Evaluation of IFNAR2 and TYK2 transcripts' prognostic role in COVID-19 patients: a retrospective study.

Background and objectives: This study aimed to investigate the possible prognostic significance of interferon alpha-beta receptor subunit 2 (IFNAR2) and tyrosine kinase 2 (TYK2) expressions. Methods: We conducted a retrospective study including COVID-19 adult patients. All blood samples were collected before any interventions. The expressions of IFNAR2 and TYK2 were assessed using real-time PCR in venous blood samples of 54 cases and 56 controls. The transcript quantities of IFNAR2 and TYK2 genes were assessed using a Delta-Ct method. Results: Our findings show no significant differences in gene expression levels for IFNAR2 and TYK2 between patients who required oxygen (O2) therapy and those who did not (p-value = 0.732 and p-value = 0.629, respectively). Likewise, there were no significant differences in IFNAR2 and TYK2 expressions between patients hospitalized for less than 7 days and those hospitalized for 7 days or more (p-value = 0.455 and p-value = 0.626, respectively). We also observed a weak correlation between IFNAR2 expression and CRP (p-value = 0.045, r = 0.192). There was a negative correlation between the expression levels of IFNAR2 and TYK2 transcripts in COVID-19 patients (p-value = 0.044; partial correlation coefficient = -0.283). Additionally, IFNAR2 and TYK2 were significantly downregulated in the COVID-19 group compared to healthy subjects (p-value = 0.002 and p-value = 0.028, respectively). However, neither IFNAR2 nor TYK2 expression was significantly different between the case subgroups based on COVID-19 severity. The IFNAR2 ΔΔCt (B = -0.184, 95% CI: -0.524-0.157, p-value = 0.275) and the TYK2 ΔΔCt (B = 0.114, 95% CI: -0.268-0.496, p-value = 0.543) were not found to be significant predictors of hospitalization duration. The area under the curve (AUC) for IFNAR2 expression is 0.655 (p-value = 0.005, 95% CI: 0.554-0.757), suggesting its poor discriminative value. Conclusion: We were unable to comment definitively on the prognostic power of IFNAR2 and TYK2 expressions in COVID-19 patients, and larger-scale studies are needed. The principal limitations of this study included the lack of longitudinal analysis and limited sample size.

Association between Interleukin-21 and Interleukin-21 receptor gene polymorphisms with susceptibility to chronic hepatitis B virus infection and HBV spontaneous clearance in Iranian population.

Hepatitis B virus (HBV) infection is a major public health concern due to the infection often leads to chronic infection, liver cirrhosis and also liver cancer. The host immune response to HBV infection and also genetic background play significant role in outcome of infection. Single nucleotide polymorphisms (SNPs) are the most important kind of variation in genetic sequences that caused by point mutations. As cytokines have major roles in viral infections, it seems that cytokine gene polymorphisms are independently associated with response to viral infections. Interleukin 21 (IL-21) plays an influential role in both innate and adaptive immune responses. Its specific receptor, IL-21R, produced and located on the surface of T, B and natural killer (NK) cells and is critical for the proliferation and differentiation of these immune effector cells. Many studies confirmed that the IL-21 involved in response to viral infections. We aimed to investigate the association of G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) gene polymorphisms with chronic hepatitis B virus infection and HBV spontaneous clearance in Iranian population. METHODS: In this study, blood samples were gathered from 320 patients with chronic HBV and 310 healthy controls and also 120 HBV spontaneous clearance individuals. Following genomic DNA extraction, genotypes of the selected SNPs determined by PCR and restriction fragment length polymorphism (RFLP) method. The results were analyzed by SPSS software using Chi-square, Logistic Regression, ANOVA and Independent Samples t-Test. RESULTS: According to our results, in IL-21R (rs3093390 C/T) gene polymorphism, allele frequency of T is statistically different in the HBV spontaneous clearance group compared to chronic HBV cases. But there is no significant difference between G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) genotypes distribution in three groups. Also we found that higher serum aspartate transaminase (AST) level in HBV spontaneous clearance group is significantly associated with TT genotype of IL-21 (rs2055979) compared to GG genotype (P value = 0.006). DISCUSSION: Our results showed that T allele frequency in IL-21R (rs3093390 C/T) gene polymorphism could consider as a host genetic factor for HBV spontaneous clearance. Probably we can serve it as a potential prognostic genetic marker for spontaneous clearance of HBV infection.

Changing the cause of liver cirrhosis from hepatitis B virus to fatty liver in Iranian patients.

AIM: The objective of this study was to determine the epidemiologic characteristics of patients with liver cirrhosis. BACKGROUND: Liver cirrhosis is an end-stage condition of chronic liver disease. Liver disease is an important cause of morbidity and mortality worldwide. METHODS: In this cross-sectional study, demographic and epidemiologic characteristics of 203 patients with liver cirrhosis who were admitted in Taleghani Hospital over a period of two years were determined. RESULTS: A total of 203 patients with liver cirrhosis consisted of 136 (67%) males and 67 (33%) females and the mean age was 53.7±15.2 years. No etiology were found in (59.6%) cirrhotic patients; therefore, they were labeled as cryptogenic cirrhosis, but according to clinical evidence and ultrasonography findings, (29.7%) of these patients were probable NAFLD. The other causes of liver cirrhosis in this study were HBV (20.2%), HCV (11.8%) and autoimmune hepatitis (AIH) (8.4%), respectively. Esophageal varices were present in (41.9%), ascites in (36.5%), variceal bleeding in (8.9%), encephalopathy in (7.4%) and spontaneous bacterial peritonitis (SBP) in (5.4%) of patients. When cirrhotic patients were grouped according to Child-Pugh classification, 26.1%, 54.7% and 19.2% were in classes A, B and C respectively. The mean MELD score was 16.16±7.7. CONCLUSION: In this study we found that the leading etiology of cirrhosis is cryptogenic cirrhosis 59.6% (in all age groups) and followed by HBV. Noteworthy, according to the clinical and ultrasonography findings, 29.7% of patients who were labeled as cryptogenic cirrhosis were consistent with NAFLD.

Lack of Association Between Transforming Growth Factor Beta 1 -509C/T and +915G/C Polymorphisms and Chronic Hepatitis B in Iranian Patients.

BACKGROUND: Chronic hepatitis B is one of the world's major health concerns [corrected]. The etiological agent of this infection is hepatitis B virus (HBV), which can evade the immune system response. Transforming growth factor beta 1 (TGF-ß1) can act against HBV by suppressing the viral replication. The TGF-ß1 also plays an important role in preventing liver damage in chronically HBV infected patients. OBJECTIVES: In this study, the association of TGF-ß1 +915G/C and -509C/T gene polymorphisms with chronic hepatitis B was evaluated in Iranian patients. MATERIALS AND METHODS: A population-based case-control study was conducted in Taleghani Hospital, Tehran. A number of 220 patients with chronic hepatitis B and the same number of healthy control subjects were designated the case and the control groups. The PCR-Restriction Fragment Length Polymorphism Method (PCR-RFLP) method was used for genotyping both polymorphisms. Ten percent of the control samples were sequenced to confirm the results. RESULTS: No statically significant differences in genotype distribution and allele frequency were observed for both polymorphisms between healthy controls and patients with chronic hepatitis B. CONCLUSIONS: There was no association between TGF-ß1 -509C/T and +915G/C polymorphisms with chronic hepatitis B and it seems that these changes do not play a significant role in increasing the risk of chronic infection in Iranian patients [corrected].