Epidemiology of hepatitis b and c viruses a global overview

In many areas, indigenous peoples experience a higher prevalence of CHB and also an increased burden of associated liver disease.

Other specific ethnic groups have been shown to have a higher prevalence of CHB in countries, such as India Batham et al. The reason for higher prevalence among indigenous peoples is not completely understood, but is likely to be multifactorial.

Possible contributions include earlier age of pregnancy relating to greater likelihood of high-maternal viral load among women with CHB , greater residential density, specific HBV genotypes Davies et al. Recent estimates of global CHB infection prevalence were developed following a systematic literature review and subsequent age-specific estimation of global HBsAg prevalence for the years and , published in Ott et al.

This collaboration between the World Health Organization and the U. Centers for Disease Control emphasized the regional differences in prevalence discussed above, and also highlighted reducing population hepatitis B prevalence, predominantly attributable to the influence of infant hepatitis B vaccination. At a global level, it was estimated that the prevalence of CHB reduced from 4. Earlier GBD studies had not categorically assigned deaths from cirrhosis and liver cancer to their ultimate causes, arguably contributing to the underestimated impact of viral hepatitis on human health Cowie et al.

This is reflected in the historical lack of public health priority for viral hepatitis globally Lemoine et al. This represents a substantial change over the preceding two decades Table 1. Global Burden of Disease Study estimates of the attributable mortality of hepatitis B, — Adapted from data in Lozano et al. When considered together with deaths attributable to hepatitis C, these infections resulted in 1. The increasing recognition of the burden of viral hepatitis globally has led to increased international attention, represented by the passing of resolutions in the World Health Assembly and creation of a Global Hepatitis Programme by the World Health Organization see below.

The natural history of CHB can be complex, and varies significantly under the influence of a variety of host and viral factors Table 2. Host factors include sex, age at infection, and the presence of comorbidities, coinfections, and exposure to alcohol, tobacco, and dietary aflatoxin Fattovich et al. Viral factors that affect natural history include genotype and, possibly, the presence of specific mutations associated with progressive liver disease Kramvis and Kew ; Fattovich et al. Factors associated with progression to cirrhosis and hepatocellular carcinoma HCC in people living with chronic hepatitis B.

Adapted from data in Fattovich et al. As discussed by Tan et al. This highlights the importance of primary prevention through vaccination in infancy to prevent long-term adverse outcomes of HBV, particularly in high-HBV-prevalence populations Zoulim and Durantel These phases, described in more detail in Tan et al. In early life, CHB generally involves asymptomatic infection and does not result in significant liver damage Fattovich et al. However, HBV still accounts for a considerable number of hepatocellular carcinoma HCC cases in children living in endemic areas and incidence of HCC in children has decreased since the implementation of universal vaccination in some countries, such as Taiwan Chang et al.

A similar relationship was shown with alanine aminotransferase ALT level Chen et al. Further study is needed to determine whether these associations are replicated in other populations, as these studies have most commonly been conducted in individuals of Asian background, and largely those with hepatitis B genotype B or C. There is a strong relationship between HBV genotype see Lin and Kao and geography worldwide, and genotype has been shown to influence the natural history and, in turn, transmission patterns of hepatitis B infection.

The distribution of genotypes worldwide is shown in Table 3. Adapted from data in Kramvis et al. Genotype also influences the progression of viral infection through phases see above , which, in turn, determines infectivity and age at transmission or infection.

In Asia, where genotypes B and C predominate, transmission is most commonly vertical at the time of birth; where genotypes A, D, and E are most common, such as Africa, Eastern Europe, and the Middle East, transmission is more commonly horizontal in early childhood McMahon HBV genotypes and subgenotypes may also have relevance to hepatitis B control efforts through vaccination.

Mismatch between the strain used to derive hepatitis B vaccine serotype adw and that which is prevalent in a given population may result in increased vaccine escape and reduced efficacy at a population level Viviani et al. Overlapping patterns of endemicity are observed between HBV and other blood-borne viruses because of shared modes of transmission. Coinfection with HBV and one or more of the other blood-borne viruses is associated with modification of the natural history of liver disease and typically poorer outcomes than are observed in HBV mono-infection.

Of the estimated The frequency of coinfection varies considerably according to population group and region, and is related to both CHB and HIV endemicity and transmission patterns.

In low-HBV-prevalence countries, HBV and HIV transmission largely occur in adulthood through sexual contact and injecting drug use; and although overall prevalence of coinfection is low, it can be significant in some groups, such as men who have sex with men and people who inject drugs Kourtis et al.

In addition to adverse impact on the natural history of CHB, antiretroviral treatment in the setting of coinfection can be more complex owing to the potential of selecting for resistance mutations in HBV, the possibility of immune reconstitution flares in hepatitis B on initiation of antiretroviral therapy, and poor outcomes when HBV-active regimens are inadvertently ceased Thio In people with more advanced immunodeficiency, the efficacy of hepatitis B vaccination is also reduced Landrum et al.

In the era of increased access to antiretroviral therapy, liver disease is a major cause of non-AIDS-related mortality in individuals living with HIV Puoti et al.

In contrast, the scaling up of access to antiretroviral regimens in low-resource settings, which are also endemic for CHB, can lead to a situation in which the only people able to access treatment for hepatitis B are those who are coinfected with HIV Cowie et al. Although this increased access for those at greater risk for progressing to advanced liver disease is a very positive development, the lack of access to those living with HBV mono-infection in these countries remains a substantial concern.

Like HBV infection, HCV is one of the most common chronic infectious diseases worldwide, affecting an estimated to million people globally Mohd Hanafiah et al. Reflecting the epidemiology of HCV in general, risk factors for HCV coinfection in people living with CHB include injecting drug use, a history of blood transfusion, and other parenteral exposures.

Regional differences in prevalence are observed within some countries Gaeta et al. HDV is transmissible through blood-borne, sexual, percutaneous, permucosal, and perinatal means, although perinatal transmission is less common than for HBV.

The predominant modes of transmission are thought to be through intrafamilial horizontal transmission such as between young children , sexual, injecting drug use, and other parenteral exposures, such as unsafe medical procedures Hughes et al. However, the prevalence of HDV has been shown to be declining in a number of regions, such as Southern Europe Gaeta et al.

Conversely, prevalence has shown an increase in some previously low-prevalence areas, predominantly caused by increasing migration from endemic areas Wedemeyer et al.

Coinfection with HDV is associated with a higher likelihood of progressions to cirrhosis and related mortality; however, the impact of HDV on HCC risk specifically remains uncertain Wedemeyer ; Hughes et al. HCC is a major adverse outcome of HBV infection, and an important cause of mortality in a global context. In , , people were diagnosed with liver cancer and it caused , deaths Ferlay , with HCC making up the vast majority of all liver cancers Jemal et al.

As a cause of cancer morbidity and mortality, this makes liver cancer the second most common cause of cancer death worldwide, responsible for one in ten cancer deaths. The burden of liver cancer is geographically disparate, and, in , nearly two-thirds of all liver cancer cases were in the Western Pacific world region.

This disproportionate impact is largely driven by high incidence in China, where half of worldwide liver cancer cases occurred. Other regions of high burden include the Africa region, where, although the number of cases is much lower, the relative burden is high, with liver cancer ranking as the fourth most common cancer, and the Eastern Mediterranean region, where it ranks as fifth most common.

This geographic distribution is largely driven by HBV, which is estimated to be responsible for most cases of HCC globally Jemal et al.

This also influences the overall etiology of liver disease according to country, with those of high-HBV prevalence shown to have a relatively higher ratio of HCC compared with cirrhosis-related liver deaths.

Global incidence of liver cancer, age standardized rates per , population, in A males, and B females. Data from Ferlay The disproportionately high incidence of HCC in some regions is also influenced by other factors, such as the presence of aflatoxin B1 contamination, which has a synergistic relationship with HBV in promoting HCC development.

HBV genotype is another factor that is geographically determined and related to HCC incidence, with studies demonstrating that in the Asia-Pacific region, genotype C is associated with more rapid progression to HCC than genotype B. Survival following liver cancer diagnosis remains poor even in well-resourced health systems with multiple therapeutic options, including liver transplantation Nguyen et al.

For example, despite the substantial improvements in cancer mortality overall, liver cancer mortality continues to increase in these settings, with liver cancer the fastest increasing cause of cancer death in the United States and Australia MacLachlan and Cowie ; El-Serag and Kanwal This emphasizes the need for increased attention to diagnosis, management, and treatment of hepatitis B along with hepatitis C and other causes of chronic liver disease , with increasing evidence that antiviral therapy can substantially reduce the incidence of liver cancer Papatheodoridis et al.

In response, the World Health Organization WHO established the Global Hepatitis Programme in Geneva, with focal points in each WHO regional office, to coordinate global efforts to address viral hepatitis and to support member states in developing the necessary capacity and policies to reduce the burden of viral hepatitis globally.

The goal of the WHO viral hepatitis strategy is to reduce transmission, morbidity, mortality, and socioeconomic impact of viral hepatitis globally, using a health systems approach. The framework presented in this publication consists of four axes:. From the perspective of enhanced epidemiological information, proposed activities under Axis 2 include updating global prevalence estimates for viral hepatitis, developing standards for communicable disease surveillance relating to viral hepatitis, and provision of guidance for serological surveys to monitor trends and evaluate the impact of prevention measures.

Appropriate implementation of this framework will require substantial political commitment and mobilization of funding at national, regional, and global levels. The burden of adverse outcomes related to hepatitis B on individuals and communities, particularly in high-prevalence populations, is increasingly recognized. Although ensuring high coverage of infant vaccination will have a profound impact on this burden in coming decades, attention must be given to comprehensive policy responses now.

Understanding the epidemiology of HBV infection will enable evidence-based and cost-effective public health and clinical interventions within countries and at the global level. Editors: Christoph Seeger and Stephen Locarnini. National Center for Biotechnology Information , U. Cold Spring Harb Perspect Med. Jennifer H. MacLachlan 1, 2 and Benjamin C. Cowie 1, 2, 3. Benjamin C. Author information Copyright and License information Disclaimer.

Correspondence: Email: ua. This article has been cited by other articles in PMC. Abstract The epidemiology of hepatitis B virus HBV infection is geographically diverse, with population prevalence, age and mode of acquisition, and likelihood of progression to chronic infection mutually interdependent. Open in a separate window. Figure 1. Indigenous Peoples In many areas, indigenous peoples experience a higher prevalence of CHB and also an increased burden of associated liver disease.

Global Estimates of Hepatitis B Prevalence Recent estimates of global CHB infection prevalence were developed following a systematic literature review and subsequent age-specific estimation of global HBsAg prevalence for the years and , published in Ott et al.

Table 1. Table 2. Genotype There is a strong relationship between HBV genotype see Lin and Kao and geography worldwide, and genotype has been shown to influence the natural history and, in turn, transmission patterns of hepatitis B infection. However, several factors were shown to accelerate the progression of fibrosis. Fibrosis was higher in older patients, patients with extensive periportal necrosis on initial liver biopsy, and those with higher serum alanine and aspartate aminotransferase.

The current estimate for HCV-related mortality in the United States is to 10, deaths per year. This 3. As patients progressed through fibrosis to cirrhosis, changes in laboratory values suggested biochemical progression of liver dysfunction.

One of the main conclusions in this study was that maintenance therapy with interferon did not impact clinical outcomes. These factors comprised the CTP score, which was used as an overall assessment of disease severity. Patients with fibrosis or cirrhosis were compared with respect to mortality. The mortality rate was Disease progression is therefore impacted by many factors, but a recent meta-analysis demonstrated that patients who experienced SVR when treated for HCV had improvements in mortality relative risk [RR], 0.

HCV is an important public health concern because it is frequently underdiagnosed and undertreated. The prevalence of HCV infection is increasing, and increased awareness of the disease and its consequences is needed among both clinicians and patients.

In addition to the development of cirrhosis and consequent liver disease manifestations, the risks of mortality and cancer are increased with HCV. The first step in improving outcomes in HCV is ensuring diagnosis and treatment.

Effective treatment, the focus of the next article in this supplement, is associated with reductions in mortality, HCC, and hepatic decompensation. Authorship information: Drafting of the manuscript; critical revision of the manuscript for important intellectual content; administrative, technical, or logistic support; and supervision. Address correspondence to: E-mail: TranT cshs. Institute for Value-Based Medicine. About AJMC. December 31, Tram T.

Tran, MD. Download RIS. All of the structu res and functions have yet to be completely determined. Summary HCV is an important public health concern because it is frequently underdiagnosed and undertreated. Estimating the future health burden of chronic hepatitis C and human immunodeficiency virus in the United States. J Viral Hepat. Overcoming barriers to care in hepatitis C. Currently, no specific recommended treatment for HDV is recommended[ 23 ].

There is one vaccine under development against HEV in China, which is yet to implemented routinely[ 76 ]. The viral hepatitis outbreaks can be controlled with comprehensive global action plans and collaborations. A number of models have been used for viral hepatitis management.

WHO has a vision and its goal is to eliminate viral hepatitis worldwide as a major public health problem[ 69 - 74 ]. In this global strategy, five core interventions have been proposed and the targeted areas are vaccination plans for hepatitis B, A and E, prevention of vertical transmission of hepatitis B, injection and blood products safety, harm reduction and treatment[ 77 - 79 ].

Elimination of viral hepatitis requires strong national and international commitments. Comprehensive action plans for prevention, screening, diagnosis and treatment of viral hepatitis should be implemented through collaborations between government, health service providers and society[ 78 , 79 ]. This model for hepatitis C management was established in prison and provided advice on harm minimisation, diagnosis and treatment.

HCV infected persons often face obstacles to access treatment such as not being aware of availability of modern therapies, high cost, fear and distrust of healthcare professionals.

Some studies suggested that nurse-led models provided a good opportunity for instituting intervention against transmission and spread of HCV but it was minimally successful in reducing HCV transmission among prisoners[ 79 - 81 ]. However, it has also been shown that professional care and specialist-managed treatment models for chronic HCV do result in improved treatment uptake and low disease burden[ 49 , 82 ].

People who recover successfully from the infection can work closely with multidisciplinary clinical care team to offer extensive viral hepatitis support, care and access to treatment specifically for those who have barriers to clinical care[ 70 ]. Major obstacles that hinder care among HCV infected intravenous drug users should be overcome by strategies such as on-site treatment, addiction management plan, multidisciplinary teams work, intensive model of care, directly peer observed treatment and group treatment[ 79 - 81 ].

It has been shown that combination of clinical and behavioral interventions can result in reduction of HCV among substance users[ 80 - 82 ]. The prevalence of HCV infection among intravenous recreational drug users remains high worldwide. Despite the availability of well-tolerated successful treatment, morbidity and mortality due to liver disease among people with HCV infection is still increasing.

The Kirby Institute, The University of New South Wales Sydney and the International Network on Hepatitis in Substance Users have organised an expert roundtable panel to evaluate current issues and implemented future research priorities for the prevention and management of HCV among people who inject drugs.

International experts in drug and alcohol, infectious diseases, and hepatology have come together on one platform to identify the current scientific evidence, issues in research, and develop research priorities[ 79 ].

Providing outreach services is important in viral hepatitis management. One example includes mobile health clinics which are an innovative and flexible way to provide healthcare for chronic viral hepatitis patients. They have been proven effective in giving the health screenings, initiating chronic disease management and providing immediate intervention when required. The mobile van clinic has been a novel approach for controlling viral hepatitis[ 75 ].

HCV is prevalent among the injecting drug users especially those in prison, the aboriginal population and people coming from culturally and linguistically diverse background. These are the people who are disconnected from traditional health providers and have poor retention in care systems. To engage these people in the health care system and to provide the appropriate treatment requires innovative action plans[ 75 , 49 ]. The above-mentioned mobile outreach vans will bring the treatment services to these people and will also make it easier for them to access the health services particularly for those who have comorbid psychiatric and substance use disorders.

It will create a link between clinical and community-based settings and will remove geographic, socioeconomic and structural obstacles. Successful treatment of HCV infections will decrease the risk of chronicity of the disease and liver cancer, improve the quality of life and will also increase the survival rates[ 77 , 78 ].

The mobile outreach system will also help in reducing the transmission of disease by providing the early treatment, improved viral clearance and reduced risk behaviors[ 75 ]. Many cases of viral hepatitis occur among health workers due to accidental needle injuries. Preventing work-related accidents in health organisations should be urgently reviewed. Prompt IgG treatment option should be in place as soon as exposure to virus is confirmed. This treatment may stop the infection from developing.

Patients exposed to viruses should undergo similar treatment. This prompt strategy could serve as an efficient therapeutic modality and prevent development of infection and minimise outbreaks. Although there has been some success with preventative strategies globally, still many hurdles need to be overcome if we are to reduce viral transmission significantly.

WHO has published its technical report manual for the development and assessment of national viral hepatitis plans in [ 49 ]. This guidance could help to control viral hepatitis outbreaks. These actions need to be strengthened and reinforced in order to stop the outbreaks and provide a viral hepatitis-free future for the next generation. One of the important actions to be adopted to control outbreak is prompt immune serum treatment.

WHO can include post-exposure prophylaxis in their global strategy which at first can be implemented in resource-rich settings and gradually adopted in developing and underdeveloped countries. For global success in controlling viral hepatitis, international organisations can establish round tables to exchange ideas for action plans.

There is no one single measure strong enough to curb viral hepatitis epidemics but having a global vision and implementing multiple strategies will go some way towards reducing global disease burden. Conflict-of-interest statement: Nothing to declare. Manuscript source: Invited manuscript. Peer-review started: May 29, First decision: July 9, Article in press: October 16, Specialty type: Medicine, research and experimental.

Country of origin: Australia. Peer-review report classification. Grade A Excellent : 0. Grade B Very good : B, B. National Center for Biotechnology Information , U. World J Clin Cases. Published online Nov 6. Author information Article notes Copyright and License information Disclaimer. Author contributions: Jefferies M conducted literature search, sifted the titles, identified full texts, created the content, abstracted the data wrote the first version of the manuscript, reviewed the references, completed final revision of the manuscript; Rauff B helped with literature search and revision of the manuscript; Rafiq S updated the figures, prepared video record; Rashid H and Lam T provided study concept and critical revision of the manuscript.

Published by Baishideng Publishing Group Inc. All rights reserved. This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. This article has been cited by other articles in PMC. Abstract Viral hepatitis is one of the major public health concerns around the world but until recently it has drawn little attention or funding from global health policymakers. Open in a separate window.

Figure 1. Hepatitis B Hepatitis B is globally one of the most common and severe infectious diseases that leads to significant morbidity and mortality[ 13 ]. Figure 2. Hepatitis C It is estimated that 71 million people globally have chronic hepatitis C infection[ 16 ], who are at risk of developing liver cirrhosis and liver cancer[ 17 ].

Figure 3. Hepatitis D HDV is commonly seen in the people who are exposed to infected blood products or infected needles of previously infected HBV[ 21 ]. Figure 4. Hepatitis E HEV causes food and waterborne diseases with outbreaks seen worldwide.

Figure 5. Americas The prevalence of hepatitis A is high in the Americas, with exception of high-income North American countries. European continent The prevalence of HAV increases from west to east; childhood transmission is less frequent in Eastern Europe while adult transmission is more common[ 40 ]. South-East Asia In most parts of South East Asia HAV seroprevalence continues to be very high, but recent reports suggest that in some parts such as India infection rates are declining.

Education Education programs directed towards disease awareness lowers disease transmission[ 54 , 62 ]. Improvement of socio-economic condition Improvement in socioeconomic status has shown to reduce the prevalence of all types of viral hepatitis. Screening and early detection Screening, early detection and initiation of treatment will prevent further transmission of the virus and reduce morbidities and mortalities among infected individuals[ 68 , 69 ].

Implementing WHO global model The viral hepatitis outbreaks can be controlled with comprehensive global action plans and collaborations. Multi-sectoral coordination Elimination of viral hepatitis requires strong national and international commitments. Nurse-led approach This model for hepatitis C management was established in prison and provided advice on harm minimisation, diagnosis and treatment.

Peer navigation model People who recover successfully from the infection can work closely with multidisciplinary clinical care team to offer extensive viral hepatitis support, care and access to treatment specifically for those who have barriers to clinical care[ 70 ].

Outreach treatment Providing outreach services is important in viral hepatitis management. Post-exposure prophylaxis Many cases of viral hepatitis occur among health workers due to accidental needle injuries.

Footnotes Conflict-of-interest statement: Nothing to declare. References 1. World Health Organization. Epidemiology and natural history of HCV infection. Nat Rev Gastroenterol Hepatol. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Hepatitis E. Hepatitis A virus seroprevalence by age and world region, and The global burden of viral hepatitis: better estimates to guide hepatitis elimination efforts. Eliminate Hepatitis: WHO.

The global prevalence of hepatitis A virus infection and susceptibility: a systematic review. Geneva: World Health Organization; Hepatitis A: Epidemiology and prevention in developing countries. World J Hepatol. Jacobsen KH. Cold Spring Harb Perspect Med. Hepatitis B: Epidemiology and prevention in developing countries.