Can HLA-G polymorphisms predict the development of cardiac allograft vasculopathy?

A 14 bp insertion/deletion polymorphism in exon 8 of the HLA-G gene is associated with mRNA stability and HLA-G expression. In cardiac transplantation, the 14 bp deletion polymorphism plays an important role in the expression of HLA-G and is associated with fewer episodes of cellular rejection. We investigated the association between the 14 bp insertion/deletion HLA-G polymorphism and cardiac allograft vasculopathy (CAV) post heart transplantation. There were no statistically significant differences in the presence of the three HLA-G genotypes (−14 bp/−14 bp, +14 bp/−14 bp, +14 bp/+14 bp) between patients without CAV and patients with CAV at 1 year (p = 0.61) or 5 years (p = 0.76) post-transplant. We found no correlation between HLA-G genotypes and CAV progression from baseline to 5 years post-transplant (p = 0.55). HLA-G polymorphism appears to play an important role as a genetic indicator for cellular rejection post-transplant; however, it is not a reliable marker to identify patients at risk of CAV.     

Polymorphisms of interleukin 6 and interleukin 10 in Egyptian people with Behcet's disease

Cytokines play critical roles in the pathogenesis of Behçet's disease (BD). They mediated many of the effectors and regulatory functions of immune and inflammatory responses. Many studies have linked Interleukin-6 (IL-6) and Interleukin-10 (IL-10) pathologically to BD. Thus, this study aimed to investigate the associations between IL-6 and IL-10 promoter single-nucleotide polymorphisms (SNPs) and the susceptibility to BD and their implication on plasma levels. We genotyped IL-6 −174 G/C (rs1800795) using Mutagenically Separated Polymerase Chain Reaction PCR (MS-PCR) and IL-10 −1082 G/A (rs1800896) and −819 C/T (rs1800871) using Sequence Specific Primer PCR (SSP-PCR) in 87 Egyptian patients and 97 controls. The plasma levels of IL-6 and IL-10 were measured using Enzyme-linked Immunosorbent Assay (ELISA). Significant increase in the frequency of −1082 GG genotype (P < 0.05, OR = 2.25, 95%CI = 1.03–4.91) and significant decrease in the frequency of −1082 GA genotype (P < 0.05, OR = 0.53, 95%CI = 0.29–0.96) was demonstrated in BD patients compare to controls. Patients with genital ulcer had significantly lower frequency of −1082 GG (P < 0.05, OR 0.2, 95% CI = 0.04–0.99) and G allele (P < 0.05, OR = 0.28, 95%CI = 0.08–0.93), while patients with ocular manifestations had significantly higher frequency of −1082 G allele (P < 0.01, OR = 2.28, 95%CI = 1.19–4.36). BD patients had significantly higher level of IL-6 (P < 0.001) and significantly lower level of IL-10 (P < 0.001) compared to controls. The changes in the level of cytokines were independent of any genotype of IL-6 or any genotype/haplotype of IL-10. Patients with active disease state had significantly higher level of IL-6 compared to patients in remission (P < 0.05). In conclusion, our preliminary study indicates that the polymorphism at IL-10 −1082 G/A may play a role in BD susceptibility. The significant increase in IL-6 level and the significant decrease in IL-10 level in BD patients were independent of any particular genotype in IL-6 or any particular genotype/haplotype in IL-10.     

Analysis of HLA-G gene polymorphism and protein expression in invasive breast ductal carcinoma

The human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule predominantly expressed in trophoblastic placental cells to protect the fetus during pregnancy. However, evidence has shown that this molecule may be implicated in the immune escape mechanism of tumor cells. Thus, the aim of this study was to evaluate the frequency of 14-bp insertion/deletion HLA-G polymorphism, as well as the expression of this molecule in patients with invasive breast ductal carcinoma (IDC). A significant association between the expression of HLA-G and the presence of metastasis in lymph nodes (p = 0.01) was observed and the expression of HLA-G was significantly higher in patients with shorter survival time (p = 0.03). The analysis suggests that the polymorphism observed in patients with IDC may be inducing a higher expression of the HLA-G molecule, which may possibly contribute to shorter survival time and a worse clinical prognosis for such patients.     

Promising link of HLA-G polymorphism,tobacco consumption and risk of Head and Neck Squamous Cell Carcinoma (HNSCC) in North Indian population

Human leukocyte antigen (HLA-G) is a potent immune-tolerant molecule and has a critical role in various pathological conditions of cancer. The aim of the study was to analyze the association of HLA-G polymorphism as a risk factor in Head and Neck Squamous Cell Carcinoma (HNSCC). The HLA-G polymorphism at 3′UTR 14bp INDEL (rs371194629) and +3142G/C (rs1063320) were studied in 383 HNSCC patients and 383 ethnically similar-aged healthy controls in North Indian population. The genotyping study of two polymorphisms of HLA-G was documented using DNA-PAGE and RFLP-PCR method. 14bp INDEL Del/Ins, Ins/Ins genotype and Ins allele were more pronounced in HNSCC patients in compared to controls. Whereas, +3142 C/C genotype and C allele were associated with risk factors in HNSCC. Furthermore, the dual effect of polymorphisms; both variants (Del/Ins-Ins/Ins & G/C-C/C) carrying loci was significantly (OR = 2.78) associated with the disease compared to one variant (Del/Del-G/C or Del/Del-C/C or Ins/Ins-G/G). Moreover, both polymorphisms showed promising link in terms of tobacco influence on HNSCC risk. It can be concluded that this study first time reports that C/C, Del/Ins and Ins/Ins genotype as well as C and Ins allele could be major risk factors with strong impact of tobacco for HNSCC in North Indian population.     

Meta-analysis of the relationship between 14bp insertion/deletion polymorphism of HLA-G gene and susceptibility to systemic lupus erythematosus

We performed a meta-analysis to examine the relationship between the human leukocyte antigen-G (HLA-G) 14 base pairs sequence (14bp) insertion (ins)/deletion (del) polymorphism to systemic lupus erythematosus (SLE). Eligible studies were extracted in PubMed, Embase, Cochrane Library and CNKI (Chinese) up to March 31, 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated to evaluate the strength of the association. Finally, 7 studies with 1864 cases and 2259 controls were involved in this meta-analysis. Overall, the HLA-G 14bp ins/del polymorphism was significantly associated with SLE susceptibility (ins vs. del: OR = 1.179, 95%CI = 1.037–1.341, P = 0.012; ins/ins vs. del/del: OR = 1.394, 95%CI = 1.153–1.684, P = 0.001; ins/del vs. del/del: OR = 1.199, 95%CI = 1.041–1.382, P = 0.012; ins/ins + ins/del vs. del/del: OR = 1.252, 95%CI = 1.097–1.430, P = 0.001). When stratified by ethnicity, significance was found in Asians (ins/ins vs. del/del: OR = 1.326, 95%CI = 1.001–1.756, P = 0.049) and Caucasians (ins/ins vs. del/del: OR = 1.454, 95%CI = 1.126–1.878, P = 0.004; ins/del vs. del/del: OR = 1.288, 95%CI = 1.051–1.579, P = 0.015; ins/ins + ins/del vs. del/del: OR = 1.340, 95%CI = 1.106–1.623, P = 0.003). Our results suggest that the HLA-G 14bp insertion allele might act as an increased risk against SLE. Besides, this is the first meta-analysis to report an association between the HLA-G 14bp ins/del polymorphism and SLE. Larger and well-designed studies are needed to further confirm these findings.     

Human leukocyte antigen G is associated with esophageal squamous cell carcinoma progression and poor prognosis

Human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule thought to play a key role in maternal-fetal tolerance and cancer immune evasion. This study aimed to investigate the HLA-G expression in lesion sections and plasma sHLA-G levels of primary esophageal squamous cell carcinoma (ESCC) patients and its clinical significance in diagnosis and prognosis of ESCC. 60 ESCC patients and 28 healthy controls were recruited, and the positive expression of HLA-G in ESCC lesions and adjacent normal tissues were 70% (42/60) and 8.6% (5/60) (P < 0.05), respectively, while no expression was found in normal controls. HLA-G1 and HLA-G5 were determined to be dominating isoforms measured by RT-PCR. There was a significant difference in plasma sHLA-G levels between patients with ESCC (15.04 U/ml, range 4.33–250.00 U/ml) and healthy controls (6.81 U/ml, range 0–29.27 U/ml) (P < 0.01). The plasma IL-10 level was higher in ESCC patients than the controls (23.86 pg/ml vs. 12.81 pg/ml, P < 0.01). HLA-G expression in lesion tissues was correlated with cancer cell differentiation (P = 0.033), lymph node metastasis (P = 0.035) of ESCC. However, no obvious correlations were demonstrated between the plasma sHLA-G levels and the clinicopathological parameters. There was a significant correlation between sHLA-G and IL-10 expression (r = 0.353, P = 0.006) in patients with Esophageal squamous cell carcinoma. HLA-G positive expression showed poorer prognosis of ESCC. HLA-G positive expression might serve as a potential marker in the diagnosis or prediction of ESCC.     

HLA-G 14-bp insertion/deletion polymorphism and risk of coronavirus disease 2019 (COVID-19) among Iraqi patients

Human leukocyte antigen (HLA)-G molecules are proposed to influence susceptibility to coronavirus disease 2019 (COVID-19). A case-control study was conducted on 209 patients with COVID-19 and198 controls to assess soluble HLA-G (sHLA-G) levels and HLA-G 14-bp insertion [Ins]/deletion [Del] polymorphism. Results revealed that median levels of sHLA-G were significantly higher in serum of COVID-19 patients than in controls (17.92 [interquartile range: 14.86–21.15] vs. 13.42 [9.95–17.38] ng/mL; probability <0.001). sHLA-G levels showed no significant differences between patients with moderate, severe or critical disease. Del allele was significantly associated with the risk of COVID-19 (odds ratio = 1.89; 95% confidence interval = 1.44–2.48; corrected probability = 0.001), while a higher risk was associated with Del/Del genotype (odds ratio = 2.39; 95% confidence interval = 1.25–4.58; corrected probability = 0.048). Allele and genotype frequencies of HLA-G 14-bp Ins/Del polymorphism stratified by gender or disease severity showed no significant differences in each stratum. Further, there was no significant impact of genotypes on sHLA-G levels. In conclusion, sHLA-G levels were up-regulated in COVID-19 patients regardless of disease severity. Further, it is suggested that HLA-G 14-bp Ins/Del polymorphism is associated with COVID-19 risk.     

The HLA-G 14-bp insertion/deletion polymorphism is associated with chronic hepatitis B in Southern Brazil: A case-control study

There is growing evidence that the non-classical HLA-G has a role in the process of the immune response against pathogens, including HBV and HIV. Previous studies demonstrated that a 14-bp insertion/deletion (indel) polymorphism at 3′-untranslated region of HLA-G gene interferes in the mRNA stability and expression. The present study aimed to evaluate the association of the 14-bp indel polymorphism (rs371194629) with HBV infection in chronic hepatitis B (CHB) mono-infected and HBV/HIV co-infected patients from Southern Brazil. A total of 817 individuals were analyzed, including 357 CHB patients, 134 HBV/HIV co-infected patients and 326 healthy controls. The 14-bp indel polymorphism was analyzed by DNA amplification using PCR. Logistic regression models were performed to compute adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs). To control for multiple comparisons, the Bonferroni correction was applied to the p-values. The 14-bp Ins allele was observed in 47.6% of the CHB mono-infected patients and in 41.6% of the controls (aOR = 1.33; 95% CI: 1.05–1.60; p = 0.02; p _corrected = 0.08). The results also showed that the 14-bp Ins/Ins genotype was present in 21.8% of the CHB mono-infected patients and in 12.9% of the controls (aOR = 1.91; 95% CI: 1.21–3.01; p < 0.01; p _corrected = 0.02). There was significant association between the 14-bp indel and CHB monoinfection, but not in HBV/HIV co-infection. In conclusion, the 14-bp indel polymorphism was associated with CHB in this specific population.     

KIR3DL1-HLA-Bw4 combination and IL28B polymorphism predict response to Peg-IFN and ribavirin with and without telaprevir in chronic hepatitis C

Natural killer cells play a key role in the immune control of viral infections. Killer immunoglobulin-like receptors (KIRs) regulate natural killer cell activation and inhibition through the recognition of their cognate HLA class I ligands. We assessed the predictive factors of a sustained virological response (SVR) in 200 Japanese patients with chronic genotype 1b hepatitis C who were treated with telaprevir (TVR), pegylated-interferon-α2b (PEG-IFN), and ribavirin (RBV) triple therapy (92 patients) or PEG-IFN/RBV therapy alone (108 patients). Sixteen KIR genotypes, HLA-A, -B and -C ligands, and an interleukin (IL) 28B polymorphism (rs8099917) were analyzed. We observed that triple therapy, white blood cell count, hemoglobin value, hepatitis C viral load, a rapid virological response (RVR), IL28B TT genotype, and KIR3DL1-HLA-Bw4 genotype were associated with an SVR. In multivariate regression analysis, we identified an RVR (P < 0.000001; odds ratio [OR] = 20.95), the IL28B TT genotype (P = 0.00014; OR = 5.53), and KIR3DL1-HLA-Bw4 (P = 0.004, OR = 3.42) as significant independent predictive factors of an SVR. In conclusion, IL28B and KIR3DL1/HLA-Bw4 are independent predictors of an SVR in Japanese patients infected with genotype 1b HCV receiving TVR/PEG-IFN/RBV or PEG-IFN/RBV therapy.     

CXC chemokine expression profiles in aqueous humor of patients with different clinical entities of endogenous uveitis

Aqueous humor (AH) samples from patients with Behçet's disease (BD) (n = 29), Vogt-Koyanagi-Harada (VKH) disease (n = 21), and HLA-B27-associated uveitis (n = 8), and 42 control patients were assayed for the neutrophil chemoattractants CXCL1/GRO-α and CXCL8/IL-8 and the lymphocyte chemoattractants CXCL9/MIG, CXCL10/IP-10 and CXCL12/SDF-1 with the use of a multiplex chemokine assay. Chemokine levels except SDF-1 were significantly higher in the 3 disease groups than in normal controls. Considering all patients, mean GRO-α levels were 15-fold higher than IL-8 levels and mean IP-10 levels were 22-fold higher than MIG levels. In patients with the same disease activity, AH levels of GRO-α and IP-10 were significantly higher in patients with BD than in patients with VKH disease and HLA-B27-associated uveitis (p = 0.0474; p < 0.001, respectively). These data suggest that GRO-α and IP-10 are the predominant CXC chemokines involved in neutrophil and activated T lymphocyte chemoattraction in endogenous uveitis, particularly in BD.     

Circulating levels of GDNF in bipolar disorder

Neurotrophic factors regulate the survival and growth of neurons, and influence synaptic efficiency and plasticity. Several studies suggest the existence of a relationship between changes in neurotrophic levels and bipolar disorder (BD). The glial cell-line derived neurotrophic factor (GDNF) influences monoaminergic neurons and glial cells, but its role in BD patients is controversial. In order to elucidate it we evaluated plasma levels of GDNF in a sample of 70 BD patients (35 in mania and 35 in euthymia) and compared with 50 healthy controls matched for age, gender and educational levels. GDNF plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). Patients were assessed by a Mini-International Neuropsychiatric Interview (MINI-plus), Young Mania and Hamilton Depression Rating Scales. Plasma GDNF levels were significantly increased in BD patients in euthymia compared with BD patients in mania and healthy controls (p < 0.05). GDNF plasma levels were correlated with age (ρ = 0.30, p < 0.05) and negatively correlated with manic symptoms in BD patients (ρ = −0.54, p < 0.05). Our results provide evidence that peripheral levels of GDNF are related with different mood states in BD, reinforcing the involvement of neurotrophic factors in its physiopathology.     

IL10 polymorphisms associated with Behçet’s disease in Chinese Han

Objective

IL-10 is a potent anti-inflammatory cytokine that plays important roles in the pathogenesis of Behçet’s disease (BD). Two genome-wide association studies have identified IL10 as a potential risk factor for BD. Here, we investigated the association between IL10 polymorphisms and BD in Chinese Han.

Methods

407 BD patients and 679 healthy controls were enrolled, and genotyped by Sequenom MassArray system (Sequenom iPLEX assay, San Diego, CA).

Results

The frequency of risk allele of rs1800871 was notably higher in BD patients than in controls (71.9% vs. 66.2%, OR: 1.30, 95%CI: 1.08–1.58, p_c = 0.024). Similarly, rs1518111, which showed strong linkage disequilibrium (r² = 1) with allele rs1800871, was also associated with BD (p_c = 0.026). Rs3021094 was in association with BD in a dominant model (p_c = 0.035), and the haplotype (GACC) formed by rs1518111, rs3021094, rs3790622, and rs1800871 was associated with BD (p_c = 0.023). Results obtained from meta-analysis combined with our data showed that rs1800871 and rs1518111 were associated with BD.

Conclusion

IL10 may be the susceptibility gene for BD in Chinese Han population.     

The HLA-G Genetic Contribution to Bipolar Disorder: A Trans-Ethnic Replication

Bipolar disorder (BD) is frequently associated with immune dysfunctions. Studying the genetic diversity of the immuno-modulatory human leukocyte antigen (HLA)-G locus in a French BD cohort, we previously reported an association between a functionally relevant 14 bp Ins/Del polymorphism and BD risk. The present study investigated the genetic and expression diversities of HLA-G in a geographically distinct South Indian population-group BD patients, as well as the influence of exposure to the neurotropic Toxoplasma gondii pathogen. Three functionally relevant HLA-G polymorphisms, i.e. HLA-G 14 bp Ins/Del (rs66554220), +3142G>C (rs1063320) and +3187A>G (rs9380142) were genotyped by polymerase chain reaction (PCR) and real-time PCR. Sub-samples of BD patients and healthy controls (HC) were investigated for plasma levels of soluble HLA-G (sHLA-G) isoforms, as well as circulating stigma of T. gondii infection.

Findings indicate: (i) the frequency of the HLA-G 14 bp Del/Del genotype was higher in BD cases, as compared to HC; (ii) the HLA-G + 3142 C allele and CC genotype were more prevalent in BD patients than in HC; (iii) sHLA-G levels were significantly higher in BD cases, especially in females and in the early onset sub-group; and (iv) the InsGA haplotype was more prevalent in HC.

Our findings further support the genetic contribution of HLA-G to BD risk, as well as indicate relevant expression profiles. Such data may also indicate a potential developmental role in BD etiology, given that HLA-G is an important immune regulator from the intrauterine period and across development.     

Anterior genu corpus callosum and impulsivity in suicidal patients with bipolar disorder

Suicidality is a life-threatening symptom in patients with bipolar disorder (BD). Impulsivity and mood instability are associated with suicidality in mood disorders. Evidence suggests that gray and white matter abnormalities are linked with impulsivity in mood disorders, but little is known about the association between corpus callosum (CC) and impulsivity in BD. We examined the relationship between CC areas, impulsivity and suicidality in BD patients. We studied 10 female BD patients with a history of suicide attempt (mean ± SD age 36.2 ± 10.1 years), 10 female BD patients without suicide attempt history (44.2 ± 12.5 years) and 27 female healthy subjects (36.9 ± 13.8 years). Impulsivity was evaluated by the Barratt Impulsivity Scale (BIS). We traced MR images to measure the areas of the CC genu, anterior body, posterior body, isthmus and splenium. The genu was divided into anterior, middle and posterior regions. The suicidal and non-suicidal BD patients had significantly higher BIS total, attention and non-planning scores than the healthy subjects (ps < 0.01), and the suicidal BD patients had significantly higher BIS motor scores than the non-suicidal BD and healthy subjects (ps < 0.01). There were no significant differences among the three groups on any regional CC areas, although the suicidal BD patients had the smallest areas. The suicidal BD patients showed a significant inverse correlation between anterior genu area and the BIS total (r = −0.75, p = 0.04), motor (r = −0.79, p = 0.02) and non-planning scores (r = −0.79, p = 0.02). These correlations were not found in the non-suicidal BD patients or healthy subjects. The results suggest that the anterior medial frontal region may be involved in the pathophysiology of impulsive and suicidal behaviors in BD.     

Ingested soluble CD14 contributes to the functional pool of circulating sCD14 in mice

Soluble CD14 (sCD14) is a pattern recognition receptor and Toll-like co-receptor observed in human milk (5–26 μg/mL) and other bodily fluids such as blood (3 μg/mL). The most well defined role of sCD14 is to recognize lipopolysaccharide of Gram-negative bacteria and signal an immune response through Toll-like receptor 4 (TLR4). Previous research has shown ingested sCD14 to transfer from the gastrointestinal tract and into the blood stream in neonatal rats. The contribution of human milk sCD14 to circulating levels in the infant and the functionality of the protein, however, remained unknown. Using CD14^−/− mouse pups fostered to wild type (WT) mothers expressing sCD14 in their milk, we show herein that ingestion of sCD14 resulted in blood sCD14 levels up 0.16 ± 0.09 μg/mL. This represents almost one-third (26.7%) of the circulating sCD14 observed in WT pups fostered to WT mothers (0.60 ± 0.14 μg/mL). We also demonstrate that ingested-sCD14 transferred to the blood remains functional in its ability to recognize lipopolysaccharide as demonstrated by a significant increase in immune response (IL-6 and TNF-α) in CD14^−/− pups fostered to WT mothers in comparison to control animals (P = 0.002 and P = 0.007, respectively). Using human intestinal cells (Caco-2), we also observed a significant decrease in sCD14 transcytosis when TLR4 was knocked down (P < 0.001), suggesting sCD14 transfer involves TLR4. The bioavailability of human milk sCD14 established in this report confirms the importance of human milk proteins for the infant and demonstrates the need to improve infant formulas which are lacking in immune proteins such as sCD14.     

Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes

Genetic and pharmacological studies have suggested that brain-derived neurotrophic factor (BDNF) may be associated with the pathophysiology of bipolar disorder (BD). The present study investigated serum BDNF levels in manic, depressed, euthymic BD patients and in matched healthy controls, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum BDNF levels were decreased in manic (p = 0.019) and depressed (p = 0.027) BD patients, as compared with euthymic patients and controls. Serum BDNF levels were negatively correlated with the severity of manic (r = −0.37, p = 0.005) and depressive (r = −0.30, p = 0.033) symptoms. These findings further support the hypothesis that the BDNF signaling system may play a role in the pathophysiology of BD.     

Association between the HLA-G molecule and lymph node metastasis in papillary thyroid cancer

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and can present as lymph node metastasis in 30 to 65% of cases when initially diagnosed. High frequency recurrence, distant metastasis and treatment resistance can be found in cases of PTC so early diagnosis and treatment are critical for improved prognosis and better survival rates. The characterization of new biomarkers has proved useful for the diagnosis and follow-up of these patients. HLA-G is a non-classical HLA class I molecule whose expression in cancer cells has been associated with tumor evasion of immune response. Therefore, the aim of this study was to investigate the HLA-G expression and its clinical significance in PTC. Paraffin-embedded thyroid biopsies of 70 PTC patients (40 of whom had presented with metastasis) were evaluated. HLA-G-staining was observed in tumor cells in PTC, and the HLA-G expression was significantly associated with an increased occurrence of lymph node metastasis (p = 0.0006) and capsular invasion (p = 0.02). This preliminary data shows the HLA-G expression in thyroid carcinoma specimens for the first time and suggests that this expression could impair efficient anti-tumor immunity in PTC. This would indicate that HLA-G could have an independent prognostic value in PTC, principally for tumor recurrence.     

The rs2030324 SNP of brain-derived neurotrophic factor (BDNF) is associated with visual cognitive processing in multiple sclerosis

Purpose: To investigate the associations between the rs2030324 SNP of brain-derived neurotrophic factor (BDNF) and neuropsychological (NP) test measures in multiple sclerosis (MS) patients. Background: BDNF regulates the survival of neuronal and non-neuronal cells and plays a critical role in neurochemical processes underlying learning and memory. Methods: A total of 209 MS patients (161 females; 48 males) underwent brain MRI and genotyping for BDNF rs2030324. The NP testing (n = 108) assessed processing speed, working memory, new learning and executive control. The MRI measurements included T1 and T2 lesion volume, whole brain, white and gray matter volumes, magnetization transfer imaging and regional subcortical brain volumes. Results: The T/T rs2030324 genotype group performed poorly on the Brief Visuospatial Memory Test-Revised (p = 0.031) and the Symbol Digit Modalities Test (p = 0.045) compared to the C/C genotype group. Because these NP tests both involve visual processing, the relationship with the volume of the thalamus was assessed. The BDNF rs2030324 genotype was associated with the volume of the left thalamus (p = 0.036). There were no significant associations with whole brain lesional and atrophy MRI measures. Conclusions: The C allele of BDNF rs2030324 is associated with protection against visual cognitive processing deficits via mechanisms that appear associated with the volume of the thalamus.     

Role of hepatic HCV-RNA level on the severity of chronic hepatitis C and response to antiviral therapy

Background

Correlation between hepatic HCV-RNA and serum HCV-RNA, severity of liver disease and response to therapy is poorly known.

Objectives

To assess the influence of hepatic HCV-RNA level on severity of liver disease and response to therapy in a large cohort of chronic hepatitis C (CHC) patients.

Study Design

HCV-RNA was measured in frozen liver biopsies and serum samples from 130 CHC patients the day of liver biopsy prior to treatment. Liver fibrosis was assessed by Ishaq scoring. A Sustained Virological Response (SVR) was observed in 52% of the patients, non-response (NR) in 34%.

Results

Mean ± standard deviation hepatic HCV-RNA level was 7.69 ± 0.67 log₁₀ copies/mg of liver. Mean serum HCV-RNA level was 6.21 ± 0.72 log₁₀ copies/ml. There was a correlation between hepatic and serum HCV-RNA in genotype 1 and 4 (p = 0.008 and p = 0.03) and age (p = 0.006). Mean hepatic HCV-RNA was 7.70 ± 0.69 vs 7.67 ± 0.68 log₁₀ copies/mg of liver, in patients with significant fibrosis vs those with mild fibrosis, respectively (p = 0.7); 8.04 ± 0.68; 7.44 ± 0.47; 7.43 ± 0.49 and 7.44 ± 0.71 log₁₀ copies/mg of liver in genotypes 1, 2, 3 and 4, respectively (p = 0.0001); higher in women than in men (p = 0.04); 7.60 ± 0.63, 7.71 ± 0.54 and 7.96 ± 0.73 log₁₀ copies/mg in SVR, relapsers and NR, respectively (p = 0.1). Multivariate analysis showed that high hepatic HCV-RNA level was independently associated with genotype and response to therapy was associated with genotype independently from hepatic HCV-RNA level.

Conclusions

Hepatic HCV-RNA level was not associated with severity of liver disease. High level was strongly associated with HCV genotype independently from response to therapy.