Navigating TREAT-B in resource-limited settings
Authors: Anna Kramvis, Daryl T Y Lau
Journal: The Lancet Global Health (2023)

WHO is aiming to eliminate hepatitis as a public health problem by 2030. Interventions that can lead to hepatitis B virus (HBV) elimination include prevention with an effective HBV vaccine and identifying infected individuals for treatment. According to the 2017 WHO Global Hepatitis Report, the WHO Western Pacific region has the highest number of HBsAg-positive individuals (115 million, prevalence estimated at 6·2% [95% uncertainty interval 5·1–7·6]), followed by the African region (60 million, 6·1% [4·6–8·5]).1WHOGlobal hepatitis report, 2017.https://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/Date: April 19, 2017Date accessed: November 4, 2023Google Scholar With approximately 20% of the global burden of HBV, sub-Saharan Africa has a high incidence of HBV-associated hepatocellular carcinoma, especially among young adults.2Spearman CW Dusheiko G Jonas E et al.Hepatocellular carcinoma: measures to improve the outlook in sub-Saharan Africa.Lancet Gastroenterol Hepatol. 2022; 7: 1036-1048Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar An alarming statistic in sub-Saharan Africa is that only 0·1% of individuals who are aware of being infected and eligible for treatment will go on to receive antiviral therapy.3The Polaris Observatory CollaboratorsGlobal prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study.Lancet Gastroenterol Hepatol. 2018; 3: 383-403Summary Full Text Full Text PDF PubMed Scopus (1183) Google Scholar Suboptimal HBV screening and unavailable cost-effective diagnostic tools, including HBV DNA PCR tests, are important contributors to low HBV treatment rates in sub-Saharan Africa. In a timely study, Liem B Luong Nguyen and colleagues4Luong Nguyen LB Lemoine M Ndow G et al.Treat All versus targeted strategies to select HBV-infected people for antiviral therapy in The Gambia, west Africa: a cost-effectiveness analysis.Lancet Glob Health. 2024; 12: e66-e78Google Scholar have compared different treatment algorithms to identify a cost-effective regimen that can address the disparities in The Gambia and, potentially, similar resource-limited settings. Such studies focusing on the demographics of low-middle income countries are necessary to inform policy makers and national action plans to meet the WHO goal of hepatitis elimination by 2030. The HBV treatment algorithms compared by Nguyen and colleagues included the European Association for the Study of the Liver (EASL) 2017 guideline,5European Association for the Study of the LiverEASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.J Hepatol. 2017; 67: 370-398Summary Full Text Full Text PDF PubMed Scopus (3596) Google Scholar a simplified algorithm using only hepatitis B e antigen (HBeAg) and alanine aminotransferase (Treatment Eligibility in Africa for the Hepatitis B Virus [TREAT-B] score),4Luong Nguyen LB Lemoine M Ndow G et al.Treat All versus targeted strategies to select HBV-infected people for antiviral therapy in The Gambia, west Africa: a cost-effectiveness analysis.Lancet Glob Health. 2024; 12: e66-e78Google Scholar and a Treat All approach for all HBV-infected individuals. These algorithms were compared with the WHO 2015 HBV treatment criteria,6WHOGuidelines for the prevention, care and treatment of persons with chronic hepatitis B infection.https://www.who.int/publications/i/item/9789241549059Date: March 1, 2015Date accessed: November 27, 2023Google Scholar as the base-case scenario. The authors found that disability-adjusted life years averted were highest for the Treat All approach, followed by the TREAT-B, WHO, and EASL algorithms in decreasing order. In an ideal world, the Treat All strategy would be the most effective in averting both morbidity and mortality, and such a Treat All strategy has been effective for HIV in sub-Saharan Africa.7WHOConsolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach, 2nd edn.https://www.who.int/publications/i/item/9789241549684Date: June 1, 2016Date accessed: November 27, 2023Google Scholar However, considering the resource limitations, operational constraints, and competing priorities in sub-Saharan Africa,8Kramvis A Challenges for hepatitis B virus cure in resource-limited settings in sub-Saharan Africa.Curr Opin HIV AIDS. 2020; 15: 185-192Crossref Scopus (11) Google Scholar a modified selective treatment approach such as TREAT-B would be better than no roll-out of antiviral therapy for HBV in this region. As the antiviral drugs used for HIV also act against HBV, co-infected individuals in sub-Saharan Africa can currently receive treatment. A dedicated treatment strategy is thus urgently needed to target HBV monoinfected individuals. Although the infrastructure and capacity that have been developed for HIV can potentially be utilised in implementing effective HBV testing strategies in sub-Saharan Africa, a unique cost-effective diagnosis and treatment cascade might be needed for those with HBV monoinfection. In their study, Nguyen and colleagues showed that US$0·66 million versus $1·14 million would be required to treat 5000 Gambians aged 20 years for 5 years with TREAT-B versus Treat All. Importantly, in their analysis of projected health outcomes over a lifetime in 100 000 individuals, the incremental cost-effectiveness ratio for Treat All ($2149 per disability-adjusted life year averted) was six times higher than the cost-effectiveness threshold for The Gambia ($352). The current oral medications for chronic hepatitis B viral infection require long-term treatment, and thus medication compliance and regular monitoring also need to be factored into the cost-effectiveness treatment model. With the TREAT-B algorithm, HBeAg-positive people would be given treatment priority over HBeAg-negative people. In The Gambia, HBeAg-negative chronic hepatitis B virus infection has been estimated to account for about 80% of infected adults, with 7–18% of these individuals having HBV DNA concentration higher than 5 log copies per mL.9Mendy ME McConkey SJ Sande van der MAB et al.Changes in viral load and HBsAg and HBeAg status with age in HBV chronic carriers in The Gambia.Virol J. 2008; 5: 49Crossref PubMed Scopus (0) Google Scholar Thus, HBeAg-negative chronic hepatitis B virus infection could potentially be undertreated with a TREAT-B approach. Furthermore, the disability weights associated with hepatocellular carcinoma and antiviral therapy might be different in other sub-Saharan Africa countries and resource-limited regions. Confounding factors such as exposure to the fungal toxin aflatoxin (from eating foods contaminated with Aspergillus species), poverty, and high HIV prevalence, with long-standing treatment with lamivudine-containing regimens for HIV, might lead to disabilities in these low-income regions that are different to those in higher income countries. It is important that these factors are taken into consideration in evaluating effective HBV treatment strategies. For far too long, HBV has been overshadowed by the infectious agents causing AIDS, malaria, and tuberculosis, with the relative amount of funding targeted to viral hepatitis being disproportionate to its burden of morbidity and mortality.10Stanaway JD Flaxman AD Naghavi M et al.The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013.Lancet. 2016; 388: 1081-1088Summary Full Text Full Text PDF PubMed Scopus (981) Google Scholar Time is already running out to meet the WHO elimination target by 2030, and there is an urgency to address the unmet needs of HBV therapy. Action is required, and the cost-effectiveness study presented by Nguyen and colleagues on alternative simplified HBV testing and treatment algorithms is a step in the right direction. Simplified strategies such as TREAT-B need to be validated in sub-Saharan Africa and various settings to establish its potential effectiveness before universal implementation. However, the benefit of expanded testing and treatment will probably outweigh any risks associated with treatment. We declare no competing interests. AK is a member and DTYL the co-chairperson of the Management of Chronic Hepatitis B in Resource-Limited Settings Working Group of the International Coalition to Eliminate Hepatitis B Virus. Treat All versus targeted strategies to select HBV-infected people for antiviral therapy in The Gambia, west Africa: a cost-effectiveness analysisAlthough the Treat All strategy might be the most effective, it is unlikely to be cost-effective in The Gambia. A simplified strategy such as TREAT-B might be a cost-saving alternative. Full-Text PDF Open Access