Acute Hepatitis C Virus Research Articles

Enhancing Surveillance Protocols for Acute Hepatitis C Virus Infection, Utah, 2014-2019.

During 2014-2019, the Utah Department of Health (UDOH) enhanced its surveillance program for acute hepatitis C virus (HCV) infections by mandating electronic reporting of negative HCV test results in 2015 and liver function test results in 2016. UDOH also engaged with blood and plasma donation centers beginning in 2014 and syringe exchange programs in 2018 to encourage manual reporting of negative HCV test results from facilities without electronic reporting capabilities. UDOH hepatitis surveillance staff also provided training for case investigations in 2017. The number of cases detected increased 14-fold, from 9 during 2012 to 127 during 2019. In 2019, of 127 cases, 55% (n = 70) were detected through negative HCV test results reported electronically before positive test results (ie, recent seroconversions), 25% (n = 32) through positive HCV test results and elevated liver function test results, 18% (n = 23) through manually reported negative HCV test results, and 2% (n = 2) through positive HCV test results and clinical evidence. Challenges to surveillance included accessing patients for investigations and engaging donation centers in reporting negative test results. Utah's experience demonstrates practical considerations for improving surveillance of acute HCV infections.

Internet‐guided HCV‐RNA testing: A promising tool to achieve hepatitis C micro‐elimination among men who have sex with men

In the Netherlands, hepatitis C virus (HCV) transmission occurs primarily in men who have sex with men (MSM). By early diagnosis and immediate treatment of acute HCV infections, HCV micro‐elimination in MSM is within reach. In cooperation with the community affected, we developed an online HCV‐RNA home‐based self‐sampling test service. This service combined online HCV self‐risk assessment with the possibility to test anonymously for HCV‐RNA. The service was available in the Netherlands from February 2018 till December 2020 and was promoted online on various dating sites and offline by community volunteers. Using website user data, test results and an online post‐test user survey, we evaluated the service and user experiences. The website page with information about testing was visited by 3401 unique users, of whom 2250 used the HCV‐risk assessment tool, 152 individuals purchased 194 HCV‐RNA tests, and 104 tests were used, of which 101 gave a conclusive result. The target population of MSM at risk was successfully reached with 44.1% of users receiving the advice to test. The test service had a satisfactory uptake (6.8%, 152/2250), a very high HCV‐RNA positivity rate (10.9%, 11/101) and was considered acceptable and easy to use by most MSM.We demonstrate that an HCV‐RNA home‐based self‐sampling test service is successful in diagnosing HCV infections among MSM. This service could be a valuable addition to existing sexual healthcare services as it may reach men who are otherwise not tested.

Performance of Hepatitis C Virus (HCV) Core Antigen Assay in the Diagnosis of Recently Acquired HCV Infection among High-Risk Populations.

ABSTRACTHow the hepatitis C virus (HCV) core antigen (HCVcAg) assay performs in detecting recently acquired HCV infection among people living with HIV (PLWH) and HIV-negative men who have sex with men (MSM) is rarely assessed in the Asia-Pacific region. High-risk participants, including PLWH with sexually transmitted infections (STIs), HCV clearance by antivirals or spontaneously, or elevated aminotransferases, HIV-negative MSM with STIs or on HIV preexposure prophylaxis, and low-risk PLWH were enrolled. Blood samples were subjected to 3-stage pooled-plasma HCV RNA testing every 3 to 6 months until detection of HCV viremia or completion of the 1-year follow-up. The samples at enrollment and all of the archived samples preceding the detection of HCV RNA during follow-up were tested for HCVcAg. During June 2019 and February 2021, 1,639 blood samples from 744 high-risk and 727 low-risk PLWH and 86 HIV-negative participants were tested for both HCV RNA and HCVcAg. Of 62 samples positive for HCV RNA, 54 (87.1%) were positive for HCVcAg. Of 1,577 samples negative for HCV RNA, 1,568 (99.4%) were negative for HCVcAg. The mean HCV RNA load of the 8 individual samples positive for HCV RNA but negative for HCVcAg was 3.2 (range, 2.5 to 3.9) log10 IU/mL, and that of the remaining 54 samples with concordant results was 6.2 (range, 1.3 to 8.5) log10 IU/mL. The positive predictive value (PPV) and negative predictive value (NPV) of HCVcAg were 85.7% and 99.5%, respectively. In at-risk populations, HCVcAg has a high specificity and NPV but lower sensitivity and PPV, particularly in individuals with low HCV RNA loads.IMPORTANCE The HCV core antigen assay has a high specificity of 99.4% and negative predictive value of 99.5% but a lower sensitivity of 87.1% and positive predictive value of 85.7% in the diagnosis of recently acquired HCV infection in high-risk populations. Our findings are informative for many countries confronted with limited resources to timely identify acute HCV infections and provide effective direct-acting antivirals to halt onward transmission.

Three-Stage Pooled Plasma Hepatitis C Virus RNA Testing for the Identification of Acute HCV Infections in At-Risk Populations.

ABSTRACTTimely diagnosis and treatment of hepatitis C virus (HCV) infection may prevent its transmission. We evaluated the performance and cost reductions of the pooled plasma HCV RNA testing strategy to identify acute HCV infections among people living with HIV (PLWH). PLWH with sexually transmitted infections, elevated aminotransferases within the past 6 months or past HCV infections (high-risk) and those without (low-risk) were enrolled prospectively. Participants underwent three-stage pooled plasma HCV RNA testing every 12 to 24 weeks until detection of HCV RNA or completion of a 48-week follow-up. The three-stage strategy combined 20 individual specimens into a stage 1 pool, 5 individual specimens from the stage 1 pool that tested positive for HCV RNA in the stage 2 mini-pool, followed by testing of individual specimens of the stage 2 mini-pool tested positive for HCV RNA. A simulation was constructed to investigate the cost reductions and pooled sensitivity and specificity under different combinations of HCV prevalence and pool/mini-pool sizes. Between June 25, 2019 and March 31, 2021, 32 cases of incident HCV viremia were identified in 760 high-risk PLWH that were enrolled 834 times, giving an incidence rate of 56.6 per 1000 person-years of follow-up (PYFU). No cases of HCV viremia were identified in 557 low-risk PLWH during a total of 269.2 PYFU. Simulation analysis suggested that this strategy could reduce HCV RNA testing cost by 50% to 86% with HCV viremia prevalence of 1% to 5% and various pooled sizes despite compromised pooled sensitivity. This pooled plasma HCV RNA testing strategy is cost-saving to identify acute HCV infections in high-risk populations with HCV viremia prevalence of 1% to 5%.IMPORTANCE Our three-stage pooled plasma HCV RNA testing successfully identified HCV viremia in high-risk PLWH with a testing cost reduction of 84.5%. Simulation analysis offered detailed information regarding the selection of pool and mini-pool sizes in settings of different HCV epidemiology and the performance of HCV RNA testing to optimize the cost reduction.

Genotype Distribution and Demographic Characteristics of Hepatitis C Virus Nucleic Acid Testing Yield Cases Among US Blood Donors.

Hepatitis C virus (HCV) infection rates among US blood donors have been well characterized; however, few studies evaluated HCV genotypes among blood donors. Monitoring trends in disease and demographic patterns contributes to understanding the safety of the blood supply. We examined the demographic characteristics and distribution of HCV genotypes/subgenotypes for nearly a 16-year period among blood donors confirmed positive for HCV RNA but antibody negative (defined as nucleic acid testing [NAT] yield). A retrospective assessment of demographic characteristics and testing data was used to determine temporal trends and geographical distribution of HCV genotypes/subgenotypes among American Red Cross blood donors confirmed positive as HCV-NAT yield. From 2003-2018, 343 donors (0.38/100 000 donations; 95% CI, .35-.43) were confirmed positive as HCV-NAT-yield cases. Temporal analysis revealed a significant increase in HCV-NAT-yield cases of 54.1% between 2009 and 2014 (P = .014), followed by a significant decline of 31.4% between 2015 and 2018 (P = .002). Significantly more HCV-NAT-yield cases were detected among first-time donors, non-Hispanic Whites, donors aged 20-29 years, equally likely to be males as females, with the highest frequency in the South (0.52/100 000 donations). Subgenotype 1a (49.6%) was most frequent, followed by 3a (18.7%), 2b (12.5%), 1b (8.5%), and 2a (1.7%). Voluntary nonremunerated blood donors are at low risk for HCV infection. Since 2015, the frequency of HCV-NAT-yield cases decreased despite an increase in acute HCV infection in the general population. HCV subgenotypes 1a and 3a continue to remain predominant among US blood donors with recent HCV infection.

Cardiac Allograft Vasculopathy in Heart Transplant Recipients from Hepatitis C Viremic Donors, Data from Two Large Academic Transplant Centers

<h3>Purpose</h3> Heart transplantation from Hepatitis C (HCV) viremic donors is an increasingly utilized strategy, though long-term outcomes with respect to cardiac allograft vasculopathy (CAV) are unknown. HCV is implicated as a potent trigger of the inflammatory cascade and may be associated with CAV. We report the incidence of CAV and subclinical disease in recipients of HCV-viremic donors (nucleic amplification test positive: NAT+) vs non-viremic donors (nucleic amplification test negative: NAT-) <h3>Methods</h3> We retrospectively reviewed coronary angiograms with intravascular ultrasound (IVUS) of patients who received NAT+ and NAT- hearts between January 2014 and July 2020 at two large academic institutions. Donor-derived acute HCV infection was treated with a direct-acting antiviral agent per site protocol. CAV was graded according to ISHLT guidelines. Maximal intimal thickness (MIT) of the left main and left anterior descending artery was measured by IVUS. MIT ≥ 0.5mm was considered significant subclinical disease. Two-sample t tests were performed for continuous variables. Chi-square or Fisher's exact test were used for categorical variables. <h3>Results</h3> Among 178 patients, 65 received NAT+ donor hearts. Average recipient age was 58 and 55 years in the NAT+ and NAT- groups respectively and 15% vs 27% were female. NAT- donors were older (42 vs 36 years), but with no significant difference in cardiac risk factors including tobacco use, hypertension, and diabetes. CAV ≥ grade 1 was present in 9.1% of the NAT+ vs 18.8% of the NAT- group at 1 year (p=0.16), and 19.4% vs 21.0% at 2 years (p=1). Rates of significant IVUS disease were 53.7% in NAT+ vs 70.5% in NAT- at 1 year (p=0.068), and 72.2% vs 78.3% at 2 years (p=0.3). <h3>Conclusion</h3> Among heart transplant recipients from HCV viremic donors our data show no difference in rates of angiographic CAV or subclinical disease by IVUS at 1 or 2 years. While these results are encouraging, longer follow up is needed to assess CAV risk in this population.

The 'Viennese epidemic' of acute HCV in the era of direct-acting antivirals.

The recently reported epidemic of acute hepatitis C virus (HCV) infections —observed predominantly among men who have sex with men (MSM)—may now decline due to wide availability of direct‐acting antivirals (DAAs). This study aimed to investigate the current trends of acute hepatitis C in Vienna. Patients presenting with acute hepatitis C between 01/2007 and12/2020 at the Vienna General Hospital were retrospectively enrolled and followed after virologic clearance/eradication. The introduction of unrestricted DAA access after 09/17 defined the ‘DAA era’, as compared to the ‘pre‐DAA era’ prior to 09/17. We identified 134 acute hepatitis C cases in 119 patients with a mean age of 39 ± 9 years at inclusion. The majority of patients were male (92%), HIV‐positive (88%) and MSM (85%). In the DAA era, a history of prior chronic HCV infection at inclusion was found in 24% (11/46) compared to 7% (5/73) in the pre‐DAA era (p = .012). The annual rate of acute hepatitis C cases increased in the DAA era (17.11 per year) compared to the pre‐DAA era (7.76 per year). The DAA era included an AHC‐genotype‐2 cluster and more HIV‐negative acute hepatitis C cases (0% (0/73) vs. 30% (14/46), p < .001). Patients were followed after spontaneous clearance or sustained virologic treatment response (SVR) for a total of 251.88 patient‐years (median 1.39 years per patient). In the DAA era, we recorded 15 acute hepatitis C‐reinfections — corresponding to an incidence rate of 5.96 (95% CI: 3.57–9.66) reinfections per 100‐patient‐years. We continue to observe a high incidence of acute hepatitis C in Vienna in the DAA era—primarily among HIV‐positive MSM, but increasingly also in HIV‐negative MSM.

Global incidence and mortality of hepatitis B and hepatitis C acute infections, cirrhosis and hepatocellular carcinoma from 2010 to 2019.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) contribute to significant healthcare burden globally. We aim to provide an updated and comprehensive analysis of global trends in the incidence and mortality of HBV and HCV related acute infections, cirrhosis and hepatocellular carcinoma (HCC). Estimates of annual cause-specific disease incidence and mortality for HBV and HCV were analysed using the 2010-2019 Global Burden of Diseases, Injuries and Risk Factors Study database. Three distinct disease states were evaluated: acute infections, cirrhosis and HCC. Age-standardized disease incidence and mortality were presented per 100,000 population and stratified by age, sex, year and 21 world regions. From 2010 to 2019, overall incidence of acute HBV declined by 19.3% (95% CI 4.1-32.0, p<.05) and HBV cirrhosis declined by 15.0% (95% CI 9.8-20.7, p<.05). Incidence of HCV cirrhosis increased by 5.6% (95% CI 0.3-10.2, p<.05) and HCV HCC remained stable. Incidence of acute HCV declined until 2015, after which it began increasing. From 2010 to 2019, overall mortality for HBV cirrhosis and HCV cirrhosis declined, whereas mortality for acute infections and HCC remained stable. Major differences in HBV and HCV incidence and mortality trends were observed when stratified by world regions. In conclusion, while our analyses of global trends in HBV and HCV incidence and mortality demonstrate encouraging trends, disparities in disease epidemiology were observed across world regions. These observations will identify regions and populations where greater focus and resources are needed to continue progressing towards viral hepatitis elimination.

The HCV Envelope Glycoprotein Down-Modulates NF-κB Signalling and Associates With Stimulation of the Host Endoplasmic Reticulum Stress Pathway.

Following acute HCV infection, the virus establishes a chronic disease in the majority of patients whilst few individuals clear the infection spontaneously. The precise mechanisms that determine chronic HCV infection or spontaneous clearance are not completely understood but are proposed to be driven by host and viral genetic factors as well as HCV encoded immunomodulatory proteins. Using the HIV-1 LTR as a tool to measure NF-κB activity, we identified that the HCV E1E2 glycoproteins and more so the E2 protein down-modulates HIV-1 LTR activation in 293T, TZM-bl and the more physiologically relevant Huh7 liver derived cell line. We demonstrate this effect is specifically mediated through inhibiting NF-κB binding to the LTR and show that this effect was conserved for all HCV genotypes tested. Transcriptomic analysis of 293T cells expressing the HCV glycoproteins identified E1E2 mediated stimulation of the endoplasmic reticulum (ER) stress response pathway and upregulation of stress response genes such as ATF3. Through shRNA mediated inhibition of ATF3, one of the components, we observed that E1E2 mediated inhibitory effects on HIV-1 LTR activity was alleviated. Our in vitro studies demonstrate that HCV Env glycoprotein activates host ER Stress Pathways known to inhibit NF-κB activity. This has potential implications for understanding HCV induced immune activation as well as oncogenesis.

Geographic Variation in the Utilization of HCV-viremic Donors into HCV-negative Recipients

We read with great interest the article by Cotter et al1 in which they identified that the practice of liver transplantation (LT) from hepatitis C virus (HCV)-viremic donors to HCV-negative recipients (D HCV+/R−) has increased with notable geographic variation. While the authors should be congratulated on a substantial effort, we wish to place emphasis on several points to place their studies in the proper context. First, the geographic variation is driven by a variety of factors. As the authors described, the rate of acute HCV infections in each geographic region appeared to be concordant with the practice of D HCV+/R−. However, that alone does not account for the variation in geographic utilization. Da et al2 reported a regional difference of 59.7% to 84.2% in conversion rates of HCV donors from the potential to actually used donors, likely reflective of regional experience and institutional policies. In addition, marginal grafts in LT such as those from old donors3 and donation after circulatory death (DCD)4 are known to show geographical and center differences in their utilization. The geographical variation in the practice of D HCV+/R− likely derives from a combination of these factors. Second, “racial disparity” in the practice of D HCV+/R− is prone to be influenced by several factors. The proportion of Caucasian recipients in the D HCV+/R− was significantly higher than other ethnic groups, which “raises the possibility of racial disparity” in authors’ study.1 However, additional demographics are important to take into consideration. The proportions of Caucasians as donors, not only as recipients, in the D HCV+/R− group was significantly higher, which could arise from the geographic variation. In addition, this study examined recipients without evidence of HCV infection. Liver disease cause varies on the waiting list by race: Caucasians make up 93.2% of HCV− LT candidates, whereas African Americans account for 79.8%.5 These characteristics could have influenced the differences of race in the D HCV+/R− practice. Nonetheless, more research is warranted to explore this important observation. Finally, there seems to be a causal relationship between the practice of D HCV+/R− and median Model for End-Stage Liver Disease (MELD) scores. The highly utilizing regions are “among the regions with the lowest median MELD scores.” Among the regions with the lowest rates of the D HCV+/R− practices, “regions 4 and 7 have many of the states with higher waitlist mortality rates.” The authors conclude that higher utilization of D HCV+/R− may improve waitlist mortality and decrease median MELD scores. However, the practice of using other marginal grafts showed different patterns. The majority of elderly donors were used in region 9, where waiting times and MELD scores are among the highest.3 Region 4 has significantly increased the DCD LT utilization.4 These results suggest that factors other than the practice of marginal grafts also play a role in median MELD scores and waiting list mortality. Despite these critiques, LT from HCV-viremic donors is a promising strategy to expand donor pool. Further detailed investigations in long-term outcomes and patient selection criteria would be helpful to further advance the practice of LT from HCV-viremic donors.

Peripheral blood iNKT cell activation correlates with liver damage during acute hepatitis C.

Invariant NK T (iNKT) cells are implicated in viral clearance; however, their role in hepatitis C virus (HCV) infection remains controversial. Here, iNKT cells were studied during different stages of HCV infection. iNKT cells from patients with acute HCV infection and people who inject drugs (PWID) with chronic or spontaneously resolved HCV infection were characterized by flow cytometry. In a longitudinal analysis during acute HCV infection, frequencies of activated CD38+ iNKT cells reproducibly declined in spontaneously resolving patients, whereas they were persistently elevated in patients progressing to chronic infection. During the first year of infection, the frequency of activated CD38+ or CD69+ iNKT cells strongly correlated with alanine transaminase levels with particularly pronounced correlations in spontaneously resolving patients. Increased frequencies of activated iNKT cells in chronic HCV infection were confirmed in cross-sectional analyses of PWID with chronic or spontaneously resolved HCV infection; however, no apparent functional differences were observed with various stimulation protocols. Our data suggest that iNKT cells are activated during acute hepatitis C and that activation is sustained in chronic infection. The correlation between the frequency of activated iNKT cells and alanine transaminase may point toward a role of iNKT cells in liver damage.

Imprint of unconventional T-cell response in acute hepatitis C persists despite successful early antiviral treatment.

Unconventional T cells (UTCs) are a heterogeneous group of T cells that typically exhibit rapid responses toward specific antigens from pathogens. Chronic hepatitis C virus (HCV) infection causes dysfunction of several subsets of UTCs. This altered phenotype and function of UTCs can persist over time even after direct-acting antiviral (DAA)-mediated clearance of chronic HCV. However, it is less clear if and how UTCs respond in acute, symptomatic HCV infection, a rare clinical condition, and if rapid DAA treatment of such patients reverses the caused perturbations within UTCs. Here, we comprehensively analyzed the phenotype and reinvigoration capacity of three major UTC populations, mucosal-associated invariant T (MAIT) cells, γδ T cells, and CD4 and CD8 double-negative αβ T cells (DNT cells) before, during, and after DAA-mediated clearance of acute symptomatic HCV infection. Furthermore, MAIT cell functionality was systematically studied. We observed a reduced frequency of MAIT cells. However, remaining cells presented with a near-to-normal phenotype in acute infection, which contrasted with a significant dysfunction upon stimulation that was not restored after viral clearance. Notably, DNT and γδ T cells displayed a strong activation ex-vivo in acute HCV infection, which subsequently normalized during the treatment. In addition, DNT cell activation was specifically associated with liver inflammation and inflammatory cytokines. Altogether, these data provide evidence that UTCs respond in a cell type-specific manner during symptomatic HCV infection. However, even if early treatment is initiated, long-lasting imprints within UTCs remain over time.

Safety and efficacy of grazoprevir/elbasvir in the treatment of acute hepatitis C in hemodialysis patients.

Treatment of hepatitis C virus (HCV) infection with direct‐acting antiviral agents (DAAs) in hemodialysis patients requires extensive consideration. At present, studies regarding DAAs for acute HCV infection in such patients are limited. The present study aims to evaluate the efficacy and safety of grazoprevir (GZR) plus elbasvir (EBR) treatment in acute hepatitis C (AHC) patients undergoing hemodialysis. Patients undergoing hemodialysis who had a nosocomial acute HCV infection were enrolled. All patients received GZR 100 mg/EBR 50 mg once daily for 12 weeks and were followed up for 12 weeks. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and HCV RNA levels were monitored during treatment and follow‐up periods. Sustained virologic response at 12 weeks after treatment cessation and treatment‐emergent adverse events (AEs) were assessed. A total of 68 AHC patients were enrolled. All patients were infected with HCV genotype 1b and achieved SVR12. Decreasing ALT, AST, and TBIL were observed over time in the first 4 weeks and became steady thereafter. Forty‐eight (70.59%) patients reported at least one AEs. The most common AEs were fatigue, headache, and nausea. Two AHC patients discontinued treatment due to serious but drug‐unrelated AEs. In conclusion, GZR/EBR has a high efficacy and safety profile in hemodialysis‐dependent patients with genotype 1b AHC.

The Epidemiological Patterns of Hepatitis C in Lithuania: Changes in Surveillance from 2005 to 2018.

Background and Objectives: Viral hepatitis C infection is an important public health concern worldwide because it is one of the major global causes of death and morbidity. The early identifi-cation of infected people, together with the provision of proper treatment, are the key strategies used in preventing HCV infection. However, data regarding the epidemiological patterns of hep-atitis C in Lithuania are limited. The aim of this research was to evaluate trends in acute HCV cases registered via the national surveillance system in Lithuania during 2005–2018. Materials and Methods: Incidence rates were calculated for data, stratified by gender, age group (0–24, 25–54, 55–74, and 75+), place of residence (urban or rural), and the Lithuanian county where the case was recorded. The crude incidence rate of hepatitis C was defined as the number of new infec-tions per 100,000 people during a one-year time period. A linear regression was applied to evalu-ate IR trends during the period of 2005–2018. Results: From 2005 to 2018, 572 cases of acute hepa-titis C were registered, and the incidence rate ranged from 2.03 cases per 100,000 people in 2005 to 0.55 in 2016. A statistically significant decreasing trend in the incidence rate was found during the study period (p < 0.0001). Almost 63% of the acute HCV infections recorded via the national surveillance system were in individuals aged from 25 to 54 years. Conclusions: Being male, aged between 25 and 34 years, and living in the city might be important factors for understanding the epidemiological patterns of HCV in Lithuania. Although the number of HCV cases recorded in Lithuania is decreasing, our country has one of the highest IRs compared to other European countries. This shows that a new approach to hepatitis C virus screening strategies is needed.

HIV, HCV and SARS-CoV-2: friends or foes? A case report

Data about co-infection of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), HIV, and hepatitis C virus (HCV) are still scarce. We describe a patient hospitalized for sore throat, fatigue, and myalgia with a personal history of HIV and occult HBV infection. His antiretroviral therapy included bictegravir/emtricitabine/tenofovir alafenamide. The nasopharyngeal swab was positive for SARS-CoV-2 and laboratory testing showed acute HCV. Antiretroviral therapy was continued, but no specific therapy for SARS-CoV-2 was started. After 4 weeks, the nasopharyngeal swab resulted negative for SARS-CoV-2 and biochemical tests revealed undetectable HCV RNA with normalization of transaminases. To the best of our knowledge, this is the first reported case of acute HCV in a patient with HIV and SARS-CoV-2 co-infection.

The distribution of hepatitis C virus infection in Shanghai, China: a time-spatial study

BackgroundShanghai, as a pilot city of China to achieve the goal of eliminating hepatitis C, its strategy of allocating medical resources is a pressing problem to be solved. This study aims to infer the time-spatial clustering patterns of HCV-infected cases, and grasp the dynamic genotype distribution of HCV, thereby inform elimination strategies of HCV with efficacy and efficiency.MethodsReported HCV cases including their demographic information in Shanghai city from 2005 to 2018 were released from the National Infectious Disease Reporting Information System, population data at community scale, geographical layers of hospitals, communities and districts were gathered from former research. Blood samples of HCV-infected individuals were collected during 2014–2018 from 24 sentinel hospitals, HCV-antibody test, qualitative nucleic acid test and NS5B/5’UTR gene amplification were performed accordingly to determine the genotypes of the specimen. Furthermore, global and local spatial self-correlation analysis of both acute and chronic HCV infections were conducted at community scale year by year, then time-spatial clusters of acute and chronic HCV infections and HCV genotype distribution of specimen collected from sentinel hospitals by districts were mapped by using Arcmap10.1.ResultsA total of 2631 acute HCV cases and 15,063 chronic HCV cases were reported in Shanghai from 2005 to 2018, with a peak in 2010 and 2017, respectively. The mean age of chronic HCV patients was 49.70 ± 14.55 years, 3.34 ± 0.32 years older than the acute (t = 10.55, P-value < 0.01). The spatial distribution of acute HCV infection formed one primary cluster (Relative Risk = 2.71), and the chronic formed one primary cluster and three secondary clusters with Relative Risk ranged from 1.94 to 14.42, meanwhile, an overlap of 34 communities between acute and chronic HCV clusters were found with time period spans varied from 6 to 12 years. Genotype 1 (N = 257, 49.71%) was the most prevalent HCV genotype in Shanghai, genotype 3 infections have increased in recent years. Baoshan district presented cluster of acute HCV and the highest proportion of genotype 2, Pudong new area was the cluster of chronic HCV and occupied the highest proportion of genotype 3.ConclusionsDespite the low prevalence of HCV infection, it is still needed to push forward the elimination process in Shanghai, as there is a certain amount of HCV infected people waiting to be treated. The time-spatial clustering patterns and the dynamic of HCV genotype distribution together indicated a changing constitution of different transmission routes of HCV infection, thus, a focused strategy may be needed for high-risk population related to genotype 3 infection like drug users, in addition to an enforcement of the existing measures of preventing the iatrogenic and hematogenic transmission of HCV.

Expansion of Unique Hepatitis C Virus-Specific Public CD8+ T Cell Clonotypes during Acute Infection and Reinfection.

Hepatitis C virus (HCV) infection resolves spontaneously in ∼25% of acutely infected humans where viral clearance is mediated primarily by virus-specific CD8+ T cells. Previous cross-sectional analysis of the CD8+ TCR repertoire targeting two immunodominant HCV epitopes reported widespread use of public TCRs shared by different subjects, irrespective of infection outcome. However, little is known about the evolution of the public TCR repertoire during acute HCV and whether cross-reactivity to other Ags can influence infectious outcome. In this article, we analyzed the CD8+ TCR repertoire specific to the immunodominant and cross-reactive HLA-A2-restricted nonstructural 3-1073 epitope during acute HCV in humans progressing to either spontaneous resolution or chronic infection and at ∼1 y after viral clearance. TCR repertoire diversity was comparable among all groups with preferential usage of the TCR-β V04 and V06 gene families. We identified a set of 13 public clonotypes in HCV-infected humans independent of infection outcome. Six public clonotypes used the V04 gene family. Several public clonotypes were long-lived in resolvers and expanded on reinfection. By mining publicly available data, we identified several low-frequency CDR3 sequences in the HCV-specific repertoire matching human TCRs specific for other HLA-A2-restricted epitopes from melanoma, CMV, influenza A, EBV, and yellow fever viruses, but they were of low frequency and limited cross-reactivity. In conclusion, we identified 13 new public human CD8+ TCR clonotypes unique to HCV that expanded during acute infection and reinfection. The low frequency of cross-reactive TCRs suggests that they are not major determinants of infectious outcome.

Characterization of Acute HCV Infection and Transmission Networks in People Who Currently Inject Drugs in Catalonia: Usefulness of Dried Blood Spots.

Accurate identification of recent HCV infections is critical for tracing the extent and mechanisms of ongoing transmission. We aimed to validate dried blood spot (DBS) samples for the assessment of Hepatitis C virus (HCV) genetic diversity and to determine epidemiological parameters including incidence, determinants of acute infection, and phylogenetic clustering in people who inject drugs (PWID). HCV nonstructural protein 5B next-generation sequencing was performed from plasma and/or DBS in 220 viremic PWID from the HepCdetect II study. No significant differences were found in consensus sequences or Shannon entropy (SE) intrahost diversity estimate between paired plasma/DBS specimens. SE values were used to identify acute infections with 93.3% sensitivity (95% CI, 0.81-1.06) and 95.0% specificity (95% CI, 0.88-1.02) in a set of well-defined controls. An acute HCV infection (either primary infection or reinfection) was detected in 13.5% of viremic participants and was associated with age ≤30years (OR,8.09), injecting less than daily (OR,4.35), ≤5years of injected drug use (OR,3.43), sharing cocaine snorting straws (OR,2.89), and being unaware of their HCV status (OR,3.62). Annualized HCV incidence was estimated between 31 and 59/100 person-years. On phylogenetic analysis, 46.8% of viremic cases were part of a transmission pair or cluster; age ≤30years (OR,6.16), acute infection (OR,5.73), and infection with subtype 1a (OR,4.78) were independently associated with this condition. The results obtained from plasma and DBS characterize PWID with acute infection and those involved in ongoing HCV transmission and allow estimating incidence from cross-sectional data. This information is critical for the design and assessment of targeted harm reduction programs and test-and-treat interventions and to facilitate monitoring of HCV elimination in this key population.

Late presentation of chronic hepatitis C patients in the era of direct-acting antivirals-Data from the German Hepatitis C-Registry.

Late presentation for care in chronic viral hepatitis has been estimated to occur in approximately 25% of patients initiating treatment with direct acting antivirals. We evaluated the extent of late presentation since the implementation of direct acting antivirals and established differences between HCV monoinfected and HIV/HCV coinfected patients. The German Hepatitis C Registry is a multicenter non-interventional registry study. We analysed patients enrolled between 02/2014 and 12/2018. Advanced liver disease was defined as an aspartate aminotransferase to platelet-ratio-index score ≥ 1.5, a FibroScan ≥ 9.5 kPa or a METAVIR stage ≥ F3. HCV monoinfected and HIV/HCV coinfected patients were analysed separately and baseline characteristics of both subgroups were compared. 8003 treatment naive patients were analysed. Overall, 2197/8003 (28%) patients presented late for care (HCV monoinfection: 2067/7452 (28%); HIV/HCV coinfection: 130/551 (24%)). Late presentation decreased comparing the year 2014 to the years 2015 (p≤0.001), 2017 (p≤0.001) and 2018 (p≤0.001) and was significantly lower in 2018 in HIV/HCV coinfected patients compared to HCV monoinfected patients (HIV/HCV: 15/89 (17%) vs. 415/1566 (27%); p=0.047). We observed a significant decrease of late presentation from 2014 to 2018. Despite the decrease during the observation period, approximately one in four patients continued to be affected in 2018, with a lower proportion of late presentation being seen in patients coinfected with HIV/HCV. This trend might indicate effects of a closer linkage to care and a more frequent detection of acute HCV infections of HIV+ patients.

Acute hepatitis C virus infection and direct-acting antiviral drugs: Perfect combination to eliminate the epidemic?

Early diagnosis and treatment of incident cases of hepatitis C virus (HCV) infection is fundamental to eliminate HCV in HIV-positive patients. From January 2016 to December 2019, we attended 40 episodes of acute HCV infection (AHC) in 35 subjects (9 reinfections) who were coinfected with HIV. The patients were treated with direct-acting antiviral agents (DAAs) in seven hospitals in Andalusia, Spain. All were men who have sex with men (MSM), mean age was 42.9 (±8.3) years and median time of HIV infection was 46.6months (IQR: 20.4-67.2). All received antiretroviral therapy and had undetectable HIV viral load (except 2 with 65 and 68 copies/mL); median CD4 count was 632 cells/mm3 (IQR: 553-896). Over half (74.3%) also had another concomitant sexually transmitted infection, syphilis (48.6%) being the most common. AHC was asymptomatic in 32 cases (80%). Genotypic distribution was G1a 65%, G4 32.5% and G1b 3%. Median time to DAA was 6weeks (IQR: 4.3-18.3) and median baseline HCV RNA was 6.1 Log (IQR: 5.6-6.5). DAA regimens were SOF/LDV (19 episodes), SOF/VEL (14), ELB/GZV (5) and GLP/PIB (2). All presented sustained viral response and none discontinued due to adverse effects. In conclusion, early treatment with DAA in AHC patients proved effective and safe. It could be an excellent strategy to eliminate HCV infection in HIV-coinfected MSM.