Acute Hepatitis C Virus Research Articles

Phylogenetic analysis in the clinical risk management of an outbreak of hepatitis C virus infection among transfused thalassaemia patients in Italy

Occurrence of hepatitis C virus (HCV) infection is reduced by effective risk management procedures, but patient-to-patient transmission continues to be reported in healthcare settings. To report the use of phylogenetic analysis in the clinical risk management of an HCV outbreak among 128 thalassaemia outpatients followed at a thalassaemia centre of an Italian hospital. Epidemiological investigation and root-cause analysis were performed. All patients with acute hepatitis and known chronic infection were tested for HCV RNA, HCV genotyping, and NS3, NS5A, and NS5B HCV genomic region sequencing. To identify transmission clusters, phylogenetic trees were built for each gene employing Bayesian methods. All patients with acute hepatitis were infected with HCV genotype 1b. Root-cause analysis, including a lookback procedure, excluded blood donors as the source of HCV transmission. The phylogenetic analysis, conducted on seven patients with acute infection and eight patients with chronic infection, highlighted four transmission clusters including at least one patient with chronic and one patient with acute HCV infection. All patients in the same cluster received a blood transfusion during the same day. Two patients with acute hepatitis spontaneously cleared HCV within four weeks and nine patients received ledipasvir plus sofosbuvir for six weeks, all achieving a sustained virological response. Combined use of root-cause analysis and molecular epidemiology was effective in ascertaining the origin of the HCV outbreak. Antiviral therapy avoided the chronic progression of the infection and further spread in care units and in the family environment.

Pathogenesis, MicroRNA-122 Gene-Regulation, and Protective Immune Responses After Acute Equine Hepacivirus Infection.

Background and AimsEquine hepacivirus (EqHV) is phylogenetically the closest relative of HCV and shares genome organization, hepatotropism, transient or persistent infection outcome, and the ability to cause hepatitis. Thus, EqHV studies are important to understand equine liver disease and further as an outbred surrogate animal model for HCV pathogenesis and protective immune responses. Here, we aimed to characterize the course of EqHV infection and associated protective immune responses.Approach and ResultsSeven horses were experimentally inoculated with EqHV, monitored for 6 months, and rechallenged with the same and, subsequently, a heterologous EqHV. Clearance was the primary outcome (6 of 7) and was associated with subclinical hepatitis characterized by lymphocytic infiltrate and individual hepatocyte necrosis. Seroconversion was delayed and antibody titers waned slowly. Clearance of primary infection conferred nonsterilizing immunity, resulting in shortened duration of viremia after rechallenge. Peripheral blood mononuclear cell responses in horses were minimal, although EqHV‐specific T cells were identified. Additionally, an interferon‐stimulated gene signature was detected in the liver during EqHV infection, similar to acute HCV in humans. EqHV, as HCV, is stimulated by direct binding of the liver‐specific microRNA (miR), miR‐122. Interestingly, we found that EqHV infection sequesters enough miR‐122 to functionally affect gene regulation in the liver. This RNA‐based mechanism thus could have consequences for pathology.ConclusionsEqHV infection in horses typically has an acute resolving course, and the protective immune response lasts for at least a year and broadly attenuates subsequent infections. This could have important implications to achieve the primary goal of an HCV vaccine; to prevent chronicity while accepting acute resolving infection after virus exposure.

Infección aguda por el virus de la hepatitis C: ¿en qué personas se está produciendo la transmisión?

ObjectiveTo know the transmission patterns of the acute infection by the hepatitisC virus at a time when we are close to its elimination. Patients and methodsA prospective descriptive clinical-epidemiological study of cases of acute HCV infection diagnosed between 2016 and 2020 was carried out in a reference hospital in the island of Gran Canaria. ResultsTwenty-two cases of acute HCV were diagnosed (10 primary infections and 12 reinfections). There was an increase in the incidence from 0.6 in 2016 and 2017 to 2.3 cases per 100,000 inhabitants in 2020. The median age was 46years. From these, 77.3% were men and 68.2% were HIV-positive. According to the risk factors, 54.5% had high-risk sexual practices, 83.3% were men who had sex with men (70% with a concomitant STI), 31.8% were drug users, 9.1% were women with neuropsychiatric disorders, and one woman (4.5%) had a previous surgical intervention. There were thirteen patients (40.9%) who presented symptoms and eleven out of the thirteen patients who were asymptomatic were HIV-positive. ConclusionsAn increase in incidence was observed in the last years of the study and the main route of infection was high-risk sexual practice, mainly in men who have sex with men and who are HIV positive. Cases related to unsafe sex in other non-HIV groups are probably under-diagnosed. Microelimination strategies may not be sufficient to diagnose these cases, so in order to achieve elimination of the HCV the best strategy would be a population-based screening.

Absence of interferon-λ 4 enhances spontaneous clearance of acute hepatitis C virus genotypes 1-3 infection

Objectives Absence of a functional interferon-λ 4 (IFN-λ4) gene (IFNL4) predicts spontaneous resolution of acute hepatitis C virus (HCV) infections in regions with a predominance of genotype 1, whereas variants of the inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) entailing reduced activity associate with increased sustained virologic response rates following some therapeutic regimens. This study aimed at investigating the impact of IFNL4 on acute HCV genotype 2 or 3 infections, and whether ITPase activity influenced outcome. Materials and Methods Two hundred and seven people who injected drugs (PWID) with documented anti-HCV seroconversion, and 57 PWID with reinfection with HCV were analyzed regarding IFNL4 (rs368234815 and rs12979860) and ITPA (rs1127354 and rs7270101), and longitudinally followed regarding HCV RNA. Results The spontaneous clearance of HCV infection in anti-HCV seronegative PWID was enhanced when IFN-λ4 was absent (44% vs. 20% for IFNL4 TT/TTrs1368234815 and ΔGrs1368234815 respectively, p < .001; OR 3.2) across genotypes 1-3. The proportion lacking IFN-λ4 was further increased following resolution of repeated re-exposure to HCV (74% among re-infected participants who had cleared at least two documented HCV infections). ITPA genetic variants did not independently impact on the outcome, but among males lacking IFN-λ4, reduced ITPase activity markedly augmented the likelihood of resolution (65% vs. 29% for <100% and 100% ITPase activity, p = .006). Conclusions Absence of IFN-λ4 entails an enhanced likelihood of spontaneous resolution both following primary acute infection and repeated re-exposure to HCV across genotypes 1-3. Among men lacking IFN-λ4, reduced ITPase activity improved outcome.

Sofosbuvir/velpatasvir for 12 vs. 6 weeks for the treatment of recently acquired hepatitis C infection

Shortened duration therapy for acute and recent HCV infection has been shown to be highly effective inseveral small non-randomised studies with direct-acting antiviral regimens; however, large randomised studies are lacking. REACT was an NIH-funded multicentre international, open-label, randomised, phase IV non-inferiority trial examining the efficacy of short course (6-week) vs. standard course (12-week) therapy with sofosbuvir-velpatasvir for recent HCV infection (estimated duration of infection ≤12 months). Randomisation occurred at week 6. The primary endpoint was sustained virological response 12 weeks after treatment end (SVR12) in the intention-to treat (ITT) population. A total of 250 participants were due to be enrolled, but on advice of the data safety and monitoring board the study was halted early. The primary analysis population consisted of 188 randomised participants at termination of study enrolment; short arm (n= 93), standard arm (n= 95). Ninety-seven percent were male and 69% HIV positive. ITT SVR12 was 76/93, 81.7% (95% CI 72.4-89.0) in the short arm and 86/95, 90.5% (95% CI 82.7-95.6) in the standard arm. The difference between the arms was -8.8 (95% CI -18.6 to 1.0). In modified ITT analysis, wherein non-virological reasons for failure were excluded (death, reinfection, loss to follow-up), SVR12 was 76/85, 89.4% (95% CI 80.8-95.0) in the short arm and 86/88, 97.7% in the standard arm (95% CI 92.0-99.7; difference -8.3%, p= 0.025). In this randomised study in recent HCV infection, a 6-week course of sofosbuvir-velpatasvir did not meet the criteria for non-inferiority to standard 12-week therapy. In this randomised trial, 188 people with recently acquired hepatitis C infection were randomly assigned to treatment using either a short 6-week course (93 people) or standard 12-week course (95 people) of the hepatitis C treatment sofosbuvir/velpatasvir. There were 9 cases of relapse after treatment with the short course and 2 following the standard course. A shortened course of 6-week therapy for hepatitis C infection appeared to be less effective than a standard 12-week course in people with recently acquired hepatitis C infection. CLINICALTRIALS. NCT02625909.

The Relationship Between Hepatitis C Virus Rates and Office-Based Buprenorphine Access in Ohio.

BackgroundThe United States is experiencing an epidemic of hepatitis C virus (HCV) infections due to injection drug use, primarily of opioids and predominantly in rural areas. Buprenorphine, a medication for opioid use disorder, may indirectly prevent HCV transmission. We assessed the relationship of HCV rates and office-based buprenorphine prescribing in Ohio.MethodsWe conducted an ecological study of the county-level (n = 88) relationship between HCV case rates and office-based buprenorphine prescribing in Ohio. We fit adjusted negative binomial models between the county-level acute and total HCV incidence rates during 2013–2017 and 1) the number of patients in each county that could be served by office-based buprenorphine (prescribing capacity) and 2) the number served by office-based buprenorphine (prescribing frequency) from January–March, 2018.ResultsFor each 10% increase in acute HCV rate, office-based buprenorphine prescribing capacity differed by 1% (95% CI: –1%, 3%). For each 10% increase in total HCV rate, office-based buprenorphine prescribing capacity was 12% (95% CI: 7%, 17%) higher. For each 10% increase in acute HCV rate, office-based buprenorphine prescribing frequency was 1% (95% CI: –1%, 3%) higher. For each 10% increase in total HCV rate, office-based buprenorphine prescribing frequency was 14% (95% CI: 7%, 20%) higher.ConclusionsRural counties in Ohio have less office-based buprenorphine and higher acute HCV rates versus urban counties, but a similar relationship between office-based buprenorphine prescribing and HCV case rates. To adequately prevent and control HCV rates, certain rural counties may need more office-based buprenorphine prescribing in areas with high HCV case rates.

Initial HCV infection of adult hepatocytes triggers a temporally structured transcriptional program containing diverse pro- and anti-viral elements.

Transcriptional profiling provides global snapshots of virus-mediated cellular reprogramming, which can simultaneously encompass pro- and antiviral components. To determine early transcriptional signatures associated with HCV infection of authentic target cells, we performed ex vivo infections of adult primary human hepatocytes (PHHs) from seven donors. Longitudinal sampling identified minimal gene dysregulation at six hours post infection (hpi). In contrast, at 72 hpi, massive increases in the breadth and magnitude of HCV-induced gene dysregulation were apparent, affecting gene classes associated with diverse biological processes. Comparison with HCV-induced transcriptional dysregulation in Huh-7.5 cells identified limited overlap between the two systems. Of note, in PHHs, HCV infection initiated broad upregulation of canonical interferon (IFN)-mediated defense programs, limiting viral RNA replication and abrogating virion release. We further find that constitutive expression of IRF1 in PHHs maintains a steady-state antiviral program in the absence of infection, which can additionally reduce HCV RNA translation and replication. We also detected infection-induced downregulation of ∼90 genes encoding components of the EIF2 translation initiation complex and ribosomal subunits in PHHs, consistent with a signature of translational shutoff. As HCV polyprotein translation occurs independently of the EIF2 complex, this process is likely pro-viral: only translation initiation of host transcripts is arrested. The combination of antiviral intrinsic and inducible immunity, balanced against pro-viral programs, including translational arrest, maintains HCV replication at a low-level in PHHs. This may ultimately keep HCV under the radar of extra-hepatocyte immune surveillance while initial infection is established, promoting tolerance, preventing clearance and facilitating progression to chronicity.IMPORTANCEAcute HCV infections are often asymptomatic and therefore frequently undiagnosed. We endeavored to recreate this understudied phase of HCV infection using explanted PHHs and monitored host responses to initial infection. We detected temporally distinct virus-induced perturbations in the transcriptional landscape, which were initially narrow but massively amplified in breadth and magnitude over time. At 72 hpi, we detected dysregulation of diverse gene programs, concurrently promoting both virus clearance and virus persistence. On the one hand, baseline expression of IRF1 combined with infection-induced upregulation of IFN-mediated effector genes suppresses virus propagation. On the other, we detect transcriptional signatures of host translational inhibition, which likely reduces processing of IFN-regulated gene transcripts and facilitates virus survival. Together, our data provide important insights into constitutive and virus-induced transcriptional programs in PHHs, and identifies simultaneous antagonistic dysregulation of pro-and anti-viral programs which may facilitate host tolerance and promote viral persistence.

An Outbreak of Hepatitis C Virus Infection Among Transfused Thalassemia Patients: Root Cause Analysis, Phylogenetic Epidemiology and Antiviral Therapy

Background: Occurrence of HCV infection is reduced by effective risk management procedures, but patient-to-patient transmission continues to be reported in healthcare settings. We report an outbreak of 11 patients with HCV acute hepatitis (seven new infections and four re-infections) among 128 thalassemia patients followed at a Hospital in Sicily. Methods All patients with acute hepatitis and known chronic infection were tested for HCV-RNA, HCV genotyping, and NS3, NS5A and NS5B HCV-genomic regions sequencing. To identify transmission clusters we built phylogenetic trees for each gene employing Bayesian methods. Findings All patients with acute hepatitis were infected with HCV genotype 1b. Root-cause analysis, including a lookback procedure, led us to exclude blood donors as the source of HCV transmission. The phylogenetic analysis, conducted on seven patients with acute infection and eight patients with chronic infection, highlighted four transmission clusters including at least one patient with chronic and one patient with acute HCV infection. All patients in the same cluster received a blood transfusion at the Thalassemia Unit during the same day. Two patients with acute hepatitis spontaneously cleared HCV within four weeks and nine patients received ledipasvir plus sofosbuvir for six weeks, all achieving a sustained virological response. Interpretation Combined use of root cause analysis and molecular epidemiology was effective in ascertaining the origin of the HCV outbreak. Antiviral therapy avoided the chronic progression of the infection and further spread in care units and in the family environment. Funding Regional Health System of Sicily and by the Italian Ministry of Health (RF-2016-02362422). Declaration of Interest: V.D.M received speaking and/or consulting fees by Abbvie, Gilead, MSD, Intercept. F.C-S. received speaking and/or consulting fees by Abbvie, Gilead, Janssen, Merck/MSD, ViiV . All other authors have nothing to declare. Ethical Approval: This study was conducted in agreement with the Helsinki Declaration. Since the available DAAs were not licensed for acute hepatitis, the regional health authorities and local ethics committee authorized DAA therapy in patients with diagnosis of acute hepatitis

False Positive Hepatitis C Virus Serologies in Pediatric Patients with Left Ventricular Assist Devices

Introduction Left ventricular assist devices (LVAD) are being used more frequently in pediatric patients with advanced heart failure as a bridge to transplant. Pediatric centers began implanting the HeartMate 3 LVAD in 2017 and it has become the LVAD of choice at many centers, including our own. Allosensitization is commonly observed after LVAD placement, resulting in higher frequencies of auto-antibodies, though the pathophysiology of this phenomenon is not well understood. Viral hepatitis screening is done prior to transplant, but there are no current guidelines on type of testing and timing with regards to LVAD placement. Case Report Three pediatric patients, aged 7-12 years old, each received an LVAD as bridge to orthoptic heart transplant (OHT) between May 2019 - September 2020. All were otherwise healthy and had negative hepatitis C (HCV) antibody tests prior to Heartmate 3 LVAD placement as part of the pre-transplant infectious work up. Repeat HCV serologic testing obtained shortly before cardiac transplant were positive in all three patients. The patients had no signs or symptoms of acute HCV infection, received infrequent blood transfusions between LVAD placement and OHT, and had no increased risk behaviors. Concurrent HCV quantitative PCR testing was done in two patients and both were negative. HCV antibody testing repeated within six weeks from LVA removal was negative in all three patients. Summary False positive HCV serology secondary to immunogenicity of LVADs has been described in adult literature. Our case series is the first, to our knowledge, to be described in pediatric patients. Adult data suggests that the false positive HCV serology can occur in 16-59% of cohorts post-LVAD. This is thought to be due to immunogenicity of the LVAD as serologies revert after the LVAD is explanted. Our experience demonstrates the importance of standardizing HCV testing in patients both pre- and post-LVAD as a bridge to OHT. Furthermore, acquisition of hepatitis C infection is rare in children and pediatric cardiac transplant providers should be aware of the possibility of false positive HCV antibody tests in this clinical scenario and the importance of confirmatory testing with quantitative PCR if concerned.

The Changing Epidemiology of Hepatitis C Virus Infection in the United States During the Years 2010 to 2018.

Hepatitis C virus (HCV) infection remains an important cause of morbidity and mortality throughout the world, leading to serious health problems among those who are chronically infected. Since 1992, the Centers for Disease Control and Prevention has been collecting data on the incidence of HCV infection in the United States. In 2018, more than 50 000 individuals were estimated to have acute HCV infection.The most recently reported data on the prevalence of infection indicate that approximately 2.4 million people are living with hepatitis C in the United States. Transmission of HCV occurs predominantly through sharing contaminated equipment for injecting drugs.Two major events have had a significant impact on the incidence and prevalence of hepatitis C in the past few decades: the US opioid crisis and the discovery of curative treatments for HCV infection. To better understand the impact of these events, we examine reported trends in the incidence and prevalence of infection.

Predictors of Mid-Term Glomerular Filtration Rate after Deceased Donor Renal Transplantation: Kidney Donor Profile Index as a Predictor of Mid-Term GFR

Glomerular filtration rate (GFR) is an excellent indicator of renal function; however, it is rarely evaluated as an endpoint. We investigated donor and recipient factors for associations that might be predictive of mid-term GFR after renal transplantation. We performed a retrospective review of 828 deceased donor renal transplantations performed at Montefiore Medical Center between the years 2009-2015. Donor characteristics included KDPI, [low (&lt;20%), medium (20-80%), high (&gt;80%)], age, graft types [extended criteria (ECD), cardiac death (DCD), standard criteria (SCD)], CDC high risk, HCV status and cold ischemic time (CIT). Recipient factors included age at transplant, induction agent, BK status, CMV status, acute and chronic rejection, cPRA and DSA status. Primary outcome is 3-year GFR calculated via the MDRD equation. In univariate analysis, donor age, KDPI, ECD, and chronic rejection were significantly associated with changes in 3-year GFR (p&lt;0.001). In the multivariable regression analysis, donor age, KDPI, and chronic rejection remained associated with changes in 3-year GFR (p&lt;0.001). Acute rejection, DCD, HCV status, CIT, BK and CMV viremia, PRA, pretransplant or de novo DSA were not associated with changes in 3-year GFR (p&gt;0.05). We conclude that donor age, KDPI, and chronic rejection are independently associated with 3-year GFR while acute rejection, DCD, HCV status, CIT, BK and CMV viremia, PRA, existing or de novo DSA were not. Based on these findings, current scoring systems may need refinement to address the prognosis of mid-term GFR.

Long-Lasting Imprint in the Soluble Inflammatory Milieu Despite Early Treatment of Acute Symptomatic Hepatitis C.

BackgroundTreatment with direct-acting antivirals (DAAs) in patients with chronic hepatitis C infection leads to partial restoration of soluble inflammatory mediators (SIMs). In contrast, we hypothesized that early DAA treatment of acute hepatitis C virus (HCV) with DAAs may normalize most SIMs.MethodsIn this study, we made use of a unique cohort of acute symptomatic hepatitis C patients who cleared HCV with a 6-week course of ledipasvir/sofosbuvir. Plasma samples were used for proximity extension assay measuring 92 proteins.ResultsProfound SIM alterations were observed in acute HCV patients, with marked upregulation of interleukin (IL)-6 and CXCL-10, whereas certain mediators were downregulated (eg, monocyte chemoattractant protein-4, IL-7). During treatment and follow-up, the majority of SIMs decreased but not all normalized (eg, CDCP1, IL-18). Of note, SIMs that were downregulated before DAA treatment remained suppressed, whereas others that were initially unchanged declined to lower values during treatment and follow-up (eg, CD244).ConclusionsAcute hepatitis C was associated with marked changes in the soluble inflammatory milieu compared with both chronic hepatitis patients and healthy controls. Whereas early DAA treatment partly normalized this altered signature, long-lasting imprints of HCV remained.

Viral Hepatitis C: Epidemiology, ­Pathogenesis, Transmission, And ­Natural History

Chronic infection with the hepatitis C virus (HCV) remains a significant global health issue, with more than 71 million infected worldwide and accounting for over 720,000 deaths annually in the United States alone. It can be associated with significant liver-related morbidity and mortality owing to complications from cirrhosis and end-stage liver disease. The aging HCV population, together with changing patterns of drug use, has seen an increase in these complications of HCV and an increase in the number of acute HCV infections. Screening and managing complications of chronic hepatitis C are an important consideration. The changing epidemiology, risk factors, transmission, diagnosis, natural history (including complications) and patient evaluation and education are discussed. This review contains 4 figures, 2 tables, and 70 references Key words: epidemiology, hepatitis C virus, transmission, risk factors, natural history, patient education, evaluation

Viral Hepatitis C: Epidemiology, ­Pathogenesis, Transmission, And ­Natural History

Chronic infection with the hepatitis C virus (HCV) remains a significant global health issue, with more than 71 million infected worldwide and accounting for over 720,000 deaths annually in the United States alone. It can be associated with significant liver-related morbidity and mortality owing to complications from cirrhosis and end-stage liver disease. The aging HCV population, together with changing patterns of drug use, has seen an increase in these complications of HCV and an increase in the number of acute HCV infections. Screening and managing complications of chronic hepatitis C are an important consideration. The changing epidemiology, risk factors, transmission, diagnosis, natural history (including complications) and patient evaluation and education are discussed. This review contains 4 figures, 2 tables, and 70 references Key words: epidemiology, hepatitis C virus, transmission, risk factors, natural history, patient education, evaluation

Viral Hepatitis C: Epidemiology, ­Pathogenesis, Transmission, And ­Natural History

Chronic infection with the hepatitis C virus (HCV) remains a significant global health issue, with more than 71 million infected worldwide and accounting for over 720,000 deaths annually in the United States alone. It can be associated with significant liver-related morbidity and mortality owing to complications from cirrhosis and end-stage liver disease. The aging HCV population, together with changing patterns of drug use, has seen an increase in these complications of HCV and an increase in the number of acute HCV infections. Screening and managing complications of chronic hepatitis C are an important consideration. The changing epidemiology, risk factors, transmission, diagnosis, natural history (including complications) and patient evaluation and education are discussed. This review contains 4 figures, 2 tables, and 70 references Key words: epidemiology, hepatitis C virus, transmission, risk factors, natural history, patient education, evaluation

Early T follicular helper cell activity accelerates hepatitis C virus-specific B cell expansion.

Early appearance of neutralizing antibodies during acute hepatitis C virus (HCV) infection is associated with spontaneous viral clearance. However, the longitudinal changes in antigen-specific memory B cell (MBCs) associated with divergent HCV infection outcomes remain undefined. We characterized longitudinal changes in E2 glycoprotein-specific MBCs from subjects who either spontaneously resolved acute HCV infection or progressed to chronic infection, using single-cell RNA-seq and functional assays. HCV-specific antibodies in plasma from chronically infected subjects recognized multiple E2 genotypes, while those from spontaneous resolvers exhibited variable cross-reactivity to heterotypic E2. E2-specific MBCs from spontaneous resolvers peaked early after infection (4-6 months), following expansion of activated circulating T follicular helper cells (cTfh) expressing interleukin 21. In contrast, E2-specific MBCs from chronically infected subjects, enriched in VH1-69, expanded during persistent infection (> 1 year), in the absence of significantly activated cTfh expansion. Early E2-specific MBCs from spontaneous resolvers produced monoclonal antibodies (mAbs) with fewer somatic hypermutations and lower E2 binding but similar neutralization as mAbs from late E2-specific MBCs of chronically infected subjects. These findings indicate that early cTfh activity accelerates expansion of E2-specific MBCs during acute infection, which might contribute to spontaneous clearance of HCV.

Discovery and Development of Antiviral Therapies for Chronic Hepatitis C Virus Infection.

At the beginning of this decade, an estimated 71 million people were living with chronic hepatitis C virus (HCV) infection worldwide. After the acute stage of HCV infection, 18-34% of individuals exhibit spontaneous clearance. However, the remaining 66-82% of infected individuals progress to chronic HCV infection and are at subsequent risk of progression to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Chronic hepatitis C progression is generally slow during the first two decades of infection, but can be accelerated during this time in association with advancing age and cofactors, such as heavy alcohol intake and human immunodeficiency virus (HIV) co-infection. Since acute HCV infection is generally asymptomatic, HCV goes undiagnosed in a significant percentage of infected individuals. In 2014, direct-acting antiviral (DAA) therapy for chronic HCV was developed, which has increased the cure rates to nearly 100%. DAA therapy is among the best examples of success in the fight against viral infections. DAAs have transformed HCV management and have opened the door for the global eradication of HCV.

Acute Hepatitis C Virus Infections in Spouses: The Utility of a Genetic Analysis of the Hepatitis C Virus Hypervariable Region Sequence for Identifying the Infectious Source

A married couple who developed hepatitis was referred to our hospital. The husband was diagnosed with acute hepatitis C virus (HCV) infection based on HCV RNA positivity and seroconversion to HCV antibody. The wife was also diagnosed with HCV-related hepatitis; however, she could not be confirmed to have acute hepatitis due to the lack of information on her HCV negativity just before this event. The HCV strains recovered from the couple were genotype 2b and shared 100% identities within the 5’-untranslated region-core region sequence (655 nucleotides/nt) and non-structural (NS)5B region sequence (502 nt). The amplified hypervariable region 1 (HVR-1) sequence indicated that all 10 clones from the wife shared 100% identity and were identical to 3 of 10 heterogeneous clones (separable into 4 groups) from the husband. The husband had a history of intravenous drug use. These results suggested that one of four quasispecies 2b HCV strains was transmitted from the husband to the wife, with the husband being the infectious source for acute HCV infection in the wife, most likely via sexual intercourse. A sequence analysis of the HCV genomes and the further comparison of the HVR-1 amino acid sequence variability may be useful for defining the infectious source of HCV, especially in couples or cluster cases.

1053. The Ecological Relationship Between County-Level HCV Case Rates and Office-Based Buprenorphine in Ohio

BackgroundThe United States is experiencing an epidemic of hepatitis C virus (HCV) infections due to injection drug use, especially in rural areas. Counties may be expanding access to buprenorphine, an evidence-based treatment that has been shown to reduce injection drug use, to control the HCV epidemic. We assessed the county-level relationship between HCV rates in 2013-2015 and office-based buprenorphine prescribing in 2018 in Ohio. We also assessed if this relationship varied between rural and urban counties.MethodsWe fit crude and adjusted negative binomial models to assess the relationship between HCV incidence rates in 2013-2015 and office-based buprenorphine prescribing capacity and frequency in Ohio in 2018. We examined effect measure modification of this relationship by rural-urban status using an interaction term.ResultsWe found that a 1% higher acute HCV rate was associated with an 18% (95% Confidence Interval [CI]: -3%, 44%) higher office-based buprenorphine prescribing capacity and an 22% (95% CI: -4%, 55%) higher office-based buprenorphine prescribing frequency. We found that a 1% higher total HCV rate was associated with a 239% (95% CI: 179%, 317%) higher office-based buprenorphine prescribing capacity and a 273% (95% CI: 183%, 405%) higher office-based buprenorphine prescribing frequency. We found no evidence of effect measure modification by rural-urban status.ConclusionCounties across Ohio may have expanded access to office-based buprenorphine in response to high rates of total HCV. Expansion of office-based buprenorphine may be less associated with acute HCV rates due to the low frequency with which these cases are seen in outpatient settings.Disclosures All Authors: No reported disclosures

1073. The Time is Now for Rapid Initiation of Hepatitis C Virus (HCV) Treatment

BackgroundAn estimated 65,000 New Mexicans are infected with HCV, accounting for ~3% of the state’s population with intravenous drug use being the most common risk factor for the acquisition of HCV. In 2020, the US Preventive Service Task Force recommended universal HCV screening for all adults aged 18 to 79 years old. HCV screening requires a two-step process involving a HCV antibody (Ab) test followed by a confirmatory HCV ribonucleic acid (RNA) test to detect active infection. Acute HCV infections are typically asymptomatic leaving many individuals unaware of their diagnosis for years. New Mexico was one of the first states to abandon the requirement for specialist referral, fibrosis staging, and abstinence from substance abuse to facilitate HCV treatment. Despite removal of these barriers, major gaps in access to HCV treatment still persist. The objective was to develop a HCV connect-to-care cascade for the University of New Mexico Hospital (UNMH) to understand the potential barriers preventing patients from receiving appropriate care.MethodsThis was a retrospective, single center, descriptive study conducted at UNMH, a level 1 trauma, tertiary care academic medical center with 527 beds. All patients with a positive HCV Ab, RNA, or genotype obtained in 2018 were included in this study. There were no exclusions.ResultsIn 2018, over 11,000 unique patients received HCV testing in any form resulting in a total of 14,566 HCV tests being performed.2018 UNMH Connect-to-Care Cascade ConclusionOf the patients who screened positive, only 61.7% were referred for treatment, representing the largest gap in the cascade. However, once patients were seen in the clinic, 88.5% completed treatment with 100% having sustained virologic response (SVR). With the pan-genotypic HCV treatments having fewer side effects and high clinical success rates, it’s feasible that HCV treatment may no longer require a specialist. Similar to the rapid initiation of antiretrovirals in newly diagnosed HIV patients, where immediate access to treatment within days of diagnosis resulted in improved retention in care, decreased time to viral suppression, and decreased viral transmission, rapid initiation of HCV treatment may be the wave of the future.Disclosures All Authors: No reported disclosures