[Investigation of Anti-HCV S/CO Value in Detecting Viremia in Patients with Hepatitis C Virus Infection].
Mikrobiyol Bul. 2020 Jan;54(1):110-119
Authors: Aydın G, Adaleti R, Boz ES, Yücel FM, Özhan HK, Aksaray S
Anti-HCV and HCV RNA tests are used in laboratory diagnosis of hepatitis C virus (HCV) infections. False positive results are frequently observed in anti-HCV tests used as screening tests in societies with low prevalence of HCV. The HCV RNA test, which is a confirmatory test, is not performed in every laboratory because it is a high-cost and high-tech test, which can lead to delay in the diagnosis and treatment of patients. In this study, it was aimed to obtain an optimal anti-HCV S/CO value in our laboratory for demonstrating true antibody positivity and viremia in patients by analyzing the relationship between anti-HCV, alanine aminotransferase (ALT) and HCV RNA using retrospective data. Between July 2014 and July 2017, 754.190 anti-HCV tests were performed. Patients aged 18 years or older who were reactive with anti-HCV and those with simultaneous HCV RNA and ALT prompts were included in the study. The second generation CMIA (Abbott, USA) method was used for anti-HCV detection. For quantitative HCV RNA analysis, viral nucleic acid extraction was performed with the QIAsymphony SP/AS (Qiagen, Germany) using the QIAsymphony DSP Virus/Pathogen Midi Kit; and PCR was performed by Rotor-Gene Q (Qiagen, Germany) using Artus HCV QS-RGQ kit. ARCHITECT c and AEROSET systems (Abbott, USA) were used for ALT measurement. HCV genotype determination (622 cases) was performed using GenoSen's HCV Genotyping 1/2/3/4 RG qualitative real time PCR kit (Corbett Research, Australia) and GEN-C 2.0 Reverse Hybridization Strip Assay (NLM Diagnostics, Italy) kit at different periods covered by our study. The optimal threshold value for the relationship between anti-HCV, ALT and HCV RNA was selected based on ROC analysis. Statistical significance was accepted as p<0.05. Of the anti-HCV test results, 10.679 were found to be reactive. 1754 data of 1290 cases with anti-HCV reactivity who were simultaneously tested for HCV RNA and ALT in the same serum were evaluated. Of these, 742 (42%) were found to be HCV RNA positive and 1012 (58%) were found to be HCV RNA negative. ALT and anti-HCV levels of those who were positive for HCV RNA were significantly higher than those with negative HCV RNA (p= 0.001). The threshold point for anti-HCV S/CO according to HCV RNA was found to be 7.13 (sensitivity of 97.4%, specificity of 50.3%, positive predictive value 58.9%, negative predictive value 96.4%), and the cut-off point for ALT was found to be 27.5 IU/L (sensitivity of 77.6%, specificity of 80.8%). For HCV RNA positivity, the area under the ROC curve for anti-HCV and ALT was significantly higher than 0.5 (p= 0.001). No statistically significant difference was found between HCV genotypes in terms of ALT and anti-HCV levels. By using our new threshold in the laboratory workflow, the need to verify with HCV RNA can be reduced, especially in some patients who have been screened for antiHCV for screening purposes. Anti-HCV values below 7.13 S/CO, considering the high negative predictive value of this threshold; a false positive result in a patient presenting for screening can be predicted without waiting for the HCV RNA result. In anti-HCV reactivities determined above 7.13, the possibility of absence of viremia should be considered due to the low positive predictive value.
PMID: 32050882 [PubMed - indexed for MEDLINE]
[Evaluation of Histological Response in Chronic Hepatitis B Patients with Tenofovir or Entecavir Therapy].
Mikrobiyol Bul. 2020 Jan;54(1):95-109
Authors: Çerçioğlu D, Kınıklı S, Cesur S, Ataman Hatipoğlu Ç, Arslan K, Gönültaş M
Chronic hepatitis B (CHB) is an important public health problem in the world and Turkey. The aim of this study was to evaluate the histological, virological, serological and biochemical response rates in CHB patients receiving tenofovir or entecavir therapy. Control liver biopsies were performed on patients who received tenofovir or entecavir therapy for one year or longer. Histopathological grading was scored according to the modified Knodell system. Eighty-seven CHB patients were included in this study, 56 patients were receiving tenofovir and 31 patients were receiving entecavir therapy. Patients in two treatment groups were similar in terms of baseline parameters (p> 0.05). At the end of the treatment, there was a significant decrease in mean values of HBV DNA, alanine aminotransferase and necroinflammatory scores for both groups (p<0.001); however, no statistically significant change was observed in fibrosis scores (p> 0.05). Histological responses were obtained 66.1% from the tenofovir group and 54.8% from the entecavir group. Treatment with tenofovir and entecavir resulted with improvement in Ishak fibrosis scores in 12.5% and 12.9% of the patients, respectively. For 14.3% of the tenofovir-treated patients and for 22.6% of the entecavir-treated patients, the Ishak fibrosis scores worsened. Baseline intermediate/ advanced fibrosis stage (Ishak fibrosis score: 3-6) was found as independent determinant factor on histological response and improvement of fibrosis score (OR= 3.99, p= 0.01; OR= 31.67, p= 0.002; respectively) and treatment duration longer than five years is an independent determinant for improvement of necroinflammatory score (OR= 5.79, p= 0.02). There was no significant difference in the virological, serological, biochemical and, histological responses and improvement of necroinflammatory and fibrosis scores between tenofovir and entecavir groups (p> 0.05). Similar histological, virological, serological and biochemical responses were obtained in patients with CHB receving tenofovir and entecavir treatments. Further studies involving a large number of patients receiving long-term therapy should be done to understand the effects of antiviral treatments on healing of liver histology.
PMID: 32050881 [PubMed - indexed for MEDLINE]
[Comparison of mRNA Levels of Stimulator of Interferon Genes (STING) in Individuals with Natural Immunity to Hepatitis B Virus (HBV), and in those with Chronic Hepatitis B Infection and without HBV].
Mikrobiyol Bul. 2020 Jan;54(1):66-78
Authors: Kasap B, Buruk CK, Kaklıkkaya N, Özkaya E, Aydın Kasap Z, Aydın F
It has been estimated that currently 350-400 million people have been chronically infected with the hepatitis B virus (HBV) worldwide and approximately one million people die each year due to HBV related diseases. It has been suggested that the viral and host factors, especially the host immune system, may play a role in the chronicity of the HBV infection. Stimulator of interferon genes (STING) is one of the members of the pattern recognition receptor (PRR) that detects the presence of DNA in a human cell, activate synthesis of various cytokines and this protein is thought to be an important member of the immune system against HBV infection. Based on the assumption that there may be a relationship between the differences of STING expression in individuals and HBV chronicity, the aim of this study was to investigate STING gene expression levels in individuals naturally immunized against HBV, in chronic hepatitis B infected patients and in normal individuals who have not been exposed to HBV. A total of 90 volunteers have been included in the study from the age range of 18 to 65, in which the first group consists of 30 individuals naturally immunized against HBV, the second group consists of 30 chronically hepatitis B infected patients while the third group consists of 30 healthy population members who have not been exposed to HBV. Whole blood samples were taken from each participant and peripheral blood mononuclear cells (PBMC) were isolated afterwards. Total RNA was isolated from PBMC. After the synthesis of cDNA from the total RNA, STING gene expression levels were determined by real time polymerase chain reaction (Rt-PCR) method. Normalization was performed by applying the 2-ΔΔCT formula after Rt-PCR procedure. STING expression level of the naturally immunized group was calculated as 0.084 ± 0.026 on average, average STING expression level of healthy population group was 0.082 ± 0.032 and STING expression level of chronically infected patients group was 0.075 ± 0.022 on average. There was no statistically significant difference between the groups (p> 0.05). To our knowledge, this is the first study investigating the role of STING expression in the chronicity of HBV. Although there was no statistically significant difference between the groups, the data that showed STING expression levels in naturally immunized individuals were approximately 10% higher than those in chronic hepatitis B patients and was considered as an important finding.
PMID: 32050879 [PubMed - indexed for MEDLINE]