Among the many initiatives of the World Health Organization (WHO), the ‘integrated global alert and response system for epidemics and other public health emergencies’ (http://www.who.int/csr/en/) is one of the most important for confronting and preventing global epidemics. Hepatotropic viruses are an important part of this project because of their universal diffusion and their impact on liver-related mortality. Among them, the hepatitis B virus (HBV) is the most prevalent worldwide. It is estimated that 2 billion people have had contact with the virus and that about 350 million people are chronic carriers (1). More importantly, almost half of the people in the world live in geographical areas of high HBV endemicity, and a number of these areas suffer from poor economic conditions and weak national health systems (Table 1). In countries that have significant constraints on resources, the implementation of effective strategies for the prevention of viral transmission and the creation of national programmes to diagnose and treat HBV-related chronic liver disease are of paramount importance (2). However, it is extremely difficult to balance the weight of economic costs and desirable health benefits for the entire population. With this in mind, a team of experts in the field of viral hepatitis was asked by the WHO to write a concept paper aimed at providing solid guidelines for the implementation of treatment strategies in developing countries. The report is published in this issue of the journal (3).
|Africa||All countries except Algeria, Djibouti, Egypt, Libya, Morocco, Tunisia|
|Western Pacific||All countries except Australia, Guam, Japan and New Zealand|
|Southeast Asia||All countries except Afghanistan, Bangladesh, Bhutan, India, Malaysia, Maldives, Nepal, Pakistan and Sri Lanka|
|East Asia||China, Hong Kong, Mongolia, North Korea, South Korea, Taiwan|
|Middle East||Jordan, Saudi Arabia|
|Eastern Europe and Northern Asia||Albania, Armenia, Azerbaijan, Bulgaria, Croatia, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Tajikistan, Turkmenistan and Uzbekistan|
|America||North Alaskan Natives, indigenous populations in Northern Canada, Greenland, Amazonian areas of Bolivia, Brazil, Columbia, Peru, Venezuela|
The paper analyses two major concerns: the feasibility of offering therapeutic options to patients with chronic HBV infection in resource-constrained settings and possible strategies for increasing access to therapies that are aimed at reducing liver-related mortality.
At present, there are a number of antiviral agents with great potency against HBV [see table 2 of reference (3)]. These drugs are also very effective against HIV infection, raising the opportunity of treating both diseases simultaneously. This is important because there is considerable overlap in the epidemiology (risk factors, routes of transmission, geographical areas) of HBV and human immunodeficiency virus (HIV), and it is estimated that at least 4 million patients are co-infected, 3 million in Africa alone (4). Given the fact that highly active antiretroviral therapy (HAART) is not effective for HBV infection in about 10% of coinfection, treatment with tenofovir plus lamivudine or emtricitabine in these patients is highly recommended. Moreover, the initiation of therapy for HIV infection should be undertaken with great caution in order to avoid the possibility of HBV viral resistance in coinfected patients, which would undermine all possible benefits of HAART in terms of life expectancy.
For HBV-monoinfected patients, the panel suggests following relevant continental society guidelines in choosing the most appropriate drug, with the primary indication being the treatment of patients with progressive disease. However, because HBV-DNA testing and liver biopsy are not widely available in most resource-constrained countries, treatment should be largely restricted to cirrhotic patients, compensated or decompensated, and to patients with active disease documented by elevated transaminases.
The second part of the paper is dedicated to the development of strategies for greater availability of antiviral therapy for HBV infection in order to decrease morbidity and mortality. Taking into account the limited economic resources, the use of drugs should be prioritized for patients with cirrhosis or HIV/HBV coinfection. The panel also recommends the use of tenofovir and entecavir as first-line treatment, given their high genetic barrier, and suggests avoiding the use of lamivudine, emtricitabine and telbivudine as single agents because of the objective impracticality of monitoring and managing the emergence of viral mutants. Entecavir is also very effective in treating chronic HBV infections, but is more expensive, and acts as a potent partial inhibitor of HIV-1 replication; hence, the extensive use of entecavir in this setting should be evaluated very carefully (5). The last part of the paper is a road map for new research projects, indicating areas of possible interventions, such as estimating the prevalence of HIV and HCV infection in HBsAg-positive patients, evaluating the impact of anti-viral therapy on the natural progression of liver disease and developing new and inexpensive tools for testing for HBV-DNA and assessing liver fibrosis.
There are some points that the expert panel did not cover. The first is the need for screening for the hepatitis delta virus (HDV) in areas of high endemicity for HBV and HIV. It is well known that HDV coinfection is responsible for a more aggressive disease and poor outcome (6). Because diffusion of this disease is evolving continuously (7, 8), new data on seroepidemiology in many developing countries are sorely needed. Finally, no formal pharmacoeconomic evaluation was suggested for forecasting the progressive escalation of health expenditures through the use of drugs such as nucleos(t)ide analogues, which are life-long and will, therefore, create an annual increase in the number of patients under treatment.