Simplifying Viral Hepatitis Testing Will Slow the Spread of Disease

Viral hepatitis B (HBV) and C (HCV) continue to spread because most people who are infected are unaware of their status.¹ However, as technology evolves, more clinicians will be able to test and treat people in whom chronic hepatitis had formerly gone unchecked. Just 9% of people infected with HBV and only 20% of those with HCV are aware that they have the infection.¹ In low-income countries, <1% of those infected know they have the virus.²

The Imperative to Stop Viral Hepatitis

Approximately 257 million people are living with chronic hepatitis B, and approximately 71 million people are living with hepatitis C.³ In 2015, viral hepatitis resulted in 720,000 cirrhosis-related deaths and 470,000 deaths from hepatocellular carcinoma.³

One of the many reasons why viral hepatitis goes unchecked is that few clinicians are aware of emerging technology that allows them to diagnose hepatitis B or C quickly.¹ To stem the epidemic of viral hepatitis, the World Health Organization (WHO) has established targets to remove hepatitis as a public health threat by 2030. Their goal is to reduce new infections by 90% and the number of deaths by 65%.³ Based on earlier studies, the WHO sees this goal as realistic. HCV could be eliminated within 20 years.⁴

Experts, however, have a different perspective. “Scale-up of testing for [hepatitis] B and C is still at a very low level, and we are far from the global targets set for 2020,” explains Philippa Easterbrook, MD, from the World Health Organization’s HIV/AIDS department in Geneva, Switzerland, in an interview with Infectious Disease Advisor.

Challenges to Testing

For a program to be successful, it requires many stakeholders to harmonize a system of testing, supply chain, scalability, and treatment coordination.² Health systems working in concert with governments need better surveillance of viral hepatitis data and must provide testing and care algorithms. Moreover, the cost of the test must be affordable for both patients and the healthcare system.

It takes a worldwide effort to adopt standards for testing protocols and algorithms, including consults with WHO, the Centers for Disease Control and Prevention, and individual departments of health. “This is usually a role for national laboratory program managers or reference laboratory leads, with technical support from external partners,” says Rosanna Peeling, PhD, professor and chair of diagnostics research of the International Diagnostics Centre at the London School of Hygiene and Tropical Medicine in the United Kingdom, in an interview with Infectious Disease Advisor. “We would usually expect this to be done in collaboration with viral hepatitis programs within ministries of health.”

Populations at risk for HCV and HBV are difficult to reach. Stigma against injection drug users and men who have sex with men (MSM) still drives many away from testing centers and clinics.¹ In resource-poor countries, low awareness of HBV and HCV as well as scant availability of testing locations hampers efforts to fight hepatitis transmission.¹

More accurate tests require sophisticated, expensive equipment and laboratories, luxuries not available in low- and middle-income countries.¹ Such regions also have a dearth of skilled healthcare workers to collect and test specimens. In addition, poor transportation and infrastructure mean that specimens cannot reach laboratories in a timely fashion.

“Awareness of these simplified algorithms is still low and so there is a need to improve dissemination,” explains Dr Easterbrook. “WHO encourages and supports countries to develop first a national hepatitis strategic plan, testing, and treatment guidance as a key first step, and to undertake a validation process of rapid diagnostic tests and development of a national testing algorithm. This all requires government commitment and funding, and establishment of designated testing and treatment sites.”

Future of Testing

Borrowing from the HIV testing paradigm, tests in development for viral hepatitis will be easier to administer. At-home self-testing became a boon to populations that were stigmatized and for those in low-resource areas. Because HIV coinfection with HBV and HCV is common, the self-testing paradigm might uncover new cases for those at highest risk for transmission. Living with both HIV and HBV or HIV and HCV coinfection affects 7.4% and 6.4% of the global population, respectively.^5,6 Most of those with HIV/HCV coinfection are people who inject drugs.⁶ Indeed, in regions where HIV carries a stigma, self-testing is the preferred method over traditional testing.⁷

As an adjunct to self-testing, Wang and colleagues found that real-time instruction and follow-up counseling boosted HIV testing rates in MSM significantly.⁸ Of the 430 MSM, 89.8% who received instruction on self-testing and counseling got tested vs 50.7% of the control group (P <.001).⁸

When point-of-care tests become more sophisticated, multiplex systems that detect the presence of HIV, HBV, HCV, syphilis, and other diseases may funnel more infected people to treatment.² Tests that circumvent blood draws — including dried blood spots (DBS), saliva, and self-testing — may speed the diagnosis and linkage to care because they do not require skilled healthcare workers to collect specimens.¹

Lange and colleagues showed that in a meta-analysis of 12 studies using DBS for HBV-DNA, the pooled estimates of sensitivity and specificity were 95% (95% CI, 83%-99%) and 99% (95% CI, 53%-100%), respectively.⁹ The same team found in a 15-study meta-analysis of HCV-RNA accuracy that pooled sensitivity and specificity were 98% (95% CI, 95%-99%) and 98% (95% CI, 95%-99%), respectively.⁹

When the same research team compared HBV surface antigen and HCV antibody and DBS test results with those of venous blood samples, they found minor differences.¹⁰ The pooled meta-analysis HBV surface antigen sensitivity and specificity in a 19-study meta-analysis were 98% (95% CI, 95%-99%) and 100% (95% CI, 99%-100%), respectively. In the 19-study pooled meta-analysis of HCV antibody, sensitivity and specificity were 98% (CI 95%, 95%-99%) and 99% (CI 95%, 98%-100%), respectively.¹⁰

Which region or country is leading the charge to slow the transmission of viral hepatitis? “For hepatitis C, there are several champion countries for action and scale up, including Egypt, Mongolia, Georgia, Australia, Punjab, India, Pakistan, and Brazil,” says Dr Easterbrook. “For hepatitis B, China has an extensive treatment program, and is now moving to achieve triple (HIV, HBV, and syphilis) elimination of mother-to-child transmission through antenatal care screening.”

Summary and Clinical Applicability

Most people who have HBV or HCV are unaware of their status. Taking a page from the HIV testing paradigms, viral hepatitis tests in development may soon be easier to perform and will detect the presence of HBV or HCV quickly. Novel testing methods will allow faster diagnosis and transition into care.

References

1. Peeling RW, Boeras DI, Marinucci F, Easterbrook P. The future of viral hepatitis testing: innovations in testing technologies and approaches. BMC Infect Dis. 2017;17(suppl 1):699.
2. Easterbrook PJ, Roberts T, Sands A, Peeling R. Diagnosis of viral hepatitis. Curr Opin HIV AIDS. 2017;12:302-314.
3. World Health Organization. Global Hepatitis Report, 2017. April 2017. Accessed December 27, 2017.
4. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol. 2014;61(1 suppl):S45-S57.
5. World Health Organization. WHO hepatitis B fact sheet. July 2017. Accessed December 27, 2017.
6. Platt L, Easterbrook P, Gower E, et al. Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis. 2016;16:797-808.
7. Johnson CC, Kennedy C, Fonner V, et al. Examining the effects of HIV self-testing compared to standard HIV testing services: a systematic review and meta-analysis. J Int AIDS Soc. 2017;20:21594.
8. Wang Z, Lau JTF, Ip M, et al. A randomized controlled trial evaluating efficacy of promoting a home-based HIV self-testing with online counseling on increasing HIV testing among men who have sex with men. AIDS Behav. 2018;22:190-201.
9. Lange B, Roberts T, Cohn J, et al. Diagnostic accuracy of detection and quantification of HBV-DNA and HCV-RNA using dried blood spot (DBS) samples – a systematic review and meta-analysis. BMC Infect Dis. 2017;17(suppl 1):693.
10. Lange B, Cohn J, Roberts T, et al. Diagnostic accuracy of serological diagnosis of hepatitis C and B using dried blood spot samples (DBS): two systematic reviews and meta-analyses. BMC Infect Dis. 2017;17(suppl 1):700.