Hepatitis C Virus Viremia Research Articles

LB10. A Randomized, Double-Blind, Placebo-Controlled Efficacy Trial of a Vaccine to Prevent Chronic Hepatitis C Virus Infection in an at-Risk Population

BackgroundThe development of a safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of elimination efforts, providing the rationale for the first HCV vaccine efficacy trial.MethodsIn a randomized, multicenter, double-blind, placebo-controlled efficacy trial (NCT01436357), we evaluated a recombinant chimpanzee adenovirus 3 vector vaccine prime followed by a recombinant modified vaccinia Ankara boost, both encoding nonstructural proteins of HCV. HCV-uninfected adults 18–45 years old at-risk for HCV infection due to injection drug use were randomized to receive the prime-boost regimen or placebo at Days 0 and 56. Trial participants were monitored for vaccine reactogenicity, adverse events, and HCV viremia. Vaccine safety, immunogenicity, and efficacy against progression to chronic HCV infection were assessed.ResultsA total of 455 subjects received the prime-boost regimen or two doses of placebo, with 202 and 199 in the respective groups included in the according-to-protocol efficacy cohort. Overall incidence of infection was 14.1 infections per 100 person-years. There were no differences in development of chronic infection between vaccine and placebo arms, with 14 chronically infected subjects in each group. Specifically, the vaccine efficacy in preventing chronic infection was −0.53 (95% confidence interval [CI], −2.5 to 0.34). Of vaccinated subjects, 78% generated T-cell responses to ≥1 vaccine-encoded HCV antigens. The vaccine was generally safe and well tolerated with no serious vaccine-related adverse events. There were more solicited reports of adverse events after either injection in the vaccine group (81%) than in the placebo group (59%), with the difference mainly due to injection-site reactions. Serious adverse events and deaths occurred with similar frequencies in the two groups.ConclusionA randomized, placebo controlled, Phase I/II trial of a prime-boost vaccine to prevent chronic HCV infection was completed in an at-risk population, demonstrating the feasibility of conducting rigorous vaccine research in people who inject drugs. The regimen elicited robust immune responses without evident safety concerns, but did not provide protection against chronic HCV infection.DisclosuresVentzislav Vassilev, PhD, GlaxoSmithKlein Vaccines (Employee), Lan Lin, MD, GlaxoSmithKlein Vaccines (Employee), Alfredo Nicosia, PhD, ReiThera (Employee, Shareholder), Antonella Folgori, PhD, ReiThera (Employee), ReiThera (Employee, Shareholder. Other Authors: No reported disclosures.

114. Chorioretinal Lesions in Persons Who Inject Drugs and Are Hospitalized with Bloodstream and Related Infections

BackgroundEye infection is one of the many potential sites of infection in persons who inject drugs (PWID). The purpose of this study was to determine the prevalence of chorioretinal (CR) lesions, identify causative organisms, and correlate symptoms with ophthalmic involvement in PWID hospitalized with bloodstream infection (BSI) and/or related metastatic foci of infection (MFI).MethodsActively using PWID 18 years or older admitted to Wake Forest Baptist Med Ctr with documented BSI or MFI related to injection drug use (IDU) were prospectively enrolled after providing informed consent. All patients, whether or not they had eye symptoms, received a dilated retinal examination as soon as feasible after admission. Ocular symptoms, visual acuity, and ocular examination findings were recorded and fundus photos were obtained as indicated. Patients could be re-enrolled if re-admitted with a different infection.ResultsFifty-three PWID with 55 episodes of disseminated infection related to IDU underwent ophthalmic exams at a median of 7 days post-admission. Mean age was 33.4 years and 51% were female. Twenty (38%) patients had HCV viremia but none had active HIV infection. Heroin was the injection drug of choice in 55% of patients. Of the 55 episodes of systemic infection, 33 were classified as infective endocarditis (IE), 6 were BSI only, 10 were BSI with MFI, and 5 were MFI without active BSI. Nine (17%) patients had CR involvement on examination but only 33% (3/9) were symptomatic. Of those with ocular involvement, 1 had fungal endophthalmitis due to Candida albicans. Single or multifocal subretinal infiltrates were found in 5/9 patients (MSSA 2, MRSA 2, H. parainfluenzae 1), 2/9 had cotton wool spots (S. mitis 1, MRSA 1), and 7/9 had intraretinal or white-centered hemorrhages (MSSA 3, MRSA 2, S. mitis 1, H. parainfluenzae 1). Of the 9 patients with CR lesions, 7 had IE. Interestingly, 3.8% (3/53) had old multifocal CR scars, possibly related to prior disseminated infection.ConclusionPWID admitted with BSI or MFI may have ophthalmic involvement even in the absence of ocular symptoms, especially in the setting of IE. Further study is needed to characterize the epidemiology of these infections, to identify risk factors for ocular involvement, and to optimize diagnosis and management.Disclosures All authors: No reported disclosures.

Prevention of viral transmission during lung transplantation with hepatitis C-viraemic donors: an open-label, single-centre, pilot trial

A substantial proportion of organ donors test positive for hepatitis C virus (HCV) infection. To date, only a few studies have evaluated the safety of using lungs from these donors for transplantation, and no direct interventions to donor organs have been done with the aim of preventing HCV transmission via organ transplantation. We aimed to assess the safety and efficacy of lung transplantation in humans from HCV-positive donors to HCV-negative recipients after application of ex-vivo lung perfusion (EVLP) plus ultraviolet C (UVC) perfusate irradiation. We did a single centre, prospective, open-label, non-randomised trial in which donor lungs from HCV-viraemic donors (HCV-positive) were transplanted into HCV-negative recipients at Toronto General Hospital, University Health Network (Toronto, ON, Canada). Donors were younger than 65 years old and tested positive for HCV by nucleic acid testing. Donors who tested positive for hepatitis B virus, HIV, human T-lymphotropic virus 1 or 2 were excluded. Recipients were on the lung transplant waiting list without significant liver disease (stage 2 fibrosis or higher were excluded) or active HCV infection. Before implantation, all HCV-positive donor lungs were treated with EVLP with or without UVC perfusate irradiation to reduce the concentration of HCV RNA and infectivity. For the first week after transplantation, patients' HCV RNA blood concentrations were measured once daily, then once per week for 12 weeks. All patients received 12 weeks of oral sofosbuvir 400 mg plus velpatasvir 100 mg, starting at least 2 weeks after transplantation. The primary endpoint was a composite of survival and HCV-free status at 6 months after transplantation in all patients who received HCV-positive lungs. Patient outcomes such as survival, time in hospital, and incidence of acute rejection were compared between those receiving HCV-positive lungs and all patients who received HCV-negative lung transplants during the study period. The study is registered with ClinicalTrials.gov, NCT03112044. From Oct 1, 2017, to Nov 1, 2018, 209 patients had a transplantation; of 27 donors who were HCV-positive and initially considered, 22 were suitable for transplantation. The remaining 187 donors were HCV-negative. Before implantation, 11 of the HCV-positive donor lungs were treated with EVLP alone and the other 11 were treated with EVLP plus UVC. Lung disease, urgency status, and positive donor-recipient HLA crossmatch were similar between the patients who received HCV-positive and HCV-negative lungs. 20 (91%) patients in the HCV-positive group developed HCV viraemia within the first week after transplantation and had sofosbuvir plus velpatasvir treatment, starting at a median of 21 days after transplantation (IQR 16·76-24·75). Donor organ treatment with EVLP plus UVC was associated with significantly lower recipient viral loads in blood within the first week after transplantation than with EVLP alone (median of 167 IU/mL [IQR 20-12 000] vs 4390 IU/mL [1170-112 000] at day 7; p=0·048) and prevented transmission in two (18%) of 11 patients. All 20 infected patients achieved negative HCV PCR within 6 weeks of treatment initiation. The primary endpoint of survival and HCV-free status at 6 months after transplantation was achieved in 19 (86%) of 22 patients in the HCV-positive group. 6-month survival was 95% in recipients receiving lungs from HCV-viraemic donors versus 94% in recipients receiving lungs from HCV-negative donors. The most common grade 3-4 adverse events in the HCV-positive group were respiratory complications (five [23%]) and infections (four [18%]). Serious adverse events requiring admission to hospital occurred in ten (45%) patients. One (5%) patient who did not develop HCV infection died at day 31 from multiorgan failure related to pseudomonas sepsis. Two patients presented with HCV relapse within 3 months after sofosbuvir plus velpatasvir completion and required retreatment. Early and intermediate clinical outcomes were not significantly different between patients receiving viraemic HCV donor lungs and HCV-negative donor lungs. Donor organ treatment with UVC perfusate irradiation during EVLP significantly decreased HCV viral loads within the first 7 days after transplantation and shows the proof-of-concept for a novel approach of minimising viral load ex vivo before transplantation, with intent of preventing donor-recipient transmission. Canadian Institutes of Health Research.

1084 Does Viremia in Patients With Hepatitis C Antibody Positivity Alter Mortality in People Who Inject Drugs With Infective Endocarditis?

INTRODUCTION: Injection drug use [IDU] is a well-known risk factor for both infective endocarditis [IE] and hepatitis C virus [HCV] infections. In parallel with the opioid epidemic, the incidence of both infections has increased in recent years. In this retrospective study, the impact of HCV on mortality of people who inject drugs [PWID] with IE is assessed. METHODS: Electronic medical records of adult patients diagnosed with IE according to modified Duke criteria from January 2012 through May 2018 at an academic tertiary medical center were analyzed. Patients were identified as PWID based on IDU documentation within 3 months of admission. The study included all patients with a positive HCV antibody. Patients were then stratified into two groups: “Positive HCV viremia” [positive HCV antibody and viral load] or “Negative HCV viremia” [positive HCV antibody but negative viral load]. Prior HCV treatment, HIV infection, and absence of documented HCV seropositivity precluded study enrollment. Pertinent demographic, clinical, laboratory, microbiologic, and outcome data were recorded and analyzed. RESULTS: One hundred and twenty-nine PWID with IE were identified, of whom 110 [85.2%] had a positive HCV antibody. Of these, 23 patients were excluded due to lack of testing for viral RNA. , resulting in 87 HCV study patients [67.4%]. Fifty-three [61.0%] patients had viremia and 34 [39.1%] did not. Of the 87 study patients, 85.1% were Caucasian and 52.9% were female with a median age of 25. Six [6.9%] patients had previous IE. The most commonly injected drug was prescription opioids [69.0%]. The tricuspid valve was involved in 56.3% of patients and the most common pathogen was Staphylococcus aureus [71.3%]. Prescription opioid injection, S. aureus infection, tricuspid valve involvement, and 10-week mortality did not differ between the viremic and non-viremic HCV groups [Table 1]. CONCLUSION: While several host and clinical factors affect mortality in PWID with IE, HCV viremia does not appear to increase mortality. However, larger, prospective studies will be required to better delineate the significance of HCV viremia among PWID with IE.

1055 Results of a Hepatitis C Outreach Initiative and Identification of Barriers to Treatment

INTRODUCTION: Over 80% of veterans born between 1945-1965 in the Veterans Affairs system have been tested for hepatitis C (HCV). In December 2016 the Providence VA Medical Center implemented an outreach initiative that targeted veterans who were untreated for HCV. The purpose of this study is to evaluate the impact of the outreach program on HCV treatment initiation rates. The study also aims to identify factors associated with successful linkage to care and barriers to treatment. METHODS: Veterans with HCV viremia were targeted for outreach. Outreach entailed mailing letters to patients offering treatment, followed by telephone calls. The outreach team collaborated with primary care providers (PCP), social workers, the homeless clinic, and addiction services. Medical records were reviewed for demographics, disease characteristics and co-morbidities. The primary outcome was initiation of HCV treatment. Differences in characteristics between treated and untreated patients were studied to identify potential treatment barriers. RESULTS: 334 patients were treated for HCV prior to the start of the outreach initiative in December 2016. The outreach program targeted 175 patients with untreated HCV. Among these 175 patients, 116 (66.3%) were initiated on treatment, while 59 (33.7%) were not. Characteristics associated with treatment initiation include presence of psychiatric co-morbidities (P = 0.055), history of substance use (P = 0.03), and having a PCP located in-state (P = 0.02). Patients treated before the outreach initiative had higher rates of cirrhosis (P = 0.001), and higher APRI (P = 0.01), FIB-4 (P = 0.001), and Fibroscan scores (P = 0.001). CONCLUSION: The outreach program successfully initiated treatment in two-thirds of targeted patients. Prior to the program, HCV treated patients had higher rates of cirrhosis and more advanced liver disease based on non-invasive markers. This disparity may be related to increased screening in high-risk populations or a higher likelihood of establishment in the hepatology clinic. These findings suggest that outreach may improve access for patients who do not see a hepatologist. Higher rates of substance use and psychiatric disease in patients who were treated highlight the impact of coordinating care with mental health and addiction specialists. The data also shows that having a PCP out-of-state or not having a PCP listed is associated with non-treatment. Training more local providers in HCV management may aid in increasing treatment rates.

Impact of IFNL4 Genetic Variants on Sustained Virologic Response and Viremia in Hepatitis C Virus Genotype 3 Patients

Hepatitis C virus (HCV) genotype 3 is very prevalent in Europe and Asia and is associated with worst outcomes than other genotypes. Genetic factors have been associated with HCV infection; however, no extensive genome-wide study has been performed among HCV genotype 3 patients. In this study, using a large cohort of 1,759 patients infected with HCV genotype 3, we explore the role of genetic variants on the response to interferon (IFN) and direct-acting antiviral (DAA) regimens and viremia in a combined candidate gene and genome-wide analysis. We show that genetic variants within the IFN lambda 4 (IFNL4) locus are the major factors associated with the studied traits, accordingly with observations in other HCV genotypes and with comparable effect sizes. In particular, the functional dinucleotide polymorphism rs368234815 was associated with IFN-based sustained virologic response (SVR) [odds ratio (OR) = 1.5, P = 2.3 × 10−7], viremia (beta = −0.23, P = 8.8 × 10−10), and also DAA-based SVR (OR = 1.7; P = 4.2 × 10−4). Our results provide evidence for a role of genetic variants on HCV viremia and SVR, notably DAA-based, in patients infected with HCV genotype 3.

Prevalence of Viremic Hepatitis C Virus Infection by Age, Race/Ethnicity, and Birthplace and Disease Awareness Among Viremic Persons in the United States, 1999-2016.

Athough curative therapy is now available for hepatitis C virus (HCV) infection in the United States, it is not clear whether all affected persons have been diagnosed and/or linked to care. This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (1999-2016) and included 46 465 nonincarcerated and noninstitutionalized participants. Viremic HCV prevalence decreased from 1.32% in 1999-2004 to 0.80% in 2011-2016, although most of the decrease occurred in US-born whites and blacks but not the foreign-born or those born after 1985. In 2011-2016, approximately 1.90 million US adults remained viremic with HCV, and 0.33 million were at higher risk for advanced fibrosis, but only 49.8% were aware of their HCV infection, with higher disease awareness in those with health insurance coverage and US-born persons. The prevalence of viremic HCV has decreased in recent years among US born whites and blacks but not in other race/ethnicities and foreign-born persons and birth cohort born after 1985. Less than half of the viremic population was aware of having HCV infection. Improved HCV screening and linkage to care are needed, especially for the uninsured, foreign-born, birth cohort after 1985 and certain ethnic minorities.

HCV reinfections after viral clearance among HIV-positive patients with recent HCV infection in Taiwan.

Higher rates of hepatitis C virus (HCV) reinfection after viral clearance have been well described among HIV-positive men who have sex with men (MSM) in Europe. The epidemiology of HCV reinfection, however, has rarely been investigated among HIV-positive patients in Asia-Pacific region. We retrospectively identified HIV-positive patients with recent HCV infection who had cleared their primary infection, either spontaneously or via treatment, between January 2011 and May 2018. All included patients were observed until 31 March 2019. HCV reinfection was defined as recurrent HCV viraemia after achieving viral clearance with anti-HCV treatment or after spontaneous clearance. During the study period, 219 HIV-positive patients (90.4% MSM) were diagnosed with recent HCV infection. Viral clearance with successful treatment was achieved in 108 patients (49.3%) and spontaneous clearance occurred in 20 (9.1%); of them, 18 (14.1%) acquired HCV reinfections, resulting in an incidence rate of 8.2 per 100 person-years of follow-up (95% CI 5.2-13.1). With the adjusted Cox proportional hazards model, we found a higher reinfection risk in patients with syphilis (adjusted hazard ratio 10.3, 95% CI 1.4-77.8, P=.023) compared to those without syphilis. HCV RNA testing, if performed only following syphilis and elevated aminotransferases, might miss 44.4% and 33.3% of HCV reinfections, respectively. Similar to the findings in Europe, we observed a high incidence of HCV reinfection among HIV-positive Taiwanese with recent HCV infection, which was significantly associated with syphilis. To identify HCV reinfections, annual HCV RNA testing should be instituted instead of testing driven by symptoms, syphilis or elevated aminotransferases.

Successful early sofosbuvir-based antiviral treatment after transplantation of kidneys from HCV-viremic donors into HCV-negative recipients.

Transplanting kidneys from deceased donors with hepatitis C virus (HCV) viremia has been controversial for some time. Direct-acting antiviral agents have been shown to be highly effective in treating HCV infection. We report our experience with transplanting kidneys from HCV-positive donors with detectable viremia into HCV-negative recipients, followed by early treatment with a sofosbuvir-based antiviral regimen. Data were collected from seven HCV-negative recipients receiving kidneys from five deceased HCV-viremic donors. Before transplantation, all intentional transplanted recipients had given informed consent regarding the acceptance of an HCV-viremic kidney. Recipients were closely monitored after transplant with measurements of HCV viremia, liver and renal function, and trough levels of immunosuppressive drugs. Four donors were infected with HCV genotype 1; the other with HCV genotype 3a. HCV viremia was detectable in all seven renal transplant recipients within 3days after transplant. After determination of HCV genotype, antiviral treatment with a sofosbuvir-based regimen (sofosbuvir/ledipasvir, n=4; sofosbuvir/velpatasvir, n=3) was initiated within a median of 7days after transplantation and was continued for 8 to 12weeks. For all recipients, viral load was below the level of detection at the end of treatment, and all exhibited a sustained virologic response 12weeks later. All recipients exhibited normal liver enzyme activity at the end of treatment. Renal allograft function and trough levels of tacrolimus remained stable. Early administration of a sofosbuvir-based regimen to HCV-negative recipients of kidneys from HCV-viremic donors is feasible and safe. The definition of an optimal therapeutic approach warrants further investigation.

Low Hepatitis C Reinfection Following Direct-acting Antiviral Therapy Among People Who Inject Drugs on Opioid Agonist Therapy.

Direct-acting antiviral (DAA) therapy is highly effective in people who inject drugs (PWID); however, rates, specific injection behaviors, and social determinants associated with hepatitis C virus (HCV) reinfection following DAA therapy among PWID on opioid agonist therapy (OAT) are poorly understood. PREVAIL was a randomized controlled trial that assessed models of HCV care for 150 PWID on OAT. Those who achieved sustained virologic response (SVR) (n = 141; 94%) were eligible for this extension study. Interviews and assessments of recurrent HCV viremia occurred at 6-month intervals for up to 24 months following PREVAIL. We used survival analysis to analyze variables associated with time to reinfection. Of 141 who achieved SVR, 114 had a least 1 visit in the extension study (62% male; mean age, 52 years). Injection drug use (IDU) was reported by 19% (n = 22) in the extension study. HCV reinfection was observed in 3 participants. Over 246 person-years of follow-up, the incidence of reinfection was 1.22/100 person-years (95% CI, 0.25-3.57). All reinfections occurred among participants reporting ongoing IDU. The incidence of reinfection in participants reporting ongoing IDU (41 person-years of follow-up) was 7.4/100 person-years (95% CI, 1.5-21.6). Reinfection was associated with reporting ongoing IDU in the follow-up period (P < .001), a lack confidence in the ability to avoid contracting HCV (P < .001), homelessness (P = .002), and living with a PWID (P = .007). HCV reinfection was low overall, but more common among people with ongoing IDU following DAA therapy on OAT, as well as those who were not confident in the ability to avoid contracting HCV, homeless, or living with a PWID. Interventions to mediate these risk factors following HCV therapy are warranted.

Hepatitis C virus core antigen is cost-effective in community-based screening of active hepatitis C infection in Taiwan

Hepatitis C virus (HCV) core antigen is highly sensitive and specific in viremic HCV diagnosis. This study evaluated the cost-effectiveness of HCV core antigen (HCVcAg) in community-based screening for active HCV infection. Between 2017/07 and 2018/07, community-based screenings for active HCV infection with two-step (anti-HCV for screening and HCVRNA for diagnosis) and one-step processes (HCVcAg for screening and diagnosis) were conducted in two districts in Kaohsiung City. While HCVcAg test was positive at ≥3fmol/L, the lowest level of HCV-RNA detection was 12IU/mL. We analyzed the cost-effectiveness of two algorithms in identifying active HCV infection. There were two large-scale screenings using the two-step process with a total of 2452 residents enrolled; while six hundred and forty-four residents participated in continuous small-scale screening with the one-step process. The prevalence of anti-HCV and positive HCVcAg was 3.4% and 2.8%. The viremic rate was 1.4% and 2.8% for two- and one-step processes (p<0.001). While all positive HCVcAg were viremic, 42.4% of positive anti-HCV patients had viremia. The positive predictive value was 42.2% and 100% for two- and one-step processes in detecting active HCV infection (p<0.001). In identifying one active HCV infection, the cost was $755.3 and $711.1 dollars for two- and one-step processes respectively. Compared to the two-step process in community-based screening, continuous screening with the HCVcAg test as a one-step tool for active HCV infection was cost-effective in areas with low seroprevalence of HCV in Taiwan.

Introducing hepatitis C virus healthcare pathways in addiction care in the Netherlands with a Breakthrough project: a mixed method study

BackgroundPeople who inject drugs (PWID) are disproportionally affected by the hepatitis C virus (HCV) infection. In the Netherlands, active HCV transmission in PWID has practically been halted but uptake of HCV testing and linkage to care remains insufficient in this risk group. A national HCV in Addiction Care (HAC) quality improvement project based on the Breakthrough methodology (i.e. Breakthrough project) aimed to secure proper linkage to care in PWID by introducing local HCV healthcare screening and treatment pathways in addiction care units.AimTo qualitatively appraise the local HCV healthcare pathways; to evaluate the yield in terms of number of PWID screened, diagnosed, referred, and treated; and to identify best practices and barriers to successful participation in the HAC Breakthrough project.MethodsBetween 2013 and 2016, 12 units of addiction care centers throughout the Netherlands participated in two series of a HAC Breakthrough project. Local multidisciplinary teams created HCV healthcare pathways. Quality assessment of HCV healthcare pathways was performed retrospectively and data on screening results was collected. In-depth interviews were conducted to elucidate best practices and essential elements for successful participation.ResultsIn total, six HCV healthcare pathways were submitted by ten teams of which 83% was judged to be of “good” or “sufficient” quality. Uptake of HCV-antibody screening was 40% (N = 487/1219) and uptake of HCV-RNA in HCV-antibody positives was 59% (N = 107/181). The project resulted in 76 (6%) newly detected cases of persistent HCV viremia. Of all HCV-RNA positives, 92% was referred to a hepatitis treatment center. In 39% (N = 27/70) of those referred, treatment initiation was documented and 82% (N = 22/27) achieved a sustained virological response. Teams identified several best practices including motivational counseling training, oral swabs for anti-HCV testing, facilitating complementary HCV RNA testing, and supervised hospital visits.ConclusionThe HAC Breakthrough project has brought about good quality HCV healthcare pathways in the majority of participating addiction care centers and has successfully linked PWID with ongoing HCV viremia to care. Uptake of HCV screening and treatment after referral were identified as the main gaps to be closed in the HCV cascade of care to achieve final HCV elimination in Dutch PWID (i.e. micro-elimination).

Screening a nation for hepatitis C virus elimination: a cross-sectional study on prevalence of hepatitis C and associated risk factors in the Rwandan general population

ObjectivesWe analysed data collected during programmatic screening activities conducted in 2017 to describe hepatitis C virus (HCV) seroprevalence in the general population and identify associated factors.DesignWe analysed data collected between...

Impact of diabetes on the risk of serious liver events and liver-related deaths in people living with HIV and hepatitis C co-infection: data from the ICONA Foundation Cohort Study.

To investigate the association between diabetes and HCV infection in persons living with HIV and to determine the impact of diabetes on the occurrence of serious liver events (SLEs) and liver-related deaths (LRDs) among HIV/HCV-co-infected patients. Patients were included if they had at least one follow-up visit. In a cross-sectional analysis among all HIV patients, we have investigated the association between diabetes and HCV infection. A further longitudinal analysis was performed in the population of HIV/HCV-co-infected free from SLE with FIB-4 index < 3.25 at baseline, using the following endpoints: (A) first event between SLE and LRD; (B) liver fibrosis progression defined as the first of two consecutive FIB-4 > 3.25; (C) first event between SLE, LRD, and liver fibrosis progression. Data from 15,571 HIV patients were analyzed: 2944 (18.9%) were HCV-Ab positive, and 739 (4.7%) presented a diagnosis of diabetes at their last follow-up. Among HIV/HCV-co-infected population, 107 patients had a diagnosis of diabetes. Viremic HCV-co-infected patients had 3-fold risk of diabetes onset than HCV-uninfected patients. On HIV/HCV-co-infected population, 85 SLEs/LRDs occurred over 20,410 person-years of follow-up (PYFU), for an incidence rate of 4.2/1000 PYFU (95%CI 3.4-5.2). Diabetic patients had 3-fold risk of pooled SLE and LRD than patients without diabetes. Furthermore, viremic HCV infection was independently associated with a higher risk of SLE/LRD (aIRR 3.35 [95%CI 1.14-9.83]). In HIV-infected patients, viremic HCV co-infection is a strong predictor of diabetes. Among HIV/HCV-co-infected population, diabetic patients showed an increased risk of SLE/LRD compared with those without diabetes.

The impact of hepatitis C viremia status on lung functions in chronic hepatitis c patients.

Previous trials have investigated the effect of hepatitis C on lung functions; however, the role of viral load levels is unclear. The aim of this study was to investigate the effect of HCV viremia status on lung functions. This study was in 60 patients with chronic hepatitis C (CHC). Patients were classified into three groups (non-viremic, low-viremic and high-viremic) based on serum HCV RNA levels. Spirometric parameters (FEV1, FVC, FEV1/FVC) and the proportion of patients with spirometric abnormalities were compared between three groups. High-viremic and low-viremic patients showed a significantly higher prevalance of spirometric abnormality than observed in non-viremic patients (p=0.02). Moreover, there was a significant moderate correlation between viremia level and the percentage of spirometric abnormalities (Cramer's U value=0.452, p=0.002). High-viremic patients were 14.2 times more likely to exhibiting pulmonary dysfunction than non-viremic patients. Additionally, spirometric parameters FEV1 and FVC were significantly reduced in high-viremic and low-viremic patients compared to those in non-viremic patients (p=0.013 and p<0.001 respectively). These results indicate that persistent HCV infection may be associated with reduced pulmonary functions, especially in patients with high viremia levels. Therefore, these patients should be carefully monitored for lung function.

Hepatitis C virus antigens enzyme immunoassay for one-step diagnosis of hepatitis C virus coinfection in human immunodeficiency virus infected individuals.

BACKGROUNDCurrent diagnosis of hepatitis C virus (HCV) infection requires two sequential steps: testing for anti-HCV followed by HCV RNA PCR to confirm viremia. We have developed a highly sensitive and specific HCV-antigens enzyme immunoassay (HCV-Ags EIA) for one-step diagnosis of viremic HCV infection.AIMTo assess the clinical application of the HCV-Ags EIA in one-step diagnosis of viremic HCV infection in human immunodeficiency virus (HIV)-coinfected individuals.METHODSThe study blindly tested HCV-Ags EIA for its performance in one-step diagnosing viremic HCV infection in 147 sera: 10 without HCV or HIV infection; 54 with viremic HCV monoinfection; 38 with viremic HCV/HIV coinfection; and 45 with viremic HCV and non-viremic HIV coinfection.RESULTSUpon decoding, it was 100% accordance of HCV-Ags EIA to HCV infection status by HCV RNA PCR test. In five sera with HCV infection, HCV RNA was as low as 50-59 IU/mL, and four out of five tested positive for HCV-Ags EIA. Likewise, it was also 100% accordance of HCV-Ags EIA to HCV infection status by HCV RNA PCR in 83 sera with HCV and HIV coinfection, regardless if HIV infection was active or not.CONCLUSIONThe modified HCV-Ags EIA has a lower detection limit equivalent to serum HCV RNA levels of approximately 100 IU/mL. It is highly sensitive and specific in the setting of HIV coinfection, regardless of HIV infection status and CD4 count. These data support the clinical application of the HCV-Ags EIA in one-step diagnosis of HCV infection in HIV-infected individuals.

Prevalence of cryoglobulinemia and cryoglobulinemic vasculitis in chronically HCV-infected Brazilian patients

Introduction and ObjectivesCryoglobulinemia is one of the most frequent extrahepatic manifestations of chronic hepatitis C virus (HCV) infection and it may evolve to cryoglobulinemic vasculitis (CryoVas) which is a systemic vasculitis that affects small-sized vessels. The objective of this study was to evaluate the prevalence of cryoglobulinemia and CryoVas in HCV patients in São Paulo, Brazil. Materials and methodsA cross-sectional study was conducted and included sixty-eight viremic HCV patients, without HIV or hepatitis B coinfection. A thorough clinical and laboratory evaluation was performed including the detection of serum cryoglobulins and measurement of serum complement components. The classification criteria for CryoVas were applied. ResultsThe study population comprised mainly women (61.8%) with long term HCV infection (median 11.0 years). Advanced hepatic fibrosis was detected in 20.6% (14/68) of cases. Cryoglobulins were detected in 48.5% (33/68) of HCV-patients with type III cryoglobulinemia being the most frequent. CryoVas was present in 10.3% (7/68) and the main manifestations were peripheral neuropathy (85.7%), palpable purpura (42.8%), arthralgias (42.8%) and renal involvement (42.8%). Life-threatening manifestations were rare. Low hemolytic C2, C4 and total hemolytic complement (CH100) levels were common findings in the cryoglobulinemia group. Low C4 levels were independently associated with the development of CryoVas. ConclusionA high prevalence of cryoglobulinemia and CryoVas was found in Brazilian HCV-patients. CryoVas patients mostly presented non-life-threatening manifestations, especially peripheral neuropathy. Complement abnormalities were common in patients with cryoglobulinemia and low serum C4 levels were associated with CryoVas.

Evaluation of the application of the diagnostic protocol in a single step of Hepatitis C

Direct-acting antivirals for chronic hepatitis C (HCV) infection have reduced the need for on-treatment HCV RNA monitoring. We assessed the accuracy and cost implications of using HCV core antigen testing to replace HCV RNA testing for confirmation of diagnosis, on-treatment monitoring, and determination of sustained virological response (SVR).In a retrospective screening cohort study, de-identified residual serum from unselected samples were obtained from commercial laboratories in Ontario, Canada. Samples from each 5-year age-sex band from birth years 1945–74 collected from Aug 1, 2014, to Feb 28, 2015, were included. All samples that tested positive for HCV antibodies, and 10% of samples that tested negative for HCV antibodies, were tested for HCV core antigen and HCV RNA. A retrospective clinical cohort study was also done using blood samples from patients with confirmed HCV infection collected at four tertiary academic centres: one in Canada, two in Germany, and one in the USA. For assessment of SVR, we included samples from patients who started direct-acting antiviral-based treatment (excluding telaprevir and boceprevir) with or without peginterferon, ribavirin, or both, from Jan 1, 2014, to March 31, 2015. To ensure inclusion of adequate numbers for analysis, patients who relapsed after any treatment regimen were included. Serum samples included in the study were from baseline, week 4 on-treatment (only for patients treated with direct-acting antivirals), end of treatment, and week 12 or 24 of follow-up. The sensitivity and specificity of core antigen testing as a diagnostic tool was assessed in the screening cohort, using HCV RNA as a reference. The sensitivity and specificity of core antigen testing as well as its concordance with HCV RNA testing in the clinical cohort was assessed at baseline, week 4 on-treatment, and at weeks 12 or 24 after the end of treatment in patients undergoing therapy with direct-acting antivirals. The cost-effectiveness of core antigen testing with and without confirmatory HCV RNA testing for negative samples was also assessed.From 10 006 samples in the screening cohort, 75 of 80 viraemic (HCV RNA-positive) samples tested positive for HCV core antigen (sensitivity 94%, 95% CI 86–98), and none of the 993 HCV RNA-negative samples tested positive for HCV core antigen (specificity 100%, 95% CI 94–100). The five viraemic samples that tested negative for HCV core antigen had low corresponding HCV RNA concentrations. In the clinical cohort, two (1%) of 202 baseline samples tested negative for HCV core antigen; one had a low HCV RNA concentration (468 IU/mL), the other had a high HCV RNA concentration (>2 000 000 IU/mL). By week 4 of treatment, HCV core antigen concentrations decreased in all patients but were not predictive of SVR. Although there was good concordance between HCV RNA and HCV core antigen results at 12 weeks after the end of treatment (r=0·97; p<0·0001), three of the 148 patients who achieved SVR at 12 weeks tested HCV core antigen positive. 12 weeks after the end of treatment, HCV core antigen was undetectable in one (1%) of 71 samples from patients who were identified as having relapsed according to HCV RNA detection. On-treatment and end-of-treatment testing of core antigen or HCV RNA provided little clinical value. The use of HCV core antigen testing as a confirmatory diagnostic strategy was cost saving relative to HCV RNA testing, with a reduction of CAD$0·29–3·70 per patient screened depending on whether HCV RNA testing was used to confirm HCV core antigen-negative results.These data support the use of HCV core antigen testing to document HCV viraemia in a cost-saving diagnostic algorithm. In a treatment setting, HCV core antigen testing can be used instead of HCV RNA testing for diagnosis and documentation of treatment adherence, but it might not be adequate to determine SVR. This approach might improve access to care, particularly in low-income and middle-income countries.Abbott Diagnostics and Toronto Centre for Liver Disease.

Center-level trends in utilization of HCV-exposed donors for HCV-uninfected kidney and liver transplant recipients in the United States.

Several single-center reports of using HCV-viremic organs for HCV-uninfected (HCV-) recipients were recently published. We sought to characterize national utilization of HCV-exposed donors for HCV- recipients (HCV D+/R-) in kidney transplantation (KT) and liver transplantation (LT). Using SRTR data (April 1, 2015-December 2, 2018) and Gini coefficients, we studied center-level clustering of 1193 HCV D+/R- KTs and LTs. HCV-viremic (NAT+) D+/R- KTs increased from 1/month in 2015 to 22/month in 2018 (LTs: 0/month to 12/month). HCV-aviremic (Ab+/NAT-) D+/R- KTs increased from<1/month in 2015 to 26/month in 2018 (LTs: <1/month to 8/month). HCV- recipients of viremic and aviremic kidneys spent a median (interquartile range [IQR]) of 0.7 (0.2-1.6) and 1.6 (0.4-3.5) years on the waitlist versus 1.8 (0.5-4.0) among HCV D-/R-. HCV- recipients of viremic and aviremic livers had median (IQR) MELD scores of 24 (21-30) and 25 (21-32) at transplantation versus 29 (23-36) among HCV D-/R-. 12 KT and 14 LT centers performed 81% and 76% of all viremic HCV D+/R- transplants; 11 KT and 13 LT centers performed 76% and 69% of all aviremic HCV D+/R- transplants. There have been marked increases in HCV D+/R- transplantation, although few centers are driving this practice; centers should continue to weigh the risks and benefits of HCV D+/R- transplantation.

Role of HCV Viremia in Corroborated HCV Transmission Events Within Young Adult Injecting Partnerships.

BackgroundHepatitis C virus (HCV), a major cause of morbidity and mortality, is common and rising among young persons who inject drugs (PWID). Reducing the level of viremia may be an intervention, yet the impact of viremia on HCV transmission is unknown.MethodsWe conducted a prospective study of injecting partnerships (Partner Study) of young adult (age < 30 years) PWID within the UFO Study, which enrolled those at risk for HCV or with seronegative viremic infection and up to 3 HCV RNA–positive regular injecting partners. We examined the level of HCV viremia and stage of infection in the HCV-positive partner in regression analyses of HCV transmission events that were corroborated via HCV phylogenetic linkage analyses.ResultsWe enrolled 69 at-risk/acutely infected PWID. There were 25 new HCV infections (incidence rate, 35.9 per 100 person-years; 95% confidence interval [CI], 24.3–53.2 per 100 person-years); 12/25 (48%) were phylogenetically linked to at least 1 partner. We found no association between the infected partner’s quantitative level of HCV viremia and likely transmission in multivariate analyses (adjusted odds ratio [AOR], 0.90; 95% confidence interval [CI], 0.55–1.46); however, seronegative viremic infection in the infected partner was associated with increased transmission (AOR, 28.02; 95% CI, 5.61–139.95).ConclusionsThe HCV viremia level was not associated with increased odds of transmission, yet acute HCV infection (seronegative viremic) was. Explanations include high-risk behavior during acute infection or missed fluctuations in viremia during acute infection. Both point to the need for frequent testing to detect new infection and attempt to prevent onward transmission.