RESUMO
INTRODUCTION AND AIM: Hepatitis C virus (HCV) infection is a global medical problem. HLA -DRB1 alleles have an important role in immune response against HCV. The aim of this study is to clarify the contribution of HLA -DRB1 alleles in HCV susceptibility in a multicentre family-based study. MATERIAL AND METHODS: A total of 162 Egyptian families were recruited in this study with a total of 951 individuals (255 with chronic hepatitis C (CHC), 588 persons in the control group(-ve household contact to HCV) and 108 persons who spontaneously cleared the virus (SVC). All subjects were genotyped for HLA -DRB1 alleles by SSP-PCR and sequence based typing (SBT) methods. RESULTS: The carriage of alleles 3:01:01 and 13:01:01 were highly significant in CHC when compared to that of control and SVC groups [OR of 3 family = 5.1289, PC (Bonferroni correction ) = 0.0002 and 5.9847, PC = 0.0001 and OR of 13 family = 4.6860, PC = 0.0002 and OR = 6.5987, PC = 0.0001 respectively]. While DRB1*040501, DRB1*040101, DRB1*7:01:01 and DRB1*110101 alleles were more frequent in SVC group than CHC patients (OR = 0.4052, PC = 0.03, OR: OR = 0.0916,PC = 0.0006, OR = 0.1833,PC = 0.0006 and OR = 0.4061, PC = 0.0001 respectively). CONCLUSIONS: It was concluded that among the Egyptian families, HLA-DRB1*030101, and DRB1*130101 alleles associated with the risk of progression to CHC infection, while DRB1*040101, DRB1*040501, DRB1*7:01:01and DRB1*110101 act as protective alleles against HCV infection.
Assuntos
DNA Viral/análise , Família , Predisposição Genética para Doença , Cadeias HLA-DRB1/genética , Hepacivirus/genética , Hepatite C Crônica/virologia , Polimorfismo Genético , Adulto , Alelos , Egito/epidemiologia , Feminino , Frequência do Gene , Genótipo , Cadeias HLA-DRB1/metabolismo , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/genética , Humanos , Incidência , MasculinoRESUMO
UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: Chronic HCV is a major cause of HCC development. Caspase Recruitment Domains (CARD) is protein modules that regulate apoptosis and play an important role in various carcinogenesis processes, our aim is to assess the possible role of CARD9, CARD10 and Caspase only protein (COP) in progression of liver fibrosis and pathogenesis of HCC in Egyptian chronic HCV patients. MATERIAL AND METHODS: 130 patients were recruited and classified into 4 groups; I: chronic HCV, II: chronic active hepatitis, III: liver cirrhosis, IV: HCV related HCC. Biochemical, virological studies, abdominal ultrasonography and liver biopsy were performed. Quantitative estimation of mRNA of CARD9, CARD10 and COP gene expression was performed by RT- PCR in liver biopsy from all patients. RESULTS: In HCC patients; age, AFP and liver profile were significantly higher, HB and platelets were significantly lower (p value <0.01). The expression levels of mRNA of CARD9, CARD10 and COP in liver biopsies of HCC were significantly higher than other groups with direct correlation with age and no correlation with AFP, viral load, liver fibrosis or necroinflammatory activity. On differentiation between HCC and non HCC patients each CARD was assessed separately and combined, on combing the 3 CARDs, the sensitivity was 100%, specificity was 48%, positive predictive value 47% and negative predictive value 100%. CONCLUSIONS: CARD9, CARD10 and COP had no role in liver fibrosis but may be involved in hepatic carcinogenesis and they could be used as markers for HCC diagnosis and candid genes for molecular target therapy.
Assuntos
Biomarcadores Tumorais/genética , Proteínas Adaptadoras de Sinalização CARD/genética , Carcinoma Hepatocelular/genética , Hepatite C Crônica/complicações , Neoplasias Hepáticas/genética , Adolescente , Adulto , Biópsia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Egito , Feminino , Testes Genéticos/métodos , Hepatite C Crônica/diagnóstico , Humanos , Cirrose Hepática/genética , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Prognóstico , RNA Mensageiro/análise , Regulação para Cima , Carga Viral , Adulto Jovem , alfa-Fetoproteínas/análiseRESUMO
BACKGROUND: The main causes of liver fibrosis in transfusion-dependent thalassemia major are hepatitis C virus (HCV) infection and hepatic iron overload. The study aimed to assess liver fibrosis in Egyptian adolescents and young adult poly-transfused beta thalassemia patients infected with HCV using liver FibroScan in relation to iron overload and Liver iron concentration (LIC). MATERIAL AND METHODS: Fifty-one regularly transfused beta thalassemia patients above 12 years old were subjected to measurement of serum alanine transaminase (ALT), serum ferritin (SF), HCV (antibody and RNA), LIC assessed by hepatic R2* and transient elastography (TE) (FibroScan). FibroTest and liver biopsy were done to 25 patients. RESULTS: Eighty two% of studied thalassemia patients were HCV antibody positive; 21(49%) of them were viremic (HCV RNA positive); median LIC was 12 mg/gm dry weight. There were strong positive correlation between the degree of liver stiffness and Ishak fibrosis score assessed in liver biopsy specimens (P = 0.002) and between FibroScan and FibroTest results (P < 0.001). Patients with HCV viremia showed significantly higher ALT, γ-glutamyl transpeptidase (GGT), SF, LIC and increased liver stiffness compared to patients with no viremia (P = 0.0001, 0.001, 0.012, 0.006 and 0.001) respectively. Liver cirrhosis (TE values > 12.5kPa) was encountered in 23.5% and variable degrees of liver fibrosis (TE values > 6-12.5 kPa) in 35% of studied thalassemic patients. CONCLUSION: Young beta thalassemia patients with active hepatitis C infection may have hepatic cirrhosis or fibrosis at young age when accompanied with hepatic siderosis. Non invasive Liver FibroScan and Fibro-Test were reliable methods to assess liver fibrosis in young thalassemic-patients.
Assuntos
Transfusão de Eritrócitos/efeitos adversos , Hemossiderose , Hepatite C/transmissão , Quelantes de Ferro/uso terapêutico , Cirrose Hepática , Talassemia beta/terapia , Adolescente , Algoritmos , Apolipoproteína A-I/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Biópsia com Agulha de Grande Calibre , Criança , Estudos Transversais , Egito , Técnicas de Imagem por Elasticidade , Feminino , Ferritinas/sangue , Haptoglobinas/análise , Hemossiderose/diagnóstico por imagem , Hemossiderose/tratamento farmacológico , Hemossiderose/patologia , Hepacivirus/genética , Hepatite C/complicações , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Imageamento por Ressonância Magnética , Masculino , Adesão à Medicação , RNA Viral/sangue , Adulto Jovem , alfa-Macroglobulinas/análise , Talassemia beta/complicações , gama-Glutamiltransferase/sangueRESUMO
UNLABELLED: INTRODUCTION-AIM: Health-Related Quality of Life (HRQOL) has become an important focus of patient care and clinical outcomes research with the improvement in patient and graft survival after liver transplantation (LT). The current study was designed to evaluate the post-transplant HRQOL profiles using the Liver Disease Quality of Life 1.0 (LDQOL 1.0) Questionnaire and demonstrate the possible effect of peri-transplant clinical covariates on these profiles. MATERIAL AND METHODS: Participants included pre-transplant group (waiting-list patients n = 50) and post-transplant group (mean 5 ± 4 years after deceased or living donor LT n = 103) who were recruited from 3 specialized centers in Egypt. We applied the LDQOL 1.0 questionnaire; a 111-item containing the Short Form-36 version 2.0 (SF-36v2) as a generic component supplemented by 75 disease-specific items. The etiology of cirrhosis, co-morbidities, model for end-stage liver disease (MELD), Child-Pugh class and post-operative complications were analyzed. RESULTS: All recipients had significant higher HRQOL scores than patients in waiting-list using both questionnaire components. Recipients with pre-LT MELD ≥ 15, Child-Pugh class C, history of hepatocellular carcinoma (HCC) demonstrated low HRQOL scores. Recipients without post-operative surgical complications had a statistically better HRQOL using the disease-specific, but not the SF-36v2 component. On the other hand, both components demonstrated non-significant lower scores in recipients with rejection episodes, cytomegalovirus (CMV) infection and hepatitis C recurrence had compared to those without medical complications. CONCLUSION: Generally HRQOL improves dramatically after LT as assessed by LDQOL questionnaire. Moreover, combined questionnaires can provide accurate information about the possible impaired HRQOL post-LT due to pre-transplant disease severity and post-operative complications.
Assuntos
Hepatopatias/cirurgia , Transplante de Fígado/psicologia , Qualidade de Vida , Distribuição de Qui-Quadrado , Comorbidade , Egito , Feminino , Humanos , Hepatopatias/diagnóstico , Hepatopatias/psicologia , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/psicologia , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Listas de EsperaRESUMO
Natural killer cells can be divided into five subpopulations based on the relative expression of CD16 and CD56 markers. The majority of natural killer cells are CD56(dim), which are considered to be the main cytotoxic effectors. A minority of the natural killer cells are CD56(bright), and function as an important source of immune-regulatory cytokines. Shifts of these subsets have been reported in patients with chronic hepatitis C virus infection. We sought to investigate the shift of natural killer subsets among Egyptian patients with chronic HCV and to analyze the influence of interferon therapy on this shift. We applied a flow cytometric analysis of peripheral blood natural killer subsets for 12 interferon-untreated and 12 interferon-treated patients with chronic HCV, in comparison to 10 control subjects. Among interferon-untreated patients, there was a significant reduction of CD56â»16(+) (immature natural killer) cells. Among interferon-treated patients, the absolute count of natural killer cells was reduced, with expansion of the CD56(bright) subset and reduction of the CD56(dim)16(+) subset. Natural killer subset counts were not significantly correlated to HCV viral load and were not significantly different among interferon responders and non-responders. In conclusion, HCV infection in Egyptian patients has been observed to be statistically and significantly associated with reduction of the CD56â»16(+)NK subset, while a statistically significant expansion of CD56(bright) and reduction of CD56(dim)16(+) subsets were observed after interferon therapy. Further studies are required to delineate the molecular basis of interferon-induced shift of natural killer subsets among patients with HCV.
Assuntos
Antivirais/uso terapêutico , Antígeno CD56/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Células Matadoras Naturais/efeitos dos fármacos , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Natural killer cells can be divided into five subpopulations based on the relative expression of CD16 and CD56 markers. The majority of natural killer cells are CD56dim, which are considered to be the main cytotoxic effectors. A minority of the natural killer cells are CD56bright, and function as an important source of immune-regulatory cytokines. Shifts of these subsets have been reported in patients with chronic hepatitis C virus infection. We sought to investigate the shift of natural killer subsets among Egyptian patients with chronic HCV and to analyze the influence of interferon therapy on this shift. We applied a flow cytometric analysis of peripheral blood natural killer subsets for 12 interferon-untreated and 12 interferon-treated patients with chronic HCV, in comparison to 10 control subjects. Among interferon-untreated patients, there was a significant reduction of CD56-16+ (immature natural killer) cells. Among interferon-treated patients, the absolute count of natural killer cells was reduced, with expansion of the CD56bright subset and reduction of the CD56dim16+ subset. Natural killer subset counts were not significantly correlated to HCV viral load and were not significantly different among interferon responders and non-responders. In conclusion, HCV infection in Egyptian patients has been observed to be statistically and significantly associated with reduction of the CD56-16+NK subset, while a statistically significant expansion of CD56bright and reduction of CD56dim16+ subsets were observed after interferon therapy. Further studies are required to delineate the molecular basis of interferon-induced shift of natural killer subsets among patients with HCV.