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10 Million IDUs HCV+ Globally - 6.4 HBV+
 
 
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significance of viral hepatitis needs to receive greater attention than it does at present....Our global systematic review suggested that around 10.0 million IDUs are HCV positive and around 1.2 million are HBsAg positive. Clear geographical differences exist in prevalence. Eastern Europe, east Asia, and southeast Asia have the largest populations of IDUs infected with viral hepatitis. - pdf attached published article

World Hepatitis Day: a new era for hepatitis control: "Control of viral hepatitis receives only a fraction of the attention and resources that are dedicated to other major public health threats with similar or lesser morbidity and mortality.....immediate action is necessary to raise awareness, build collaborations to implement interventions that are appropriate for epidemiological patterns, and motivate policy makers to support better systems of prevention, care, and treatment of viral hepatitis. The level of suffering from viral hepatitis is unacceptable"

Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews

"midpoint prevalence estimates suggested 60-80% of IDUs had anti-HCV in 25 countries and more than 80% of IDUs did so in 12 countries. About 10.0 million (range 6.0-15.2) IDUs worldwide might be anti-HCV positive. China (1.6 million), USA (1.5 million), and Russia (1.3 million) had the largest such populations. We identified eligible HBsAg reports for 59 countries, with midpoint prevalence estimates of 5-10% in 21 countries and more than 10% in ten countries. Worldwide, we estimate 6.4 million IDUs are anti-HBc positive (2.3-9.7 million), and 1.2 million (0.3-2.7 million) are HBsAg positive."


The Lancet, Early Online Publication, 28 July 2011

John W Ward a bEmail Address, Francisco M Averhoff a b, Howard K Koh b

In recognition of a public health issue that affects more than half a billion people worldwide,1 the World Health Assembly has designated July 28 as World Hepatitis Day.2 Every year, this day will challenge the world to meet the urgent need for prevention and control of viral hepatitis and to ensure the best possible care and treatment for those infected. July 28 coincides with the birthday of Baruch Blumberg (1925-2011), who not only discovered the hepatitis B virus (HBV) in 1967 and developed the first hepatitis B vaccine in 1969, but also won the Nobel Prize in Physiology or Medicine in 1976 for these achievements.3 Much progress has since been made, and hepatitis B vaccination is now the most effective tool for preventing viral hepatitis and liver cancer. Vaccines can also prevent hepatitis A, and hepatitis E vaccines show promise in clinical trials.1, 4

Screening of donated blood for HBV and hepatitis C virus (HCV) has substantially lowered the number of viral hepatitis infections caused by transfusions. Provision and proper disposal of medical equipment can reduce transmission of HBV and HCV in health-care settings.1 With diagnostic assessment, patients can readily learn their infection status and, if infected, can access care services-for example, a rapid test for HCV antibody is now available in Europe and the USA.5 Antiviral therapies for people with HBV and HCV can reduce or eliminate viral replication, decreasing development of associated liver cirrhosis and liver cancer.1, 6 The potential for the combined global impact of these tools is tantalising. For example, for the past 11 years the GAVI Alliance has been committed to supporting the introduction of paediatric hepatitis B vaccination in 67 countries7 and, in 2009, about 70% of infants worldwide received the three-dose series of hepatitis B vaccine.8 Furthermore, the US Department of Health and Human Services has unveiled an action plan for the first comprehensive federal response to viral hepatitis.9 Such developments raise hope for a new era of hepatitis control.

Unfortunately, inadequate capacity to deliver effective interventions compromises outcomes everywhere, irrespective of a country's level of available resources. For example, only about one in five infants worldwide receives a birth dose of hepatitis B vaccine, which is necessary to prevent perinatal transmission of HBV.10 Additionally, many adults in the USA at risk for hepatitis B remain unvaccinated, including 58% of adults at risk for hepatitis B.9, 11 Inadequate screening of donated blood in many countries might result in up to 80 000 HBV infections and 500 000 HCV infections annually.12 Suboptimum infection control continues to threaten lives-sharps injuries place health-care workers and patients at risk for viral hepatitis, and unsafe injections can cause as many as 20 million HBV and 2 million HCV infections every year.13 Drug use and other high-risk behaviours result in HIV and viral hepatitis co-infections.9 Although new antiviral drugs create opportunities for reducing the morbidity and mortality from HBV and HCV,1, 6 their public health impact depends on awareness and access to care and treatment. In the USA, up to 75% of people are unaware of their infection status, and few of those who are aware receive appropriate care and treatment.9, 11 Barriers to testing, care, and treatment include health-care costs, insufficient training of providers, restricted public health capacity for surveillance and testing, and low community awareness. These barriers are magnified in resource-constrained settings.

World Hepatitis Day confronts the worldwide gap between the promise and the reality of hepatitis control. The main priority is the recognition that, worldwide, about 500 million people (one in 12 individuals) are living with viral hepatitis, of whom 1 million will die every year.1, 2 Control of viral hepatitis receives only a fraction of the attention and resources that are dedicated to other major public health threats with similar or lesser morbidity and mortality.11 Hence immediate action is necessary to raise awareness, build collaborations to implement interventions that are appropriate for epidemiological patterns, and motivate policy makers to support better systems of prevention, care, and treatment of viral hepatitis. The level of suffering from viral hepatitis is unacceptable. July 28 represents a call to action that can catalyse commitment worldwide. Public health leaders, policy makers, non-governmental organisations, and others must join together to confront and combat this silent epidemic. World Hepatitis Day should celebrate forward progress and rejection of the status quo.

We declare that we have no conflicts of interest.

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Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews

Paul K Nelson MHSc a, Bradley M Mathers MBChB a, Benjamin Cowie PhD b, Holly Hagan PhD c, Prof Don Des Jarlais PhD d, Danielle Horyniak BBioMedSci e, Prof Louisa Degenhardt PhD e f Corresponding AuthorEmail Address

Summary

Background


Injecting drug use is an important risk factor for transmission of viral hepatitis, but detailed, transparent estimates of the scale of the issue do not exist. We estimated national, regional, and global prevalence and population size for hepatitis C virus (HCV) and hepatitis B virus (HBV) in injecting drug users (IDUs).

Methods

We systematically searched for data for HBV and HCV in IDUs in peer-reviewed databases (Medline, Embase, and PsycINFO), grey literature, conference abstracts, and online resources, and made a widely distributed call for additional data. From 4386 peer-reviewed and 1019 grey literature sources, we reviewed 1125 sources in full. We extracted studies into a customised database and graded them according to their methods. We included serological reports of HCV antibodies (anti-HCV), HBV antibodies (anti-HBc), or HBV surface antigen (HBsAg) in studies of IDUs with more than 40 participants (<100% HIV-positive) and sampling frames that did not exclude participants on the basis of age or sex. With endorsed decision rules, we calculated prevalence estimates with anti-HCV and anti-HBc as proxies for exposure and HBsAg as proxy for current infection. We combined these estimates with IDU population sizes to calculate the number of IDUs with positive HBV or HCV statuses.

Findings

We located eligible reports with data for prevalence of anti-HCV in IDUs for 77 countries; midpoint prevalence estimates suggested 60-80% of IDUs had anti-HCV in 25 countries and more than 80% of IDUs did so in 12 countries. About 10.0 million (range 6.0-15.2) IDUs worldwide might be anti-HCV positive. China (1.6 million), USA (1.5 million), and Russia (1.3 million) had the largest such populations. We identified eligible HBsAg reports for 59 countries, with midpoint prevalence estimates of 5-10% in 21 countries and more than 10% in ten countries. Worldwide, we estimate 6.4 million IDUs are anti-HBc positive (2.3-9.7 million), and 1.2 million (0.3-2.7 million) are HBsAg positive.

Interpretation


More IDUs have anti-HCV than HIV infection, and viral hepatitis poses a key challenge to public health. Variation in the coverage and quality of existing research creates uncertainty around estimates. Improved and more complete data and reporting are needed to estimate the scale of the issue, which will inform efforts to prevent and treat HCV and HBV in IDUs.

Funding

WHO and US National Institutes of Health (NIDA R01 DA018609).

Introduction

Injecting drug use is an important public health issue around the world: 16 million people injected drugs in 2007 (range 11-21 million).1 Much of the estimated burden of disease attributable to the use of illicit drugs is probably due to blood-borne viral infections through unsafe drug injection.2 Hepatitis B and C viruses (HBV and HCV, respectively) are even more efficiently spread by this practice than is HIV.3

About 80% of individuals exposed to HCV develop chronic infection,4 and 3-11% of people with chronic HCV infection will develop liver cirrhosis within 20 years,5 with associated risks of liver failure and hepatocellular carcinoma.6 Transmission of HCV increasingly occurs through injecting drug use,7 but in many developing countries unsafe medical injections and transfusions are predominant sources of infection. The emergence of injecting drug use is an additional threat in settings where the prevalence of HCV is high (eg, Africa, the Middle East, and southeast Asia).

HBV is highly contagious through parenteral, sexual, and vertical (perinatal transmission) routes. About 5% of adults exposed to HBV develop chronic HBV infection;4 most of the 350 million chronically infected people worldwide were infected in childhood.8 Cirrhosis and death because of hepatocellular carcinoma are important sequelae of chronic HBV infection.9

Despite the higher prevalence and transmissibility of viral hepatitis, the disease has received far less global attention than has HIV. WHO called prevention and control efforts "successful but fragmentedÉ[with no] comprehensive strategy for viral hepatitis".10 At WHO's 63rd World Health Assembly in May, 2010, a resolution was passed to establish "goals and strategies for disease control, increasing education and promoting screening and treatment"10 of people infected with HBV and HCV.WHO argues that injecting drug users (IDUs) are a key group that need to be specifically targeted for prevention and treatment of viral hepatitis.10 For such efforts to be appropriately scaled and targeted, policy makers and health-care professionals need accurate and detailed data for the size of the population at risk, as exist for HIV.1

There have been no global systematic reviews of HBV prevalence in IDUs.11 Previous reviews of HCV in this population have been selective in their geographical coverage,12 have not provided sources or estimation methods,13 or did not make estimates of population size.14 Here, we report a systematic search and critical review of the peer-reviewed and grey literature on hepatitis C antibodies (anti-HCV), hepatitis B core antibodies (anti-HBc), and hepatitis B surface antigens (HBsAg) in IDUs, showing the best available country-level data, and the first regional and global estimates of the number of IDUs living with HCV and HBV.

We do not report estimates of chronic hepatitis A, D, or E viral infection (HAV, HDV, and HEV, respectively). Chronic HAV infection does not occur, and in developing countries most adults are immune, making epidemics uncommon; however, with increased sanitation this epidemiological pattern might change in some populations.15 HDV has been associated with injecting drug use; however, the extent of the published work on HDV (which needs concurrent HBV for infection to be established) is small and the diversity in prevalence, even in countries with a high prevalence of HBV, makes extrapolation between countries difficult.16 HEV is enterically transmitted and HEV data for IDUs is scarce.

Results

We identified eligible reports on anti-HCV in IDUs for 77 of the 152 countries or territories where injecting drug use has been reported (figure 2, Table 1, Table 2, Table 3, Table 4, Table 5, webappendix pp 9-16); these 77 countries hold 82% of the world's estimated population of IDUs. Anti-HCV prevalence varied greatly: midpoint reports ranged from 9.8% to 97.4% (Table 1, Table 2, Table 3, Table 4, Table 5).19, 20 Anti-HCV prevalence was 60-80% in IDUs in 25 countries, and 80% or higher in a further 12. The countries with the largest estimated populations of IDUs were China (midpoint estimate 67.0%), Russia (72.5%), and the USA (73.4%; Table 1, Table 2, Table 3). No studies were located for Caribbean countries or Pacific Island states and territories (table 3 and table 4).

HBV exposure (anti-HBc positive) was measured in 43 countries, accounting for 65% of the world's population of IDUs (webappendix p 17). Rates varied widely between countries, from 4.2% in Slovenia to 85.0% in Mexico (Table 1, Table 2, Table 3, Table 4, Table 5). Prevalence of HBsAg was measured in 59 countries, accounting for 73% of the world's population of IDUs (figure 3, Table 1, Table 2, Table 3, Table 4, Table 5). The highest rates of HBsAg were in countries (mostly in Asia) that have endemic HBV in the general population. HBsAg prevalence reports in IDUs varied substantially within countries; for example, prevalence reports of HBsAg ranged from 3.5% to 20.0% in the USA and 3.7% to 30.9% in Iran (table 3 and table 4).

Data quality varied between all three indicators of hepatitis, with only 20 countries having eligible grade A reports (panel 1) for at least one marker, and few of these reports were nationally representative (Table 1, Table 2, Table 3, Table 4, Table 5). In many countries, prevalence reports came from samples from different sites (grade B1). For most countries, we were able to use reports produced since 2000; however, about 25% of countries only had HBV reports from before 2000 (Table 1, Table 2, Table 3, Table 4, Table 5).

After extrapolation to all countries, we estimated that about 10.0 million IDUs (range 6.0-15.2) in 2010 were anti-HCV positive (table 6; a midpoint prevalence of 67.0% in IDUs globally). This value is about 3.5 times larger than the 2.8 million IDUs (range 0.8-6.2 million) who are estimated to be living with HIV (webappendix p 18).

The largest populations of HCV-positive IDUs lived in eastern Europe (2.3 million, range 1.2-3.9) and east and southeast Asia (2.6 million, 1.8-3.6). The three countries with the largest populations of IDUs living with HCV were China (1.6 million, range 1.1-2.2), Russia (1.3 million, range 0.7-2.3), and the USA (1.5 million, range 1.0-2.2).

We estimate that globally in 2010, 1.2 million (range 0.3-2.7) IDUs were HBsAg positive, with an IDU population-weighted global prevalence of 8.4%. The largest populations by region are east Asia and southeast Asia (0.3 million, range 0.1-0.7) and eastern Europe (0.3 million, 0.1-0.5 million). The large ranges around all these estimates shows the uncertainty resulting from varying prevalence between different subpopulations of IDUs and different recruitment settings.

Discussion

Our global systematic review suggested that around 10.0 million IDUs are HCV positive and around 1.2 million are HBsAg positive. Clear geographical differences exist in prevalence. Eastern Europe, east Asia, and southeast Asia have the largest populations of IDUs infected with viral hepatitis.

Notably, the population size estimates we reported refer to the estimated number of current or recent users of injected drugs who were positive for anti-HCV, anti-HBc, or HBsAg, and not people who have ever injected drugs. Many people who inject drugs cease injecting at some point,25 so our estimations cannot be interpreted as the total number of cases of HCV or HBV attributable to injecting drug use. Because of the limitations in understanding of the natural history of injecting drug use (such as the range in duration of injecting, and the likelihood and timing of resumption after cessation), especially in low-income and middle-income countries, defensible regional and global estimates cannot be made for the number of former IDUs, or concomitantly, the numbers of whom might be positive for anti-HCV, anti-HBc, and HBsAg. An estimate of the burden of chronic viral hepatitis in current IDUs is essential for assessment of secular trends in the risk of infection, the effect (and importance of implementation) of control strategies, and implications for future burden of disease and health-care needs.

Efforts to prevent, treat, and reduce harms related to liver disease in IDUs are essential-especially in situations in which HIV has successfully been prevented or managed-because the large numbers of IDUs infected with HCV and significant morbidity resulting from this infection mean that the health and economic costs of HCV transmitted by injecting drug use might be as high as (or higher than) those of HIV. Nonetheless, HCV treatment is underused.10 Part of the reason for this neglect is the high cost, which will remain a substantial barrier to increasing of treatment coverage in low-resource settings until costs are reduced. There is increasing attention on this issue among international groups who are advocating for cost reductions, generic manufacturing, and changes to licensing conditions.10, 26 Not long ago, the high cost of HIV antiretrovirals similarly prevented access in high prevalence, low-income countries: in recognition of this barrier, there are growing efforts to bring viral hepatitis treatments into the same (lower cost) access framework as HIV antiretrovirals.10 Nonetheless, another barrier is the toxic effects of HCV treatment, although a large number of new HCV drugs are in development that will revolutionise HCV treatment in the next few years.27

More attention needs to be paid to reduction of the effect of other causes of progression of liver disease in people who are chronically infected with viral hepatitis. This attention includes addressing problems of alcohol use, and provision of HAV and HBV vaccination, particularly because liver-related disease will become a main cause of mortality as IDUs get older.28

Evidence about the effect of needle and syringe programmes29 and provision of other injection equipment on prevention of HCV infection is scarce, but reduction of risk is paramount, particularly during the period of initiation to injecting when incidence of HCV is highest.6, 14 The potential for HCV treatment to reduce HCV prevalence in IDU populations and therefore reduce the force of infection acting on susceptible members of these populations has been supported by mathematical modelling.30 This potential role of HCV treatment in the prevention of HCV transmission in IDU populations warrants further investigation.

Although we noted substantial variability in HBsAg prevalence reports, prevalence typically mirrored the differences in the rate of HBV infection in the general population. In countries with a low-intermediate rate, the prevalence of HBsAg in IDUs was typically less than 10%, whereas in countries with a high rate of HBV infection, prevalence of HBsAg in IDUs was around 10-20% (eg, east Asia and southeast Asia). Because of the high rate of chronic HCV infection in IDUs, HBV infection is particularly likely to show HBV and HCV co-infection, which is associated with more rapid progression of liver disease and attendant mortality;31 this outcome is similarly the case for co-infection between HIV and viral hepatitis.32

Effective treatments for chronic HBV infection are available, which reduce progression of liver disease and complications such as hepatocellular carcinoma.33 However, antiviral therapy for chronic HBV infection is often of indefinite duration, and access to modern, potent drugs with high resistance barriers is restricted in many high-prevalence, low-resource settings. Barriers to accessing treatment and care for chronic HBV infection result in poor outcomes for those affected, and ongoing transmission to susceptible contacts.

Vaccination against HBV must be prioritised for all susceptible IDUs, especially those already infected with HCV. However, selective vaccination programmes against HBV in this group have often been characterised by low uptake and difficulty reaching the most at-risk individuals.34 A substantial reduction in the burden of HBV infection in IDUs is expected in countries with universal infant vaccination programmes, once these individuals reach the age at which acquisition of HBV through injecting drug use is most common. Correctional facilities provide one opportunity to vaccinate, treat, and reduce the transmission of viral hepatitis in a population with high rates of injecting drug use, HBV, and HCV, many of whom cycle in and out of the community.35, 36

There are several key limitations to the existing data. One issue concerns the way in which HCV and HBV infection are measured and reported between studies: reporting of data was typically done on the basis of only one (or perhaps two) markers, making estimates of the true prevalence of chronic HBV and HCV difficult. Without the measurement and reporting of several markers (anti-HCV plus HCV RNA PCR, or HBsAg plus anti-HBc, and ideally anti-HBs) more accurate estimation of chronic infection, past infection, susceptibility or immunity is not possible. For HCV, we estimated the number of present IDUs who were anti-HCV positive; however, this assessment is not a measure of total chronic HCV infection but rather HCV exposure in IDUs, because a minority (~20%) of those infected with HCV (who would test positive for anti-HCV) will probably clear the virus.4

For HBsAg, we noted wide ranges in reports that met inclusion criteria. Furthermore, if anti-HBc was not reported, assessment of the proportion of individuals who were positive for HBsAg, acutely infected, and within the window before anti-HBc seroconversion was not possible. Future studies should include both markers to allow a more accurate understanding of study results. Additional sample details, including country of birth and ethnicity, would also assist interpretation.37 An additional limitation of the existing data is the scarcity of data for the age range of samples and duration of drug-injecting history and therefore time of raised exposure to viral hepatitis, which would permit more accurate understanding of varying prevalence of both HCV and HBV between samples. Our reliance on older studies, with less accurate serological testing techniques and small sample sizes, and those undertaken in countries where laboratory capacity is low, increases uncertainty about the validity of both HCV and HBV reports.

A final issue relates to the representativeness of samples of people who inject drugs. Some studies of HBV and HCV recruited participants who had ever injected drugs, whereas others recruited those who had injected in the past year or were current users. Studies also recruited from various locations, including prisons, drug-treatment centres, outpatient clinics, and other medical settings, in which IDUs might differ in their risk behaviour and exposure to viral hepatitis. Moreover, convenience sampling is most often used, so samples possibly do not represent the IDU population from which they are drawn. Data were also typically subnational and from a small number of locations that might or might not be representative of the epidemic nationally, particularly in larger countries where there might be much geographical variation, potentially restricting national representativeness.

We have used the same methods as in our previous reports.1 As in these previous investigations, limitations of this report included the concentration of peer-reviewed data from high-income countries, the small team who undertook the analysis, and the potential for papers in languages other than English to be overlooked. We attempted to address these limitations by consulting widely with experts and stakeholders, seeking unpublished reports and verifying the data from reports included, and enlisting the support of UN and other agencies, who helped gain access to data and contact with relevant in-country personnel.

The public-health response to blood-borne virus transmission in IDUs has mainly centred on HIV. Maintenance and strengthening of the response to HIV in IDUs remains crucial, but the significance of viral hepatitis needs to receive greater attention than it does at present. Investment in, and development of, comprehensive and effective strategies to prevent the transmission of viral hepatitis and reduce resultant morbidity and mortality in IDUs are urgently required. The viral hepatitis resolution of the 63rd World Health Assembly10 requested that the Director General of WHO collaborate with all relevant stakeholders in supporting surveillance, prevention, and treatment goals, especially in developing countries. Policies and strategies for viral hepatitis need to include IDUs, who are at increased risk and often have poorer access to services than do the general population. Our report provides estimates of the scale of this problem at country, regional, and global scales, and the findings should inform efforts to accurately scale and appropriately target the response.

 
 
 
 
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