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Chronic Hepatitis B Infection and Liver Cancer

Hepatitis B is the world's most common serious viral infection of the liver and can cause premature death from liver disease or liver cancer. Hepatitis B virus (HBV) is recognized as a human carcinogen and is the cause of 60-80% of liver cancer worldwide. Each year approximately 700,000 people die of liver cancer or liver disease caused by hepatitis B. Because liver cancer is the third most common form of cancer death in the world, and the majority is attributable to hepatitis B, HBV is the third leading cause of cancer death worldwide after tobacco and Helicobacter pylori. The initial or acute HBV infection is associated with a 0.5-1% risk of death from sudden and severe liver failure, and those who fail to clear the infection and become chronically infected are at significantly increased risk of developing liver cancer or other life-threatening liver disease. The World Health Organization (WHO) estimates one third of the world's population has been infected and 1 in 20 people (350-370 million) have chronic hepatitis B. Despite the availability of the hepatitis B vaccine since 1982, vaccination rates are low in many populations, leaving many children unvaccinated and many adults chronically infected throughout the world, including in the US.

Hepatitis B in Asian Americans and Native Hawaiians and Other Pacific Islanders

Chronic hepatitis B and liver cancer caused by hepatitis B in Asian Americans, Native Hawaiian and Other Pacific Islanders comprise one of the most serious but frequently neglected racial and ethnic health disparities in the United States (US)ⁱ. Among foreign-born AAs and NHOPIs in the US, the prevalence of chronic hepatitis B is consistently found to be approximately 10%ⁱⁱ, ⁱⁱⁱ, ^iv, ^v. By contrast, the prevalence in the overall US population is below 0.5% and among non-Hispanic whites it is below 0.2%^vi, ^vii, ^viii. The CDC estimates that as many as 2 million people in the country are living with chronic hepatitis B, and over half are AAs and NHOPIs. Not only is chronic hepatitis B the basis of a wide racial and ethnic health disparity in the US, but it is also a particularly menacing one: if left unmonitored and untreated, up to one out of four individuals with chronic hepatitis B will die from liver cancer or cirrhosis^ix. Thus, AAs and NHOPIs have not only the highest rates of chronic hepatitis B among all racial/ethnic groups in the US, but they are also at disproportionately high risk of liver cancer, which is the third leading cause of cancer death among AAs and NHOPIs in the US (whereas it is the 16th leading cause of cancer death among non-Hispanic whites).

Although the incidence of acute hepatitis B across the US has declined substantially in recent years, the high prevalence of chronic hepatitis B among AAs and NHOPIs, particularly the foreign-born, appears to have remained relatively constant ^x. Because most public health departments that conduct surveillance for hepatitis B have typically focused on tracking acute disease, there is a shortage of population-based data on trends and patterns in the prevalence of chronic hepatitis B. Routine surveillance for chronic hepatitis B can inform planning for targeted public screening, prevention, and awareness programs, as well as facilitate case management of chronically infected individuals^xi. An additional benefit of chronic hepatitis B surveillance is the opportunity to link viral hepatitis registries with other population-based health and disease registries, enabling a better understanding of health care management, outcomes, and other aspects of chronic hepatitis B.

Most AAs and NHOPIs chronically infected with HBV were born in HBV-endemic regions or have parents who were born in endemic countries. With the exception of breast milk, the modes of transmission of HBV are somewhat similar to those of HIV: from an infected mother to her newborn at birth, direct contact with infected blood, and unprotected sex. HBV is known to be 50-100 times more infectious than HIV. Although most new infections in the US occur in close contacts of an infected person, health care and public safety workers, people with many sex partners, injection drug users, and children born to infected mothers, the majority of chronically infected persons are those born in other countries, especially in Asia. Many AAs and NHOPIs unknowingly acquired their infection at birth through vertical transmission of the virus, or during early life through horizontal transmission from close contacts^xii. More than 90% of newly infected infants, 25-50% of children infected between ages 1 and 5 years, and 6-10% of acutely infected older children and adults develop chronic, or lifelong, HBV infection; the remainder generally develops natural immunity after acute infection^xii. Thus, by adulthood, many AAs and NHOPIs born in an HBV-endemic country or whose parents were born in an HBV-endemic country have already acquired chronic HBV infection. Prevention of chronic hepatitis B can be achieved in a relatively straightforward manner through early-life vaccination against HBV, perinatal immunoprophylaxis in newborns born to chronically infected mothers, and public education, especially among high-risk groups, about routes of HBV transmission^xiii, ^xiv. However despite the availability of a safe and effective recombinant vaccine for more than 20 years, many HBV-endemic countries in Asia have adopted free universal newborn HBV vaccination programs only in the past decade^xv.

HBV and Newborns

Newborns infected with HBV have the greatest risk of developing chronic hepatitis B. Therefore, the perinatal period is a critical time for intervention to prevent HBV transmission. According to the 2005 recommendations of the US Advisory Committee on Immunization Practices (ACIP), all infants born to hepatitis B surface antigen (HBsAg)-positive women should receive the hepatitis B vaccine and hepatitis B immune globulin (HBIG) within 12 hours of birth, complete the hepatitis B vaccine series by 24 weeks of age, and undergo post-vaccination serological testing for hepatitis B surface antibody (anti-HBs) and HBsAg between 9 and 18 months of age^xiii. However, adoption of these recommendations is far from universal; of the estimated 20,000 infants born each year to women with chronic hepatitis B, fewer than half are currently identified by national perinatal hepatitis B prevention programs^xvi. Delivery hospitals are central to preventing perinatal transmission, as these institutions are the only health care system organizations responsible for verifying maternal HBsAg status and providing timely administration of HBIG and hepatitis B vaccine. Although the ACIP recommended universal administration of a birth dose of hepatitis B vaccine, the National Immunization Survey estimated in 2006 that nationwide birth dose coverage was only 50%. Hospital performance indicators are important tools for measuring and boosting birth dose coverage in delivery hospitals. Advances in prevention of perinatal HBV transmission will require improvements to achieve 100% vaccination coverage with the birth dose, raise public and health care provider awareness of hepatitis B, establish routine reporting and documentation procedures in health care facilities, and enhance infrastructure support for public health case management programs.

Screening for Hepatitis B

Chronic hepatitis B is known as a silent killer; many chronically infected individuals feel healthy and are not aware of their infection because they have not been screened. Even blood tests for liver enzymes can be normal in the presence of chronic hepatitis B. In the US, many AA and NHOPI youth and adults have not been tested for hepatitis B. Although most people with chronic hepatitis B have no symptoms, they can still transmit the infection and develop liver cancer. Screening with a simple and inexpensive blood test for HBsAg is the only way to determine if an individual has chronic hepatitis B infection. In a study of 3,163 AA and NHOPI adults in the San Francisco Bay Area who were screened for HBV infection, approximately 8.9%, including 10.7% of those born in Asia or the Pacific Islands, were found to be chronically infected with HBV^v. Up to two-thirds of those chronically infected were not aware of their infection prior to testing. The high prevalence of undiagnosed infection is particularly alarming, since early detection and treatment can greatly decrease the cost of further complications, and vaccination of close contacts of infected individuals can prevent disease transmission. Among individuals with chronic hepatitis B, prevention of death from liver cancer may be accomplished through routine screening using liver ultrasound and a blood test for alpha-fetoprotein and, if appropriate, antiviral therapy^xvii, ^xviii. A recent study showed that it is cost-effective to screen all AAs and NHOPIs for hepatitis B, as this strategy will lead to the identification of chronically infected persons for medical management, as well as identification and potential vaccination of their uninfected close contacts^xix. Vaccination is another cost-effective strategy when combined with testing to offer an opportunity to further advance disease prevention. Families of youth or adults with HBV, as well as AA and NHOPI youth and adults who undergo testing and discover they do not have HBV, should be vaccinated if they are not already protected against HBV.

Patient Awareness and Education

Not only do AAs and NHOPIs have a high prevalence of chronic hepatitis B and a high incidence rate of liver cancer, but they are also poorly informed about the transmission, prevention, symptoms, risks, and occurrence of chronic hepatitis B. Fewer than 60% of highly educated AA and NHOPI adults in San Francisco reported having been tested for hepatitis B, and only 31% reported having been vaccinated against hepatitis B^xx. Half were misinformed about the routes of HBV transmission, and one-fourth did not know that HBV infection can be prevented by vaccination. Likewise, Traditional Chinese Medicine (TCM) practitioners and acupuncturists, who serve a predominantly AA and NHOPI patient population, lack basic knowledge about hepatitis B. In a 2005 survey of non-Western health care providers in San Francisco, only 47% knew how to test for immunity against HBV, 54% could identify all common routes of HBV transmission, and 18% were aware that newborn infants are at highest risk of developing chronic hepatitis B upon exposure to the virus^xxi. Thus, there is a clear need for expanded hepatitis B education and improved community-based interventions to increase hepatitis B awareness and prevent HBV-related liver disease in the AA and NHOPI community.

Provider Awareness

Additionally, many physicians and health care providers are not aware that a higher proportion of their AA and NHOPI patients may be infected already with HBV and that a lack of awareness of their infection might make them more likely to transmit hepatitis B. A recent survey distributed by the San Francisco Public Health Department and the University of California, San Francisco demonstrated that 45% of physicians surveyed could not correctly select the proper test for chronic hepatitis B, 46% were unaware of treatment options, and 40% incorrectly stated that chronic hepatitis B was curable^xxii. This is problematic for physicians practicing in a city where over a third of the population is at high risk for chronic hepatitis B.

Therefore, it is reasonable to believe that, through a concerted effort involving public health professionals, health care providers, scientists, community leaders, local legislators and the general population, it is possible not only to reduce the racial and ethnic health disparity due to chronic hepatitis B, but to eliminate the disease altogether.