Decentralizing HCV Diagnosis for Vulnerable Populations

A study with people who inject drugs evaluated a minimally invasive test based on dried blood spots (DBS) for monitoring hepatitis C virus (HCV) infection. Using DBS samples for HCV RNA detection and genotyping, the researchers were able to effectively assess cure after treatment and differentiate between reinfection and treatment failure.

The results supported the viability of decentralizing treatment and posttreatment monitoring in people who inject drugs, who frequently face challenges accessing the health care system. Published in the Journal of Medical Virology, the study was carried out as part of a project with support from the Conquering Hepatitis Via Microelimination (CHIME) program and a PFIS grant.

Investigators from various research institutions collaborated on the project, including the Clinical Virology and New Diagnostic Tools research group, led by Elisa Martró, PhD, at Germans Trias i Pujol Research Institute (IGTP), in Catalonia, Spain, and Sabela Lens, MD, PhD, from Hospital Clínic's Viral Hepatitis Group in Barcelona

Toward eliminating hepatitis C

Aligned with both the WHO’s proposed strategy to eliminate hepatitis as a public health threat by 2030 and the Plan for Prevention and Control of Hepatitis in Catalonia, for years, Martró and her group have focused on simplifying the diagnosis of HCV by developing and validating an assay to detect viral RNA using DBS samples. 

These minimally invasive samples can be collected at harm reduction centers or drug dependence care and follow-up centers (known as CAS in Catalan), improving access to HCV diagnosis for people who inject drugs and vulnerable populations. 

While this new test has demonstrated good clinical performance as a diagnostic tool for detecting HCV RNA before treatment in previous studies conducted by the Clinical Virology and New Diagnostic Tools research group, the use of DBS samples had not been evaluated as a test for cure after treatment or for detecting reinfection after treatment.

Now, using point-of-care diagnosis, treatment, and reinfection follow-up at the REDAN La Mina harm reduction center, a multidisciplinary research group led by Martró and Lens has been able to pursue a project with a new model of care for hepatitis C. Since 2019, approximately 750 individuals who inject drugs have been tested through this initiative in collaboration with the Clinical Virology and New Diagnostic Tools Research Group at IGTP, as well as CEEISCAT and the Public Health Agency of Catalonia.

A model of decentralized hepatitis care

In this project, Martró's group aimed to evaluate the clinical performance of a previously developed HCV–RNA assay that used DBS to assess cure after treatment and detect recurrent viremia after on-site treatment at the harm reduction center compared to the commercially available HCV–RNA point-of-care test. Furthermore, they sought to assess the possibility of distinguishing between reinfection and treatment failure through HCV genotyping from baseline and follow-up DBS samples.

Typically, these assessments (cure and reinfection) are performed using venipuncture blood samples collected at health care centers, which can be difficult for people who inject drugs and have often limited access to the health care system. The recently published results demonstrate how collecting DBS samples before and after treatment can simplify these assessments through decentralized test-and-treat programs.

 "The success of the CHIME project lies in the decentralized diagnosis and treatment provided at REDAN La Mina. A nurse trained in hepatology assessments was included in the study to enroll and visit participants. The hepatologists at Hospital Clínic also reviewed each case and prescribed decentralized treatment. Additionally, Martró's group carried out HCV detection and sequencing from DBS samples collected before and after treatment. This pilot program involves on-site HCV diagnosis in less than an hour, treatment at the same center, and follow-up to assess reinfection," said Lens.

Hepatitis C detection made easier

Reinfection is common in people who inject drugs and must be treated to prevent further transmission of the virus. During early reinfection, low levels of the virus may be present, making detection in DBS samples challenging, as they only contain a small amount of blood.

Of the 193 DBS samples tested after treatment, the DBS-based assay showed 100 percent specificity and 84–96 percent sensitivity based on different relevant viral load cutoffs, as well as showed similar rates as a test of cure three months after treatment. Among the patients with recurrent viremia after treatment, 10 percent had low viral loads. Moreover, HCV genotyping allowed researchers to classify 73 percent of viremic cases as either reinfection or treatment failure.

DBS samples were collected before and after antiviral treatment if recurrent viremia was detected by the commercially available point-of-care assay. "The use of DBS allowed us to sequence the virus before and after treatment and compare the sequences to determine if the virus was the same (indicating a treatment failure) or if it was different (indicating reinfection). This information enabled the hepatologist to decide on the most appropriate antiviral combination for the second treatment," said Not.

The research shows the potential of using DBS samples for determining cure and differentiating between reinfection and relapse after antiviral treatment for HCV in people who inject drugs. The use of DBS samples makes it possible to decentralize treatment and follow-up, improving access to care for these people. Even so, Martró points out that "a small number of patients had low viral loads, which can hinder the detection of viremia and genotyping in DBS. As a result, repeat testing (e.g., every six months) is advised for individuals who are at risk of HCV reinfection."

 - This press release was originally published on the Germans Trias i Pujol Research Institute (IGTP) website