Eliminating hepatitis B virus as a global health threat (2016)

In The Lancet Infectious Diseases, Shevanthi Nayagam and colleagues1Nayagam S Thursz M Sicuri E et al.Requirements for global elimination of hepatitis B: a modelling study.Lancet Infect Dis. 2016; (published online Sept 13.)http://dx.doi.org/10.1016/S1473-3099(16)30204-3Summary Full Text Full Text PDF PubMed Scopus (208) Google Scholar report a modelling study on the effectiveness of different interventions on the incidence and mortality rate of chronic hepatitis B virus (HBV) infection. To appreciate the implications of this report, we need to understand the context. Chronic viral hepatitis is the seventh leading cause of death worldwide.2WHOViral hepatitis.http://www.wpro.who.int/about/regional_committee/66/documents/wpr_rc66_04_viral_hepatitis.pdfDate: Sept 11, 2015Google Scholar Chronic HBV infection alone affects over 240 million people worldwide and is one of the most common causes of cirrhosis and liver cancer.3Schweitzer A Horn J Mikolajczyk RT Krause G Ott JJ Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013.Lancet. 2015; 386: 1546-1555Summary Full Text Full Text PDF PubMed Scopus (1799) Google Scholar In May, 2014, the World Health Assembly requested WHO to provide the necessary technical support to enable member states to develop robust national viral hepatitis prevention, diagnosis, and treatment strategies. In response, WHO set ambitious goals of reducing new cases of chronic viral hepatitis by 90%, and reducing mortality rates from these infections by 65% between 2015 and 2030.4WHODraft global health sector strategies. Viral hepatitis, 2016–2021.http://apps.who.int/gb/ebwha/pdf_files/WHA69/A69_32-en.pdf?ua=1Date: April 22, 2016Google Scholar Achievement of these goals might at least eliminate chronic viral hepatitis as a major global health threat. What can we do to make this happen? Nayagam and colleagues1Nayagam S Thursz M Sicuri E et al.Requirements for global elimination of hepatitis B: a modelling study.Lancet Infect Dis. 2016; (published online Sept 13.)http://dx.doi.org/10.1016/S1473-3099(16)30204-3Summary Full Text Full Text PDF PubMed Scopus (208) Google Scholar first assessed the situation at present and compared it with a hypothetical situation where no intervention had previously been used to combat HBV.1Nayagam S Thursz M Sicuri E et al.Requirements for global elimination of hepatitis B: a modelling study.Lancet Infect Dis. 2016; (published online Sept 13.)http://dx.doi.org/10.1016/S1473-3099(16)30204-3Summary Full Text Full Text PDF PubMed Scopus (208) Google Scholar It is gratifying to note that current interventions have already had a huge impact: averting 210 million new chronic HBV infections by 2015 and 1·1 million deaths between 2015 and 2030. Nonetheless, 63 million new cases and 17 million HBV-related deaths will still occur between 2015 and 2030. The authors then evaluated five strategies, including scaling-up infant vaccination coverage to 90%, birth-dose vaccination coverage to 80%, peripartum antivirals coverage for mothers with positive hepatitis B e antigen to 80%, increasing access to antivirals to 80%, and developing a cure for HBV infection. The first three interventions target new infections, whereas HBV treatments prevent disease progression, cirrhotic complications, and liver cancer. Compared with the present state, scaling-up infant vaccination can prevent 4·3 million new infections from 2015 to 2030, but the real impact comes from birth-dose vaccination, which prevented 18·7 million new cases of HBV infection. The smaller effect of infant vaccination compared with birth-dose vaccination is because infant vaccination is ineffective against mother-to-child transmission, which is the primary route of transmission in endemic areas. Even with vaccination or hepatitis B immunoglobulin at birth, women with very high viral loads might still transmit HBV to their children,5Wen WH Chang MH Zhao LL et al.Mother-to-infant transmission of hepatitis B virus infection: significance of maternal viral load and strategies for intervention.J Hepatol. 2013; 59: 24-30Summary Full Text Full Text PDF PubMed Scopus (195) Google Scholar and the use of antivirals during late pregnancy has been shown to almost eliminate mother-to-child transmission in this situation.6Chen HL Lee CN Chang CH et al.Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to-infant transmission of hepatitis B virus.Hepatology. 2015; 62: 375-386Crossref PubMed Scopus (189) Google Scholar, 7Pan CQ Duan Z Dai E et al.Tenofovir to prevent hepatitis B transmission in mothers with high viral load.N Engl J Med. 2016; 374: 2324-2334Crossref PubMed Scopus (379) Google Scholar In Nayagam and colleagues' model,1Nayagam S Thursz M Sicuri E et al.Requirements for global elimination of hepatitis B: a modelling study.Lancet Infect Dis. 2016; (published online Sept 13.)http://dx.doi.org/10.1016/S1473-3099(16)30204-3Summary Full Text Full Text PDF PubMed Scopus (208) Google Scholar peripartum antivirals can further prevent 0·6 million new cases. Further studies are needed to define the long-term safety of peripartum antivirals in mothers and children. Based on these data, low-income countries should prioritise birth-dose vaccination over peripartum antivirals if they do not have the resources to implement both strategies at the same time because the birth-dose vaccination will have a bigger impact than peripartum antivirals. Because most cases of cirrhosis and liver cancer occur during or after middle age, prevention of new infections will not have a major effect on HBV-related mortality rates until decades later. Management of patients who have already been infected is, therefore, important. Although only one placebo-controlled trial has used clinical outcomes as the primary endpoint,8Liaw YF Sung JJ Chow WC et al.Lamivudine for patients with chronic hepatitis B and advanced liver disease.N Engl J Med. 2004; 351: 1521-1531Crossref PubMed Scopus (1991) Google Scholar several observational studies suggest that antivirals can reduce the risk of liver cancer and mortality.9Wong GL Chan HL Mak CW et al.Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients with liver cirrhosis.Hepatology. 2013; 58: 1537-1547Crossref PubMed Scopus (359) Google Scholar The main drawback of antiviral therapy is that long-term treatment is often needed, but drug resistance and side effects are rare with entecavir or tenofovir, which makes long-term treatment acceptable.10Wong GL Tse YK Wong VW Yip TC Tsoi KK Chan HL Long-term safety of oral nucleos(t)ide analogs for patients with chronic hepatitis B: a cohort study of 53,500 subjects.Hepatology. 2015; 62: 684-693Crossref PubMed Scopus (66) Google Scholar Based on the estimations in Nayagam and colleagues' study, providing antivirals to 80% of patients with treatment indications can meet the goal of reducing HBV-related mortality rate by 65% by 2030. Conversely, development of a cure for chronic hepatitis B would not have an additional effect on mortality rate. This is hardly surprising because the authors assume that adequate HBV suppression by available antivirals is as effective as curing HBV. However, antivirals reduce, but do not eliminate, the risk of liver cancer,11Wong GL Chan HL Chan HY et al.Accuracy of risk scores for patients with chronic hepatitis B receiving entecavir treatment.Gastroenterology. 2013; 144: 933-944Summary Full Text Full Text PDF PubMed Scopus (135) Google Scholar so the effect of curing HBV should be revisited when such a drug becomes available. We commend the authors for extensively reviewing data from different regions and providing information that is urgently needed.1Nayagam S Thursz M Sicuri E et al.Requirements for global elimination of hepatitis B: a modelling study.Lancet Infect Dis. 2016; (published online Sept 13.)http://dx.doi.org/10.1016/S1473-3099(16)30204-3Summary Full Text Full Text PDF PubMed Scopus (208) Google Scholar But knowing the effectiveness of the strategies is only the first step. The benefits will not materialise if the interventions are not implemented. Some policies that sound straightforward in the developed world can face major hurdles in low-income and middle-income countries. For example, the transportation of vaccines to remote areas and temperature control can already be a challenge, not to mention the need to train health-care providers and educate the public. Patient management would not be possible without access to diagnostic tests and monitoring instruments. Safe needles and blood products should be available to all countries. Finally, these programmes cannot be sustained without adequate funding. According to Nayagam and colleagues' forecast, the annual expenditure between 2015 and 2030 needed to achieve the goals will be US$5·5 billion. Although this will be a good investment because cirrhosis and liver cancer could be avoided, governments still need to find ways to finance these programmes. With determination, the WHO 2030 goals for chronic viral hepatitis can be and should be achieved. Achievement of this goal calls for concerted effort from policy makers, clinicians, and societies. The tools to combat HBV are already at hand, and now is the time for action. GL-HW has served as an advisory board member for Gilead and has received paid lecture fees from AbbVie, Bristol-Myers Squibb, Echosens, Gilead, Janssen, and Roche. VW-SW has served as an advisory board member for Gilead and Janssen; as a consultant for AbbVie, Merck, and NovoMedica; and has received paid lecture fees from AbbVie, Echosens, Gilead, Merck, and Roche. Requirements for global elimination of hepatitis B: a modelling studyScale-up of vaccination coverage, innovations in scalable options for prevention of mother-to-child transmission, and ambitious population-wide testing and treatment are needed to eliminate HBV as a major public health threat. Achievement of these targets could make a major contribution to one of the Sustainable Development Goals of combating hepatitis. Full-Text PDF Open Access