RESUMEN
Inherited pathogenic variants account for 5% to 10% of all breast cancer (BC) and colorectal cancer (CRC) cases. Here, we sought to profile the pathogenic variants in 25 cancer susceptibility genes in Turkish population. Germline pathogenic variants were screened in 732 BC patients, 189 CRC patients and 490 cancer-free elderly controls, using next-generation sequencing-based multigene panel testing and multiplex ligation-dependent probe amplification testing. Pathogenic variants were detected in 17.2% of high-risk BC patients and 26.4% of high-risk CRC patients. More than 95% of these variants were clinically actionable. BRCA1/2 and mismatch repair genes (MLH1, MSH2 and MSH6) accounted for two-thirds of all pathogenic variants detected in high-risk BC and CRC patients, respectively. Pathogenic variants in PALB2, CHEK2, ATM and TP53 were also prevalent in high-risk BC patients (4.5%). BRCA1 exons 17-18 deletion and CHEK2 c.592+3A>T were the most common variants predisposing to BC, and they are likely to be founder variants. Three frequent MUTYH pathogenic variants (c.884C>T, c.1437_1439delGGA and c.1187G>A) were responsible for all MUTYH biallelic cases (4.4% of high-risk CRC patients). The total pathogenic variant frequency was very low in controls (2.4%) and in low-risk BC (3.9%) and CRC (6.1%) patients. Our study depicts the pathogenic variant spectrum and prevalence in Turkish BC and CRC patients, guiding clinicians and health authorities for genetic testing applications and variant classification in Turkish population.
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Neoplasias de la Mama Masculina/genética , Neoplasias de la Mama/genética , Neoplasias Colorrectales/genética , Mutación de Línea Germinal , Adulto , Factores de Edad , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Neoplasias de la Mama Masculina/epidemiología , Neoplasias de la Mama Masculina/patología , Estudios de Casos y Controles , Estudios de Cohortes , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Turquía/epidemiologíaRESUMEN
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD is a complex disease and inflammation is a crucial component in the disease pathogenesis. Recent genome wide association studies in hepatology area highlighted significant relations with human leukocyte antigen (HLA) DQ region and certain liver diseases. The previous animal models also emphasized the involvement of adaptive immune system in the liver damage pathways. To investigate possible polymorphisms in the HLA region that can contribute to the immune response affecting the NAFLD, we enrolled 93 consecutive biopsy proven NAFLD patients and a control group consisted of 101 healthy people and genotyped HLA DQB1 alleles at high resolution by sequence specific primers-polymerase chain reaction. The mean NAFLD activity score (NAS) was 5.2 ± 1.2, fibrosis score was 0.9 ± 0.9, ALT was 77 ± 47.4 U/L, AST was 49.4 ± 26.3 U/L. Among 13 HLA DQB1 alleles analyzed in this study, DQB1*06:04 was observed significantly at a more frequent rate among the NAFLD patients compared to that of healthy controls (12.9 vs. 2 % χ(2) = 8.6, P = 0.003, P c = 0.039, OR: 7.3 95 % CI 1.6-33.7). In addition, the frequency of DQB1*03:02 was significantly higher in the healthy control group than the NAFLD patients (24.8 vs. 7.5 %, χ(2) = 10.4, P = 0.001, P c = 0.013, OR: 0.2, 95 % CI 0.1-0.6). NAFLD patients were grouped according to their fibrosis score and NAS. The distribution of DQB1 alleles over stratified NAFLD patients did not reveal any statistically significant relation. Taken together, immune repertoire of individuals may have an effect on NAFLD pathogenesis and therefore, in NAFLD, adaptive immunity pathways should be investigated.
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Alelos , Predisposición Genética a la Enfermedad , Cadenas beta de HLA-DQ/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo GenéticoRESUMEN
Sirtuins are members of the silent information regulator 2 (Sir2) family, a group of Class III histone/protein deacetylases. There are 7 different sirtuins in mammals (SIRT1-7), of which SIRT1 is the best known and most studied. SIRT1 is responsible for the regulation of protein activation by means of deacetylating a variety of proteins that play important roles in the pathophysiology of metabolic diseases. Recently, it has been shown that SIRT1 plays key roles in the regulation of lipid and glucose homeostasis, control of insulin secretion and sensitivity, antiinflammatory effects, control of oxidative stress and the improvements in endothelial function that result due to increased mitochondrial biogenesis and ß-oxidation capacity. Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease, and it has been accepted as the hepatic component of metabolic syndrome. Recent studies have shown that SIRT expression in the liver is significantly decreased in an NAFLD model of rats fed a high-fat diet, and moderate SIRT1 overexpression protects mice from developing NAFLD. In addition to resveratrol, a natural SIRT1 activator, small-molecule pharmacologic SIRT1 activators have positive effects on metabolic diseases. These effects are particularly promising in the case of diabetes mellitus, for which phase studies are currently being performed. With this information, we hypothesized that the pharmacologic activation of SIRT1, which has been implicated in the pathogenesis of NAFLD, will be a potential therapeutic target for treating NAFLD. In this paper, we review the metabolic effects of SIRT1 and its association with the pathophysiology of NAFLD.
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Sirtuina 1/metabolismo , Animales , Activadores de Enzimas/farmacología , Hígado Graso/terapia , Humanos , Insulina/metabolismo , Secreción de Insulina , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Enfermedad del Hígado Graso no AlcohólicoRESUMEN
BACKGROUND/AIMS: Fibrinogen-like protein 2 (fgl2), has recently been identified as a new member of the fibrinogen-like family of proteins. In this study we assayed plasma levels of fgl2 in patients with biopsy proven non-alcoholic fatty liver disease (NAFLD) and examined their association with clinical, biochemical and histological phenotypes. METHODOLOGY: Levels of plasma fgl2 were measured by enzyme linked immunosorbent assay and compared between the study groups. Moreover, concentrations of fgl2 were assessed in relation to the general characteristics of the study participants and the results of the liver biopsy. RESULTS: Levels of fgl2 were significantly higher in patients with definite non-alcoholic steatohepatitis (NASH) (788±190pg/mL, p<0.001) and borderline NASH (710 ± 140pg/mL, p<0.001) compared with controls (515±174pg/mL). No significant differences were found in patients with simple steatosis (649 ± 162pg/mL) as compared with controls. There were no associations between the plasma fgl2 levels with the fibrosis stage and steatosis grade. CONCLUSIONS: Although subject to future confirmation, our data suggest that fgl2 levels are elevated in the more severe forms of NAFLD.
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Hígado Graso/sangre , Fibrinógeno/análisis , Adulto , Estudios Transversales , Hígado Graso/patología , Femenino , Humanos , Hígado/patología , Cirrosis Hepática/sangre , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no AlcohólicoRESUMEN
Autoimmune hepatitis may be frequently associated with chronic hepatitis C (HCV) infection, but there are few case reports regarding hepatitis B and Delta infection (HBV+HDV) as possible triggers. In this report, we present a 44 years old man who was diagnosed as autoimmune hepatitis (AIH) following the treatment of HBV+HDV hepatitis with pegylated interferon (PegIFN). He presented with complaint of fatigue. Laboratory indicated elevated liver enzymes, AST 64IU/L and ALT 112IU/L. The results revealed HBsAg and anti-delta antibody positivity. HBV-DNA was <31.6 IU/mL and HDV-RNA 487.300 copy/mL. Peg-IFN was initiated for 96 weeks. Without a serious adverse effect, the enzymes regressed to normal within 24 weeks. After 96 weeks of treatment, there was a three-fold increase in aminotransferases, with no cholestasis. Immunoglobulin-G (IgG) was 3686 mg/dL (reference 540-1822 mg/dL), anti-smooth muscle antibody (ASMA) and anti-nuclear antibody (ANA) were positive. The liver biopsy had all diagnostic clues for AIH. Methylprednisolone and azathioprine treatment was initiated with tenofovir (TdF) prophylaxis. Due to unresponsiveness, even with doubling the dosage for immunosuppressives, treatment was stopped and shifted to mycophenolate mofetil. The patient responded in the 6th month and still under treatment with TdF and mycophenolate mofetil with normal enzymes and negative HDV RNA.
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BACKGROUND: Higher hemoglobin levels have been associated with an increased risk for nonalcoholic fatty liver disease. Although the mechanism underlying this association is elusive, smoking has been previously related to both higher hemoglobin concentrations and an increased risk of fibrosis in nonalcoholic fatty liver disease. The present study was conducted to investigate formally the interaction among current smoking, hemoglobin levels, and risk for advanced fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease. PATIENTS AND METHODS: We examined 433 Turkish patients with biopsy-proven nonalcoholic fatty liver disease. Advanced fibrosis (F ≥ 3) was identified on liver biopsy in 80 cases, whereas 84 patients were current smokers. Logistic regression models were used to evaluate the effect of current smoking on risk for advanced fibrosis, after adjusting for the effects of age, sex, BMI, diabetes, and metabolic syndrome. RESULTS: Preliminary analyses revealed the presence of substantial statistical interaction between current smoking and hemoglobin levels (P < 0.001). In separate multivariable analyses conducted in the entire cohort and in the subgroups of patients with high and low hemoglobin levels (according to median value in the study cohort: 14.4 g/l), current smoking was associated with increased risk for advanced fibrosis in patients with high hemoglobin (odds ratio: 3.32, 95% confidence interval: 1.23-7.21, P < 0.01) but neither in those with low hemoglobin (odds ratio: 0.71, 95% confidence interval: 0.28-1.81, P = 0.52) nor in the entire study cohort (odds ratio: 1.18, 95% confidence interval: 0.73-2.14, P = 0.79). CONCLUSION: Hemoglobin acts as a modifier in the association between current smoking and advanced fibrosis in nonalcoholic fatty liver disease.
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Hemoglobinas/análisis , Cirrosis Hepática/etiología , Enfermedad del Hígado Graso no Alcohólico , Fumar/efectos adversos , Adolescente , Adulto , Anciano , Biopsia , Femenino , Humanos , Hígado/patología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/patología , Estudios Retrospectivos , Adulto JovenRESUMEN
A 37-year-old female patient with a history of iron deficiency anemia for three years had been hospitalized and followed up with subileus. An obstruction at the proximal part of the jejunum was found by enteroclysis method and a filling defect due to a polypoid mass was determined. The small intestine was resected. It was reported as a submucosal lipoma based on results of the histopathological examination. In conclusion, benign tumors of the small intestine, including intestinal lipomas, should be considered during the diagnostic process of clinical ileus and anemia.
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Neoplasias Intestinales/diagnóstico , Lipoma/diagnóstico , Adulto , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/etiología , Femenino , Humanos , Ileus/diagnóstico , Ileus/etiología , Neoplasias Intestinales/complicaciones , Neoplasias Intestinales/cirugía , Lipoma/complicaciones , Lipoma/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is one of the major causes of abnormal liver function tests in hepatology practice. However, not all patients with NAFLD have increased aminotransferase levels. The aim of this study was to compare the clinical and histologic characteristics of patients with biopsyproven NAFLD showing normal versus elevated aminotransferase levels. METHODS: We retrospectively reviewed 515 patients with biopsy-proven NAFLD. Patients with ALT ≤ 40 U/L and AST ≤ 37 U/L were considered as having normal liver enzymes. A histological fibrosis score F ≥ 3 was used to define advanced fibrosis. RESULTS: Of the 515 study participants, 107 (20.8%) had normal liver enzymes. Compared with patients showing elevated liver enzymes, those with normal aminotransferase levels were older and most commonly women. Moreover, they had a higher body mass index and more frequently showed metabolic risk factors (metabolic syndrome, diabetes mellitus, hypertension, higher waist and hip circumferences). Although liver histology tended to be less severe in patients with normal liver enzymes, the prevalence of advanced fibrosis was similar in the two groups. Diabetes mellitus (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.46-3.91, p < 0.001) and age (OR = 1.14, 95% CI = 1.07-1.24, p < 0.05) were identified as independent predictors of advanced fibrosis in patients with normal aminotransferase levels. CONCLUSIONS: NAFLD with normal aminotransferase levels is characterized by a severe metabolic profile and a prevalence of advanced fibrosis similar to that identified in cases with elevated aminotransferase levels.
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Enfermedad del Hígado Graso no Alcohólico/enzimología , Transaminasas/sangre , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Biopsia , Índice de Masa Corporal , Femenino , Humanos , Hígado/enzimología , Hígado/patología , Cirrosis Hepática/enzimología , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND AND STUDY AIMS: The success rate of Helicobacter pylori (H. pylori) eradication with the classical triple therapy is gradually declining. In this study, we aimed to compare and assess the efficacies of six different eradication regimens including sequential protocols. PATIENTS AND METHODS: Endoscopically confirmed nonulcer dyspepsia patients were enrolled. H. pylori presence was determined either histologically or by a rapid urease test. Treatment-naive patients were randomly assigned to an either one of three 10-day (OAC, OTMB, and OACB) or one of three sequential protocols (OA+OCM, OA+OCMB, and OA+OMDB) (O=omeprazole, A=amoxicillin, C=clarithromycin, T=tetracycline, M=metronidazole, B=bismuth, D=doxycycline). The eradication was assessed 6-8weeks after the completion of the treatment by a 14C-urea breath test. RESULTS: In total, 301 patients were included. Fifty-two percent of the participants (n=157) were female, and the mean age was 44.9years (range=18-70). The intention to treat (ITT) and per protocol (PP) eradication rate for each regimen is as follows: OAC (ITT=61.2%, PP=75%), OTMB (83.3%, 87%), OACB (76.5%, 79.6%), OA+OCM (72.3%, 73.9%), OA+OCMB (82.7%, 89.6%), and OA+OMDB (59.3%, 65.3%). Smoking significantly affected the eradication rate (P=0.04). CONCLUSION: In this study, OTMB and OA+OCMB were significantly superior to the triple therapy and succeeded to reach the eradication rate proposed by the Maastricht consensus (over 80%). These two bismuth-containing regimens could be considered for first-line therapy in the regions with high clarithromycin resistance.
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Antiácidos/uso terapéutico , Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Compuestos Organometálicos/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Adolescente , Adulto , Anciano , Amoxicilina/uso terapéutico , Pruebas Respiratorias , Claritromicina/uso terapéutico , Doxiciclina/uso terapéutico , Esquema de Medicación , Quimioterapia Combinada/efectos adversos , Femenino , Infecciones por Helicobacter/diagnóstico , Humanos , Análisis de Intención de Tratar , Masculino , Metronidazol/uso terapéutico , Persona de Mediana Edad , Omeprazol/uso terapéutico , Estudios Prospectivos , Fumar/efectos adversos , Tetraciclina , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND/AIMS: Ulcerative colitis (UC) and Crohn's disease are chronic inflammatory diseases. Genetic, immunologic, and microbial factors play an important role in their pathogenesis. Extracellular matrix protein 1 (ECM1), a gene related to mucosal barrier function, has been shown to be associated with UC. This study aims to determine the relationship between ECM1 gene rs3737240 single nucleotide polymorphism (SNP) and UC in a group of Turkish patients. MATERIALS AND METHODS: Ninety-four UC patients and 120 healthy controls were enrolled in the study. ECM1 gene rs3737240 SNP genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: TT genotype was significantly more common in UC patients than in the healthy control group [p=0.034; odds ratio (OR) 2.34; 95% confidence interval (CI) 1.04-5.25]. The presence of C allele significantly lowered the UC risk (p=0.034; OR 0.42; 95% CI 0.19-0.95). TT genotype was significantly associated with azathioprine use in UC patients (p=0.037; OR 3.0; 95% CI 1.04-8.65). The C allele significantly reduced the probability of azathioprine use in UC patients (p=0.037; OR 0.33 CI 95% 0.11-0.96). No relation was found between rs3737240 SNP genotype and the phenotypical characteristics of UC patients. CONCLUSION: The TT genotype of ECM1 gene rs3737240 SNP significantly increased susceptibility for UC and azathioprine use in UC patients in a Turkish population.
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Colitis Ulcerosa/genética , Proteínas de la Matriz Extracelular/genética , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Pueblo Asiatico/genética , Azatioprina/uso terapéutico , Estudios de Casos y Controles , Colitis Ulcerosa/tratamiento farmacológico , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , TurquíaRESUMEN
AIM: Chronic hepatitis B (CHB) is a global health problem. Recent genome-wide association studies (GWAS) exposed signifi-cant association between the human leukocyte antigen (HLA) class II region, including both DP and DQ loci, and chronic hepatitis B. Previous research also indicated the involvement of adaptive immune system in Hepatitis B seroconversion. The aim of this study is to investigate possible polymorphisms in the HLA-DP locus that can contribute to immune response to Hepatitis B virus (HBV). METHODS: We enrolled 94 chronic hepatitis B (CHB) patients and a control group of 85 spontaneous seroconverted healthy subjects and genotyped HLA-DPB1 alleles by polymerase chain reaction followed by restriction length polymorphism (PCR-RFLP) and Sanger sequencing. RESULTS: Among the 19 DPB1 alleles analyzed in this study, DPB1*15:01 allele was more frequent in the spontaneous sero-converted control group compared to CHB patients (15.3% vs. 1.1%, χ2 = 12.5, OR = 0.06, 95% CI = 0.08-0.046 P < 0.001, Pcorrected < 0.001). DPB1*02:01 and DPB1*10:01 were the other alleles observed more frequently in the control group (38.8% vs. 22.3% P = 0.02 and 16.5% vs. 5.3% P = 0.02, respectively). However associations of these two alleles were lost their significance after Bonferoni's correction (Pcorrected = 0.4 for all). CONCLUSIONS: In conclusion, this study demonstrates that HLA alleles may participate in spontaneous HBsAg seroconversion which is the ultimate target in CHB in Turkish CHB patients.
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Cadenas beta de HLA-DP/genética , Hepatitis B Crónica , Seroconversión/genética , Alelos , Femenino , Antígenos de Superficie de la Hepatitis B/inmunología , Hepatitis B Crónica/genética , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Humanos , Fenómenos del Sistema Inmunológico/genética , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores Protectores , TurquíaRESUMEN
OBJECTIVE: Chronic hepatitis B (CHB) is a major health problem. The outcome of hepatitis B virus (HBV) infection is associated with variations in HLA-DPA1 alleles. The aim of this study was to investigate possible associations of HLA-DPA1 alleles with treatment response and with hepatitis B virus e antigen (HBeAg) seroconversion. METHODS: Eight different HLA-DPA1 alleles from 246 CHB patients were genotyped by polymerase chain reaction with sequence-specific primers at high resolution to investigate the association of HLA-DPA1 alleles with treatment response, development of cirrhosis, HBeAg seroconversion, and disease reoccurrence upon HBeAg loss. RESULTS: There was no significant association between HLA-DPA1 alleles and treatment response, development of cirrhosis, or HBeAg seroconversion. However, HLA-DPA1*04:01 allele was significantly more frequently found in patients who redeveloped disease upon HBeAg seroconversion (100% vs 36.8%: p=0.037; Fisher's exact test). CONCLUSION: HLA-DPA1*04:01 allele may be a risk factor for reoccurrence of CHB after HBeAg seroconversion.
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BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Along with the increase in the incidence of NAFLD and associated obesity, an increase in gallbladder disease (GD) has been noted. This has led to the identification of a new disease entity called fatty GD. There is a gap in the literature on the dynamics of gallbladder function in patients with NAFLD. METHODS: An observational case-control study, a total of 50 patients with biopsy proven NAFLD without gallbladder stone/sludge and 38 healthy comparison subjects were enrolled. Fasting, postprandial gallbladder volumes (PGV), gallbladder ejection fraction (GEF), and fasting gallbladder wall thickness (FGWT) were measured by real-time 2-dimensional ultrasonography. RESULTS: Fasting gallbladder wall thickness, fasting gallbladder volumes and PGV were significantly higher in patients with NAFLD than control subjects (P < 0.001, P = 0.006, and P < 0.001, respectively). Gallbladder ejection fraction was significantly lower in the NAFLD group than the controls (P = 0.008). The presence of NAFLD was an independent predictor for GEF, PGV, and FGWT. Also, steatosis grade was an independent predictor for GEF, and GEF was significantly lower in the nonalcoholic steatohepatitis (NASH) subgroup than the controls. CONCLUSIONS: Gallbladder dysfunction and increase in gallbladder wall thickness exists in asymptomatic (without stone/sludge and related symptoms) patients with NAFLD and are useful in identifying fatty GD. Measurement of these variables in NAFLD patients may be useful in identifying those at higher risk for GD.
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OBJECTIVE: Low baseline viremia and an early treatment response predict the best outcomes in hepatitis B virus (HBV)-infected patients treated with nucleoside analogues with low barriers to resistance. The aim of this study was to assess the long-term results and effectiveness of lamivudine in patients with low baseline viremia and early virological treatment response. METHODS: In this multicenter, real-life setting study, 111 antiviral-naive patients with low baseline viremia (HBV DNA <10(7) copies/mL) plus an early virological response (HBV DNA <300 copies/mL at week 24) treated with lamivudine were enrolled. The primary end-point was treatment failure, defined as the re-emergence of detectable viremia or at least a 1 log increase in HBV DNA, resulting in a titer of ≥ 300 copies/mL with lamivudine treatment after week 24, which required treatment modification. RESULTS: Altogether 111 patients, including 78 non-cirrhotic and 33 cirrhotic patients, were included in the study. Treatment failure occurred in 30.8% of the non-cirrhotic patients over a median follow-up period of 32.5 months, and the 1-, 2-, 3-, 4- and 5-year treatment failure rates were 6.5%, 14.0%, 31.4%, 39.6% and 43.1%, respectively. Treatment failure occurred in 28.8% of the whole group. There were no differences between the cirrhotic and non-cirrhotic patients. CONCLUSIONS: Lamivudine treatment had a high treatment modification rate in patients with low baseline viremia and early virological response over a long-term follow-up in a real-life setting. The pretreatment and on-treatment favorable characteristics found in the studies with telbivudine appeared to be inapplicable to lamivudine.
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Antivirales/uso terapéutico , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Viremia/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , ADN Viral , Femenino , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del Tratamiento , Adulto JovenRESUMEN
In this report we present a case of a 28-year-old woman who was admitted to our emergency room complaining of chest pain. Her clinical ECG and biochemical evaluation was consistent with acute nonatherogenic myocardial infarction. Subsequent work is revealed that she was suffering from ulcerative colitis with acute exacerbation since last week. We discussed triggering factors for thrombogenic and inflammatory tendency of patient with comprehensive review of literature to clarify the causal relationship.
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Colitis Ulcerosa/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/etiología , Adulto , Colitis Ulcerosa/diagnóstico , Angiografía Coronaria , Ecocardiografía Doppler , Electrocardiografía , Femenino , Estudios de Seguimiento , Heparina/administración & dosificación , Humanos , Infarto del Miocardio/tratamiento farmacológico , Medición de Riesgo , Índice de Severidad de la Enfermedad , Sulfasalazina/administración & dosificación , Terapia Trombolítica/métodosRESUMEN
OBJECTIVES: Recent studies have suggested that bacterial overgrowth and endotoxemia along with its receptor, Toll-like receptor 4 (TLR-4), play a role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The present study was designed to test and evaluate the TLR4 gene polymorphism in patients with NAFLD in comparison to healthy controls. METHODS: A total of 119 patients [mean (standard deviation, SD) age 43.4 (11.5) years, 55.5% were males] with NAFLD and 80 healthy controls [mean (SD) age 40.9 (8.1) years, 67.5% were females)] were evaluated in terms of patient demographics, anthropometrics, blood biochemistry, liver histology, and ultrasonographic (USG) findings. Histological evaluation was performed in 111 patients, and blood samples were collected from 119 patients with NAFLD and 80 healthy persons. Allelic variants of TLR4 (Asp299Gly and Thr399Ile) were assayed by real-time PCR. Genomic DNA was amplified using FAM/VIC primers specific for allelic variants of TLR4 Asp299Gly and Thr399Ile with real-time PCR. Amplicons were analyzed with high-resolution melting on a Light Cycler 480 for detecting different melting patterns of polymorphic and wild-type alleles. RESULTS: The number of the subjects with heterozygous mutation at genotype 299 (Asp299Gly) was significantly lower in the NAFLD than in the control group (23.8 vs. 10.9%, P=0.027). Logistic regression analysis revealed that female gender [odds ratio (OR)=2.984, 95% confidence interval (CI) 1.561-5.360, P=0.001] and heterozygous (Asp299Gly) mutation at codon 299 (OR=2.998, 95% CI 1.325-6.783, P=0.008) were the significant predictors of higher likelihood of TRL4 gene polymorphism-related prevention of NAFLD. CONCLUSIONS: As the first-time-in-humans controlled study related to investigation of TLR4 gene polymorphism in NAFLD, our findings contribute to the available data that TLR-4 signaling is pivotal for the pathogenesis of NASH and indicate that the TLR4 codon 299 heterozygous gene mutation (Asp299Gly) in humans may have a preventive role against the genesis of NAFLD.
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Hígado Graso/genética , Receptor Toll-Like 4/genética , Adulto , Codón/genética , ADN/genética , ADN/aislamiento & purificación , Hígado Graso/patología , Femenino , Genotipo , Humanos , Desequilibrio de Ligamiento , Hígado/patología , Masculino , Persona de Mediana Edad , Mutación/genética , Enfermedad del Hígado Graso no Alcohólico , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Caracteres SexualesRESUMEN
AIM: To investigate the effect of human leukocyte antigen (HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B. METHODS: Patient records at a single institution's hepatology clinic were reviewed. Demographic data, laboratory results, endoscopy results, virological parameters, biopsy scores and treatment statuses were recorded. In total, 355 patients were eligible for the study, of whom 226 (63.7%) were male. Overall, 82 (23.1%) were hepatitis B early antigen (HBeAg) positive, 87 (24.5%) had cirrhosis, and 66 (18.6%) had inactive disease. The presence of DQB1 and DRB1 alleles was determined by polymerase chain reaction with sequence-specific primers. The distribution of the genotyped alleles among patients with cirrhosis and patients with chronic active hepatitis was analyzed. RESULTS: The most frequent HLA DQB1 allele was DQB1*03:01 (48.2%), and the most frequent HLA DRB1 allele was DRB1*13/14 (51.8%). DQB1*05:01 was more frequent in patients with active disease than in inactive patients (27% vs 9.1%; P = 0.002, Pc = 0.026). DRB1*07 was rare in patients with cirrhosis compared with non-cirrhotics (3.4% vs 16%; P = 0.002, Pc = 0.022). Older age (P < 0.001) and male gender (P = 0.008) were the other factors that affected the presence of cirrhosis. In a multivariate logistic regression analysis, DRB1*07 remained a significant negative predictor of cirrhosis (P = 0.015). A bioinformatics analysis revealed that a polymorphic amino acid sequence in DRB1*07 may alter interaction with the T-cell recognition site. CONCLUSION: This study demonstrates that HLA alleles may influence cirrhosis development and disease activity in Turkish chronic hepatitis B patients.
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Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Hepatitis B Crónica/genética , Cirrosis Hepática/genética , Factores de Edad , Secuencia de Aminoácidos , Distribución de Chi-Cuadrado , Biología Computacional , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/inmunología , Cirrosis Hepática/virología , Modelos Logísticos , Masculino , Datos de Secuencia Molecular , Análisis Multivariante , Fenotipo , Reacción en Cadena de la Polimerasa , Pronóstico , Factores Protectores , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , TurquíaRESUMEN
Sirtuins (SIRTs) are members of the silent information regulator-2 family and act as nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases. The de-acetylation of proteins and histones results in an up- or down-regulation of gene transcription and protein function. In recent years, the regulatory action of the deacetylation activity of SIRT1 has been shown to have a positive impact on the pathophysiological mechanisms of nonalcoholic fatty liver disease (NAFLD). Among the effects of SIRT1 are: its healing activity on insulin sensitivity, thereby ameliorating glycemic regulation; its mimetic activity on calorie restriction; its antihyperlipidemic activity on lipid homeostasis via the liver, adipose tissues and skeletal muscles; its anti-inflammatory activities; its protective effects against cardiovascular events and endothelial dysfunction; its positive influence on autophagy, apoptosis and cancer; and finally, its anti-aging activity. The current approach for the treatment of NAFLD involves the treatment of etiological factors and recommendation of life-style changes including more physical activity and a low-calorie diet. However, there is no specific medical treatments for NAFLD. The therapeutic potential of SIRT1 activity in the treatment of NAFLD discovered in humans has been presented in this article. In this review, the potential effects of SIRT1 activation on NAFLD-related pathophysiological mechanisms and on the treatment of NAFLD are discussed.
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Activadores de Enzimas/uso terapéutico , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Sirtuina 1/metabolismo , Animales , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Diseño de Fármacos , Metabolismo Energético/efectos de los fármacos , Activación Enzimática , Humanos , Hígado/enzimología , Hígado/patología , Terapia Molecular Dirigida , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/enzimología , Estrés Oxidativo/efectos de los fármacos , Transducción de SeñalRESUMEN
BACKGROUND: Chronic hepatitis B treatment with oral antiviral drugs is a long course. During this course, antiviral resistance is a serious issue, particularly, if genetically low barrier drugs are in use. Host immunity is accepted to have an effect on antiviral resistance development. The earliest clinical sign of drug resistance is virologic breakthrough. In this study, we aimed to investigate the relation between HLA-DQB1 alleles and virologic breakthrough events. SUBJECTS AND METHODS: The patient records at single institution hepatology clinic were reviewed. Local institution ethics committee approval was taken. The patients' demographic data, virologic parameters, treatment statues were noted. Patients who had received lamivudine or adefovir were recruited and grouped into two according to virologic breakthrough occurrence. Patients who were not compliant to the given treatment were excluded. Blood samples were taken for DNA extraction. HLA-DQB1 alleles were determined at high level by sequence-speciï¬c primers-polymerase chain reaction. The distribution of DQB1 alleles among groups was analyzed. RESULTS: One hundred ninety-eight patients were eligible for the study. Ninety-six of them had virologic breakthrough where 102 did not have. DQB1 0503 allele was more frequent in patients without breakthrough (28.4% vs. 12.4%, P=0.006). In univariate analysis, HBeAg seropositivity (P<0.001), absence of cirrhosis (P=0.007), younger age (P=0.002) and higher pretreatment logDNA (P<0.001) were related to breakthrough events. However, in multivariate analysis only logDNA (P<0.001) and DQB1*0503 (P=0.02) allele revealed statistically significant relation with breakthrough events. CONCLUSION: Host immunity may have an effect on outcome during treatment with oral antiviral drugs. A patient with better immunologic profile may suppress the viral replication better and this may cause less resistance occurrence during treatment with genetically low barrier drugs.
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Adenina/análogos & derivados , Antivirales/farmacología , Antivirales/uso terapéutico , Cadenas beta de HLA-DQ/genética , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Lamivudine/farmacología , Lamivudine/uso terapéutico , Organofosfonatos/farmacología , Organofosfonatos/uso terapéutico , Adenina/farmacología , Adenina/uso terapéutico , Adulto , Alelos , Farmacorresistencia Viral , Femenino , Hepatitis B Crónica/sangre , Humanos , Masculino , ARN Viral/sangreRESUMEN
OBJECTIVE: In this study, we aimed to investigate the relationship between the histological features of nonalcoholic fatty liver disease (NAFLD) and serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-5 (IGFBP-5) to determine the usefulness of this relationship in clinical practice. MATERIALS AND METHODS: Serum samples were collected from 92 patients with biopsy-proven NAFLD and 51 healthy controls and serum levels of IGF-1 and IGFBP-5 were assayed by enzyme-linked immunosorbent assay. RESULT: Serum IGFBP-5 levels were correlated with liver steatosis, fibrosis, and nonalcoholic steatohepatitis scores. IGF-1 levels were significantly decreased in patients with moderate-to-severe fibrosis compared with patients with no or mild fibrosis. CONCLUSION: Serum IGFBP-5 levels may be useful to differentiate both advanced fibrosis and definite nonalcoholic steatohepatitis from other NAFLD groups. Also, serum IGF-1 levels may be useful to differentiate advanced fibrosis in patients with NAFLD.