Treatment of hepatitis B in resource-limited settings - a pilot program in East Africa

Liver disease in Ethiopia: what are the causes and how can it be treated? Liver diseases are important causes of morbidity and mortality globally. Hepatitis B and C virus infection contribute substantially to this, and these two diseases claim more than 1 million lives each year. Modern treatment of hepatitis B is virtually unavailable in poor countries due to expensive medicines and complex treatment guidelines. This resembles the situation for HIV/AIDS 10-15 years ago, when few believed that this could be effectively treated in developing countries. Over the past decade, however, we have witnessed the successful scaling up of HIV treatment in resource-limited settings, and we believe that a similar simplified approach to hepatitis B treatment could be feasible. Ethiopia is a poor country with a high prevalence of hepatitis B. Moreover, clinicians report high prevalence of unexplained liver disease, which could be related to the widespread use of khat, a central stimulant herb. Our project had the following objectives: a) Identify the most important causes of liver disease in Ethiopia, with focus on the eastern region Harar where many patients die of unexplained liver disease. b) Set up a treatment program for chronic hepatitis B, which is simple enough and cheap enough to be feasible in a poor country. The treatment program for hepatitis B aimed to be reproducible in other poor countries. Hence, we used simple and safe methods to determine who needed treatment. We avoided advanced and risky procedures like liver biopsy, and rather used biochemical markers like APRI (based on AST and platelets) and liver stiffness measurements (using Fibroscan) to assess the degree of liver fibrosis/inflammation. Oral tenofovir was the drug of choice based on favorable cost and well documented effect. The hepatitis B clinic at St. Pauls Hospital in Addis Ababa opened in February 2015, and we included a total of 1303 patients with chronic hepatitis B. Of these, 278 started tenofovir treatment, making our program one of the largest treatment centers for hepatitis B in Africa. Patients were followed up regularly with blood tests and Fibroscan to assess treatment effect. There were no severe adverse effects of the therapy, and only a few patients were reported lost to follow-up (4.4%). We identified several simple and affordable markers of liver fibrosis, which may be suitable to determine treatment eligibility in an African setting. The prevalence of hepatitis D co-infection was low (0.9%); however, patients with co-infection had more advanced liver fibrosis and a poorer prognosis. Measurement of hepatitis B viral load is a mandatory analysis to determine whether antiviral treatment should be commenced. Unfortunately, few laboratories in Africa offer this test, and plasma degenerates rapidly during shipment. We studied the use of dried blood spots (DBS) for hepatitis B viral load, which previously has been proved to be a feasible method for HIV viral load quantification. Our data showed that this method is also reliable for the measurement of hepatitis B viral load, even after storage at room temperature for up to 12 weeks. We concluded that this method is suitable for use low-income countries, and that DBS can be an important tool to promote access to treatment in such settings. In the sub-study focusing on causes of liver disease in Ethiopia, we set up a case-control study where patients with signs and symptoms of advanced liver disease were enrolled at two public hospitals in eastern Ethiopia over a one-year period. We also recruited a control group (without liver disease) from other hospital departments. In total, 150 patients with advanced liver disease and 300 healthy controls were enrolled. All patients underwent a range of blood tests and other investigations in order to reveal the cause of their disease, including tests for hepatitis A-E, immunological diseases and parasitic infections. Moreover, we collected information on exposure to potential liver toxic compounds like alcohol, khat, pesticides, etc. Our data showed that approximately one third of the liver patients had chronic hepatitis B; however, in more than half of the patients no diagnosis could be identified. Data from this study showed, for the first time, that khat chewing is associated with a high risk of liver disease, but final results are still not published. One Norwegian and two Ethiopian PhD fellows were involved in the project, all of whom are expected to defend their thesis during 2018. In addition, four nurses, four laboratory technicians and one data clerk have been employed to take care of the hepatitis B clinic. The project is scheduled to end by October 2017, but further funding is being sought to ensure the sustainability of the hepatitis B treatment program. Result from the study have been published in high-ranking international scientific journals (PLoS One, Liver Int, BMC Infect Dis).

Chronic viral hepatitis is a major health problem globally. Each year nearly one million deaths are attributable to either hepatitis B or C. In Somaliland about 10% of the general population are infected with hepatitis B. Oral antiviral treatment of hepat itis B exists, but high costs and advanced laboratory requirements have been barriers to offer such treatment in resource-limited settings, resembling the situation in treatment of HIV/AIDS a decade ago. The present study will investigate a simplified app roach to hepatitis B treatment in resource-limited settings, inspired by the recent success of HIV treatment in such settings. The critical research question is how to identify patients with expected benefit of treatment in the absence of advanced laborat ory support. A WHO expert panel recently suggested treatment criteria for use in settings without advanced laboratory facilities, but these criteria have not yet been tested out in real life. We will build on and develop the WHO approach to treatment of h epatitis B, aiming to develop a treatment protocol that can be feasible in other resource-limited countries. The potential public health benefit for poor people in low- and middle-income countries is substantial. Furthermore, we will study causes of liver diseases in the 2 countries in a broader sense, in order to get an overview of the problem and the relative contribution of viral hepatitis in this setting. This study brings together scientific institutions in Norway, UK, Ethiopia and Somaliland, and aims to develop and support our partners in the South.