteria Hepática , Oxigenoterapia Hiperbárica/métodos , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/terapia , Trombosis/etiología , Trombosis/terapia , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Humanos , Lactante , Masculino , Resultado del TratamientoRESUMEN
Hepatocellular carcinomas are aggressive tumors with a high dissemination power. An early diagnosis of these tumors is of great importance in order to offer the possibility of curative treatment. For an early diagnosis, abdominal ultrasound and serum alpha-fetoprotein determinations at 6-month intervals are suggested for all patients with cirrhosis of the liver, since this disease is considered to be the main risk factor for the development of the neoplasia. Helicoidal computed tomography, magnetic resonance and/or hepatic arteriography are suggested for diagnostic confirmation and tumor staging. The need to obtain a fragment of the focal lesion for cytology and/or histology for a diagnosis of hepatocellular carcinoma depends on the inability of imaging methods to diagnose the lesion. Several classifications are currently available for tumor staging in order to determine patient prognosis. All take into consideration not only the stage of the tumor but also the degree of hepatocellular dysfunction, which is known to be the main factor related to patient survival. Classifications, however, fail to correlate treatment with prognosis and cannot suggest the ideal treatment for each tumor stage. The Barcelona Classification (BCLC) attempts to correlate tumor stage with treatment but requires prospective studies for validation. For single tumors smaller than 5 cm or up to three nodules smaller than 3 cm, surgical resection, liver transplantation and percutaneous treatment may offer good anti-tumoral results, as well as improved patient survival. Embolization or chemoembolization are therapeutic alternatives for patients who do not benefit from curative therapies.
Asunto(s)
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Biomarcadores de Tumor , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Estadificación de Neoplasias , Pronóstico , Factores de TiempoRESUMEN
Hepatocellular carcinomas are aggressive tumors with a high dissemination power. An early diagnosis of these tumors is of great importance in order to offer the possibility of curative treatment. For an early diagnosis, abdominal ultrasound and serum alpha-fetoprotein determinations at 6-month intervals are suggested for all patients with cirrhosis of the liver, since this disease is considered to be the main risk factor for the development of the neoplasia. Helicoidal computed tomography, magnetic resonance and/or hepatic arteriography are suggested for diagnostic confirmation and tumor staging. The need to obtain a fragment of the focal lesion for cytology and/or histology for a diagnosis of hepatocellular carcinoma depends on the inability of imaging methods to diagnose the lesion. Several classifications are currently available for tumor staging in order to determine patient prognosis. All take into consideration not only the stage of the tumor but also the degree of hepatocellular dysfunction, which is known to be the main factor related to patient survival. Classifications, however, fail to correlate treatment with prognosis and cannot suggest the ideal treatment for each tumor stage. The Barcelona Classification (BCLC) attempts to correlate tumor stage with treatment but requires prospective studies for validation. For single tumors smaller than 5 cm or up to three nodules smaller than 3 cm, surgical resection, liver transplantation and percutaneous treatment may offer good anti-tumoral results, as well as improved patient survival. Embolization or chemoembolization are therapeutic alternatives for patients who do not benefit from curative therapies.
Asunto(s)
Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Biomarcadores de Tumor , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Estadificación de Neoplasias , Pronóstico , Factores de TiempoRESUMEN
Hepatitis C virus (HCV) infection is a serious public health problem, since 80 percent to 85 percent of HCV carriers develop a persistent infection that can progress into liver cirrhosis and hepatocarcinoma. Considering that the response of hepatitis C patients to combination therapy with interferon and ribavirin depends on HCV characteristics as well as on host features, we made a retrospective analysis of demographic and anthropometrical data and HCV genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil. The medical records of 4,996 patients were reviewed, 81 percent from public and 19 percent from private institutions. Patients' median age was 46 years, and there was a higher prevalence of male (62 percent) and white patients (80 percent). The analysis of HCV-infecting strains showed a predominance of genotype 1 (64 percent) over genotypes 2 and 3. The patients' mean weight was 70.6 kg, and 65 percent of the patients weighed less than 77kg. Overweight and obesity were observed in 37.8 percent and 13.6 percent of the patients, respectively. Since a body weight of 75 kg or less has been considered an independent factor that significantly increases the odds of achieving a sustained virological response, the Brazilian population seems to have a more favorable body weight profile to achieve a sustained response than the American and European populations. The finding that 65 percent of chronic hepatitis C patients have a body weight of 77 kg or less may have a positive pharmacoeconomic impact on the treatment of genotype 1 HCV patients with weight-based doses of peginterferon.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Pesos y Medidas Corporales , Hepacivirus/genética , Hepatitis C Crónica/virología , Brasil , Genotipo , Sector Privado , Sector Público , Estudios RetrospectivosRESUMEN
Hepatitis C virus (HCV) infection is a serious public health problem, since 80% to 85% of HCV carriers develop a persistent infection that can progress into liver cirrhosis and hepatocarcinoma. Considering that the response of hepatitis C patients to combination therapy with interferon and ribavirin depends on HCV characteristics as well as on host features, we made a retrospective analysis of demographic and anthropometrical data and HCV genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil. The medical records of 4,996 patients were reviewed, 81% from public and 19% from private institutions. Patients' median age was 46 years, and there was a higher prevalence of male (62%) and white patients (80%). The analysis of HCV-infecting strains showed a predominance of genotype 1 (64%) over genotypes 2 and 3. The patients' mean weight was 70.6 kg, and 65% of the patients weighed less than 77 kg. Overweight and obesity were observed in 37.8% and 13.6% of the patients, respectively. Since a body weight of 75 kg or less has been considered an independent factor that significantly increases the odds of achieving a sustained virological response, the Brazilian population seems to have a more favorable body weight profile to achieve a sustained response than the American and European populations. The finding that 65% of chronic hepatitis C patients have a body weight of 77 kg or less may have a positive pharmacoeconomic impact on the treatment of genotype 1 HCV patients with weight-based doses of peginterferon.
Asunto(s)
Pesos y Medidas Corporales , Hepacivirus/genética , Hepatitis C Crónica/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Patients with sickle-cell anemia submitted to frequent blood transfusions are at risk of contamination with hepatitis C virus (HCV). Determination of HCV RNA and genotype characterization are parameters that are relevant for the treatment of the viral infection. The objective of the present study was to determine the frequency of HCV infection and the positivity for HCV RNA and to identify the HCV genotype in patients with sickle-cell anemia with a history of blood transfusion who had been treated at the Hospital of the HEMOPE Foundation. Sera from 291 patients were tested for anti-HCV antibodies by ELISA 3.0 and RIBA 3.0 Chiron and for the presence of HCV RNA by RT-PCR. HCV genotyping was performed in 19 serum samples. Forty-one of 291 patients (14.1%) were anti-HCV positive by ELISA and RIBA. Both univariate and multivariate analysis showed a greater risk of anti-HCV positivity in those who had started a transfusion regime before 1992 and received more than 10 units of blood. Thirty-four of the anti-HCV-positive patients (34/41, 82.9%) were also HCV RNA positive. Univariate analysis, used to compare HCV RNA-negative and -positive patients, did not indicate a higher risk of HCV RNA positivity for any of the variables evaluated. The genotypes identified were 1b (63%), 1a (21%) and 3a (16%). A high prevalence of HCV infection was observed in our patients with sickle-cell anemia (14.1%) compared to the population in general (3%). In the literature, the frequency of HCV infection in sickle-cell anemia ranges from 2 to 30%. The serological screening for anti-HCV at blood banks after 1992 has contributed to a better control of the dissemination of HCV infection. Because of the predominance of genotype 1, these patients belong to a group requiring special treatment, with a probable indication of new therapeutic options against HCV.
Asunto(s)
Anemia de Células Falciformes/terapia , Hepacivirus/genética , Hepatitis C/transmisión , Reacción a la Transfusión , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Genotipo , Hepatitis C/epidemiología , Hepatitis C/virología , Anticuerpos contra la Hepatitis C/sangre , Humanos , Immunoblotting , Lactante , Persona de Mediana Edad , Prevalencia , ARN Viral/análisis , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de RiesgoRESUMEN
Patients with sickle-cell anemia submitted to frequent blood transfusions are at risk of contamination with hepatitis C virus (HCV). Determination of HCV RNA and genotype characterization are parameters that are relevant for the treatment of the viral infection. The objective of the present study was to determine the frequency of HCV infection and the positivity for HCV RNA and to identify the HCV genotype in patients with sickle-cell anemia with a history of blood transfusion who had been treated at the Hospital of the HEMOPE Foundation. Sera from 291 patients were tested for anti-HCV antibodies by ELISA 3.0 and RIBA 3.0 Chiron and for the presence of HCV RNA by RT-PCR. HCV genotyping was performed in 19 serum samples. Forty-one of 291 patients (14.1 percent) were anti-HCV positive by ELISA and RIBA. Both univariate and multivariate analysis showed a greater risk of anti-HCV positivity in those who had started a transfusion regime before 1992 and received more than 10 units of blood. Thirty-four of the anti-HCV-positive patients (34/41, 82.9 percent) were also HCV RNA positive. Univariate analysis, used to compare HCV RNA-negative and -positive patients, did not indicate a higher risk of HCV RNA positivity for any of the variables evaluated. The genotypes identified were 1b (63 percent), 1a (21 percent) and 3a (16 percent). A high prevalence of HCV infection was observed in our patients with sickle-cell anemia (14.1 percent) compared to the population in general (3 percent). In the literature, the frequency of HCV infection in sickle-cell anemia ranges from 2 to 30 percent. The serological screening for anti-HCV at blood banks after 1992 has contributed to a better control of the dissemination of HCV infection. Because of the predominance of genotype 1, these patients belong to a group requiring special treatment, with a probable indication of new therapeutic options against HCV
Asunto(s)
Humanos , Femenino , Lactante , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anemia de Células Falciformes , Transfusión Sanguínea , Hepacivirus , Hepatitis C , Anciano de 80 o más Años , Brasil , Ensayo de Inmunoadsorción Enzimática , Genotipo , Hepatitis C , Anticuerpos contra la Hepatitis C , Immunoblotting , Prevalencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Riesgo , ARN ViralRESUMEN
To test the effect of a sucrose diet on acetaminophen hepatotoxicity, 20 male Wistar rats were fasted and 20 were maintained exclusively on a sucrose diet ad libitum for 66 h. After 42 h, acetaminophen (1 g/kg) was administered through an orogastric tube to 10 fasted animals and to 10 animals on the sucrose diet, or intraperitoneally to the remaining animals. Animals were killed 24 h later and blood was collected for the measurement of alanine and aspartate aminotransferase activity and the liver was removel for macroscopic and microscopic examination. Plasma alanine and aspeartate aminotransferase levels were significantly lower (P<0.001) in all animals maintained on the sucrose diet. Macroscopic examination revealed parenchymatous necrosis in 90% (18/20) of the fasted animals but in none of the animals fed sucrosel. Microscopic examination confirmed the macroscopic findings and permited the detection of liver necrosis in one additional fasted animal. We conclude that ingestion of a sucrose diet protected the animals from the hepatotoxic effects of acetaminophen regardless of the route of administration of the drug