Asunto(s)
Proteína C-Reactiva/metabolismo , Carcinoma Hepatocelular/sangre , Neoplasias Hepáticas/sangre , Malondialdehído/sangre , Biomarcadores/sangre , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/virología , Estudios de Casos y Controles , Femenino , Hepatitis C Crónica/complicaciones , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: Hepatitis C virus (HCV) related liver cirrhosis occurs in about 20% of chronically infected patients over a duration of 10-20 years, and within 5 years approximately 10-20% of these cirrhotic patients will develop hepatocellular carcinoma (HCC). Previous studies report that the X-ray repair cross-complementing group1 gene (XRCC1) is important in the risk of HCC development; however, results obtained from these studies are conflicting rather than conclusive. We hypothesised an association between single nucleotide polymorphisms (SNPs) in XRCC1 with the HCC risk on a background of chronic hepatitis C. MATERIALS AND METHODS: We recruited 210 subjects, 70 with HCC, 70 with cirrhosis and 70 healthy controls. Two SNPs [c.1254C>T(rs2293035) and c.1517G>C(rs139599857)] in XRCC1 were genotyped using created restriction site-polymerase chain reaction (CRS-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS: The TT genotype, CT genotype and T-allele in c.1254C>T (rs2293035) were linked to risk of HCC compared to the CC genotype: OR 3.58 [confidence interval (CI) 95%: 1.19-10.7] p = 0.019; OR 2.16 (CI 95%: 1.04-4.47) p = 0.037 and OR 2.10 (CI 95%: 1.2-3.3) p = 0.006, respectively. Regarding c.1517G>C (rs139599857), the CC genotype, GC genotype and C-allele were linked with higher risk of developing HCC compared to GG genotype: OR 4.77 (CI 95%: 1.3-16.9), p = 0.016; OR 3.02 (CI 95%: 1.46-6.2), p = 0.002 and OR 2.4 (CI 95%: 1.4-4.0), p = 0.001, respectively. CONCLUSION: We conclude that the T-allele of c.1254C>T (rs2293035) and the C allele of c.1517G>C (rs139599857) genetic variants may be associated with increased HCC risk among chronic hepatitis C patients.
Asunto(s)
Carcinoma Hepatocelular/genética , Hepatitis C Crónica/genética , Neoplasias Hepáticas/genética , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/genética , Alelos , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Hepacivirus/genética , Hepacivirus/patogenicidad , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/patología , Hepatitis C Crónica/virología , Humanos , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores de RiesgoRESUMEN
BACKGROUND: Polymorphisms of certain genes may have an effect on either persistence of infection or spontaneous clearance of hepatitis C virus (HCV). We hypothesized that one or more variants of chemokines (CCL2 and CCL5) and chemokine receptors (CC chemokine receptor type 2 [CCR2]) genes are associated with the susceptibility to HCV infection. METHODS: We recruited 1460 patients with chronic HCV (CHC), 108 subjects with spontaneous virus clearance (SVC) and 1446 individuals as a healthy control group. All were genotyped for single nucleotide polymorphisms: rs13900 C/T of CCL2, rs3817655 T/A of CCL5 and rs743660 G/A and rs1799864 G/A of CCR2 using allelic discrimination real-time PCR technique. RESULTS: The carriage of the A allele of CCR2 rs743660 was significantly higher in CHC compared to SVC (odds ratio [OR] 4.03) and to controls (1.42) and in controls compared to SVC (2.85) (all P < 0.01). Similarly, the A allele of CCR2 rs1799864 was significantly higher in the CHC group when compared with both SVC (1.97) and controls (2.13) (both P < 0.01), but the OR between controls and SVC was not significant (1.08, P = 0.723). Carriage of C allele of CCL2 rs13900 and the T allele of CCL5 rs3817655 were significantly higher in SVC group when compared with both CHC (OR = 0.19 and OR = 0.24, respectively) and control groups (OR = 0.65 and OR = 0.45, respectively [all P < 0.01]). CONCLUSIONS: Susceptibility to HCV infection is associated with A alleles of both (rs743660 and rs1799864 G/A) of CCR2 while spontaneous clearance of HCV is associated with the C allele of rs13900 of CCL2 and T allele of rs3817655 of CCL5.
Asunto(s)
Quimiocina CCL2/genética , Quimiocina CCL5/genética , Predisposición Genética a la Enfermedad , Hepacivirus/inmunología , Hepatitis C Crónica/genética , Polimorfismo de Nucleótido Simple , Receptores CCR2/genética , Adolescente , Adulto , Alelos , Estudios de Casos y Controles , Quimiocina CCL2/inmunología , Quimiocina CCL5/inmunología , Niño , Femenino , Expresión Génica , Frecuencia de los Genes , Hepacivirus/crecimiento & desarrollo , Hepacivirus/patogenicidad , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Receptores CCR2/inmunología , Remisión EspontáneaRESUMEN
BACKGROUND: The first-line treatment option for intermediate-stage hepatocellular carcinoma is trans-arterial chemoembolization (TACE). Blood indices, such as lymphocyte/monocyte ratio (LMR), lymphocyte count, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte-granulocyte/lymphocyte ratio (MGLR) and red blood cell distribution width (RDW), are prognostic biomarkers in certain diseases. The model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores have been designed for patients with cirrhosis waiting for liver transplantation and in patients with hepatocellular carcinoma. We hypothesized possible roles for these blood indices, and the MELD and CTP scores as predictors for early recurrence of hepatocellular carcinoma after TACE. METHODS: Routine laboratory indices determined the NLR, LMR, MGLR, RDW, PLR, as well as MELD and CTP scores in 147 patients. Sensitivity and specificity of the indices for hepatocellular carcinoma recurrence 36 months after TACE were estimated by receiver operator characteristic curve. RESULTS: In multivariate regression analysis, only male sex, the lymphocyte count, CTP, the MGLR and the MELD score significantly (P < 0.01) predicted recurrence. The area under curve (AUC) for detection of recurrence for MGLR at a cut-off value 2.75 was 0.63 (95% CI 0.54-0.72) with sensitivity 70.7%, specificity 59.2% and accuracy 63%. The MELD score at cut-off value 9.5 had diagnostic performance with AUC 0.71 (0.63-0.79), sensitivity 80% and specificity 55.8% and accuracy 71.3%. CONCLUSIONS: High MGLR and MELD scores are linked to increasing frequency of hepatocellular carcinoma recurrence after TACE and could be used as novel, simple, non-invasive prognostic tests.
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Carcinoma Hepatocelular/sangre , Neoplasias Hepáticas/sangre , Recurrencia Local de Neoplasia/sangre , Pronóstico , Adulto , Anciano , Plaquetas/patología , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/efectos adversos , Femenino , Granulocitos/patología , Humanos , Neoplasias Hepáticas/patología , Recuento de Linfocitos , Linfocitos/patología , Masculino , Persona de Mediana Edad , Monocitos/patología , Recurrencia Local de Neoplasia/patología , Neutrófilos/patologíaRESUMEN
BACKGROUND: Single nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) are linked with functional modification of cytokine responses. In chronic hepatitis C virus (HCV) infection, studies of TLR polymorphisms have primarily targeted receptor pathways implicated in viral immune responses. We hypothesized that one or more variant(s) of TLR3, TLR7 and TLR8 are associated with different outcomes of HCV infection. MATERIALS & METHODS: A total of 3368 subjects from 850 families were recruited and divided into three main groups categorized as chronic HCV CHC spontaneous viral clearance (SVC), and controls. All individuals were genotyped for three SNPs for TLR3, two SNPs for TLR7, and two SNPs for TLR8 using allelic discrimination real-time PCR. RESULTS: Carriage of the C allele in three SNPs of TLR3 (rs3775290, rs3775291, and rs5743312), the C allele in TLR7 (rs3853839) in females only, and the C allele in TLR8 (rs3764879) in males only were significantly higher in SVC group than CHC group (P < 0.001), while carriage of the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both males and females were significantly higher in CHC infection more than SVC group (P < 0.001). CONCLUSION: The C allele is protective of HCV in TLR3, TLR7 (rs3853839) in females only, and TLR8 (rs3764879) in males only, while risk of infection is linked to the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both sexes.
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Hepatitis C Crónica/genética , Receptor Toll-Like 3/genética , Receptor Toll-Like 7/genética , Receptor Toll-Like 8/genética , Adulto , Alelos , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Hepacivirus/genética , Hepacivirus/patogenicidad , Hepatitis C Crónica/patología , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores de RiesgoRESUMEN
BACKGROUND AND OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is diagnosed by the presence of ≥250 polymorphonuclear neutrophils (PMN)/mm3 in the ascites and the absence of surgically treatable cause of intra-abdominal infection. Blood neutrophil lymphocytic ratio (NLR) is an inexpensive and simple test for inflammation. C-reactive protein (CRP) is an inflammatory marker used for the diagnosis and follow-up of many diseases and morbidities. We aimed to evaluate the clinical utility of combined blood NLR and CRP as a non-invasive test for SBP diagnosis. METHODS: Blood NLR was calculated, and CRP value determined in 180 cirrhotic patients with ascites (126 with and 54 without SBP). Sensitivity and specificity of combined blood NLR and CRP values for SBP diagnosis were estimated by receiver operator characteristic curve. RESULTS: Both blood NLR and CRP values were significantly higher in SBP (p < 0.001). For SBP diagnosis, a blood NLR of >2.89 had a sensitivity 80.3% and specificity 88.9%. CRP >11.3 mg/dL had a sensitivity 88.9% and specificity 92.6%. In logistic regression analysis, combined blood NLR and CRP had a sensitivity 95.1% and specificity 96.3% at the same cut off values. CONCLUSIONS: Combined NLR and CRP could be used as a novel, simple, low-cost, non-invasive test for SBP diagnosis.
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Infecciones Bacterianas/sangre , Proteína C-Reactiva/metabolismo , Inflamación/sangre , Peritonitis/sangre , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/patología , Biomarcadores/sangre , Femenino , Humanos , Inflamación/microbiología , Inflamación/patología , Recuento de Linfocitos , Linfocitos/patología , Masculino , Persona de Mediana Edad , Neutrófilos/patología , Peritonitis/microbiología , Peritonitis/patologíaRESUMEN
Hepatitis C infection is a global pandemic. HLA-DQB1 alleles are believed to have an effective role in immune response against HCV including susceptibility to or protection from this infection. The aim of this study was to investigate the contribution of HLA-DQB1 alleles in the outcome of HCV genotype-4 infection through a family-based association study. Egyptian families with HCV (324) were recruited for this study (324 index positive for RNA-HCV, 225 positive relatives representing chronic hepatitis C cases and 582 family members negative for HCV-RNA [control], 63 of whom spontaneously cleared the virus. All subjects were genotyped for HLA-DQB1 alleles by sequence-specific primers (SSP-PCR) and sequence-based typing (SBT) methods. The frequency of DQB1*02:01:01 carriage was significantly higher in infected patients when compared to controls and those who spontaneously cleared virus (OR=5.47, P<.0001 and OR= 6.5234, P<.0001, respectively), and the carriage of the DQB1*03:01:01:01 allele was significantly higher in those who cleared and controls when compared to the infected patients (OR=0.2889, P<.0001 and OR=0.3016, P<.0001, respectively). On the other hand, the frequency of DQB1*06:01:01 and QB1*05:01:01:01 alleles was not associated with infection (comparison of infected and cleared patients showed OR of 2.1598 [P<.01]), but it becomes nonsignificant after adjustments with the Bonferroni formula (PC >0.05) and OR= 1.3523, P>.05, respectively. This study shows that clearance of HCV is associated with DQB1*03:01:01:01 allele and chronicity of HCV infection associated with the risk allele: DQB1*02:01:01.