Hepatitis C Virus Nucleic Acid Research Articles

Trends in candidate hepatitis C virus nucleic acid amplification test (NAT)+ listing and associated impacts on liver transplantation waitlist outcomes

Direct-acting antiviral agents have facilitated the utilization of hepatitis C virus (HCV)+ organs in HCV nucleic acid amplification test (NAT)– recipients. We evaluated trends in HCV NAT+ listing and its impact on transplant probability, waitlist mortality, and likelihood of receiving HCV NAT+ organs using the United Network for Organ Sharing data set of adult patients waitlisted for liver transplantation from January 2016 to September 2023. Multivariable regression models accounting for competing risks were fit to study waitlist outcomes. Initially, 21 776 patients were listed for HCV NAT+ organs whereas 45 378 were not. The percentage of waitlisted patients listed for these organs increased significantly from 2016 to 2023 (8.8% to 60.8%, P < .001). Initial HCV NAT+ listing was associated with a waitlist mortality benefit in 2021-2023 (subhazard ratio 0.73, 95% CI 0.68-0.79, P < .001) and 17% reduced hazard of overall mortality (hazard ratio 0.83, 95% CI 0.78-0.89, P < .001). Sixteen percent of the total protective effect associated with HCV NAT+ listing on overall survival was mediated through actual receipt of HCV NAT+ organs (total excess relative risk of –0.160 and a pure indirect effect of –0.026; P < .001). Patients not listed for HCV NAT+ organs in the modern era are relatively disadvantaged in terms of waitlist outcomes. Although listings have risen over time, there remains center-level and geographic variation.

Real-world experience in treatment of donor-derived Hepatitis C virus in kidney transplant recipients with delayed initiation, shortened course glecaprevir/pibrentasvir versus standard of care.

There is limited literature describing the real-world practice of delayed initiation and shortened duration direct-acting antiviral (DAA) in kidney transplant recipients. We compared Hepatitis C virus (HCV) cure rates among kidney transplant recipients who received an HCV nucleic acid test positive (NAT +) kidney and were treated with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks or glecaprevir/pibrentasvir (G/P) for 8 weeks, a duration that is 4 weeks shorter than the guideline recommendation for treatment delay beyond 1-week post-transplant. Retrospective study of HCV-negative adult patients who received a kidney transplant from an HCV NAT+ donor between April 2019 and April 2022 treated with either SOF/VEL for 12 weeks or G/P for 8 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy (SVR12). Secondary outcomes included time to DAA initiation, renal function, graft loss, patient death, liver function tests, and opportunistic infections. 102 kidney transplant recipients were included with 36 treated with G/P and 66 treated with SOF/VEL. All 36 (100%) treated with G/P achieved SVR12. One patient in the SOF/VEL group failed to achieve SVR12 but received additional therapy and was cured. Time to DAA initiation was similar with a mean of 4 weeks. There was no difference in AST/ALT > 3x ULN or renal function. One rejection occurred in each group. No patient death or graft loss was observed. There was no difference in cytomegalovirus and BK viremia between groups. CONCLUSION: Delayed initiation of DAA therapy with 12 weeks of SOF/VEL or 8 weeks of G/P achieves SVR12 in kidney transplant recipients without significant adverse effects.

Epidemiology of Hepatitis C over 28 years of monitoring Canadian blood donors: Insight into a low-risk undiagnosed population

BackgroundHepatitis C is a blood-borne infection with the hepatitis C virus (HCV) that can progress to cirrhosis and liver cancer. About 70% (50–80%) of infections become chronic and exhibit anti-HCV and HCV nucleic acid (NAT) positivity. Direct acting oral pan genotypic antiviral treatment became available in 2014 and was free for most Canadians in 2018. Clinical screening for HCV infection is risk-based. About 1% of Canadians have been infected with HCV, with 0.5% chronically infected (about 25% unaware) disproportionately impacting marginalized groups. Blood donors are in good health, are deferred for risks such as injection drug use and can provide insight into the low-risk undiagnosed population. Here we describe HCV epidemiology in first-time blood donors over 28 years of monitoring.MethodsAll first-time blood donors in all Canadian provinces except Quebec (1993 to 2021) were analyzed. All blood donations were tested for HCV antibodies (anti-HCV) and since late 1999 also HCV NAT. A case-control study was also included. All HCV positive donors (cases) since 2005 and HCV negative donors (1:4 ratio controls) matched for age, sex and location were invited to complete a risk factor interview. Separate logistic regression models for anti-HCV positivity and chronic HCV assessed the association between age cohort, sex, region and neighbourhood material deprivation and ethnocultural concentration. Case: control data were analysed by logistic regression.ResultsThere were 2,334,238 donors from 1993 to 2021 included. Prevalence for anti-HCV was 0.33% (0.30,0.37) in 1993 and 0.07% (0.05,0.09) in 2021 (p < 0.0001). In 2021 0.03% (0.01,0.04) had chronic HCV. Predictors for both anti-HCV positivity and chronic HCV were similar, for chronic HCV were male sex (OR 1.8, 1.6,2.1), birth between 1945 and 1975 (OR 7.1, 5.9,8.5), living in the western provinces (OR 1.4, 1.2,1.7) and living in material deprived (OR 2.7, 2.1,3.5) and more ethnocultural concentrated neighbourhoods (OR 1.8, 1.3,2.5). There were 318 (35.4%) of chronic HCV positive and 1272 (39.6%) of controls who participated in case control interviews. The strongest risks for acquisition were injection drug use (OR 96.9, 22.3,420.3) and birth in a high prevalence country (OR 24.5, 11.2,53.6).ConclusionsBlood donors have 16 times lower HCV prevalence then the general population. Donors largely mirror population trends and highlight the ongoing prevalence of untreated infections in groups without obvious risks for acquisition missed by risk-based patient screening.

Development of surface-enhanced Raman scattering-sensing Method by combining novel Ag@Au core/shell nanoparticle-based SERS probe with hybridization chain reaction for high-sensitive detection of hepatitis C virus nucleic acid.

The ultrasensitive detection of hepatitis C virus (HCV) nucleic acid is crucial for the early diagnosis of hepatitis C. In this study, by combining Ag@Au core/shell nanoparticle (Ag@AuNP)-based surface-enhanced Raman scattering (SERS) tag with hybridization chain reaction (HCR), a novel SERS-sensing method was developed for the ultrasensitive detection of HCV nucleic acid. This SERS-sensing system comprised two different SERS tags, which were constructed by modifying Ag@AuNP with a Raman reporter molecule of 4-ethynylbezaldehyde, two different hairpin-structured HCR sequences (H1 or H2), and a detection plate prepared by immobilizinga capture DNA sequence onto the Ag@AuNP layer surface of the detection wells. When thetarget nucleic acid was present, the two SERS tags were captured on the surface of the Ag@AuNP-coated detection well to generate many "hot spots" through HCR, forming a strong SERS signal and realizing the ultrasensitive detection of thetarget HCV nucleic acid. The limit of detection of the SERS-sensing method for HCV nucleic acid was 0.47 fM, and the linear range was from 1 to 105 fM.

Racial and Gender Disparities in Transplantation of Hepatitis C+ Hearts and Lungs

BackgroundTransplanting organs from hepatitis c virus (HCV) infected donors into HCV-negative recipients has led to thousands of more transplants in the US since 2016. Studies have demonstrated disparities in utilization of kidneys from these donors due to gender and education. It is still unknown, however, if the same disparities are seen in heart and lung transplantation. MethodsWe used Organ Procurement and Transplantation (OPTN)/United Network for Organ Sharing (UNOS) data on all isolated heart and lung transplants from 11/01/2018- 03/31/2023, classifying donors based on their HCV nucleic acid test (NAT) result: HCV NAT- vs HCV NAT+. We fit separate mixed effects logistic regression models (outcome: HCV-NAT+ donor) for heart and lung transplants. Primary covariates included: 1) race/ethnicity; 2) sex; 3) education level; 4) insurance type; and 5) transplant year. ResultsThe study included 26,108 adults (14,189 isolated heart transplant recipients and 11,919 isolated lung transplant recipients). 993 (7.0%) heart transplants involved an HCV-NAT+ donor, compared to 457 (3.8%) lung transplants. In multivariable models among all isolated heart transplant recipients, women were significantly less likely to receive an HCV-NAT+ donor heart (OR: 0.79, 95% CI: 0.67-0.92, P=0.003), as were Asian patients (OR: 0.52, 95% CI: 0.31=0.86, P= 0.01). In multivariable models among all isolated lung transplant recipients, Asians were significantly less likely to receive HCV-NAT+ transplants (OR: 0.31, 95% CI: 0.12-0.77, P= 0.01). ConclusionThere are disparities in utilization of heart and lungs from HCV NAT+ donors, with women and Asian patients being significantly less likely to receive these transplants.

Early Assessment of Cardiac Allograft Vasculopathy Risk Among Recipients of Hepatitis C Virus-infected Donors in the Current Era

BackgroundTransplantation of hearts from hepatitis C virus (HCV)-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral therapies for treatment and cure of HCV. Although historical data from the pre–direct-acting antiviral era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test–positive (NAT+) donors and the development of CAV in the direct-acting antiviral era remains unclear. Methods and ResultsWe performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first year after transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT– donors. Additionally, in a subsample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT– cohort) who had serial adjunctive intravascular ultrasound examination performed, we compared development of rapidly progressive CAV, defined as an increase in maximal intimal thickening of ≥0.5 mm in matched vessel segments during the first year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥1 over the first year after heart transplant compared with recipients of HCV NAT– hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of rapidly progressive CAV. ConclusionsThese findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.

Lung Transplantation from hepatitis C+ donor lungs: Reassuring midterm outcomes

The development of modern antiviral therapy for hepatitis C virus (HCV) has allowed for the transplantation of HCV nucleic acid amplification testing-positive (NAT+) donor lungs with acceptable short-term outcomes. We sought to evaluate trends and midterm outcomes of lung transplant recipients of HCV NAT+ donor allografts. All adults undergoing isolated lung transplantation in the United Network for Organ Sharing database from January 2016 to December 2022 were included in the study. Lung transplant recipients were stratified based on donor HCV status (HCV NAT+ vs NAT-). Propensity score matching was used to adjust for differences between groups. Several outcomes, including acute rejection by 1year, early (30-day and in-hospital) mortality, and both 1- and 3-year survival, were compared between matched groups. A total of 16,725 patients underwent lung transplantation during the study period, with 489 (3%) receiving HCV NAT+ donor lungs. Regions 1 (18%) and 6/8 (both 0%) had the highest and lowest proportions, respectively, of HCV NAT+ donor transplants. Utilization of HCV NAT+ donors increased throughout the study period from 2 (0.1%) in 2016 to a peak of 117 (5%) in 2019. Donors who were HCV NAT+ were younger (34 vs 36 years, p<0.001), more often female (44% vs 39%, p<0.01), and more commonly died due to drug intoxication (56% vs 15%, p<0.001). Recipients of HCV NAT+ donor lungs were similar in age (62 vs 62 years, p=0.69) and female gender (43% vs 39%, p=0.15) but had lower lung allocation scores (38 vs 41, p<0.001) compared to others. Rates of acute rejection (13% vs 17%, p=0.09), early mortality (30-day: 2% vs 1%, p=0.59, in-hospital: 3% vs 4%, p=0.38), as well as 1-year (90% vs 92%, p=0.29) and 3-year survival (69% vs 75%, p=0.13) were not significantly different between matched groups. Lung transplant recipients of HCV NAT+ donor allografts experience similar rates of acute rejection, early mortality, and 3-year survival compared to all other lung recipients. Increased use of HCV NAT+ donor allografts may help to expand the donor pool and alleviate donor shortages.

Removing hepatitis C antibody testing for Australian blood donations: A cost-effectiveness analysis.

The risk of transfusion-transmitted hepatitis C virus (HCV) infections is extremely low in Australia. This study aims to conduct a cost-effectiveness analysis of different testing strategies for HCV infection in blood donations. The four testing strategies evaluated in this study were universal testing with both HCV antibody (anti-HCV) and nucleic acid testing (NAT); anti-HCV and NAT for first-time donations and NAT only for repeat donations; anti-HCV and NAT for transfusible component donations and NAT only for plasma for further manufacture; and universal testing with NAT only. A decision-analytical model was developed to assess the cost-effectiveness of alternative HCV testing strategies. Sensitivity analysis and threshold analysis were conducted to account for data uncertainty. The number of potential transfusion-transmitted cases of acute hepatitis C and chronic hepatitis C was approximately zero in all four strategies. Universal testing with NAT only was the most cost-effective strategy due to the lowest testing cost. The threshold analysis showed that for the current practice to be cost-effective, the residual risks of other testing strategies would have to be at least 1 HCV infection in 2424 donations, which is over 60,000 times the baseline residual risk (1 in 151 million donations). The screening strategy for HCV in blood donations currently implemented in Australia is not cost-effective compared with targeted testing or universal testing with NAT only. Partial or total removal of anti-HCV testing would bring significant cost savings without compromising blood recipient safety.

Gender differences in risk exposures for acute hepatitis C infection in Taiwan: a nationwide case–control study

BackgroundIn Taiwan, medical providers are required to report all acute hepatitis C (AHC) patients to National Notifiable Disease Surveillance System (NNDSS). Identifying factors associated with AHC may inform the strategies to prevent the spread of hepatitis C virus (HCV). We used the national surveillance data to assess gender difference in risk factors associated with AHC in Taiwan and propose control measures in at-risk groups.MethodsWe conducted a nationwide case–control study using data from NNDSS and AHC case investigation questionnaires, for the period of March 6, 2014–December 31, 2016. Cases were AHC confirmed in NNDSS; controls were reported AHC with negative HCV nucleic acid test and negative serum anti-HCV antibody. We used bivariate analysis to identify characteristics and risk exposures for AHC and conducted gender stratified analyses.ResultsWe identified 602 AHC cases (66.9% males, median age 48 years) and 90 controls. Older age, male gender (OR: 1.85, 95% CI: 1.18–2.90), history of viral hepatitis (OR: 7.93, 95% CI:1.91–32.88), history of sexually transmitted infections (OR: 21.02, 95% CI: 2.90–152.43), and having healthcare-associated risk exposures (OR: 2.02, 95% CI: 1.25–3.25) were associated with AHC. Stratified analyses showed receiving intravenous infusion, history of hepatitis B, syphilis, and human immunodeficiency virus infection were risk factors for male AHC; receiving hemodialysis was risk factor for females.ConclusionsOur study demonstrates risk factors for AHC in Taiwan with gender difference. Proper infection control practices in healthcare settings and interventions targeting male patients with HIV and other STIs, remain crucial to prevent individuals from AHC.

Highly Specific and Rapid Detection of Hepatitis C Virus Using RT-LAMP-Coupled CRISPR–Cas12 Assay

Hepatitis C virus (HCV) infection can be cured with pan-genotypic direct-acting antiviral agents. However, identifying individuals with current hepatitis C remains a major challenge, especially in resource-limited settings where access to or availability of molecular tests is still limited. The goal of this study was to develop and validate a molecular assay for the rapid detection of HCV RNA in resource-limited settings. It is based on a combination of reverse transcription loop-mediated isothermal amplification (RT-LAMP) with the clustered regularly interspaced short palindromic repeats–CRISPR-associated protein 12a (CRISPR–Cas12a) cleavage assay that allows the recognition of specific HCV nucleic acid sequences. Amplified products after the cleavage reactions can be visualized on lateral flow strips or measured with a fluorescence detector. When tested on clinical samples from individuals infected with HCV, HIV, or HBV, or from healthy donors, the RT-LAMP-coupled CRISPR–Cas12 assay yielded 96% sensitivity, 100% specificity, and 97% agreement as compared to the reference method (Roche COBAS AmpliPrep/COBAS TaqMan HCV Test). This assay could detect HCV RNA concentrations as low as 10 ng/µL (an estimated 2.38 Log10 IU/mL). Therefore, this sensitive and specific assay may represent an affordable and reliable point-of-care test for the identification of individuals with active hepatitis C in low-resource settings.

Demographics and Utilization of Hepatitis C Hearts: A Single Center Experience

<h3>Purpose</h3> Since the advent of direct acting antiviral therapies as a cure for hepatitis C virus (HCV), the use of HCV nucleic acid test (NAT) positive donors in adult heart transplantation is increasing. The degree to which HCV NAT+ donor characteristics may impact donor selection remains unclear. We sought to explore the demographics and organ acceptance and transplantation rates of HCV NAT+ donor offers to our center, relative to those of other donor offers. <h3>Methods</h3> We used the United Network of Organ Sharing (UNOS) DonorNet database to evaluate 1,000 consecutive primary donor offers made to our center between January 1, 2018 and March 3, 2019. Statistical analysis was performed using ANOVA tests. <h3>Results</h3> Of 1,000 donor offers evaluated by our center, 238 were HCV antibody (Ab) positive of which 177 were HCV NAT positive. Compared to other donors, HCV NAT+ donors tended to be younger, male, and to die more often from drug overdose. Despite procurement teams having to travel longer distances to recover them, HCV NAT+ donors had higher rates of organ acceptance and ultimate transplantation relative to other donors. <h3>Conclusion</h3> Favorable demographic characteristics of HCV NAT+ donors are associated with higher rates of organ acceptance and transplantation at our center, despite longer procurement distances. Especially given the promising early outcomes among recipients of these donors, we anticipate that the rate of HCV NAT+ donor utilization will soon eclipse that of HCV naïve donor utilization nationwide.

Comparable Survival for Hepatitis C–Related Hepatocellular Carcinoma After Liver Transplantation Irrespective of Viremic Status

Direct-acting antiviral (DAA) therapy for the treatment of chronic hepatitis C virus (HCV) infection is efficacious and well-tolerated in the post-liver transplant (LT) setting, prompting increased use of donors with HCV infection in patients waitlisted for LT.1,2 Although the incidence of nonviral hepatocellular carcinoma (HCC) is rising, HCV remains the most common risk factor for HCC among patients listed for LT in the United States.3 The use and outcomes of HCV-infected donors among patients with active HCV viremia waitlisted for (HCV-HCC) is lacking. Our aim was to evaluate post-LT survival among patients with HCV-HCC based on both recipient (active vs cured HCV) and donor (HCV+ vs HCV-) viremic status. Using the United Network for Organ Sharing (UNOS) registry, we analyzed all adult patients with HCV-HCC who underwent LT and had available recipient/donor HCV nucleic acid test (NAT) results from March 31, 2015 (date UNOS began reporting donor NAT) through June 30, 2021. Patients with acute liver failure, simultaneous organ transplant, previous LT, and those missing recipient and/or donor NAT results were excluded.

Effect of Hepatitis C Virus Infection on Heart Transplants in the Current Era

The effect of hepatitis C virus (HCV) infection in recipients or donors on heart transplants is less known in the current era after the introduction of direct-acting antiviral agents (DAAs) in 2011. Using the United Network for Organ Sharing registry, 24 871 adult heart transplant recipients between 2005 and 2019 were identified. The trend in prevalence of HCV-infected recipients and in utilization of HCV-infected donors and their effect on the transplant outcomes were investigated in the past era versus the current era separated by 2011, using Cox proportional hazard regression. HCV antibody-positive recipients (n = 520, 2.1%) had stable prevalence (P = 0.18). They had a lower survival estimate when compared with HCV antibody-negative recipients in the past era (55.3% versus 70.9% at 7 y; hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.27-1.91; P < 0.001), however not in the current era (73.1% versus 71.5% at 7 y; HR, 1.00; 95% CI, 0.75-1.32; P = 0.98) (Pinteraction < 0.001). Organ use from HCV antibody-positive donors (n = 371, 1.5%) was concentrated in the recent years (P < 0.001) and provided the similar survival estimate up to 2 y (84.2% versus 87.6%; HR, 0.97; 95% CI, 0.65-1.44; P = 0.87). The similar findings were confirmed with a subgroup cohort with positive nucleic acid amplification test. Positive HCV antibody in recipients did not adversely affect the long-term transplant outcomes in the current era. Graft utilization from positive HCV antibody or nucleic acid amplification test-positive donors are rapidly more prevalent and appeared to be promising up to 2 y posttransplant.

The Impact of Treatment Delay on Hepatitis C Liver Transplant Outcomes

Background: Direct-acting antivirals for the treatment of hepatitis C virus (HCV) have improved outcomes in liver transplant recipients (LTRs). However, the timing of HCV treatment and approach to treating rejection have not been well described. Additionally, pharmacists’ roles in these comprehensive areas have not been investigated. Methods: This single-center, retrospective, cohort review compared 1-year graft and patient survival between HCV-positive and HCV-negative LTRs. Secondary endpoints included 1-year rejection rates, HCV sustained virologic response and time to HCV treatment. Results: Ninety-two HCV Nucleic Acid Amplification Test (NAT)-positive LTRs were matched 1:1 to HCV-seronegative LTRs. One-year graft and patient survival were similar between groups. HCV-positive LTRs were more likely to experience biopsy-proven acute rejection (BPAR), and despite treatment with pulse steroids, there was no impact on graft survival or occurrence of fibrosing cholestatic hepatitis (FCH). Time to HCV treatment was 5.4–6.4 months post-transplant, with no treatment failures or impact on graft or patient survival. Conclusions: No difference was seen in graft survival at 1 year between HCV-positive and HCV-seronegative LTRs. Delayed time to treatment of HCV and treatment of rejections in the HCV-positive cohort did not impact outcomes. However, pharmacist-driven protocols could ensure more efficient initiation of HCV treatment in the future.

Enhancing Linkage to Hepatitis C Virus Treatment Following Pregnancy in Women Identified During Perinatal Care.

Amid the current US opioid crisis, hepatitis C virus (HCV) infection rates continue to rise in young adults, including among pregnant women, yet few studies describe linkage to care and treatment in pregnant or postpartum women with HCV infection. We used electronic health record data to estimate HCV treatment rates for postpartum women before (January 2014‐September 2016) and during (October 2016‐March 2018) implementation of a maternal–infant HCV linkage program in combination with a multidisciplinary clinic to colocate mother and infant care. Using Poisson regression models, we compared HCV treatment initiation rates, adjusting for demographics, substance use, and treatment. From January 2014 through March 2018, 343 women who were HCV seropositive delivered at our institution. Of these, 95% completed HCV nucleic acid testing and 255 women had chronic HCV infection. Mean age was 30 years, 96% were publicly insured, and 94% had documented substance use. HCV treatment initiation increased from 28/164 (17.1%) women with chronic HCV infection in the preintervention period to 16/66 (24.2%) with the linkage‐only intervention and 13/25 (52.0%) with the linkage intervention and colocated care. Adjusted analyses demonstrated that women delivering during the intervention period initiated HCV treatment at 2.40 times (95% confidence interval [CI], 1.10‐5.25; linkage only) and 3.36 times (95% CI, 1.57‐7.17; linkage and colocated care) the rate of women delivering preintervention. Women on buprenorphine had higher HCV treatment initiation rates compared with those on methadone (rate ratio, 2.10; 95% CI, 1.05‐4.21). Conclusion: HCV linkage to care and treatment rates improved in the setting of mother–infant linkage and colocated care interventions. Perinatal care may represent a critical venue to identify, link, and treat women for HCV infection to improve their own health and prevent transmission to subsequent pregnancies.

Pretransplant Hepatitis C Virus Treatment Decreases Access to High-quality Livers.

Background.Despite the revolutionary role of direct-acting antivirals for hepatitis C virus (HCV), the treatment timing for liver transplant candidates remains controversial. We hypothesize that deferring treatment until after liver transplantation improves access to a larger and higher-quality donor pool without a detrimental impact on post-liver transplantation outcomes.Methods.This single-center study includes recipients that underwent deceased-donor liver transplant with HCV as the primary indication January 1, 2014, to December 31, 2018. For recipients that were untreated (n = 87) versus treated (n = 42) pre-LT, we compared post-LT mortality using Cox regression with inverse probability of treatment-weighted data.Results.Among pre-LT untreated recipients, 95% were willing to accept an HCV+ donor, and 44.8% received a positive HCV antibody and nucleic acid amplification test (NAT) liver. Among pre-LT treated recipients, 5% were willing to accept an HCV+ donor, and 100% received a negative HCV antibody and NAT liver. The median calculated model for end-stage liver disease at transplant was similar between pre-LT untreated (13, IQR = 9–22) and treated recipients (11, IQR = 8–14) (P = 0.1). Pre-LT treated recipients received livers from older (47 y old versus 37, P < 0.01) and higher body mass index donors (30.2 versus 26.6; P = 0.04) and spent longer on the waiting list (319 d 180, P < 0.001). Unadjusted post-LT mortality at 1 year was higher in the pre-LT treated recipients (14.6% versus 3.5%, P = 0.02). After adjusting for recipient factors, pre-LT treated recipients trended toward a 3.9 times higher risk of mortality compared with the pre-LT untreated recipients (adjusted hazard ratio = 0.973.8615.4) (P = 0.06).Conclusions.Deferring HCV treatment improves access to higher-quality donors and may improve post-LT survival.

Multiplex detection of blood-borne pathogens on a self-driven microfluidic chip using loop-mediated isothermal amplification

Detection of blood-borne pathogens such as hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is essential to ensure the safety of blood transfusion. However, traditional PCR-based pathogen nucleic acid detection methods require relatively high experimental facilities and are difficult to apply in areas with limited resources. In this study, a self-driven microfluidic chip was designed to carry out multiplex detection of HBV, HCV and HIV by using loop-mediated isothermal amplification (LAMP). Benefitting from the air permeability of the polydimethylsiloxane material, the chip could accomplish sample loading within 12min driven by the pressure difference between the reaction chambers and vacuum chambers in the chip without using pumps or any injection devices. Multiplex detection is achieved by presetting LAMP primers specific to different targets in different reaction chambers. Calcein was used as an indicator to indicate the positive amplification reaction, and the result can be recorded by a smartphone camera. After 50min of isothermal amplification at 63°C, 2 copies/μL of HBV, HCV and HIV target nucleic acids could be detected. The results of HBV detection of 20 clinical plasma samples by using the chip are consistent with that of the qPCR-based kit, indicating that the LAMP-based self-driven chip has the clinical application potential for blood-borne pathogen detection, especially in resource-limited areas.

Occult hepatitis C virus infection in the Middle East and Eastern Mediterranean countries: A systematic review and meta-analysis.

BACKGROUNDThe presence of hepatitis C virus (HCV) RNA in liver tissue or peripheral blood mononuclear cells with no identified virus genome in the serum has been reported worldwide among patients with either normal or elevated serum liver enzymes. The characterization of occult HCV infection (OCI) epidemiology in the Middle East and Eastern Mediterranean (M and E) countries, a region with the highest incidence and prevalence rates of HCV infection in the world, would be effective for more appropriate control of the infection.AIMTo estimate the pooled prevalence of OCI in M and E countries using a systematic review and meta-analysis.METHODSA systematic literature search was performed using international, regional and local electronic databases. Some conference proceedings and references from bibliographies were also reviewed manually. The search was carried out during May and June 2020. Original observational surveys were considered if they assessed the prevalence of OCI among the population of M and E countries by examination of HCV nucleic acid in peripheral blood mononuclear cells in at least 30 cases selected by random or non-random sampling methods. The meta-analysis was performed using Comprehensive Meta-analysis software based on heterogeneity assessed by Cochran’s Q test and I-square statistics. Data were considered statistically significant at a P value < 0.05.RESULTSA total of 116 non-duplicated citations were found in electronic sources and grey literature. A total of 51 non-overlapping original surveys were appraised, of which 37 met the inclusion criteria and were included in the analysis. Data were available from 5 of 26 countries including Egypt, Iran, Pakistan, Saudi Arabia, and Turkey. The overall prevalence rate of OCI was estimated at 10.04% (95%CI: 7.66%-13.05%). The lowest OCI rate was observed among healthy subjects (4.79%, 95%CI: 2.86%-7.93%). The higher rates were estimated for patients suffering from chronic liver diseases (12.04%, 95%CI: 5.87%-23.10%), and multi-transfused patients (8.71%, 95%CI: 6.05%-12.39%). Subgroup analysis indicated that the OCI rates were probably not associated with the studied subpopulations, country, year of study, the detection method of HCV RNA, sample size, patients’ HCV serostatus, and sex (all P > 0.05). Meta-regression analyses showed no significant time trends in OCI rates among different groups.CONCLUSIONThis review estimated high rates of OCI prevalence in M and E countries, especially among multi-transfused patients as well as patients with chronic liver diseases.

Outcomes of hepatitis C virus seropositive donors to hepatitis C virus seronegative liver recipients: A large single center analysis

Introduction and objectivesThe success of direct-acting antivirals (DAA) has transformed the management of hepatitis C virus (HCV) infection and has led to the expansion of the deceased donor organ pool for liver transplantation. Material and methodsWe present a single center retrospective review of liver transplantations performed on HCV-seronegative recipients from HCV-seropositive organs from 11/2017 to 05/2020. HCV nucleic acid testing (NAT) was performed on HCV-seropositive donors to assess active HCV infection. Results42 HCV-seronegative recipients underwent a liver transplant from a HCV-seropositive donor, including 21 NAT negative (20 liver, 1 simultaneous liver kidney transplant) and 21 NAT positive liver transplants. Two (9.5%) HCV antibody positive/NAT negative recipients developed HCV viremia and achieved sustained virologic response with DAA therapy. The remaining patients with available data (19 patients) remained polymerase chain reaction (PCR) negative at 6 months. 20 (95%) of HCV antibody positive/NAT positive recipients had a confirmed HCV viremia. 100% of patients with available data (15 patients) achieved SVR. Observed events include 1 mortality and graft loss and equivalent rates of post-transplant complications between NAT positive and NAT negative recipients. ConclusionsHCV-seropositive organs can be safely transplanted into HCV-seronegative patients with minimal complications post-transplant.

Donor Characteristics and Regional Differences in the Utilization of HCV-Positive Donors in Liver Transplantation

Increased utilization of hepatitis C virus (HCV)-positive liver allografts for liver transplant (LT) has been endorsed as one of several ways to combat national organ shortages. However, HCV-positive donors remain poorly characterized, and Organ Procurement and Transplantation Network regional differences in the utilization of HCV-positive liver allografts are unclear. To characterize HCV-positive donors and the allografts that come from them. In this cross-sectional study, the Scientific Registry of Transplant Recipients database was queried for all donors who underwent HCV testing from June 2015 to December 2018. Clinical and allograft characteristics were evaluated, and utilization across the United States was studied. Patients with positive or negative results for HCV antibody (Ab) and HCV nucleic acid amplification testing (NAT) were included in this study. Donors utilized for living donor transplant and pediatric (age <18 years) recipients were excluded. The primary comparison was between donors who were HCV Ab positive and those who were HCV Ab negative. Regional variations in the utilization of HCV-positive and HCV-negative donors were analyzed. Of 24 500 donors utilized for LT, 1887 (7.7%) were HCV Ab positive; 64.4% of HCV Ab-positive donors were HCV NAT positive. HCV Ab-positive donors were younger (median [interquartile range] age, 35 [29-46] years vs 40 [27-54] years) and had fewer comorbidities, such as diabetes (8.3% vs 12.0%) and hypertension (25.9% vs 35.2%), compared with HCV Ab-negative donors. These findings were even more pronounced in HCV Ab-positive /NAT-positive compared with HCV Ab-positive/NAT-negative donors. Organ Procurement and Transplantation Network regions 2, 3, 10, and 11 had the highest absolute utilization of HCV Ab-positive donors, accounting for 64.4% of all HCV Ab-positive donors used in the United States. Region 1 had the highest relative utilization of HCV Ab-positive donors (18.7%). The use of HCV Ab-positive donors in some regions was associated with the rate of drug overdose, but this was not always the case. Similar utilization results were found with HCV NAT-positive donors. In this cross-sectional study, HCV-positive donors were younger and healthier than utilized HCV-negative donors. Significant differences exist in the utilization of HCV-positive donors across the 11 Organ Procurement and Transplantation Network regions, which is not entirely explained by organ demand or by higher availability of HCV-positive livers as per the distribution of the opioid epidemic. Initiatives to increase the use of HCV-positive donors, particularly in regions of high organ demand, should be implemented.