Achieving global elimination of hepatitis C virus requires a substantial scale‐up of testing. Point‐of‐care HCV viral load assays are available as an alternative to laboratory‐based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post‐treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical‐sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low‐level virological treatment failure (defined as <1000 IU/mL). There were 5973 cases of detectable viraemia at SVR12 from the combined data set. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170–276). Females and those with minimal fibrosis were more likely to experience low‐level viraemia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30–1.97 and those with cirrhosis (AOR = 1.49 95% CI 1.15–1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low‐level treatment failure.

/pdf/determining-the-lower-limit-of-detection-required-for-hcv-kkuljdgj.pdf

Determining the lower limit of detection required for HCV viral load assay for test of cure following direct‐acting antiviral‐based treatment regimens: Evidence from a global data set

: In renal transplantation, donor hepatitis C virus (HCV) status is crucial to consider when selecting a recipient given the high likelihood of transmission. We analyzed the effect of donor HCV status on post-renal transplant rejection and virologic infectious outcomes using electronic health record data from multiple US health care organizations. : Using real world data from electronic health records of renal transplant recipients, a propensity score-matched case-control study of one-year renal transplant outcomes was conducted on cohorts of HCV-negative recipients who received an organ from an HCV-positive donor (HCV D+/R-) versus from an HCV-negative donor (HCV D-/R-). Donor HCV positivity was defined as new recipient HCV positivity within 30 days post-transplant. Cohorts were matched by major risk factors for rejection including age, gender, race, etiologies of end-stage renal disease, dialysis dependence, donor type, induction immunosuppression, and virologic lab studies. The primary outcome was one-year incidence of rejection. Secondary outcomes included longitudinal measures of liver and kidney function, incidence of non-HCV viremia, and DAA treatment pathways and responses. : Data from 900 renal transplant recipients were analyzed, 450 subjects per group (D+/R-, D-/R-). Mean age at transplant was 57.1 ± 11.9 yrs, 60% were male, and 38% were African American. Kaplan-Meier analysis showed a significantly increased incidence of one-year rejection for HCV D-/R- compared to HCV D+/R- (16.6% vs 22.8%, p= 0.02). This difference did not persist on a sub-analysis excluding subjects with delayed graft function (DGF) (16.3% vs 19.2%, p=0.25). Although mean eGFR was initially higher in HCV D+/R-, there were no significant differences in liver or kidney allograft function at 12 months. There was no significant difference for composite viremia (CMV/EBV/BK; 37.66% vs 31.60%, p = 0.07). The most common DAA regimen was glecaprevir/pibrentasvir (52.8%). DAA treatment responses were excellent, with most subjects having a negative viral load by 90 days (mean: 1.7±1.9 log units/mL). : Donor HCV positivity did not negatively impact one-year rejection outcomes post-renal transplantation. Importantly, this effect was not biased by age. Anti-HCV treatment was effective and liver and kidney function were excellent at one-year post-transplant. These data support the continued expansion of the donor pool by utilizing organs from HCV-positive donors in the era of anti-HCV direct-acting antiviral therapies. 

Donor Hepatitis C status is not associated with an increased risk of acute rejection in kidney transplantation

Nearly 60 million people worldwide are infected with Hepatitis C Virus (HCV), a bloodborne pathogen which leads to liver cirrhosis and increases the risk of hepatocellular carcinoma. Those with limited access to healthcare resources, such as injection drug users and people in low- and middle-income countries, carry the highest burden. The current diagnostic algorithm for HCV is slow and costly, leading to a significant barrier in diagnosis and treatment for those most at risk from HCV. There remains no available vaccine for HCV, and infection is often asymptomatic until significant cirrhosis has occurred, which makes screening incredibly important to prevent liver damage and transmission. Recent investigation has sought to address these issues through improvements in various aspects of the diagnostic procedure, using methods such as isothermal amplification techniques for viral RNA amplification, the use of viral protein as an analyte, and the incorporation of streamlined, self-contained testing systems to reduce administrative skill requirements. This review provides a comprehensive overview of current commercial standards and novel improvements in HCV diagnostics, as well as a framework for future integration of these improvements to develop a one-step diagnostic that meets the needs of those most affected. 

Current advances in Hepatitis C diagnostics

Dried blood spots (DBS) are a reliable tool to diagnose viremic hepatitis C virus (HCV) infection. We evaluated the clinical performance of a DBS‐based molecular assay for the assessment of cure and reinfection after on‐site treatment at a harm reduction center (HRC). Genotyping from DBS samples was also assessed to discriminate reinfection from treatment failure. People who inject drugs (PWID) from an ongoing test‐and‐treat pilot at the largest HRC in Barcelona were included in the study. HCV‐RNA detection from DBS collected after treatment (with follow‐up at 12, 36, and 60 weeks) was compared with a molecular point‐of‐care test using finger‐stick blood (GeneXpert). Baseline and follow‐up DBS samples were genotyped by NS5B sequencing or commercial real‐time PCR. Among treated patients, 193 follow‐up DBS samples were tested. The DBS‐based assay showed 100% specificity (129/129), and sensitivity ranged from 84.4% to 96.1% according to different viral load cut‐offs (from detectable to 3000 IU/mL). Sensitivity as test of cure (follow‐up 12) ranged from 85.1% to 97.4%. Among the 64 patients with recurrent viremia, 10.9% had low viral loads (≤1000 IU/mL); HCV genotyping allowed us to classify 73.5% of viremic cases either as reinfection or as treatment failure. DBS samples are useful to assess cure and differentiate reinfection from relapse after HCV antiviral treatment in the real world, facilitating decentralization of treatment and posttreatment follow‐up in PWID. However, a fraction of patients presented with low viral loads, limiting viremia detection and genotyping in DBS and, therefore, repeat testing is recommended.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmv.28544

Usefulness of dried blood spot samples for monitoring hepatitis C treatment outcome and reinfection among people who inject drugs in a test‐and‐treat program

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Determining the lower limit of detection required for HCV viral load assay for test of cure following direct‐acting antiviral‐based treatment regimens: Evidence from a global data set