Review
Strategies to control hepatitis B: Public policy, epidemiology, vaccine and drugs
Stephen Locarnini1, , , Angelos Hatzakis2, Ding-Shinn Chen3, Anna Lok4
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doi:10.1016/j.jhep.2015.01.018
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Summary
The last 50 years of hepatitis B research has resulted in the development of effective screening assays for surveillance, vaccines for prevention and antiviral drugs that significantly improve patient clinical outcomes. Not surprisingly then, the global epidemiology of hepatitis B virus (HBV) is set to change dramatically over the next decade. For example, the success and the high coverage of universal HBV vaccination and the ageing cohorts of patients with chronic hepatitis B (CHB) will result in reductions of incidence and prevalence of chronic hepatitis, cirrhosis and probably hepatocellular carcinoma. This will be further accelerated by the impressive progress in the treatment outcomes for patients with CHB. In spite of this success, challenges remain, such as planning for the impact of migration from countries with high prevalence rates to those countries with low rates of HBV infection. The recent establishment of the World Health Organisation Global Hepatitis Program with the provision of a framework for global action has become the cornerstone for all countries to now frame their own particular national responses to control hepatitis B. An effective policy framework can prevent new infections, ensure people can access clinical care, and in doing so reduce the burden of infection at an individual, country and regional level. These developments present a real opportunity to reduce the significant, social and economic burden of global hepatitis B, ultimately the critical next steps to render the world hepatitis B free.
Keywords
Epidemiology; Prevention; Hepatitis B vaccine; Acute hepatitis B; Chronic hepatitis B; Treatment; Chronic liver disease; Hepatocellular carcinoma; Public policy; WHO 作者: StephenW 时间: 2015-6-2 05:50
Progression to cirrhosis and HCC is very slow in the inactive carrier state (<1% per year), while progression to cirrhosis may occur at a rate of 2–10% per year in the immune reactive and reactivation phases. Progression from cirrhosis to HCC may occur in 2–4% of patients per year. The incidence of cirrhosis appears to be 2-fold higher in HBeAg-negative compared to HBeAg-positive patients. In cirrhotic patients the 5-year cumulative risk of HCC is 17% in East Asia, 10% in Western Europe and USA, and 5-year related death is 14% in East Asia and 15% in Europe [6]. Progression rates are mainly determined by the age of infection, gender, extent of HBV replication, particular HBV genotypes and variants, coinfection with HCV, HDV or HIV, alcohol, exposure to aflatoxin B1, host genetic factors and probably co-morbidities including metabolic syndrome, diabetes, obesity and tobacco smoking. Studies in Asia suggest a faster progression to cirrhosis and HCC if infected with genotype C compared to genotype B HBV. Studies in Europe and North America reveal that genotype D CHB has a higher progression to cirrhosis and HCC than genotype A [6], [8], [10] and [11].
The main risk factors for HBV progression to HCC include HBeAg positivity and HBV DNA levels. Seminal studies from Taiwan established these associations [12], [13] and [14]. The incidence of HCC was 1169/100,000 person-years for HBsAg and HBeAg-positive persons, 324/100,000 person-years for HBsAg positive, HBeAg-negative and 39/100,000 person-years for those who were HBsAg negative. The Risk Evaluation of Viral Load Elevation and Associated Liver Disease (REVEAL-HBV) study established HBV DNA levels as the main determinant of progression to HCC. However, even HBsAg positive carriers with low levels of HBV DNA and normal ALT had an almost 5-fold greater risk for HCC than HBsAg negative controls [13] and [15].
Did you mean: Extract: Progression to cirrhosis and HCC is very slow in the inactive carrier state (<1% per year), while progression to cirrhosis may occur at a rate of 2–10% per year in the immune reactive and reactivation phases. Progression from cirrhosis to HCC may occur in 2–4% of patients per year. The incidence of cirrhosis appears to be 2-fold higher in HBeAg-negative compared to HBsAg-positive patients. In cirrhotic patients the 5-year cumulative risk of HCC is 17% in East Asia, 10% in Western Europe and USA, and 5-year related death is 14% in East Asia and 15% in Europe [6]. Progression rates are mainly determined by the age of infection, gender, extent of HBV replication, particular HBV genotypes and variants, coinfection with HCV, HDV or HIV, alcohol, exposure to aflatoxin B1, host genetic factors and probably comorbidities including metabolic syndrome, diabetes, obesity and tobacco smoking. Studies in Asia suggest a faster progression to cirrhosis and HCC if infected with genotype C compared to genotype B HBV. Studies in Europe and North America reveal that genotype D CHB has a higher progression to cirrhosis and HCC than genotype A [6], [8], [10] and [11]. The main risk factors for HBV progression to HCC include HBeAg positivity and HBV DNA levels. Seminal studies from Taiwan established these associations [12], [13] and [14]. The incidence of HCC was 1169/100,000 person-years for HBsAg and HBeAg-positive persons, 324/100,000 person-years for HBsAg positive, HBeAg-negative and 39/100,000 person-years for those who were HBsAg negative. The Risk Evaluation of Viral Load Elevation and Associated Liver Disease (REVEAL-HBV) study established HBV DNA levels as the main determinant of progression to HCC. However, even HBsAg positive carriers with low levels of HBV DNA and normal ALT had an almost 5-fold greater risk for HCC than HBsAg negative controls [13] and [15].
摘录:
Eradicating HBV in patients who are chronically infected maybe an unachievable goal but a “functional cure” may be possible and should be pursued. While long-term entecavir or tenofovir is convenient, fairly safe, with negligible risk of drug resistance and cost is expected to decline in the coming years with the availability of generic drugs, there remains a small risk of adverse reactions and the cost of indefinite treatment will remain unaffordable for many patients as well as health departments in countries with socialized health care. Furthermore, adherence to treatment tends to diminish over time.
A multi-prong approach with antiviral drugs targeting different steps of the HBV replication cycle combined with immunotherapy to restore immune responsiveness to HBV will be needed for patients to remain in a state of “functional cure” [75]. Currently available NUCs only target the HBV reverse transcriptase/polymerase. Recent identification of a bile salt transporter – sodium taurocholate cotransporting polypeptide (NTCP) as the host receptor for HBV created opportunities to evaluate compounds that can block viral entry [76]. One example, Myrcludex B is being tested in phase 2 clinical trials. Other approaches aim at eradication or functional silencing of cccDNA through epigenetic modifications, dysregulation of nucleocapsid assembly or inhibition of virion secretion. Previous attempts of immunotherapy have failed to restore immune responsiveness to HBV in patients with chronic HBV infection even though some of these approaches were effective in uninfected volunteers. However, recent studies showed that immune response to HBV can be restored in patients who undergo HBeAg spontaneously or following antiviral treatment, and more so in those who achieve HBsAg loss [77]. These data indicate that restoration of immune response to HBV is possible particularly after HBV replication has been suppressed and HBsAg production decreased.