HCV-negative Controls Research Articles

Impaired anti-HBV vaccine response in non-cirrhotic chronic HCV is not overcome by double dose regimen: randomized control trial

Introduction and ObjectivesSome studies suggest chronic HCV infection diminishes responses to the anti-HBV vaccine. We evaluated the efficacy of double versus standard dose HBV vaccination among HCV patients without cirrhosis. Patients and Methods141 adults with untreated chronic HCV were randomized to HBV vaccination with double dose (40μg) or standard dose (20μg) at 0, 1 and 6 months; 70 healthy HCV-negative patients given standard dose served as controls. Vaccine response was defined by anti-HBs ≥10 mIU/mL. Results128 patients (60 double, 68 standard doses) completed the study. Patients were of median age 52 years, 61% female, 60% fibrosis <2 of 4, and 76% genotype 1 with median 6-log 10 IU/mL HCV RNA. Overall seroprotection rate was 76.7% (95% CI: 65-87) in the 40μg versus 73.5% (95% CI: 63-84) in the 20μg dose HCV-positive groups (p =0.68) and 91.2% (95%CI:84-99) in HCV-negative controls (p =0.011 and 0.003, respectively). In multivariate logistic regression, vaccine dose (double vs. standard dose) was not associated with vaccine response (OR=0.63, p =0.33). Of 32 HCV-infected patients who were non-responders to 3- doses, 25 received the fourth dose of vaccine. The fourth dose seroconversion rate for the 40μg and 20μg groups were 45.5% and 21.4%, respectively. ConclusionsIn HCV-infected patients without cirrhosis, impaired responses to HBV vaccination cannot be overcome by the use of double dose HBV vaccination, but adding a fourth dose of vaccine for non-responders may be an effective strategy. Other adjuvant measures are needed to enhance seroconversion rates in these patients. Trial registerU 1111-1264-2343 (www.ensaiosclinicos.gov.br)

Tubular cell damage may be the earliest sign of renal extrahepatic manifestation caused by Hepatitis C.

Chronic kidney disease (CKD) is one of the most well-known extrahepatic manifestations caused by hepatitis C infection (HCV). CKD is typically discovered at a late stage. HCV-nephropathy may show different histopathologic patterns, as both glomerular and tubulointerstitial damage have been described. Identification of patients with early renal manifestations would be beneficial to provide treatment and avoid progression to CKD. The observational prospective single-center HCVKID study assessed the prevalence of early renal manifestations in patients with chronic HCV and compared these patients with HCV-negative healthy controls cross-sectionally. HCV-positive patients with and without renal manifestations were also compared to define biomarkers suitable for identifying early manifestations in standard clinical practice. Tubular proteinuria as judged by urine α 1-microglobulin was the most common early renal manifestation found in 11% in HCV-positive patients, followed by hematuria in 8%. Kidney filtration was statistically significantly lower among HCV-positive patients with renal manifestation according to any calculation method. There were no significant differences in duration of infection or stage of liver fibrosis between patients with or without renal manifestations. Tubular cell damage may be the earliest sign of renal dysfunction caused by HCV. Complement activation also correlates with the dysfunction, indicating of contribution to HCV-induced renal manifestations even in their early phase.

Novel Polymorphism in a Promoter of MBL2 Gene Result in Lower MBL Expression in Chronic Infection Caused by HCV

The Pathogen Recognition Receptors (PRRs) is an active protein in the immune system. The PRRs that secreted in the liver and we addressed were L-ficolin, MBL and H-ficolin. Previous studies revealed that both MBL and L-ficolin were hampered the HCV entry and infectivity. However, H-ficolin impact still needs to be addressed more so as determining their role during HCV infection. For these purposes, we aimed to determine the effect of different level in the serum of these proteins on the HCV infection and treatment outcome. Initially, we selected (25) HCV positive patients and (25) HCV negative control patients from the Trent Cohort and Regional Haemophiliac Study and to present the differences in serum concentrations of MBL, H- and L-ficolin. The level of these proteins was measured by ELISA method and compared with each other based on the detected SNPs by PCR and sequencing methods in the responsible genes. Our results showed that the polymorphism at position -221 in the MBL2 promoter significantly reduce the level of MBL protein more than the SNP at position -551. Interestingly, a new deletion of six nucleotides [AGGAAG] detected in the promoter at position -319 to -324 that succeeded by four other mutations at position -328, -336, -349 and -427 in most of the analyzed sequences. The 6bp deletion was statistically decreasing the concentration of MBL below 1µg.mL-1, precisely among non-responder patients. In conclusion, the existence of the new deletion in the promoter region of MBL2 gene and the additional newly detected polymorphisms, reduce the level of MBL protein and as a result impacts on the response to treatment among HCV-infected patients.

Hepatitis C Virus Infection and Chemotherapy in Breast Cancer: A Retrospective Chart Analysis.

Breast cancer and hepatitis C virus (HCV) infection are major health problems in the U.S. Despite these highly prevalent diseases, there is limited information on the effect of HCV infection among patients with breast cancer receiving chemotherapy and the potential challenges they face during treatment. Currently, there are no guidelines for chemotherapy administration in HCV-positive patients with breast cancer. We performed a retrospective case-control analysis on six patients with breast cancer with active HCV infection and 12 HCV-negative matched controls who received chemotherapy between January 2000 and April 2015. We investigated dose delays, dose changes, hospitalization, hematologic reasons for dose delays, and variation in blood counts during chemotherapy from the patients' medical records. Fisher's exact test was used for statistical comparison of the outcome variables between the two groups. When compared with the HCV-negative patients, the HCV-positive group was at a significantly higher risk of dose delays (100% vs. 33%, p value .013), dose changes (67% vs. 8%, p value .022), hospitalization during chemotherapy (83% vs. 25%, p value .043), and hematotoxicity related dose delays (83% vs. 8%, p value .003). HCV-positive patients took a longer time to complete treatment than the HCV-negative group. Patients with HCV receiving chemotherapy for breast cancer are more likely to experience complications such as dose delays, dose modifications, and hospitalization. Future studies to confirm our findings and investigate on the effect of concurrent HCV and breast cancer treatment are warranted. This study found that hepatitis C infection is associated with a greater risk of treatment delays and dose modifications in patients with breast cancer receiving cytotoxic chemotherapy. Hepatitis C-positive patients have a higher treatment burden with dose changes, hospitalizations, and longer treatment periods than noninfected patients. Further prospective investigations to confirm these findings are warranted in a larger patient population. Given that hepatitis C infection can be curable with direct-acting antivirals, treatment of hepatitis C may alleviate treatment challenges during chemotherapy and improve survival for patients with breast cancer.

SUN-324 Kidney derangements during chronic Hepatitis-C infection – interim results from the HCVKID study

Hepatitis C infection is known to cause kidney derangements. HCV-related nephropathy may show different histopathologic patterns and both glomerular and tubulointerstitial damage have been described. Kidney injury may result from immune-mediated tissue damage or from direct effects of HCV and other, yet unknown mechanisms may be involved. HCV-related nephropathy may appear at any time during the natural history of HCV infection. Objective of the prospective, observational HCVKID-study is to assess the prevalence of renal manifestations among patients suffering from chronic HCV in Finland cross-sectionally, complemented by long-term analysis to identify changes from baseline. Assessments of renal variables are made at baseline and one year after the eradication treatment. HCV-negative control group is enrolled by an occupational healthcare provider and will be used for comparisons between HCV-positive and HCV-negative groups. This analysis compares baseline characteristics between HCV-positive patients with renal manifestations and HCV-positive patients without renal manifestations. The outcome of interest, renal deterioration, is evaluated using urine and blood testing. Baseline data includes clinical and treatment characteristics. For this analysis, 145 HCV-PCR-positive male and female patients (≥ 18 years old) were eligible for the study. Exclusion criteria were HIV or Hepatitis B positivity and other underlying diseases that may influence kidney function and had emerged before the transmission of HCV. Renal manifestation was stated if s-creatinine was > 100 µmol/l in male or > 90 µmol/l in female or eGFR < 60 ml/min/1.73m2 or spot urine analysis revealed hematuria (u-erythrocytes ≥ 20 x10(E6)/l), tubular proteinuria (u -A1Miglo ≥ 12 mg/l) or glomerular proteinuria (u-AlbCrea in men ≥ 2.5 mg/mmol, in women ≥ 3.5 mg/mmol). Prevalence of any renal finding was 15.2 %. Baseline characteristics between HCV-positive patients with and without renal manifestations did not differ significantly (Table 1). HCV-genotype profile was significantly different in patients with renal manifestations, genotype 3 being the most usual genotype. Route of infection, stage of fibrosis, estimated time since HCV-transmission or viral load did not differ significantly (Table 2). Basic laboratory tests showed no significant differences (Table 3). Dipstick proteinuria and hematuria were more common in renal manifestation group as could be expected. The most common renal manifestation was tubular proteinuria (p<0.0001 vs. without renal manifestations). The amount of glomerular proteinuria was not statistically different between those with renal manifestations and those without. The level of proteinuria did not generally exceed the level necessitating kidney biopsy. Serum creatinine was not different between the groups, but eGFR was significantly less in those with renal manifestations. Serum cystatin-C was statistically higher in males with renal manifestation (Table 4). Tubular proteinuria marker was deranged reflecting renal lesions due to tubulointerstitial damage. It may be postulated that HCV could infect several renal cell types including also renal tubular cells. Tubular cell damage may even be the earliest sign of renal dysfunction caused by HCV and warrants testing when HCV patients are being evaluated.

PIN5 - Risk of Cardiovascular Disease Among Patients with Hepatitis C Virus (HCV) Infection

The objective of the present study was to describe the profiles of cardiometabolic risk markers in subjects with and without HCV infection and to estimate 10-year risk of CVD in both groups. We examined participants in the Canadian Health Measures Survey (2007-2015) aged 30 years or older for the 10-year risk of developing CVD estimated by the Framingham Risk Score (FRS). We matched 111 HCV-positive cases to 333 HCV-negative controls on age, gender, ethnicity and smoking status. Available cardiometabolic factors included specific markers for obesity, cholesterols and inflammatory markers. Associations with these markers estimated among HCV cases and controls using partial correlation models adjusted for residual confounding. Ten-year CVD risk was estimated for each group. Ten-year CVD risk was significantly associated with obesity, HbA1C, the number of metabolic syndrome markers and homocysteine. Male HCV subjects, but not females, had higher levels of triglycerides (1.21±0.06 vs. 1.51±0.18 mmol/L, p=0.049) and fibrinogen (0.58±0.13 vs 0.95±0.26 mmol/L, p=0.010) compared to controls. In HCV patients, 10-year risk of CVD was associated with increased triglycerides (p=0.017) and fibrinogen (p=0.05). Average 10-year CVD risk was similar among cases (11±0.8%) and controls (12±0.5%) as measured by FRS. The results of the present study support the need to further explore the relationship between HCV infection and risk of CVD. Specific associations between markers for CVD risk were stronger among those with HCV infection compared to those without. HCV infection may lead to increased CVD risk by influencing inflammation and components of the metabolic syndrome. This may lead to an abnormal glucose and lipid metabolism that can be directly associated with atherosclerosis development and increased risk of CVD. The introduction of antiviral agents to treat HCV infection may also contribute to reduced CVD morbidity and mortality in patients with chronic HCV infection.

Long-term Patient and Graft Survival of Kidney Transplant Recipients With Hepatitis C Virus Infection in the United States.

Hepatitis C virus (HCV) infection is common among kidney transplant (KTx) recipients. However, the impact of HCV infection on long-term graft and recipient survival after KTx from large-scale data remains to be determined. We used the Organ Procurement and Transplantation Network database to identify all adults undergoing KTx in 2004 to 2006 in the United States. A propensity score was created to match each HCV-positive recipient with an HCV-negative control for unbiased comparisons. Survival analysis was conducted to evaluate recipient and death-censored graft survival. Out of 33 357 adult primary KTx recipients, 1470 (4.4%) were HCV-positive: 1364 HCV-positive and -negative pairs were selected by propensity score matching. Based on multivariable regression models, HCV is associated with a higher risk of death (hazard ratio [HR], 1.50; 95% confidence interval [95% CI], 1.28-1.75) and graft failure (HR, 1.26; 95% CI, 1.08-1.47). Infection was a more common cause of death in HCV-positive patients than in HCV-negative recipients (HR, 1.64; 95% CI, 1.12-2.42). The incidence of death due to liver failure was 0.23% per year among HCV-positive recipients, whereas no HCV-negative recipients died from liver failure. Graft failure due to recurrent disease was higher in HCV-positive than in HCV-negative recipients (HR, 2.00; 95% CI, 1.06-3.78). HCV infection is associated with decreased long-term recipient and graft survival. Future studies are needed to examine whether recently available, safe, and effective antiviral therapy improves the long-term clinical outcome in these patients.

Hepatitis C virus-induced natural killer cell proliferation involves monocyte-derived cells and the OX40/OX40L axis

Natural killer (NK) cells are found at increased frequencies in patients with hepatitis C virus (HCV). NK cell activation has been shown to correlate with HCV clearance and to predict a favourable treatment response. The aim of our study was to dissect mechanisms leading to NK cell activation and proliferation in response to HCV. NK cell phenotype, proliferation, and function were assessed after the 6-day co-culture of human peripheral blood mononuclear cells with either HCV replicon-containing HuH6 hepatoblastoma cells or HCV-infected HuH7.5 cells. The results obtained were confirmed by immunohistochemistry of liver biopsies from patients with HCV and from HCV-negative controls. In HCV-containing co-cultures, a higher frequency of NK cells upregulated the expression of the high-affinity IL-2 receptor chain CD25, proliferated more rapidly, and produced higher amounts of interferon γ compared with NK cells from control co-cultures. This NK cell activation was dependent on IL-2, cell-cell contact-mediated signals, and HCV replicon-exposed monocytes. The tumour necrosis factor-receptor superfamily member OX40 was induced on the activated CD25± NK cell subset and this induction was abrogated by the depletion of CD14+ monocytes. Moreover, OX40L was upregulated on CD14± monocyte-derived cells co-cultured with HCV-containing cells and also observed in liver biopsies from patients with HCV. Importantly, blocking of the OX40/OX40L interaction abolished both NK cell activation and proliferation. Our results uncover a previously unappreciated cell-cell contact-mediated mechanism of NK cell activation and proliferation in response to HCV, mediated by monocyte-derived cells and the OX40/OX40L axis. These results reveal a novel mode of crosstalk between innate immune cells during viral infection. Using a cell-culture model of hepatitis C virus (HCV) infection, our study revealed that natural killer (NK) cells become activated and proliferate when they are co-cultured with HCV-containing liver cells. The mechanism of this activation involves crosstalk with other innate immune cells and a cell-cell contact interaction mediated by the cell surface molecules OX40 and OX40L. Our study reveals a novel pathway leading to NK cell proliferation and activation against virus-infected cells that might be of relevance in antiviral immunity.

Hepatitis C virus positive diffuse large B-cell lymphomas have distinct molecular features and lack BCL2 translocations

Background:The clinical presentation of patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphoma (DLBCL) is different from their HCV-negative counterparts, but the underlying molecular and pathological characteristics are largely under investigated. The virus has a role in lymphomagenesis, as witnessed by the curative potential of antiviral therapy in HCV-related low-grade B-cell lymphomas.Methods:We performed a case-control study including 44 HCV-positive cases of de novo DLBCL, comparing them with 132 HCV-negative patients as controls (ratio 3 to 1). Cases and controls were matched for age, lactate dehydrogenase level and international prognostic index at presentation. Patients were studied by gene expression profiling for cell-of-origin determination and to perform differential expression analysis between groups, fluorescence in-situ hybridisation and immunohistochemistry for MYC, BCL2 and BCL6, TP53 mutations, and diagnostic specimens reviewed to exclude transformation from low-grade lymphoma.Results:Compared to the HCV-negative controls, patients with HCV-positive de novo DLBCL had differential expression of genes that regulate innate immune response and modulate apoptotic pathways, have higher proliferative index, and lack BCL2 translocations.Conclusions:HCV-positive DLBCL have distinct molecular and pathological features compared to the HCV-negative counterparts.

Hepatitis C infection and the risk of non-liver-related morbidity and mortality in HIV-positive persons in the Swiss HIV Cohort Study

Hepatitis C virus (HCV) infection has been associated with increased non-liver-related morbidity and mortality. However, studies have yielded inconsistent results.The incidence of clinical events in human immunodeficiency virus (HIV)–infected HCV-seropositive and incidence density–matched HCV-seronegative participants of the Swiss HIV Cohort Study from August 1994 to December 2014 was studied. We compared (1) HCV-seropositive with HCV-seronegative participants and (2) HCV-viremic with successfully treated nonviremic patients. Poisson regression was used to assess differences between these groups.We included 2503 HCV-seropositive participants (540 with spontaneous HCV clearance, 1294 untreated HCV RNA positive, 345 treated with sustained virologic response [SVR], 43 during treatment, and 281 treated without SVR), and 2503 HCV-seronegative controls. After a mean follow-up of 8.2 years, we observed (HCV seropositive and HCV seronegative, respectively) 107 and 18 liver events, 41 and 14 kidney events, 230 and 121 osteoporosis/fractures, 82 and 94 diabetes mellitus, 114 and 129 cardiovascular events, 119 and 147 non-AIDS malignancies, 162 and 126 Centers for Disease Control and Prevention HIV category B/C events, 106 and 10 liver-related deaths, and 227 and 218 non-liver-related deaths. Compared with HCV-negative controls, HCV-seropositive participants had an increased risk of liver events (incidence rate ratio [IRR], 6.29 [95% confidence interval {CI}, 3.52–11.22]), liver-related death (IRR, 8.24 [95% CI, 3.61–18.83]), kidney events (IRR, 2.43 [95% CI, 1.11–5.33]), and osteoporosis/fracture (IRR, 1.43 [95% CI, 1.03–2.01]). Among HCV-seropositive individuals, treated participants without SVR vs those with SVR had a higher risk of liver events (IRR, 6.79 [95% CI, 2.33–19.81]), liver-related death (IRR, 3.29 [95% CI, 1.35–8.05]), and diabetes mellitus (IRR, 4.62 [95% CI, 1.53–13.96]). Similar but not statistically significant differences were found between untreated HCV RNA–positive patients and those with SVR.While HCV exposure was associated with an increased risk of kidney disease and osteoporosis/fracture, this risk did not seem to be dependent of persistent HCV RNA. Successful HCV treatment was associated with a lower incidence of liver disease, liver-related death, and diabetes mellitus, whereas the other conditions studied were less affected.

Comparison of Angiographic Burden of Coronary Artery Disease in Patients With Versus Without Hepatitis C Infection

Hepatitis C virus (HCV) infection is thought to be associated with an increased risk of coronary heart disease (CHD) events, perhaps secondary to increased inflammation. We sought to examine the angiographic burden of coronary artery disease (CAD) in patients with HCV compared to HCV-negative patients. All consecutive HCV RNA-positive patients (n= 61) who underwent coronary angiography at the University of Arkansas for Medical Sciences from 2001 to 2013 were identified. A parallel group of HCV-negative controls (n= 61), matched for age, gender, and indication for coronary angiography served as control. Angiographic burden of CAD was assessed by computing Gensini scores. Statistical analysis was performed using SPSS 21.0. Patients with HCV had significantly lower levels of total and low-density lipoprotein cholesterol. Preangiographic use of aspirin and statin was significantly lower in the HCV cohort. Number of patients with obstructive CAD was less in HCV group (23% vs 39%, p <0.05). However, angiographic Gensini score was similar in both groups. There was no correlation between HCV RNA titers and Gensini score (p= 0.9, analysis of variance). In conclusion, patients with active HCV infection have similar angiographic CAD burden as HCV-negative patients. Furthermore, viral load does not appear to correlate with atherosclerosis burden. Patients with HCV have less-obstructive CAD and less-frequent use of aspirin and statins.

Association of polymorphisms in HLA antigen presentation-related genes with the outcomes of HCV infection.

Antigen-presentation genes play a vital role in the pathogenesis of HCV infection. However, the relationship of variants of these genes with spontaneous outcomes of HCV infection has not been fully investigated. To explore novel loci in the Chinese population, 34 tagging-SNPs in 9 candidate genes were genotyped for their associations with the outcomes of HCV infection. The distributions of different genotypes and haplotypes were compared among 773 HCV-negative controls, 246 subjects with HCV natural clearance, and 218 HCV persistent carriers recruited from hemodialysis patients and intravenous drug users. Our study implicated that TAP2, HLA-DOA, HLA-DOB, and tapasin loci were novel candidate regions for susceptibility to HCV infection and viral clearance in the Chinese population. Logistic regression analyses showed that TAP2 rs1800454 A (OR = 1.48, P = 0.002) and HLA-DOB rs2071469 G (OR = 1.23, P = 0.048) were significantly associated with increased susceptibility to establishment of HCV infection. However, high-risk behavior exposure and age were stronger predictors of HCV infection. Mutation of tapasin rs9277972 T (OR = 1.57, P =0.043) increased the risk of HCV chronicity, and HLA-DOA rs3128935 C (OR = 0.62, P = 0.019) increased the chance of viral resolution. With regards to the effect of rs3128925, interactions were found with high-risk behavior (P = 0.013) and age (P = 0.035). The risk effect of rs3128925 T for persistent HCV infection was higher in injecting drug users (vs. dialysis patients) and in subjects ≥ 40 years old (vs. < 40 years old).

Effects of mannose-binding lectin and mannose-binding lectin polymorphisms on treatment response in patients with chronic hepatitis C.

The natural course and clinical outcome of hepatitis C virus (HCV) infection is related to the interaction between HCV and the immune response of the host. Only a limited number of studies have investigated the role of mannose-binding lectin (MBL) levels in HCV infection. The aim of the present study was to explore the relationship between MBL levels and gene polymorphisms on treatment response in patients with chronic hepatitis C (CHC). Serum MBL levels from 50 CHC patients who completed treatment at least 24 weeks before the present study and 75 healthy HCV-negative controls were measured. In addition, the presence of codon 54 mutations was investigated. Correlational analyses were performed to determine relationships between MBL levels and treatment response. In patients, mean serum MBL levels were lower and the rate of codon 54 mutations was higher. However, these differences were not statically significant. In both patients and controls, serum MBL levels were significantly lower in individuals with codon 54 mutations. Moreover, serum MBL levels and the rate of the codon 54 mutation were similar in patients regardless of treatment response. Our findings suggest that low MBL levels do not increase the susceptibility for HCV infection. Furthermore, MBL levels were not found to have a significant effect on the course of the disease or treatment response.

Study of the impact of viral load of hepatitis C on patients with concomitant psoriasis vulgaris

Background and study aimConcomitant hepatitis C virus (HCV) infection and psoriasis vulgaris (PV) are not uncommon coexisting diseases, especially in areas with high viral hepatitis endemicity. To date, data about the interaction between both diseases are scarce. Therefore, we aimed to describe the possible interplay between the HCV viral load and psoriatic activity in concomitant Egyptian diseased patients. Patients and methodsBetween December 2011 and August 2013, all psoriatic patients attending Assiut University Hospital outpatient clinics were tested for HCV serologic assay. Patients with positively coexisting diseases were further reevaluated for psoriasis area severity index (PASI) score assessment, liver function tests, HCV-RNA-polymerase chain reaction (PCR) assays, and sonographic examination of the liver. For comparative purposes, another matched group (n=26) with psoriasis only (HCV-negative group) was enrolled as a control. ResultsDuring the period of the study, 20 patients with concomitant PV and HCV infection (HCV-positive group; 50% males, mean age of 44.15±10.66years) were recruited. The mean PASI score was 44.75±10.38 and clinical signs of liver dysfunction were observed in 40% (n=8), 100% had abnormal liver function tests (n=20), and 75% had sonographic findings of cirrhosis (n=15). The PASI score was significantly higher in the HCV-positive psoriatic group compared to the HCV-negative control (p<0.001). Significant correlations were detected between the PASI score and the viral loads, and also with alanine aminotransferase (ALT). ConclusionWhen HCV was found concomitantly with PV, a high possibility of severe disease pattern will be expected that entails special precautions in the treatment process.

Accuracy of rapid oral HCV diagnostic test among a Saudi sample.

The objective of this study was to investigate the accuracy of the OraQuick® rapid diagnostic test in the detection of hepatitis C virus (HCV) antibodies in oral fluid among a Saudi population sample. A case-control cross-sectional study was conducted on 60 HCV-positive patients and 100 HCV-negative control subjects. The HCV-positive patients were recruited from the Clinics of Infectious Diseases of King Abdulaziz University (KAU) Hospital, Jeddah, while the control group was collected from KAU, Faculty of Dentistry, including staff and students. The OraQuick® HCV rapid antibody test (OraSure Technologies, Inc. USA) utilized the oral fluid swab. Sensitivity and specificity for the test were calculated and correlated to the patients' viral load. Out of the 60 PCR + ve patients, 53 (88.33%) revealed a positive OraQuick test, whereas 7 (11.67%) patients showed negative test, revealing 88.33% sensitivity and 100% specificity for detection of salivary HCV antibodies. Only PCR level was valuable in predicting the outcome of OraQuick test. Using oral fluid for the detection of HCV antibodies could be a useful tool for epidemiological purposes and for field collection of samples in developing countries or in nonclinical settings by persons with minimal training. Millions of pilgrims visit Saudi Arabia during every year, many of whom are from countries where HCV infection is endemic; therefore, it will be very helpful to use a noninvasive, quick, simple, specific, and sensitive method for detection of HCV antibodies using oral fluid.

Interleukin-27 is differentially associated with HIV viral load and CD4+ T cell counts in therapy-naïve HIV-mono-infected and HIV/HCV-co-infected Chinese.

Human Immunodeficiency Virus (HIV) infection and the resultant Acquired Immunodeficiency Syndrome (AIDS) epidemic are major global health challenges; hepatitis C virus (HCV) co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27), a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.

Assessment of Executive Functions in Chronic Hepatitis C Virus Infected Patients

Background: Chronic infection with HCV is one of the most important causes of chronic liver disease, which can progress to cirrhosis and hepatocellular carcinoma (HCC). It is well established that advanced forms of the disease are accompanied by overt and global cognitive deficits (hepatic encephalopathy) but now there is a growing evidence that the alterations in cerebral function in patients with chronic HCV infection may appear long before the development of severe liver cirrhosis, it has been hypothesized that it is related to a direct effect of HCV on the brain; or the neurotoxic effect of HCV-related systemic inflammation. Aim: The purpose of the study was to assess the possible existence of executive dysfunction in chronic HCV infected patients without cirrhosis. Study design: case control study. Participants: 100 elderly patients aged 60 years and above, 50 patients are HCV positive (cases) and 50 patients are HCV negative (controls) both groups have no liver cirrhosis. Methods: All participants were subjected to the following: Diagnosis of HCV by detection of HCV ab using ELISA technique, non invasive assessment of liver cirrhosis using abdominal ultrasound, and evaluation of executive functions using 5 neuropsychological tests (block design, digit span backwards, animal verbal fluency, clock drawing, and EXIT 25). Results: The study showed that there is a significant difference between cases and controls regarding Exit 25 and Digit span backwards tests scores indicating affection of the phonological loop component of working memory among HCV positive patients. Conclusion: Executive functions are affected in patients with chronic HCV infection without liver cirrhosis.

Prevalence of photosensitivity in chronic hepatitis C virus patients and its relation to serum and urinary porphyrins

HCV is a major cause of chronic liver disease in Egypt. The aim was to study the prevalence of photosensitivity among asymptomatic HCV-infected patients and its possible relation to porphyrins levels and whether it can be considered an alarm for early diagnosis of the disease, which is the most important goal in the management. This study included 100 accidentally discovered HCV positive cases and 100 HCV negative healthy controls. All patients and controls were subjected to: Detailed history and clinical examination, dermatological examination including evaluation of reaction to solar exposure, measurement of serum AST, ALT, albumin, bilirubin, serum and urinary porphyrins levels. The prevalence of photosensitivity among HCV-positive cases (33%) was significantly higher compared to 10% in the control group. Serum porphyrins were positive in 46 cases (46%), twenty-three cases (23%) had positive urinary porphyrins, while only four controls (4%) showed positive serum porphyrins and one (1%) showed positive urinary porphyrins, the difference was statistically significant. Cases with photosensitivity showed significantly higher prevalence of serum and urinary porphyrins existence as well as serum porphyrins levels. Levels of viraemia showed statistically significant relation to levels of porphyrins. Asymptomatic chronic HCV infection cases showed significantly high prevalence of photosensitivity, which is related to the associated disturbance of porphyrins metabolism. Photosensitivity can thus be considered an early marker of HCV infection. Patients discovered to have recently acquired photosensitivity should be screened for HCV infection especially in endemic areas like Egypt.

Apoptosis and clinical severity in patients with psoriasis and HCV infection.

Background:It has been proposed that hepatitis C virus (HCV) antigens are involved in the pathogenesis of psoriasis and may contribute to severity of the disease. Increased expression of the apoptosis-regulating proteins p53 and tTG and decreased levels of bcl-2 in the keratinocytes of the skin of psoriatic patients have been reported.Aim:This study aims to identify the serum levels of apoptosis-regulating proteins in patients with psoriasis and without HCV infection and to study the relation between clinical severity of psoriasis and the presence of HCV infection.Materials and Methods:Disease severity was assessed by psoriasis area severity index score (PASI) of 90 patients with psoriasis grouped as mild (n = 30), moderate (n = 30) and severe (n = 30); 20 healthy individuals were used as controls. All groups were subjected for complete history taking, clinical examination, and tests for liver function and HCV infection. The serum levels of apoptosis related proteins: p53, tTG and bcl-2 were estimated by enzyme linked immune sorbent assay (ELISA).Results:There was a statistically significant (P < 0.001) correlation between clinical severity of psoriasis and presence of HCV antibodies and HCV-mRNA. In addition, significantly (P < 0.001) raised serum p53 and tTG, and reduced bcl-2 were observed among HCV-positive patients as compared to HCV-negative patients and control patients.Conclusion:These results conclude that clinical severity of psoriasis is affected by the presence of HCV antibodies and overexpression of apoptotic related proteins. In addition, altered serum levels of apoptosis-regulating proteins could be useful prognostic markers and therapeutic targets of psoriatic disease.

Dysexecutive Performance of Elderly Patients with Chronic Hepatitis C Virus Infection

Chronic infection with hepatitis C virus (HCV) is one of the most important causes of chronic liver disease, which can progress to cirrhosis and hepatocellular carcinoma (HCC). It is well established that advanced forms of the disease are accompanied by overt and global cognitive deficits (hepatic encephalopathy) but now there is a growing evidence that the alterations in cerebral function in patients with chronic HCV infection may appear long before the development of severe liver cirrhosis, it has been hypothesized that it is related to a direct effect of HCV on the brain; or the neurotoxic effect of HCV-related systemic inflammation. The purpose of the study was to assess the possible existence of executive dysfunction in chronic HCV infected patients. One hundred elderly patients aged 60 years and above agreed to participate in this study; 50 patients were HCV positive (cases) and 50 patients were HCV negative (controls). All participants were subjected to the following: diagnosis of HCV by detection of HCV antibodies using ELISA technique, non-invasive assessment of liver condition, and evaluation of executive functions using 5 neuropsychological tests. The study showed that there was a significant difference between cases and controls regarding 2 executive function tests related to the phonological loop component of working memory among HCV positive patients. The study concluded that chronic HCV infection is accompanied by dysexecutive performance.