Hepatitis C Virus PCR Research Articles

A cross-sectional study of hepatitis C among people living with HIV in Cambodia: Prevalence, risk factors, and potential for targeted screening.

The epidemiology of hepatitis C in Cambodia is not well-known. We evaluated the prevalence of hepatitis C virus (HCV) and risk factors in the HIV cohort of Sihanouk Hospital Center of Hope in Phnom Penh to strengthen the evidence for suitable HCV testing strategies among people living with HIV (PLWH) in Cambodia. All consenting adult PLWH without a history of HCV treatment were tested for HCV between November 2014 and May 2016 according to the CDC algorithm (HCV antibody II electro-chemiluminescence immunoassay, followed by COBAS® AmpliPrep/COBAS® TaqMan® HCV PCR and INNO-LIA® HCV Score immunoblot end-testing). Genotyping was performed using the line probe assay Versant HCV genotype 2.0®. The study enrolled a total of 3045 patients (43% males, median age: 42.5 years, <1% high-risk). HCV antibodies were detected in 230 (7.6%; 95% confidence interval [CI] 6.6–8.5). Upon further testing, HCV antibodies were confirmed in 157 (5.2%; 95% CI 4.4–6.0) and active HCV in 106 (3.5%; 95% CI 2.8–4.2). Viremic prevalence peaked among men aged 50–55 years (7.3%) and women aged >55 years (11.2%). Genotype 1b (45%) and 6 (41%) were predominant. Coinfected patients had a higher aspartate-to-platelet ratio index, lower platelets, a lower HBsAg positivity rate and more frequent diabetes. Based on logistic regression, blood transfusion antecedents (adjusted odds ratio 2.9; 95% CI 1.7–4.9), unsafe medical injections (2.0; 1.3–3.2), and partner (3.4; 1.5–7.6) or household member (2.4; 1.3–3.2) with liver disease were independently associated with HCV in women. However, having a tattoo/scarification (1.9; 1.1–3.4) and household member (3.1; 1.3–7.3) with liver disease were associated with HCV in men. Thus, our study found intermediate endemicity of active hepatitis C in a large Cambodian HIV cohort and provides initial arguments for targeted HCV screening (>50 years, partner/household member with liver disease, diabetes, increased aspartate-to-platelet ratio index) as efficient way forward.

Hepatitis C Virus in Peripheral Mononuclear Cells in Patients on Regular Hemodialysis

Background: Occult hepatitis C virus infection (OCI) was identified as Hepatitis C virus (HCV), characterized by undetectable HCV antibodies and HCV RNA in serum, while HCV RNA is detectable in liver and peripheral blood mononuclear cells (PBMCs) only. Nosocomial transmission in dialysis units maintains a higher prevalence of hepatitis C virus (HCV) infection in patients on maintenance dialysis than in the general population. HCV infection has a detrimental effect on survival in patients on maintenance dialysis and after renal transplantation. The excess risk for death in HCV-positive patients was partially attributed to chronic liver disease with its attendant complications, particularly hepatocellular carcinoma and liver cirrhosis(1). The aim of this study: was to evaluate the hidden infection of hepatitis C virus among regular hemodialysis patients in Bab Al Sharia University Hospital with negative ELISA and PCR by using PCR in mononuclear cells as a marker in the serum of these patients Patients and methods:in this prospective study, 60 patients with end-stage renal disease on regular hemodialysis(for at least 6 months duration)were included. For all patients thorough medical history, clinical examination, kidney function tests, liver function tests, complete blood count, pelvi-abdominal ultrasound, HCVantibodies, hepatitis C viral RNA, quantitative, HbsAg,. HCV PCR done for all patients in serum and mononuclear cells.. Patients with acute or chronic HCV infection as marked by positive hepatitis C antibody,acute or chronic HBV infections marked by hepatitis B surface antigen,other causes of liver dysfunction ( e.g., primary biliary cirrhosis, autoimmune hepatitis, HIV infection) and patient on anti HCV treatment.were excluded. Results: showed detection of HCV-PCR in PBMCs in the absence of HCV-PCR in plasma; was found in three of the 60 patients (3.3%). All patients had negative HIV, HBsAg, HCV Ab and serum HCV PCR. Conclusion: it could be concluded that testing for HCV-RNA in PBMCs is more reliable than hepatitis serological markers in identifying patients with an OCI when a liver biopsy is not available.

Correlation Between Serum Apoptotic Markers and Hepatitis C viral load In Chronic Hepatitis C Virus-Related Liver Disease

Hepatitis C virus (HCV) is considered the most common etiology of chronic liver disease in Egypt. Developing non invasive tests that can predict liver injury represents a growing medical need. Considering that hepatocyte apoptosis plays a role in chronic hepatitis C pathogenesis; evaluation of the presence of different apoptotic markers that correlate with liver injury in HCV- related liver diseases could be a way for this achievement. The aim of the present study was to identify the correlation between serum apoptotic markers Bcl-2 and Bax with hepatitis C viral load in the chronic hepatitis C virus related liver diseases. The study included three groups ; group 1: 35 compensated chronic HCV patients without any suspected evidence of liver cirrhosis and with Child - Pugh score of 5-6 (class A), Group 2: 35 decompensated chronic HCV patients with Child - Pugh score of 10-15 (class C) and group 3: 15 healthy volunteers as a control group. The results collectively suggest that statistically significant correlations were noticed between serum Bcl-2, Bax, Bcl-2/Bax ratio and HCV PCR in chronic hepatitis C virus-related liver disease.

Evaluation of Ledipasvir plus Sofosbuvir for Treatment of Compensated and Decompensated HCV Cirrhotic Patients

Background:unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct acting antiviral agent (DAA) targets are focused on HCV NS3/4A protein (protease), NS5B protein (polymerase) and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir, simeprevir and fixed combination medicines containing ledipasvir plus sofosbuvir and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the “cure HCV” goal has become a reality. The aim of this study was to assess of ledipasvir plus sofosbuvir as treatment of HCV infection in patients with advanced liver disease including cirrhotic patients with child B and C. Patients and methods:in this prospective study, seventy five HCV PCR positive patients were classified into three groups according to child score. Each group included twenty five patients. All patients received ledipasvir plus sofosbuvir for six months. For all patients thorough medical history, clinical examination, kidney function tests, liver function tests, complete blood count, pelvi-abdominal ultrasound, HCVantibodies, hepatitis C viral RNA, quantitative, HbsAg, alpha fetoprotein as baseline screening. HCV PCR done for all patients at end of treatment and three months later to detect sustained virological response (SVR12). Patients with combined HCV and HBV infection, hepatic or extrahepatic malignancies and late child C were excluded. Results: showed that no statistical significant difference were detected in patients of group A as regard liver function tests before and after treatment and SVR12 achieved by 96%. Patients of group B showed significant statistical difference as regard liver function tests before and after treatment with SVR12 achieved by 88%. In patients of group C there were significant statistical difference in liver function tests with SVR12 achieved by 80%. Also there were clinical improvement in patients of group B and C after end of treatment. Conclusion:it could be concluded that there will be a dramatic improvement in HCV therapy followed the introduction of oral medicines that directly inhibiting the replication cycle of HCV. The combination pill contains a fixed-dose of ledipasvir 90 mg and sofosbuvir 400 mg, two direct-acting antiviral agents against HCV. Ledipasvir is an inhibitor of the NS5A protein, which is required for HCV replication. Sofosbuvir inhibits the HCV NS5B RNA-dependent RNA polymerase, which is also required for viral replication. Sofosbuvir is a nucleotide prodrug that undergoes intracellular metabolism to form a pharmacologically active triphosphate that can incorporate into the HCV RNA. Ledipasvir plus sofosbuvir can be used safely in treatment of compensated and decompensated post hepatitis C liver cirrhosis. SVR12 can be achieved by 96% in patients with early cirrhosis (child A), 88% in patients with child B cirrhosis and 80% in patients with child C with subsequent improvement in liver functions.

Incidence, risk factors, and prevention of hepatitis C reinfection: a population-based cohort study

People remain at risk of reinfection with hepatitis C virus (HCV), even after clearance of the primary infection. We identified factors associated with HCV reinfection risk in a large population-based cohort study in British Columbia, Canada, and examined the association of opioid substitution therapy and mental health counselling with reinfection. We obtained data from the British Columbia Hepatitis Testers Cohort, which includes all individuals tested for HCV or HIV at the British Columbia Centre for Disease Control Public Health Laboratory during 1990-2013 (when data were available). We defined cases of HCV reinfection as individuals with a positive HCV PCR test after either spontaneous clearance (two consecutive negative HCV PCR tests spaced ≥28 days apart without treatment) or a sustained virological response (SVR; two consecutive negative HCV PCR tests spaced ≥28 days apart 12 weeks after completing interferon-based treatment). We calculated incidence rates of HCV reinfection (per 100 person-years of follow-up) and corresponding 95% CIs assuming a Poisson distribution, and used a multivariable Cox proportional hazards model to examine reinfection risk factors (age, birth cohort, sex, year of HCV diagnosis, HCV clearance type, HIV co-infection, number of mental health counselling visits, levels of material and social deprivation, and alcohol and injection drug use), and the association of opioid substitution therapy and mental health counselling with HCV reinfection among people who inject drugs (PWID). 5915 individuals with HCV were included in this study after clearance (3690 after spontaneous clearance and 2225 after SVR). 452 (8%) patients developed reinfection; 402 (11%) after spontaneous clearance and 50 (2%) who had achieved SVR. Individuals were followed up for a median of 5·4 years (IQR 2·9-8·7), and the median time to reinfection was 3·0 years (1·5-5·4). The overall incidence rate of reinfection was 1·27 (95% CI 1·15-1·39) per 100 person-years of follow-up over a total of 35 672 person-years, with significantly higher rates in the spontaneous clearance group (1·59, 1·44-1·76) than in the SVR group (0·48, 0·36-0·63). With the adjusted Cox proportional hazards model, we noted higher reinfection risks in the spontaneous clearance group (adjusted hazard ratio [HR] 2·71, 95% CI 2·00-3·68), individuals co-infected with HIV (2·25, 1·78-2·85), and PWID (1·53, 1·21-1·92) than with other reinfection risk factors. Among the 1604 PWID with a current history of injection drug use, opioid substitution therapy was significantly associated with a lower risk of reinfection (adjusted HR 0·73, 95% CI 0·54-0·98), as was engagement with mental health counselling services (0·71, 0·54-0·92). The incidence of HCV reinfection was higher among HIV co-infected individuals, those who spontaneously cleared HCV infection, and PWID. HCV treatment complemented with opioid substitution therapy and mental health counselling could reduce HCV reinfection risk among PWID. These findings support policies of post-clearance follow-up of PWID, and provision of harm-reduction services to minimise HCV reinfection and transmission. The British Columbia Centre for Disease Control and the Canadian Institutes of Health Research.

Role of primary T-cell immunodeficiency and hepatitis B coinfection on spontaneous clearance of hepatitis C: The BC Hepatitis Testers Cohort.

T-cell host immune response against hepatitis C virus (HCV) has been suggested to play an important role in determining HCV infection outcome. However, data from human studies are not available. This study examined the effect of primary T-cell deficiency along with other factors on the spontaneous clearance of HCV in a large population-based cohort in British Columbia, Canada. The BC Hepatitis Testers Cohort includes all individuals tested for HCV in BC in 1990-2013 linked with data on their medical visits, hospitalizations and prescription drugs. HCV-positive individuals with at least one valid HCV PCR test on/after HCV diagnosis (n=46783) were included in this study. To examine factors associated with the spontaneous clearance of HCV, multivariable logistic regression was fitted on the full sample, and Cox proportional hazards model on the HCV seroconverters. Spontaneous clearance was observed in 25.1% (n=11737) of those tested for HCV. After adjusting for potential confounders, the odds of spontaneous clearance of HCV was lower in people with primary T-cell immunodeficiency (adjusted odds ratio [aOR]: 0.55, 95% CI: 0.32-0.94), and higher in females (aOR: 1.61, 95% CI: 1.54-1.68) and in those coinfected with HBV (aOR: 2.31, 95% CI: 1.93-2.77). Similar results were observed in HCV seroconverters except HBV coinfection was not significant. In conclusion, primary T-cell immunodeficiency is associated with a lower spontaneous clearance of HCV while female sex and coinfection with HBV are associated with a higher spontaneous clearance.

OC-033 Nine-Gene Signature Implicated in the Early Development of Hepatitis C Virus (HCV) Related Hepatocellular Carcinoma (HCC)

Introduction HCV remains the commonest cause of HCC related deaths in the west. Dysplastic nodules (DN) harbour highly relevant genomic information based on its strong potential to progress to HCC. Copy number alterations (CNA) have not been previously studied in a large cohort of HCV related DN. In this study we used next generation sequencing (NGS) to identify potential drivers of oncogenesis in a cohort of HCV related DNs and HCCs. Methods We performed low coverage next generation DNA sequencing of 116 HCCs and 49 DNs from 63 HCV infected patients to investigate their CNA profiles. Patients with a mixed aetiology of liver disease were excluded. Significant copy number gain and loss peaks were identified using GISTIC 2.0. To identify driver from passenger alterations, we stratified the peaks according to their amplitude and frequency within included samples. We also identified peaks that were inclusive of genes causally implicated in cancer, highly associated with cancer or involved in major cell signalling pathways. We further analysed the HCC-related peaks and correlated each of them to patient and tumour clinical features. This correlation was corrected for false discovery rate (FDR) using the Benjamini-Hochberg procedure. Results We identified 86 and 79 significant CNA peaks in HCC and DN respectively. The peaks were further stratified as described above which lead to recognition of a 9 gene signature highly implicated in early HCV related HCC. This included losses of ROCK1, CARS, SBDS, DUX4 and gains of NCOA2, MYC, TPO, YWHAZ and MCM4. Our data confirmed the alteration of 51 other genes in HCC but not DN. This included gains of CCND1, NFKB1/2, MUC1, FGF2/4/19 and CKS1B and losses of CDKN2A/B, KRAS, PTEN, RB1, NOTCH1, CCNA2, BMPR1B which have previously been implicated in hepatocarcinogenesis. Out of 86 HCC-related peaks, 16/86 had significant associations with clinical features after correction for FDR. Six of the above 16 peaks overlapped with 6 out of the 9 gene signature we previously identified. Genomic features strongly correlated with tumour differentiation, number of tumours per liver and overall survival. No association was found between HCV genotype or PCR quantity. Conclusion Analysis of DNA copy number profiles of a large number of HCV related DN and HCC using NGS revealed a signature of 9 genes likely to be implicated as drivers in the early development of this cancer. Our study generates a valid hypothesis and further studies are needed to confirm causality. Disclosure of Interest W. Fateen: None Declared, H. Wood: None Declared, S. Berri Employee of: Illumina, H. Thygesen: None Declared, J. Wyatt: None Declared, M. El- Meteini: None Declared, C. Millson: None Declared, P. Quirke: None Declared

Course of hepatitis C virus (HCV) RNA and HCV core antigen testing are predictors for reaching sustained virologic response in liver transplant recipients undergoing sofosbuvir treatment in a real-life setting.

Hepatitis C virus (HCV) infection is associated with reduced graft survival in orthotopic liver transplant recipients. Treatment with the new direct-acting antivirals (DAAs) is safe and efficient, but no reliable predictive factors for sustained virologic response (SVR) have been identified so far. The HCV core antigen assay (HCV-core-Ag) is a new, inexpensive, and efficient method to detect viral antigens, but the value of this technique to predict treatment response in orthotopic liver transplantation (OLT) patients is still unclear. All OLT patients who were treated with a sofosbuvir-based antiviral regimen at our center between March 2014 and August 2014 were included in the analysis (n = 20). HCV-core-Ag and HCV RNA (polymerase chain reaction [PCR]) were determined at each visit. Primary endpoints of this study were SVR at 4 or 12 weeks after end of treatment (SVR 4 and SVR 12). HCV-core-Ag tested negative after a median of 2 weeks (range 1-16 weeks) while PCR tests became negative after a median of 4 weeks (range 2-12 weeks). Time until PCR negativity and until HCV-core-Ag negativity showed a good correlation (R = 0.711, P < 0.001, Fig. ). Seventeen of 20 patients (85%) achieved SVR 12. SVR 12 was associated with a short time interval between treatment start and HCV PCR negativity (P = 0.005) or HCV-core-Ag negativity (P = 0.003, Mann-Whitney test). No severe side effects were observed. DAA treatment is safe and well tolerated in OLT. The time points of HCV-core-Ag loss and PCR negativity were predictors of SVR 12.

Cerebral microglia activation in hepatitis C virus infection correlates to cognitive dysfunction.

Hepatitis C virus (HCV) infection may induce chronic fatigue and cognitive dysfunction. Virus replication was proven within the brain and HCV-positive cells were identified as microglia and astrocytes. We hypothesized that cerebral dysfunction in HCV-afflicted patients is associated with microglia activation. Microglia activation was assessed in vivo in 22 patients with chronic HCV infection compared to six healthy controls using [(11) C]-PK11195 Positron Emission Tomography (PET) combined with magnetic resonance tomography for anatomical localization. Patients were subdivided with regard to their PCR status, Fatigue Impact Scale score (FIS) and attention test sum score (ATS). A total of 12 patients (54.5%) were HCV PCR positive [of which 7 (58.3%) had an abnormal FIS and 7 (58.3%) an abnormal ATS], 10 patients (45.5%) were HCV PCR negative (5 (50%) each with an abnormal FIS or ATS). Patients without attention deficits showed a significantly higher accumulation of [(11) C]-PK11195 in the putamen (P = 0.05), caudate nucleus (P = 0.03) and thalamus (P = 0.04) compared to controls. Patients with and without fatigue did not differ significantly with regard to their specific tracer binding in positron emission tomography. Preserved cognitive function was associated with significantly increased microglia activation with predominance in the basal ganglia. This indicates a probably neuroprotective effect of microglia activation in HCV-infected patients.

PTU-104 Non-invasive detection, stratification and treatment of chronic hepatic c related liver disease amongst substance users in the community: a prospective study

<h3>Introduction</h3> Despite discovery of direct acting antiviral agents (DAA), a two- three fold increase in hepatitis C virus (HCV) detection/treatment is necessary to reduce the national HCV disease burden. Ninety percent of HCV positive individuals in England are people who inject drugs (PWID) with poor engagement with health services. Our aim was to assess feasibility of non-invasive detection, stratification and treatment of HCV related chronic liver disease (CLD) in the community. <h3>Method</h3> Two-year prospective study (Dec 2013–Nov 2015) conducted at a large substance misuse service in SE England. Individuals offered dry blood spot testing (DBST), mobile transient elastography (TE), and HCV treatment (pegylated interferon/ribavirin/telaprevir). Clinically significant hepatic fibrosis: liver stiffness measurement (LSM) ≥7.5 kPa. <h3>Results</h3> To date, 165 individuals recruited, mean age 39.8 ± 8.9 yrs, 84.8% male. One hundred and forty-one (85.5%) had history of injecting drug use (IDU) and 143 (86.7%) reported alcohol use. Eighty-three (50.3%) had had a psychiatric diagnosis. Uptake of DBST was 75 (45.5%), main reason for declining being recent prior testing. Overall prevalence of positive serological markers were: HBcAb 28.8% (n = 42), HCV antibody 62.2% (n = 97) and HCV PCR 75.2% (73/97) (genotype 3a 42.8%, 1a 34.3%). Of those with a positive HCV PCR (n = 73), 62 (84.9%) underwent TE, mean LSM being 7.7 ± 6.6. kPa. Twenty-one (33.9%) had LSM ≥7.5 kPa including 13 (21%) with cirrhosis (LSM ≥12 kPa), one of whom had decompensated disease. Of the 73 with a positive HCV PCR none had had prior treatment: fifteen (20.5%) were not treatment candidates (chaotic life style), interferon was inappropriate in 35 (47.9%) with 23 (31.5%) being eligible for interferon based treatment. Thirteen have commenced therapy (nine genotype 3a, three 1a and one 2b), of whom 4 have successfully completed with 8 achieving rapid virological response. <h3>Conclusion</h3> This novel community based liver service at a substance service has shown excellent uptake of both DBST and mobile TE amongst PWID, though prevalence of a positive HCV antibody (62.2%) remains high. Additionally, despite a mean age of &lt;40 yrs about a third of PWID have clinically significant HCV related hepatic fibrosis with 1:5 having established cirrhosis. Though community based interferon therapy is feasible in PWID, it is contraindicated in approximately 50% emphasising the urgent need for interferon-free regimens in this vulnerable population. <h3>Disclosure of interest</h3> S. Verma Grant/Research Support from: Gilead, Conflict with: Travel grants from Gilead, Abbvie, Roche, BMS and Janssen, M. O’Sullivan Conflict with: salary funded by Gilead, H. Williams: None Declared, A.-M. Jones: None Declared.

Utility of routine real time quantitative PCR monitoring of HCV infection in haemodialysis patients

Background: Hepatitis C virus (HCV) infection causes significant morbidity and mortality in patients of end stage renal disease (ESRD) on haemodialysis (HD). Stringent screening methods can help in its early diagnosis. Objective: The study addresses the utility of real-time quantitative polymerase chain reaction (RQ-PCR) in the diagnosis and monitoring of HCV infection especially on seronegative and normal serum alanine aminotransferase (ALT) HD patients. Material and Methods: This retrospective study was carried out from January 2010 to December 2012. Patients of ESRD on maintenance HD and on whom all the three assays HCV antibody serology, PCR and ALT were done were included in the study (n = 123). Group 1 (n = 57), comprised of patients with negative serology and normal ALT, and Group 2 (n = 66), had either raised ALT and or a positive or equivocal serology. Results: Out of the 123 cases studied, HCV serology was positive in 36.5% (45), ALT raised in 18.6% (23) and PCR positive in 67.4% (83) cases. PCR positivity was significantly higher than serology and raised ALT. Group 2 had a significantly higher PCR positivity than Group 1 (P = 0.0004), but 50.9% patients of Group 1, were also PCR positive and 69% of them had a high viral count of >8 × 105 IU/ml at the time of detection. Conclusion: Regular routine screening of HCV by RQ-PCR in ESRD patients can help in early diagnosis of HCV infection in patients with low index of suspicion.

Vitamin D status and viral response to therapy in hepatitis C infected children.

To study the frequency of vitamin D deficiency in patients with hepatitis C virus (HCV) infection and to evaluate the role of vitamin D supplementation in improving antiviral therapy. Sixty-six children aged from 7-14 years (mean ± SD, 11.17±2.293) diagnosed with HCV infection were matched to 28 healthy controls. Serum levels of 25 (OH) D3, calcium, phosphorus, alkaline phosphatase and plasma level of parathormone were measured. Quantitative PCR for HCV was performed Bone density was determined by dual energy X-ray absorptiometry. All cases received conventional therapy, and only 33 patients received vitamin D supplementation. Children with HCV showed significantly increased levels of HCV RNA (P<0.001), parathormone (P<0.01) and decreased vitamin D levels (P<0.05) (33.3% deficient and 43.3% insufficient) compared with controls. Abnormal bone status (Z score -1.98±0.75) was found in ribs, L-spine, pelvis and total body. Cases treated with vitamin D showed significant higher early (P<0.04) and sustained (P<0.05) virological response. There was a high frequency of vitamin D deficiency among the Egyptian HCV children, with significant decrease in bone density. The vitamin D level should be assessed before the start of antiviral treatment with the correction of any detected deficiency. Adding vitamin D to conventional Peg/RBV therapy significantly improved the virological response and helped to prevent the risk of emerging bone fragility.

Effects of Health Insurance Among Patients on Hepatitis C Treatment Along the Texas-Mexico Border

Introduction: The incidence of hepatitis C virus (HCV) infection is increasing along the U.S.-Mexico border and across the world. There are significant implications for patients who are non-funded and seeking treatment for hepatitis C that are faced by border communities. Having a disproportionate number of individuals without insurance and high rates of undocumented residents may influence treatment outcomes for HCV patients. The purpose of this project was to examine the effect of health insurance status and office visit compliance on sustained virologic response (SVR) in adult patients living along the Texas-Mexico border treated for HCV. Methods: We conducted a longitudinal retrospective chart review of patients who underwent treatment with dual and triple therapy in a border community in Texas. The sample included patients between the ages of 18 and 65, with a diagnosis of HCV, who underwent HCV treatment between January 01, 2010 and August 15, 2013, El Paso, Texas. Data were collected from the charts of patients who received HCV treatment with pegylated interferon, ribavirin, and a protease inhibitor. Results: A total of 76 charts were reviewed. Twenty patients met study criteria and were included in the data analysis. The other 56 (73%) patients did not complete treatment or did not return for SVR testing. Of the 20 patients who were included in the study, 19 (95%), were Hispanic, 12 (50%) were female, age included 11 (55%), age 20-29, 7 (35%), age 30-39, 2 (10%) age 40-49. Most patients were overweight with BMI 18-25 in 3 (15%), BMI 25-30 in 9 (45%), and BMI >30 in 8 (40%). Eleven patients were genotype 1, 4 were genotype 2, 5 were genotype 3. Of the 20 patients included in the study, 4 had insurance and 16 did not. Of the 16 patients who were non-funded, all 16 patients were on an indigent managed health care program. SVR was achieved in three-fourths (75%) of patients with insurance versus 12/16 (75%) without insurance (p=1.0). Gender, age, and HCV PCR baseline level did not show significant effects on SVR response using multiple logistic regression analysis. Conclusion: In conclusion, in this sample of HCV patients treated in a Texas-Mexico border community, insurance status did not affect SVR outcomes. Patients who did not have insurance, but were provided some type of assistance or managed care program, completed treatment and had high SVR rates. Disclosure - Roberta Romero DNP, RN, FNP-C has received honoraria from Genentech, Vertex, and Gilead Pharmaceuticals and is on the speaker’s bureau for Genentech and Gilead. Ogechika Alozie has received honoraria from Abbvie Pharmaceuticals and is on the speaker’s bureau for Abbvie and ViiV.

PTH-083 Management Outcomes For Patients With Positive Hepatitis C Serology Over A Three Year Period In York Hospital

IntroductionThe majority of patients with Hepatitis C Virus (HCV) in England remain undiagnosed. There are an estimated 1298 patients infected with HCV in North Yorkshire,1 but a fraction of these...

Adipokines and insulin resistance, predictors of response to therapy in Egyptian patients with chronic hepatitis C virus genotype 4

Hepatitis C virus (HCV) infection has major health impact worldwide and is a significant cause of chronic liver disease. In Egypt, HCV is highly endemic (up to 15% of the population); 91% of the patients are infected with genotype 4. Searching for new predictors of response to therapy is mandatory to decrease the cost and the adverse effects of current therapy. The aim of this study was to clarify the usefulness of serum leptin, adiponectin, and insulin resistance (IR) as predictors of response to treatment in hepatitis C virus genotype 4 (HCVG4). One hundred patients with chronic HCVG4 who were candidates for treatment with pegylated interferon α and ribavirin were included in the study. Age, sex, and BMI were determined, and quantitative HCV PCR, assessment of serum leptin, adiponectin, IR, and pretreatment liver profile, and liver biopsy were performed. The male to female ratio was 68/32; the mean age of the patients was 40.9 ± 7.8 years and BMI was 28.3 ± 10 kg/m. Sustained virological response (SVR) was achieved by 56% of the patients. On performing logistic regression, BMI [odds ratio (OR) 6.5; P=0.004], serum leptin (OR 27.8; P ≤ 0.001), aspartate aminotransferase (OR 1.06; P ≤ 0.001), IR (OR 1.15; P ≤ 0.001), histological activity index (OR 1.77; P=0.006), and fibrosis (OR 2.93; P=0.001) were found to be independent negative predictors of SVR, whereas serum adiponectin (OR 0.74; P ≤ 0.001) was found to be an independent positive predictor of SVR. Pretreatment adiponectin (cutoff 13.75; sensitivity 92.86%; specificity 86.86%) shows area under the curve of 0.879 (95% confidence interval 0.802-0.956; P<0.001) and insignificant area under the curve for leptin or IR. BMI, pretreatment high leptin levels, and IR are negative predictors for SVR and pretreatment low adiponectin levels are an independent positive predictor for SVR in HCVG4.

Mutations in the STAT1-interacting domain of the hepatitis C virus core protein modulate the response to antiviral therapy

RNA viruses, such as hepatitis C virus (HCV), have markedly error-prone replication, resulting in high rates of mutagenesis. In addition, the standard treatment includes ribavirin, a base analog that is likely to cause mutations in different regions of the HCV genome, resulting in deleterious effects on HCV itself. The N-terminal region of the core protein is reported to block interferon (IFN) signaling by interaction with the STAT1‑SH2 domain, resulting in HCV resistance to IFN therapy. In this study, mutations in the HCV core protein from IFN/ribavirin‑treated patients were analyzed, with particular focus on the N‑terminal domain of the HCV core which is reported to interact with STAT1. HCV PCR positive patients enrolled in this study were either undergoing pegylated IFN/ribavirin bitherapy and had completed 12 weeks of initial treatment or were treatment‑naïve patients. The HCV core protein was cloned and sequenced from these patients and mutations observed in the STAT1‑interacting domain of the core protein from treated patients were characterized using in silico interaction to depict the role of these mutations in disease outcomes. Our results suggest that the amino acids at positions 2, 3, 8, 16 and 23 of the HCV core protein are critical for core-STAT1 interaction and ribavirin-induced mutations at these positions interfere with the interaction, resulting in a better response of the treated patients. In conclusion, this study anticipates that HCV core residues 2, 3, 8, 16 and 23 directly interact with STAT1. We propose that IFN/ribavirin bitherapy‑induced mutations in the STAT1‑interacting domain of the HCV core protein may be responsible for the improved therapeutic response and viral clearance, thus amino acids 1-23 of the N-terminus of the core protein are an ideal antiviral target. However, this treatment may give rise to resistant variants that are able to escape the current therapy. We propose similar studies in responsive and non-responsive genotypes in order to gain a broader picture of this proposed mechanism of viral clearance.

Completely steroid‐free immunosuppression in liver transplantation: a randomized study

Corticosteroids (CS) have been standard immunosuppression to prevent and treat rejection. However, CS are associated with increased risk of infection, obesity, hypertension, hyperlipidemia, diabetes, and accelerated hepatitis C virus (HCV) recurrence post-orthotopic liver transplantation (OLT). This study assesses the safety and efficacy of CS-free immunosuppressive regimen in adult OLT. A two-yr, prospective, randomized study of CS with delayed withdrawal (CS) or CS-free regimen with basiliximab, tacrolimus, and enteric-coated mycophenolate sodium (EC-MPS) was performed in 39 patients (CS=20; CS-free=19). CS group received intra-operative methylprednisolone weaned by six months. HCV patients had HCV PCR pre-OLT and 0.5, one, three, and sixmonths post-OLT. Protocol liver biopsies were performed at OLT, 2 and 24wk post-OLT or when indicated. Rejection occurred in two patients. Patient survival at one yr (100% vs. 95%), three yr (85% vs. 63%), and five yr (80% vs. 63%) post-OLT were similar between CS and CS-free group, respectively. Death-censored graft survival at one yr (100% vs. 95%), three yr (85% vs. 63%), and five yr (75% vs. 63%) were also similar. The risk of new-onset DM, hypertension, hypercholesterolemia, and weight gain was similar between groups. CS avoidance with basiliximab, calcineurin inhibitor, and EC-MPS is safe and effective as CS- containing immunosuppression in adult OLT.

Efficacy of Ribavirin to Prevent Hepatitis Reactivation in Hepatitis C Virus-Infected Patients Treated for Non-Hodgkin Lymphoma, Single Egyptian Center Study

Background: Reports had found an association between B cell non-Hodgkin lymphomas (NHL) and Hepatitis C virus (HCV) infection. However, data on acute exacerbation and reactivation of chronic HCV infection following chemotherapy are very limited. We studied the efficacy of ribavirin to prevent hepatitis reactivation in HCV-infected patients treated for NHL. Methods: This study was carried out at Hematology and Medical Oncology unit, Internal Medicine Department, Zagazig University Hospitals and it included 57 patients with B-cell NHL who were naive to chemotherapy, among them 24 patients were positive for HCV antibody and 33 patients were negative for HCV (group C). The HCV infected group was subdivided into 11 patients who received ribavirin (group A) and 13 patients did not receive ribavirin (group B)and routine investigations for NHL were done, HCV RNA was measured for HCV infected patients before and after the end of chemotherapy. Results: HCV infection occurred in 42% of patients with B cell NHL. Acute hepatic enzyme exacerbation occurred in 8 (14%) of all patients with the highest percentage was 29.2 % among HCV infected patients (7/24), while only one patient (3%) in the HCV negative group (P = 0.007). Among the 24 NHL patients with HCV positivity, we compared group A and group B during chemotherapy as regards to hepatic enzyme flare, it was (27% and 30%, respectively, P = 0.6). Five (20.8%) of 24 NHL patients with HCV positivity were developed HCV PCR reactivation. Conclusions: The frequency of HCV infection in patients with B cell NHL was higher than in the general population and acute exacerbation and reactivation of chronic HCV infection occurred in a sizeable subset of patients with NHL during chemotherapy, However the use of ribavirin did not decrease hepatic enzyme flare or HCV PCR reactivation during chemotherapy. doi: http://dx.doi.org/10.4021/jh72w

Conversion to Sirolimus Has the Potential to Suppress Viral Replication in HCV Positive Renal Transplant Candidates

Introduction and aim of the work: The presence of hepatitis C virus (HCV) in renal transplant recipients is an independent risk factor for death and graft failure. Limiting hepatitis C virus progression in liver transplant recipients using sirolimus-based immunosuppression was recently demonstrated. The mammalian target of rapamycin (mTOR) is one of the influential molecules for the anti-hepatitis C virus (HCV) action of interferon (IFN). On the other hand, chronic allograft nephropathy (CAN) favored by the use of calcineurin inhibitors (CNI) is one of the main causes of graft loss, whereas sirolimus (SRL) has proven to maintain better graft function with lower rates of CAN. We sought to report our experience with sirolimus conversion among HCV positive patients with chronic allograft nephropathy as regards hepatic and hematologic effects that might impact the drug use. Patients and methods: Twenty five renal transplant recipients with anti-HCV-positivity and normal liver function were enrolled. Ten patients had allograft dysfunction due to CsA nephrotoxicity proved by renal biopsy. SRL was started at 2 mg/d and adjusted to 6 to 8 ng/mL blood levels. CsA was gradually tapered to low levels and eventually stopped. Fifteen patients with hepatitis C positivity on CsA maintenance immunosuppression were used as control group. Creatinine clearance, body weight, ferritin level, hematocrit, hemoglobin, MCV, leucocyte count, platelet count, reticulocyte count, and reticulocyte index were calculated for all patients. All hepatitis C virus positive patients were followed prospectively regarding transaminases, immunosuppressive target levels, and HCV RNA. SRL-related hepatitis was defined as a rise in liver transferases or alkaline phosphatase or bilirubin over twice the upper limit of normal. Viral replication was defined as elevated liver enzymes and increasing viral load and/or biopsy-proven HCV active hepatitis. Results: After conversion, creatinine clearance non significantly rose from a value of 56.67±28.40 to 58.14 ±19.96 ml/min and serum creatinine fell from 2.04±0.4mg/dl to 1.8±0.07mg/dl. Average time on therapy was 24 weeks. There was a considerable reduction of Hb and hematocrit (10±1.15 g/dl before versus 9.25±0.94 after and 33±3% before versus 25.45±3.6% after conversion respectively, (P < 0.01, and < 0.01). In one patient, immunosuppressive regimen was changed back to CsA due to anemia and hepatotoxicity leading to prompt return of hematocrite and liver enzymes to the original value. One of ten anti-HCV-positive patients (10.0%) developed sirolimus associated hepatotoxicity compared to two patients in the control group (13%). Sirolimus patients showed a significant decrease in the HCV PCR levels from 700,000 to 600,000 IU/mL, p< 0.05, compared to 680,000 to 660,000 IU/ml in CsA patients, p=NS with comparable levels of transaminases (45 IU/L for aspartate aminotransferase and 50 IU/L for alanine aminotransferase compared to 49 and 56 IU/L in CyA patients, P=NS). Conclusions: Sirolimus has been shown to be a potent immunosuppressive agent after renal transplantation however, special concern regarding anemia should be evaluated thoroughly in those patients. Our data suggests that sirolimus has the potential to suppress viral replication in HCV positive renal transplant candidates.

Hepatitis C virus-specific cellular immune responses in individuals with no evidence of infection

The detection of hepatitis C virus (HCV)-specific T cell responses in HCV-uninfected, presumably unexposed, subjects could be due to an underestimation of the frequency of spontaneously resolving infections, as most acute HCV infections are clinically silent. To address this hypothesis, HCV-specific cellular immune responses were characterized, in individuals negative for an HCV PCR assay and humoral response, with (n = 32) or without (n = 33) risk of exposure to HCV. Uninfected volunteers (n = 20) with a chronically HCV-infected partner were included as positive controls for potential exposure to HCV and HCV infection, respectively. HCV-specific T cell responses in freshly isolated peripheral blood mononuclear cells were studied ex vivo by ELISPOT and CFSE-based proliferation assays using panels of HCV Core and NS3-derived peptides. A pool of unrelated peptides was used as a negative control, and a peptide mix of human cytomegalovirus, Epstein-Bar virus and Influenza virus as a positive control. Overall, 20% of presumably HCV-uninfected subject tested had detectable T-cell responses to the virus, a rate much higher than previous estimates of HCV prevalence in developed countries. This result would be consistent with unapparent primary HCV infections that either cleared spontaneously or remained undetected by conventional serological assays.