Daniel Lavanchy

Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures

Summary.  Hepatitis B virus (HBV) infection is a serious global health problem, with 2 billion people infected worldwide, and 350 million suffering from chronic HBV infection. The 10th leading cause of death worldwide, HBV infections result in 500 000 to 1.2 million deaths per year caused by chronic hepatitis, cirrhosis, and hepatocellular carcinoma; the last accounts for 320 000 deaths per year [ 1, 2 ]. In Western countries, the disease is relatively rare and acquired primarily in adulthood, whereas in Asia and most of Africa, chronic HBV infection is common and usually acquired perinatally or in childhood. More efficacious treatments, mass immunization programs, and safe injection techniques are essential for eliminating HBV infection and reducing global HBV‐related morbidity and mortality. Safe and effective vaccines against HBV infection have been available since 1982. The implementation of mass immunization programs, which have been recommended by the World Health Organization since 1991, have dramatically decreased the incidence of HBV infection among infants, children, and adolescents in many countries [ 2 ]. However, not all countries have adopted these recommendations and there remains a large number of persons that were infected with HBV prior to the implementation of immunization programs. Antiviral treatment is the only way to reduce morbidity and mortality from chronic HBV infection. Conventional interferon alfa and lamivudine have been the primary treatments to date. Conventional interferon alfa produces a durable response in a moderate proportion of patients but has undesirable side‐effects and must be administered subcutaneously three times per week. Lamivudine also produces a response in a modest proportion of patients and causes few side‐effects [ 3 ]. However, prolonged treatment is often necessary to prevent relapse on cessation of therapy, and continuous treatment can lead to the development of lamivudine resistance [ 4 ]. Promising emerging new treatments include adefovir [ 5 ], entecavir [ 6 ] and peginterferon alfa‐2a (40 kDa) [ 7 ].

The global burden of hepatitis C

Hepatitis C is of concern both to industrialized and developing countries. Preliminary unpublished estimates of the global burden of disease (GBD) attributable to HCV‐related chronic liver disease seem to be substantial. Therefore, the reduction of global mortality and morbidity related to chronic hepatitis C should be a concern to public health authorities, and primary, secondary and tertiary prevention activities should be implemented and monitored in each country, with precise targets set to be reached. In order to decide on national health policies, there is a need to estimate the burden of disease, globally, regionally and nationally. To evaluate the GBD, three components have to be assessed: 1) The global, regional and national burden of morbidity and mortality associated with HCV infection, based on prevalence, incidence, transmission and economics; 2) The natural history of HCV infection, including ‘healthy individuals’; and 3) The areas for which more research is needed. A working group was created to assist the World Health organization (WHO) in estimating the GBD associated with HCV infection.

Worldwide epidemiology of HBV infection, disease burden, and vaccine prevention

Worldwide, hepatitis B virus (HBV) is the most common among those hepatitis viruses that cause chronic infections of the liver in humans, and it represents a global public health problem. Chronic hepatitis caused by HBV is the major cause of hepatocellular carcinoma (HCC) worldwide, and remains therefore a major public health problem globally. This fact is related to both the continuing occurrence of frequent new infections and to the presence of a large reservoir of persons chronically infected, which may develop severe and fatal complications of chronic liver disease. Hepatitis B and all of the complications resulting from it, as well hepatitis D (HDV) and its complications, are globally preventable by hepatitis B vaccination, and therefore elimination of HBV transmission and of new acute and chronic infections is a feasible goal.

Historical epidemiology of hepatitis C virus (HCV) in selected countries

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV‐infected populations are critical for addressing HCV‐related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV‐related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3–5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

Influenza and the work of the World Health Organization

Before World War I, influenza was not considered a particularly serious problem. The great pandemic of 1918-1919 changed all that, and the possibility that such a catastrophe could occur again has conditioned all subsequent developments. In epidemiological terms, the hallmark of an influenza is the excess mortality that it causes combined with an enormous burden of ill-health that saps the energy of individuals, families and communities throughout the whole world. In order to engage in influenza prevention and control, the global influenza surveillance network was set up by World Health Organization (WHO) in 1948 as a worldwide alert system for the identification of new influenza viruses, gathering information from 110 participating laboratories in 82 countries and four WHO Collaborating Centers for Influenza reference and research: Centers for Disease Control and Prevention, Atlanta (USA), National Institute for Medical Research, London (UK), WHO Collaborating Centre for Influenza Reference and Research, Melbourne (Australia) and the National Institute for Infectious Diseases, Tokyo (Japan). This network helps WHO to monitor influenza activity all over the world and provides the organization with the viral isolates and information it requires to decide which new virus strains will be used to produce influenza vaccines during the following season. Each year, information about the isolates over the previous 12 months is analyzed and used to determine the composition of the influenza vaccine to be administered during the coming influenza season both for the northern and southern hemisphere. If necessary, the recommendations for the southern hemisphere differ from the ones formulated for the northern hemisphere vaccine. The information supplied by this network enables the organization to regularly update its World Wide Web (WWW) site (FluNet), which reports on the situation of diseases. This network will also enable the WHO to detect a new influenza pandemic as early as possible.

Vaccine Safety Controversies and the Future of Vaccination Programs

In the years following the hepatitis B vaccination/multiple sclerosis controversy, a number of new issues regarding vaccine safety have been raised, in some cases leading to more debate and confusion. Against this background, an international group of experts was convened to review the current points of view concerning the use of thimerosal as a preservative and its potential risks; the suggested link between thimerosal-containing vaccines and acute lymphoblastic leukemia; the alleged association between aluminum-containing vaccines/macrophagic myofasciitis and general systemic complaints; a possible link between vaccination and autoimmune pathology; and a hypothetical link between measles-mumps-rubella vaccination and autism. At present, there are no data to conclude that childhood vaccines, and in particular hepatitis B vaccine, pose a serious health risk or justify a change in current immunization practice. However, vaccine “scares” continue to have an international impact on immunization coverage. Creating a positive environment for immunization can be achieved by repositioning the value of vaccines and vaccination, supported by evidence-based information. The role of international organizations, the media, and the industry in the implementation of communication strategies was discussed and the impact of litigation issues on vaccination was evaluated. The Viral Hepatitis Prevention Board confirms its commitment to current recommendations for universal and risk group hepatitis B vaccination and further encourages the conduct of vaccine safety studies and the dissemination of their results.

Hepatitis B virus infection in dentistry: a forgotten topic

Summary.  More than two billion people have been infected with hepatitis B virus (HBV). Globally, 350–400 million suffer from chronic HBV infection. It is postulated that dentists and dental staff are infected and transmit the virus to their patients more than any other occupation. The aim of this article is to review the HBV incidence in dental society, the points of view of dentists and their patients regarding transmission of the virus during dental procedures, the occurrence of HBV outbreaks in dental clinics and the importance of methods of preventing HBV infection in dentistry.

Viral hepatitis: global goals for vaccination.

In countries where hepatitis A is highly endemic, exposure to hepatitis A virus (HAV) is almost universal before the age of 10 years, and large-scale immunization efforts are not required. In contrast, in areas of intermediate endemicity or in transition from high to intermediate endemicity, where transmission occurs primarily from person to person in the general community (often with periodic outbreaks), control of hepatitis A may be achieved through widespread vaccination programmes. Hepatitis B virus (HBV) is one of the worlds most widespread infectious agents and the cause of millions of infections each year. Between 500,000 and 700,000 people die each year from chronic infection-related cirrhosis, hepatocellular carcinoma (HCC) or from acute hepatitis B. Hepatitis B vaccine provides protection against infection and its complications including liver cirrhosis and HCC. It is therefore, the first vaccine against a cancer, the first vaccine protecting from a sexually transmitted infection, and the first vaccine against a chronic disease ever licensed. Control and significant reduction in incidence of new HBV infections as well as hepatocellular carcinoma has repeatedly been reported in countries in East Asia (i.e. Taiwan) and Africa (i.e. The Gambia). Two experimental vaccines against hepatitis E have been developed; one of them has been recently licensed but is not yet widely available. Attempts to develop a hepatitis C vaccine were so far unsuccessful.

Treatment of chronic hepatitis B virus infection in resource-constrained settings: expert panel consensus.

Most of the estimated 350 million people with chronic hepatitis B virus (HBV) infection live in resource‐constrained settings. Up to 25% of those persons will die prematurely of hepatocellular carcinoma (HCC) or cirrhosis. Universal hepatitis B immunization programmes that target infants will have an impact on HBV‐related deaths several decades after their introduction. Antiviral agents active against HBV are available; treatment of HBV infection in those who need it has been shown to reduce the risk of HCC and death. It is estimated that 20–30% of persons with HBV infection could benefit from treatment. However, drugs active against HBV are not widely available or utilized in persons infected with HBV. Currently recommended antiviral agents used for treatment of human immunodeficiency virus (HIV) infection do not adequately suppress HBV, which is of great concern for the estimated 10% of the HIV‐infected persons in Africa who are co‐infected with HBV. Progressive liver disease has been shown to occur in co‐infected persons whose HBV infection is not suppressed. In view of these concerns, an informal World Health Organization consultation of experts concluded that: chronic HBV is a major public health problem in emerging nations; all HIV‐infected persons should be screened for HBV infection; HIV/HBV co‐infected persons should be treated with therapies active against both viruses and that reduce the risk of resistance; standards for the management of chronic HBV infection should be adapted to resource‐constrained settings. In addition, a research agendum was developed focusing on issues related to prevention and treatment of chronic HBV in resource‐constrained settings.