A new diagnostic test, called TREAT-B can accurately identify HBV positive patients who require treatment. [©inkaone/Fotolia.com]
A new diagnostic test, called TREAT-B can accurately identify HBV positive patients who require treatment. [©inkaone/Fotolia.com]

An international research team has devised a simple $20 blood test that could be used widely in low-income and middle-income countries (LMICs) to help determine which patients with hepatitis B require immediate treatment. The affordable test is based on measurements of hepatitis B virus e antigen (HBeAg), and levels of the liver enzyme alanine aminotransferase (ALT), to generate a diagnostic score, which the researchers say is as effective as existing, far more complicated, and expensive methods for assessing treatment eligibility.

The team, headed by scientists at the Pasteur Institute in Paris, Imperial College London, and the Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene & Tropical Medicine, devised the score using data from more than 800 hepatitis B patients in The Gambia who were part of the PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa) study. They subsequently validated the diagnostic assay in cohorts of African patients in other countries.

“These results show that this simple and inexpensive test could be an accurate way to diagnoses patients in need of hepatitis B treatment in countries with limited resources,” suggests Imperial's Maud Lemoine, Ph.D. who is co-author of the team’s study in the Journal of Hepatology, and who works with the MRC The Gambia Unit. “This could potentially help diagnose and subsequently treat thousands of people across Africa.” Dr. Lemoine is also a member of the World Health Organization (WHO) guideline development group for the management of chronic hepatitis B/C.

The researchers, including colleagues in organizations and institutions in Africa and Europe, describe their results in a paper entitled “Development of a Simple Score Based on HBeAg and ALT for Selecting Patients for HBV Treatment in Africa.”

Viral hepatitis is a major global health problem, and estimates suggest that hepatitis B was responsible for about half of the 1.45 million viral hepatitis-related deaths that occurred worldwide in 2013. In 2016 the WHO set in motion what the researches call “an ambitious strategy” to eliminate viral hepatitis as a public health threat by 2030, with the aim of reducing the incidence of chronic hepatitis B virus (HBV) infection by 90%, and its mortality by 65%. “The WHO also set a global target for treatment coverage in people with chronic HBV infection eligible for antiviral therapy from 8% (2015) to 80% (2030),” the team explains.

Screening for HBV infection is relatively inexpensive using the HBsAg test, and HBV treatment itself, costing less than $50 a year per patient, should no longer be an obstacle, the authors point out. Treatment is generally lifelong, and not all chronic HBV infections do result in liver-related deaths. As a result, international guidelines require the selection of patients who are most likely to benefit from antiviral therapy. However, the team suggests, determining which patients do need treatment is not simple.  “…clinical evaluation of treatment eligibility after confirming positive HBsAg remains complex and expensive.” The selection process involves evaluating viral replication, liver fibrosis, and inflammation, and, as the researchers note, “the recommended tools to assess these conditions (nucleic acid test to measure HBV DNA levels, liver biopsy and Fibroscan® to evaluate fibrosis stage) are rarely accessible and affordable in LMICs.” As they note, “To scale up and decentralize screening, clinical assessment, and treatment services in LMICs, it is essential to develop simple and validated diagnostic tests that are feasible and affordable.”

As an alternative approach to assessing treatment eligibility, the team has now developed and validated a diagnostic score, known as TREAT-B (treatment eligibility in Africa for the HBV), which is based on simple blood tests that are widely available in local laboratories in LMICs, and which don’t rely on HBV DNA, liver tests, or Fibroscan.

The researchers evaluated clinical, hematological, biochemical, and virological variables that are commonly used to assess the severity of HBV-related liver disease, in more than 800 treatment-naïve, HBsAg-positive, and HBV mono-infected patients enrolled in the PROLIFICA screen-and-treat program for HBV in the Gambia. Based on univariate, and subsequently multivariate, analyses, the researchers used these results to derive the TREAT-B score, based on measurements of just HBeAg and ALT, which could accurately determine which patients required therapy. They then validated the score using historical datasets from independent cohorts of patients in five countries: Senegal, Burkina Faso, Germany, France, and the U.K.

The TREAT-B score was found to accurately identify HBV-positive patients who required treatment with 85% sensitivity and 77% specificity. “TREAT-B correctly identified 82–85% of patients meeting the international treatment criteria based on the conventional reference tests (serum HBV DNA and liver biopsy or Fibroscan), and 77–78% of patients who do not fulfil these reference criteria,” the team writes. “Moreover, TREAT-B performed well irrespective of the age groups, HBV genotypes, the presence of obesity, or cirrhosis, and better than the WHO treatment criteria.”

Encouragingly, there was no benefit of adding HBV DNA evaluation to the TREAT-B score. Although serum HBV DNA level currently represents a key predictor for the of HBV-related liver diseases and liver cancer, the assay requires real-time PCR to measure viral load, which is not accessible or affordable for the majority of people living in LMICs, the authors point out.

They suggest that in comparison with international treatment criteria, the TREAT-B score demonstrates many advantages and is ideally suited to resource-limited settings. “… both ALT and HBeAg measurements are widely available in LMICs, and their total cost (US$ 60).”  The TREAT-B score is in addition much more user-friendly, they point out, and could feasibly be carried out by nonspecialist doctors or nurses. And while the WHO treatment criteria for LMICs necessitate several visits for ALT measurement, TREAT-B requires only a single blood sample.

“TREAT-B represents a promising simple and low-cost diagnostic score that can assist physicians to easily identify HBV-infected individuals in need of treatment in Africa,” the authors conclude. “Its use may contribute towards global HBV elimination by facilitating the scale up and decentralization of HBV treatment programs in LMICs.”

Study co-author Yusuke Shimakawa, Ph.D., from the Pasteur Institute, adds. “Once these results are validated by further studies, they could be potentially integrated into the WHO guidelines and local guidelines—and implemented in daily practice. There is great potential to diagnose more people and improve access to treatment.”



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