Viral load quantification: Hepatitis therapy barrier
Posted on April 6, 2015
Hepatitis viral load quantification is lacking in low- and middle-income countries, and this is a major barrier to the provision of therapies to patients who need them
Viral load quantification is considered a mandatory component of the diagnostic work-up in all international liver society guidelines. Low- and middle-income countries typically lack access to viral load quantification, and this has become a major barrier to the provision of hepatitis B or C therapies to patients who need them. The lack of access to costly viral load testing and hepatitis therapy in resource-limited settings makes viral hepatitis a “silent epidemic with major consequences.”
In a recent commentary in the Journal of Viral Hepatitis, Dr. A Johannessen addresses the need for reliable, cheap, and easy-to-use assays for hepatitis B and C point-of-care testing in resource-limited settings (Johannessen A, J Viral Hepat. 2015;22(4):362-365). These assays, performed at the site of patient care, would be a possible solution to the high costs, laboratory sophistication, and logistical complexity typically associated with standard, laboratory-based hepatitis testing.
Point-of-care kits for viral hepatitis load quantification are not widely available, which Dr. Johannessen notes is not the case in the HIV/AIDs market, which has gained major international investments. One product, Truenat® (Molbio Diagnostics, Goa, India), for HBV DNA quantification is advertised as a point-of-care assay, but there are no peer-reviewed publications on its performance. The US-based company Wave 80 Biosciences is developing a point-of-care kit for HBV DNA quantification as well as a qualitative assay for HCV RNA detection, building on their existing HIV viral load assay EOSCAPE-HIV® (Wave 80 Biosciences, San Francisco, CA, USA). In addition, the UK biotechnology company Epistem received a prestigious grant award in 2013 to develop an HCV point-of-care device for viral load testing and genotyping.
Point-of-care assays should be designed specifically to operate under basic conditions with minimal maintenance requirements and not just be “high-tech solutions forced to fit low-tech settings”. Dr. Johannessen outlines desired specifications for a point-of-care HBV or HCV viral load assay:
- No need for specialized laboratory facilities
- Closed system to avoid contamination
- Long shelf life in tropical climate
- No need for cold chain transportation or refrigerated storage
- Ease of use
- Adequate sensitivity
Sustainability is another major concern with all technological devices, and Dr. Johannessen notes that it should be a prerequisite that the manufacturers provide adequate training and service agreements locally.
Dried blood spots (DBS) could be a feasible and reliable alternative to point-of-care assays for hepatitis C. DBS solves the problem of storage and shipment of samples in places with poor infrastructure, as they can be stored for weeks at ambient temperature without clinically significant degradation of nucleic acids. Use of DBS is limited by the small amount of plasma per blood spot and less efficient nucleic acid extraction, which gives a reduced sensitivity in samples with low-level viremia. With regard to hepatitis C, this rarely has any practical consequences, as most untreated patients have viral loads (far) above 1000 IU/ml. This could, however, be a major drawback with regards to diagnosing chronic hepatitis B. Hepatitis B e-antigen (HBeAg) negative hepatitis is now the main type of chronic hepatitis B worldwide. These patients typically have fluctuating viral load levels in the lower to medium range, and it is often difficult to distinguish them from inactive carriers. A lack of precision in DBS could therefore jeopardize the management of these patients.
In the absence of viral load measurements, doctors in resource-limited settings are left virtually blindfolded in the management of their patients with hepatitis. Point-of-care viral load assays for hepatitis B and C have the potential to bridge this gap and prove valuable tools for expansion of treatment globally. Dr. Johannessen also notes that sustainable funding mechanisms must be established if viral hepatitis is to be successfully diagnosed and treated worldwide.