Hepatitis B elimination: Is it possible?

 

Despite the availability of safe and effective vaccines for more than three decades, the 2017 World Health Organization (WHO) Global Hepatitis Report estimated that worldwide more than 250 million persons are chronically infected with hepatitis B virus (www.who.int/hepatitis/publications/global-hepatitis-report2017/). In the United States, as many as 2.2 million persons may be chronically infected but only one-third are aware of their infection. In 2015, the WHO declared that hepatitis B and C should be eliminated as public health problems by the year 2030. In March 2017, the National Academies of Science, Engineering and Medicine (NASEM) set targets for HBV elimination in the United States by 2030 as follows: 50% reduction in deaths, 45% reduction in cirrhosis, and 33% reduction in hepatocellular carcinoma (HCC) compared to 2015. For these targets, 90% of persons chronically infected need to be diagnosed, 90% of those diagnosed linked to care, and treatment initiated in 80% of those with treatment indications. In addition, new infections among children should be eliminated through complete prevention of mother-to-child transmission.

HBV vaccination, particularly when initiated in newborns, is the most effective method of preventing HBV infection and its sequelae because the risk of chronicity is around 90% when infection occurs in newborns. Countries in which universal vaccination of newborns was initiated in the 1980s have witnessed a marked decline in HBV infection as well as HBV-related HCC in children and young adults. However, while 96% of countries worldwide have initiated nationwide HBV vaccine programs for infants, global birth dose coverage is only 39%, leaving many infants susceptible to infection during the first few months of life. Recent studies showed that administration of hepatitis B immunoglobulin and HBV vaccine within 24 hours of birth is inadequate in preventing infection of infants born to carrier mothers with high viremia. Antiviral medicine administered to highly viremic mothers during the third trimester of pregnancy is necessary to completely prevent the risk of mother-to-child transmission (Hepatology. 2016;63:261-83).

For persons who are chronically infected, antiviral therapy can suppress HBV replication, reduce hepatic inflammation, reverse hepatic fibrosis, and prevent progression to cirrhosis, hepatic decompensation, and HCC. However, currently approved treatments are associated with low rates of hepatitis B surface antigen (HBsAg) clearance and decreased but continued risk of HCC. New treatments aimed at cure are desired but complete cure of HBV may not be feasible as HBV persists in the liver even in patients with serologic recovery after transient acute HBV infection.

Functional cure aimed at restoring chronic hepatitis B patients to a state akin to those with spontaneous HBsAg clearance might be a more realistic goal. With improved understanding of the biology of HBV, including recent identification of its entry receptor, better in vitro and animal models, and revival of interest in hepatitis B research, it is conceivable that combinations of antiviral targeting different steps in HBV life cyle and immunomodulatory therapies aimed to boost T-cell response to HBV and/or remove inhibitory signals can result in functional cure (HBsAg clearance) in a high percentage of patients after a finite course of treatment (Hepatology 2017; in press).

The HBV elimination goals set by WHO and NASEM are lofty, but as both organizations stated, these goals are feasible if all stakeholders make elimination of HBV a priority and allocate resources to make it happen.
 

Dr. Lok is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine, University of Michigan Health System in Ann Arbor. Her comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

Despite the availability of safe and effective vaccines for more than three decades, the 2017 World Health Organization (WHO) Global Hepatitis Report estimated that worldwide more than 250 million persons are chronically infected with hepatitis B virus (www.who.int/hepatitis/publications/global-hepatitis-report2017/). In the United States, as many as 2.2 million persons may be chronically infected but only one-third are aware of their infection. In 2015, the WHO declared that hepatitis B and C should be eliminated as public health problems by the year 2030. In March 2017, the National Academies of Science, Engineering and Medicine (NASEM) set targets for HBV elimination in the United States by 2030 as follows: 50% reduction in deaths, 45% reduction in cirrhosis, and 33% reduction in hepatocellular carcinoma (HCC) compared to 2015. For these targets, 90% of persons chronically infected need to be diagnosed, 90% of those diagnosed linked to care, and treatment initiated in 80% of those with treatment indications. In addition, new infections among children should be eliminated through complete prevention of mother-to-child transmission.

HBV vaccination, particularly when initiated in newborns, is the most effective method of preventing HBV infection and its sequelae because the risk of chronicity is around 90% when infection occurs in newborns. Countries in which universal vaccination of newborns was initiated in the 1980s have witnessed a marked decline in HBV infection as well as HBV-related HCC in children and young adults. However, while 96% of countries worldwide have initiated nationwide HBV vaccine programs for infants, global birth dose coverage is only 39%, leaving many infants susceptible to infection during the first few months of life. Recent studies showed that administration of hepatitis B immunoglobulin and HBV vaccine within 24 hours of birth is inadequate in preventing infection of infants born to carrier mothers with high viremia. Antiviral medicine administered to highly viremic mothers during the third trimester of pregnancy is necessary to completely prevent the risk of mother-to-child transmission (Hepatology. 2016;63:261-83).

For persons who are chronically infected, antiviral therapy can suppress HBV replication, reduce hepatic inflammation, reverse hepatic fibrosis, and prevent progression to cirrhosis, hepatic decompensation, and HCC. However, currently approved treatments are associated with low rates of hepatitis B surface antigen (HBsAg) clearance and decreased but continued risk of HCC. New treatments aimed at cure are desired but complete cure of HBV may not be feasible as HBV persists in the liver even in patients with serologic recovery after transient acute HBV infection.

Functional cure aimed at restoring chronic hepatitis B patients to a state akin to those with spontaneous HBsAg clearance might be a more realistic goal. With improved understanding of the biology of HBV, including recent identification of its entry receptor, better in vitro and animal models, and revival of interest in hepatitis B research, it is conceivable that combinations of antiviral targeting different steps in HBV life cyle and immunomodulatory therapies aimed to boost T-cell response to HBV and/or remove inhibitory signals can result in functional cure (HBsAg clearance) in a high percentage of patients after a finite course of treatment (Hepatology 2017; in press).

The HBV elimination goals set by WHO and NASEM are lofty, but as both organizations stated, these goals are feasible if all stakeholders make elimination of HBV a priority and allocate resources to make it happen.
 

Dr. Lok is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine, University of Michigan Health System in Ann Arbor. Her comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

Despite the availability of safe and effective vaccines for more than three decades, the 2017 World Health Organization (WHO) Global Hepatitis Report estimated that worldwide more than 250 million persons are chronically infected with hepatitis B virus (www.who.int/hepatitis/publications/global-hepatitis-report2017/). In the United States, as many as 2.2 million persons may be chronically infected but only one-third are aware of their infection. In 2015, the WHO declared that hepatitis B and C should be eliminated as public health problems by the year 2030. In March 2017, the National Academies of Science, Engineering and Medicine (NASEM) set targets for HBV elimination in the United States by 2030 as follows: 50% reduction in deaths, 45% reduction in cirrhosis, and 33% reduction in hepatocellular carcinoma (HCC) compared to 2015. For these targets, 90% of persons chronically infected need to be diagnosed, 90% of those diagnosed linked to care, and treatment initiated in 80% of those with treatment indications. In addition, new infections among children should be eliminated through complete prevention of mother-to-child transmission.

HBV vaccination, particularly when initiated in newborns, is the most effective method of preventing HBV infection and its sequelae because the risk of chronicity is around 90% when infection occurs in newborns. Countries in which universal vaccination of newborns was initiated in the 1980s have witnessed a marked decline in HBV infection as well as HBV-related HCC in children and young adults. However, while 96% of countries worldwide have initiated nationwide HBV vaccine programs for infants, global birth dose coverage is only 39%, leaving many infants susceptible to infection during the first few months of life. Recent studies showed that administration of hepatitis B immunoglobulin and HBV vaccine within 24 hours of birth is inadequate in preventing infection of infants born to carrier mothers with high viremia. Antiviral medicine administered to highly viremic mothers during the third trimester of pregnancy is necessary to completely prevent the risk of mother-to-child transmission (Hepatology. 2016;63:261-83).

For persons who are chronically infected, antiviral therapy can suppress HBV replication, reduce hepatic inflammation, reverse hepatic fibrosis, and prevent progression to cirrhosis, hepatic decompensation, and HCC. However, currently approved treatments are associated with low rates of hepatitis B surface antigen (HBsAg) clearance and decreased but continued risk of HCC. New treatments aimed at cure are desired but complete cure of HBV may not be feasible as HBV persists in the liver even in patients with serologic recovery after transient acute HBV infection.

Functional cure aimed at restoring chronic hepatitis B patients to a state akin to those with spontaneous HBsAg clearance might be a more realistic goal. With improved understanding of the biology of HBV, including recent identification of its entry receptor, better in vitro and animal models, and revival of interest in hepatitis B research, it is conceivable that combinations of antiviral targeting different steps in HBV life cyle and immunomodulatory therapies aimed to boost T-cell response to HBV and/or remove inhibitory signals can result in functional cure (HBsAg clearance) in a high percentage of patients after a finite course of treatment (Hepatology 2017; in press).

The HBV elimination goals set by WHO and NASEM are lofty, but as both organizations stated, these goals are feasible if all stakeholders make elimination of HBV a priority and allocate resources to make it happen.
 

Dr. Lok is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine, University of Michigan Health System in Ann Arbor. Her comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.