Impact of host gene polymorphisms on susceptibility to chronic hepatitis B virus infection.

Background: non-alcoholic steatohepatitis (NASH) recently headlined hepatocellular carcinoma (HCC) worldwide. This study aims to unveil the role of some unaddressed critical players that might aid in understanding, predicting, and targeting NASH and NASH-HCC. Methods: Serum interleukin 13 (IL-13) levels and single nucleotide polymorphisms (SNPs) within interleukin (IL)-13 rs20541, IL-13 receptors (IL-13R1) rs2248841, (IL-13R2) rs5946040, signal transducer activator of transcription 6 (STAT6) rs167769, yes-associated protein (YAP1) rs11225163, programmed death-ligand 1 (PD-L1) rs2282055, and programmed death-ligand 2 (PD-L2) rs7854413 genes were analyzed by qRT-PCR. Multiple stepwise regression analysis was performed on a cohort of 134 Egyptian male patients diagnosed with NASH and NASH-HCC. RESULTS: higher serum alpha-fetoprotein (AFP) and higher serum IL-13 levels were directly associated with HCC development in NASH (odds ratio (OR) 19.6 and 1.9 p < 0.01). Reversibly, the presence of the C/C genotype in STAT6 rs167769 and the C allele carrier YAP1 rs11225163 were inversely associated with HCC in NASH patients (OR 0.015 and 0.047 p < 0.01). A predictive model was formulated with 97.5% specificity, 90.9% sensitivity, and 94.8% accuracy. Moreover, higher serum IL-13 levels and the presence of PD-L2 rs7854413 C allele carriers were associated with advanced fibrosis progression in NASH patients (OR 1.432 and 3.797 p < 0.01). Serum levels of IL-13 and C/C genotype in STAT6 rs167769 significantly increased the predictive capacity of serum AFP to predict HCC in F1–F2 and in F3–F4 fibrosis grades NASH patients. Conclusion: association between serum IL-13 and PD-L2 rs7854413 polymorphism successfully predict advanced fibrosis in NASH. However, HCC development in NASH is associated with higher serum AFP, IL-13 levels, and STAT6 rs167769, YAP1 rs11225163 polymorphisms.

https://www.mdpi.com/2079-7737/9/4/75/pdf

Polymorphisms in Interleukin 13 Signaling and Interacting Genes Predict Advanced Fibrosis and Hepatocellular Carcinoma Development in Non-Alcoholic Steatohepatitis

Cryptococcus is the major pathogen that causes fungal meningitis. In the People's Republic of China, especially in the Southwest area, cryptococcal meningitis (CM) in HIV-uninfected patients is more common than in HIV-infected patients. We compared clinical features and laboratory data pertaining to CM in patients with different immunological statuses. Demographic data, clinical manifestations, and laboratory data from inpatients in West China Hospital Sichuan University were collected from June 2009 to June 2014. Patients were grouped according to HIV status. Continuous variables were evaluated by Student t-test or Wilcoxon rank sum tests. Categorical variables were analyzed by χ2 test. Among 85 patients with CM were identified, 53 (62.4%) were HIV-uninfected patients. CM occurred more frequently in males in the HIV-infected group. Compared with HIV-infected patients, HIV-uninfected patients had more leukocytes in their blood and more leukocytes and protein in cerebrospinal fluid. More HIV-uninfected patients had increased cerebrospinal fluid (CSF)/serum albumin ratios, while intrathecal immunoglobulin G (IgG) synthesis was significantly increased. The rate of in-hospital mortality of HIV-infected CM patients was higher. Clinical signs are similar between HIV-uninfected and HIV-infected CM patients. Fewer leukocytes and protein was detected in the CSF and lower local synthesis of IgG in the central nervous system in HIV-infected patients, which reflects their diminished immune response. These characteristics should be noted in order to avoid misdiagnosis. Meningeal enhancement and intrathecal IgG synthesis in the HIV-uninfected group was significantly higher, that may be performance of aggressive inflammatory response and might contribute to a better outcome.

Different characteristics of cryptococcal meningitis between HIV-infected and HIV-uninfected patients in the Southwest of China.

Background
Cytokines are proteins that mediate innate and adaptive immunity responses. It is hypothesized that interferon lambda 3 (IFNL3) levels can influence the outcome of chronic hepatitis B virus (HBV) infection. Polymorphisms in IFN genes have been associated with response to infection.

The Correlation Between Interferon Lambda 3 Gene Polymorphisms and Susceptibility to Hepatitis B Virus Infection

BACKGROUND The aim of this study was to assess the relationship between IL-18 gene polymorphisms and HBV-related diseases and whether these polymorphisms influence its expression in the Guangxi Zhuang population. MATERIALS AND METHODS We enrolled 129 chronic HBV infected (CHB) patients, 86 HBV-related liver cirrhosis (LC) patients and 160 healthy controls in our study. Polymerase chain reaction-restriction fragment length polymorphism methods were used to detect IL-18 gene -607C/A, -137G/C polymorphisms, and an ELISA kit was employed to determine serum IL-18 levels. RESULTS No correlation was found between the -607C/A polymorphism and risk of HBV-related disease. For the -137G/C polymorphism, the GC genotype and C allele were associated with a significantly lower risk of CHB (95%CI: 0.32-0.95, p=0.034 and 95%CI: 0.35-0.91, p=0.018) and HBV-related LC (95%CI: 0.24-0.89, p=0.022 and 95%CI: 0.28-0.90, p=0.021). A similar decreased risk was also found with the A-607C-137 haplotype. With respect to IL-18 expression, it was significantly lower in both patient groups, but no association was noted between the two polymorphisms in the IL-18 gene and its expression. CONCLUSIONS Our study indicated that the -137C allele in the IL-18 gene may be a protective factor for HBV-related disease, and serum IL-18 level may be inversely associated with CHB and HBV-related LC.

/pdf/role-of-il-18-gene-promoter-polymorphisms-serum-il-18-levels-rh6yg57i2k.pdf

Role of IL-18 Gene Promoter Polymorphisms, Serum IL-18 Levels, and Risk of Hepatitis B Virus-related Liver Disease in the Guangxi Zhuang Population: a Retrospective Case-Control Study

Interleukin-18 (IL-18) is a potent proinflammatory cytokine, which can promote hepatitis B virus clearance. The latest studies find that genetic polymorphisms near the IL-28B gene are strongly associated with sustained viral response and spontaneous viral clearance in patients with chronically infected hepatitis C and hepatitis B. We investigated the effect of rs187238 and rs1946518 in IL-18 gene and rs8099917 in IL-28B gene on HBV recurrence in liver transplant patients. A total of 200 liver transplant recipients and relevant donors were enrolled in this study. The patients' mean follow-up was 39 month (range 10-65 month). All liver transplant recipients were in a stable stage. The total recipients (n = 200) were divided into end-stage liver disease secondary to hepatitis B (n = 140) and end-stage liver disease secondary to other diseases (n = 60) before transplantation. Recipients (n = 140) with hepatitis B before transplantation were defined to nonHBV recurrence group (n = 119) or HBV recurrence group (n = 21), which was positive for HBsAg or elevatory in HBV DNA (>2.0 × 10(2) IU mL(-1)) after transplantation. For the recipients (n = 140) had hepatitis B before transplantation, we studied the single-nucleotide polymorphisms (SNPs) of IL-18 gene (rs187238 and rs1946518) and IL-28B gene (rs8099917) by high-resolution melting (HRM) curve analysis. The serum levels of IL-18 and IFN-γ were tested by ELISA. The serums levels of IFN-γ were lower in HBV recurrence group than that in nonHBV recurrence group (P < 0.01). The genotype of IL-28B gene rs8099917 was associated with alanine aminotransferase (ALT) levels and aspartate aminotransferase (AST) levels in HBV-related liver transplant recipients (n = 140). The recipients with allele G (GG+GT) had higher ALT and AST levels (P < 0.05). No association was found between IL-18 gene and IL-28B gene polymorphisms with HBV recurrence in the liver transplant recipients or the donors. We identified that the IFN-γ was a protective factor of HBV recurrence after liver transplantation. The allele G of rs8099917 was associated with hepatitis B-related hepatocytes injury. The rs8099917 G allele subgroup should reinforce antiviral therapy.

Association of polymorphisms in interleukin-18 and interleukin-28B with hepatitis B recurrence after liver transplantation in Chinese Han population.

Objective: To explore the correlation of blood-cerebrospinal fluid (CSF) barrier (BCB) dysfunction with the therapeutic effect of antitubercular agents and their

The association between blood-cerebrospinal fluid barrier dysfunction and the therapeutic effect in tuberculous meningitis patients.

P0360 : STAT6 rs3024974 might predict worse prognosis in hepatocellular carcinoma patients

OBJECTIVE A genome-wide association study has identified several gene polymorphisms associated with loss of renal function. The effect of these variants on renal function in kidney transplant recipients receiving immunosuppressive treatment is unknown. MATERIALS AND METHODS A cohort of 189 kidney transplant recipients and their living donors were recruited from West China Hospital of Sichuan University, on whom we assessed the association of five single nucleotide polymorphisms with renal function after kidney transplantation. RESULTS Glomerular filtration rate estimated by serum creatinine was significantly higher in recipients carrying allograft with the A allele at rs17319721 in SHROOM3 (shroom family member 3) than those in the group with the GG genotype from month 1 to month 6 after transplantation (P=0.020). Covariate adjustment analysis showed that the variant at rs17319721 in SHROOM3 was an independent risk factor for renal dysfunction after the first month after transplantation (P=0.022). The estimated glomerular filtration rate was the lowest in recipients with allograft carrying both the A allele at rs17319721 in SHROOM3 and the CC genotype at rs1045642 in ABCB1 (P<0.05). CONCLUSION The genetic variants in SHROOM3 and ABCB1 in donors were associated closely with renal function after kidney transplantation.

The influence of living donor SHROOM3 and ABCB1 genetic variants on renal function after kidney transplantation.

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Association of polymorphisms in interleukin-18 and interleukin-28B with hepatitis B recurrence after liver transplantation in Chinese Han population.

The association between blood-cerebrospinal fluid barrier dysfunction and the therapeutic effect in tuberculous meningitis patients.

P0360 : STAT6 rs3024974 might predict worse prognosis in hepatocellular carcinoma patients

The influence of living donor SHROOM3 and ABCB1 genetic variants on renal function after kidney transplantation.