A Molecular Mission

In 2016, the WHO took the first steps toward what would become an ambitious plan to rein in viral hepatitis. Using data from 2015 as a baseline, it aims to achieve a 90 percent reduction in cases and 65 percent fewer deaths by 2030 (1). Its efforts are primarily focused on hepatitis B and C, which can lead to cirrhosis, liver cancer, and other issues associated with increased mortality; collectively, the WHO estimates this dramatic reduction in cases could help prevent 4.5 million premature deaths (2).

As part of the program, the WHO also aims to eliminate vertical transmission of hepatitis B from mother to baby before or at birth, when the infant’s risk of chronic infection is exceptionally high. Other goals are more general, such as reducing the overall incidence of hepatitis B and C. The initiative includes recommendations on how countries can monitor their progress and contribute to the reduction in hepatitis incidence and death, with diagnostic testing, vaccination, and treatment all being important components.

Testing guidelines

With so many circulating strains of hepatitis, it can be challenging for laboratory professionals to keep track of when and how to test patients in different populations. Here’s what the US Centers for Disease Control and Prevention (CDC) suggests…

For hepatitis B, screening all adults (18 years or older) at least once with a triple panel serology test covering surface antigen and antibody, plus the IgM antibody and total antibody to the hepatitis B core antigen (3). That’s an expansion beyond the original guidelines, which called for screening based solely on surface antigen detection.

The CDC also encourages tailored testing regimens for specific patient types. All pregnant women should be screened during the first trimester, if possible, for the hepatitis B surface antigen. Babies born to women with hepatitis B – including women who have tested positive for the hepatitis B surface antigen or antibodies to the surface antigen – should be tested for those same antigens and antibodies. In addition, the CDC recommends periodic testing for higher-risk groups, including: i) people with a history of sexually transmitted infections; ii) people who are or have been incarcerated; iii) people born in regions where hepatitis B is more prevalent; iv) people on dialysis; v) men who have sex with men, and; vi) people with a history of injection drug use, among others.

Recommendations for hepatitis C testing are quite similar. The CDC advises screening all adults for this virus at least once, except for those living in areas with extremely low prevalence (0.1 percent or less) of hepatitis C (4). Testing is recommended for all pregnant women, again with an exception for those in low-incidence regions.

The CDC also encourages routine hepatitis C testing for specific patient groups at increased risk: people who inject drugs or share needles with others, and people undergoing dialysis. For other high-risk groups, the CDC recommends one-time hepatitis testing regardless of age. This includes people with HIV, organ transplant or blood transfusion recipients, children whose mothers have hepatitis C, and healthcare professionals exposed to the virus.

Safe controls needed

With such a broad need for hepatitis testing, it is worth considering one of the most important — but often underappreciated — components of tests: safe, high-quality controls. Ideally, diagnostic kits will include the controls needed to run each test; however, in reality, many clinical laboratory customers find themselves scrambling to acquire their own controls for these workflows.

Too often, that search sends lab professionals to unsafe controls: an attenuated virus or remnant patient samples. With the extremely high transmissibility and durability of hepatitis strains, any viable virus is too dangerous for clinical lab teams to work with on a regular basis. Relying on patient samples also introduces the challenge of an unsteady supply, meaning lab teams cannot know for sure they will have the controls needed to meet testing demand.

To protect lab staff, the best approach is to use a synthetic control, which is designed to mimic the real viral genome but without the risk of infection. Because they are manufactured in vitro, they can be easily and rapidly customized for a wide range of targets. Synthetic non-infectious controls also simplify shipping and storage while maximizing cost savings.

Importantly, some synthetic molecular controls are designed with so-called “armor” – an extra layer of viral-like capsid protein that stabilizes and protects nucleic acids. Armoring imparts RNA and DNA degradation resistance in the majority of biological matrices. This process enables their use as an exogenous control for extraction with most nucleic acid isolation methods, giving clinical lab teams the ability to monitor assay performance across the entire testing workflow. Armored hepatitis C controls have demonstrated compatibility across several different clinical assay formats and are a valuable tool in the development of molecular diagnostics for viral hepatitis (5).

Looking ahead

Amid high-priority efforts to eliminate hepatitis as a major public health threat, diagnostics must play a crucial role. With the boon of additional molecular testing capacity built during the pandemic, many clinical laboratories now have the chance to scale up their hepatitis screening to contribute to these efforts – a rare and hard-won opportunity that could have significant benefits for global health.