Robert P. Perrillo, MD; John W. Ward, MD
CME Released: 03/14/2012; Valid for credit through 03/14/2013
Slide 1.
Robert Perrillo, MD: Hello. I am Bob Perrillo, Chair of the American Association for the Study of Liver Diseases (AASLD) Hepatitis B Special Interest Group and clinical hepatologist at Baylor University Medical Center in Dallas.
I am pleased to welcome you to this CME-certified activity titled "A Silent Epidemic: Why Chronic Hepatitis B Matters."
I am particularly delighted to be joined today by Dr John Ward, who is the director of the Division of Viral Hepatitis at the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the Centers for Disease Control and Prevention (CDC) in Atlanta.
John, why should healthcare providers in the United States be concerned about hepatitis B virus (HBV) infection?
Slide 2.
John Ward, MD: Although HBV infection is a common health problem globally and in the United States, it is known as the silent epidemic because the public and many providers are unaware of its scope. Transmission continues to be a problem here in the United States. Approximately 370 million people worldwide have HBV infection, which causes approximately 660,000 deaths every year. Acute infection may lead to chronic infection that over decades can lead to severe liver disease, liver cirrhosis, and hepatocellular carcinoma (HCC), or primary liver cancer.
Slide 3.
Liver cancer is the second leading cause of cancer deaths worldwide,[1] and a major cause of those deaths from liver cancer is HBV infection. Hepatitis B is more common in some parts of the world than others; it is a particularly large problem in Asia -- 1 of the most heavily populated areas on the planet -- as well as Sub-Saharan Africa, some areas of South America, and other regions. Persons who migrate from those regions to the United States bring hepatitis B with them. The CDC estimates that up to 1.4 million persons are living with hepatitis B infection in the United States and are at risk for cirrhosis and liver cancer. In addition, approximately 30,000 to 40,000 new infections occur every year in the United States..
Dr Perrillo: It is a worldwide health issue of great importance, and the United States is clearly affected by the effects of immigration from these areas of high endemicity. It is quite clear that clinicians in the United States can benefit from a global perspective of this serious problem. John, what can we do to prevent transmission?
Slide 4.
Dr Ward: The hepatitis B virus that causes hepatitis B disease is transmitted through blood contact in healthcare settings, among injection-drug users, and in the household setting through everyday exposures to small amounts of blood and through sexual contact among adolescents and adults. Importantly, an infected mother can transmit the virus to her infant at birth.
Slide 5.
Fortunately, we have safe and highly effective vaccines to prevent transmission via all of these routes, and our vaccine recommendations are designed to seize those opportunities to prevent transmission. We at the CDC recommend that all newborns in the United States receive the initial birth dose of HBV vaccine before leaving the birthing hospital to prevent acquisition of HBV from the infected mother. We recommend that all children receive the 3-dose vaccine series that begins in the hospital and is completed in the pediatrician's office. [Eds. note: A fourth dose is permissible if a combination vaccine that includes hepatitis B is administered after the birth dose.] The vaccines are highly effective and appear to provide protection for decades. We also recommend vaccination for adults who engage in high-risk sexual behaviors, adults who are current or recent injection-drug users, and men who have sex with men. We also recognize that healthcare workers are at high risk for occupational transmission, and we recommend vaccination for all healthcare workers.
Patients who have only recently been recognized to be at increased risk for hepatitis B transmission are persons with diabetes (in whom transmission can occur when infection control practices are not followed during blood glucose monitoring). The CDC has investigated a number of outbreaks of hepatitis B among persons with diabetes because infection control is not followed in places such as residential care facilities and medical facilities. In November 2011, the CDC recommended that all persons with diabetes younger than 60 years be vaccinated against hepatitis B. Because the vaccine is less effective in persons 60 years and older, it should be given at the discretion of the healthcare provider. I do want to emphasize the new recommendation that persons with diabetes should be offered hepatitis B vaccine. This new recommendation is part of the 2012 Recommended Adult Immunization Schedule.
Dr Perrillo: That is important new information.
One of the major challenges facing healthcare providers, as identified in the 2010 Institute of Medicine (IOM) report,[2] is the need to more conscientiously screen for hepatitis B infection. John, would you describe for us briefly the CDC screening recommendations?
Slide 6.
Dr Ward: We have an intervention available to us to prevent infection -- vaccination -- and we have interventions to prevent disease progression for persons living with hepatitis B infection -- screening and linkage to care. As treatments have improved over the past 10 to 15 years, the benefits of screening (ie, knowing your status, obtaining timely care) have increased. In 2008, the CDC for the first time issued national recommendations as to who should be screened [for HBV]. The recommendations align with the epidemiology of hepatitis B and the populations that have the highest prevalence of chronic hepatitis B infection. One group includes persons born in countries such as in Asia and Africa that have a high prevalence of hepatitis B and who live in the United States. Some Asian populations in the United States have a staggering 8% to 10% prevalence of chronic hepatitis B infection[3]; as a result, their liver disease and liver cancer rates are much higher than in other populations.To further compound the issue, many of these Asian and African HBV carriers may be uaware of their HBV status and may not have access to health care, so it is truly a health disparity for those patient populations. Screening is also recommended for men who have sex with men, injection-drug users, and persons who are about to begin immunosuppressive therapy.
One question we are often asked at the CDC is from clinicians who want guidance on how they should interpret results of the various tests for HBV infection. Bob, would you go over the various tests that are available to a clinician to screen someone for hepatitis B, what they measure, and how they should be used?
Slide 7.
Dr Perrillo: Unfortunately, this continues to be an area of confusion for clinicians. Hepatitis B surface antigen (HBsAg) is the basic test that shows whether a patient is infected; notably, HBsAg positive patients may be acutely or chronically infected. Antibody to the hepatitis B core (anti-HBc) can be a marker for ongoing infection as well as an indicator of past infection, and a small percentage of patients with isolated anti-HBc actually have low levels of HBV DNA in their serum; we call this occult infection. Antibody to the surface antigen (anti-HBs) is a neutralizing antibody, and this is the antibody that develops after vaccination and after successful immunologic recovery from either acute or chronic hepatitis B. It is important to note that HBsAg negative individuals who appear to have recovered from infection may continue to have small amounts of HBV DNA in their liver cells and other tissues, perhaps indefinitely, with the lowest amounts of HBV DNA occurring in individuals who have both anti-HBc and anti-HBs.
Many of the HBsAg negative patients we see who have recovered from hepatitis B have both anti-HBc and anti-HBs. This group of patients is at the highest state of immunologic control over future virus replication and accordingly is least susceptible to future reactivation of HBV. The patient who has isolated anti-HBc is a bit more worrisome and controversial because we do not routinely test these people for HBV DNA levels and some may have occult viremia. This factor and absence of the neutralizing antibody (anti-HBs) places them at greater risk for reactivation in the future, particularly during immunosuppressive therapy.
Dr Ward: It suggests that patients who are positive for HBsAg are actively replicating the virus.
Dr Perrillo: It may not be detectable in serum, but it is a protein. It is transcribed from the viral genome, so yes, there has to be some DNA and some replication.
Dr Ward: I have tried to describe the populations that from a public health perspective we feel are important to be screened and linked to care. Perhaps from a clinical perspective, Bob, you can describe the next steps to protect the health of the patient who has been screened and found to have hepatitis B.
Slide 8.
Dr Perrillo: Whenever an HBsAg positive patient comes to our office, we think of a possible need for treatment to forestall disease progression and to prevent the long-term complications of infection. Recently, longitudinal cohort studies have shown that the level of HBV DNA n the blood predicts the relative risk for developing complications, such as cirrhosis and HCC. In addition, data show lower rates of decompensation, liver failure, and HCC in patients with advanced fibrosis who undergo antiviral treatment compared with patients who are not treated or who are treated with placebo.[34] The data strongly suggest that maintenance treatment to suppress high rates of viral replication in older HBsAg carriers may prevent long-term complications.
Slide 9.
Additionally, when you see an HBsAg carrier in the office, you can set up surveillance for HCC with a liver ultrasound study and with alpha-fetoprotein testing every 6 months for those over the age of 40 or those with cirrhosis. The AASLD has issued very clear guidelines about providing HCC surveillance in HBsAg carriers.[4]
I mentioned reactivation due to immunosuppressive therapy, but we can only prevent this complication of immunosuppressive drugs by screening the patient for HBV and evaluating their level of risk. Furthermore, the initial office visit also is the best time to talk about vaccinating household contacts, and to educate the patient about the potential importance of hepatitis B; sadly, the patient may have been told by other providers that HBV infection is not something of great concern. These providers are typically dealing with the patient's other health issues that may appear to have greater priority.
When you see a patient in the clinic who has HBV infection, you should also ask whether other people in the household have been tested. Very often the patient does not know the results of the household contacts' tests or whether the household contacts were tested at all. We should always get this point across that household members need to be tested, particularly if perinatal transmission is suspected in your patient (in which case there might also be an infected sibling who has not yet been tested). The benefits that we just outlined could apply to other household members as well.
Dr Ward: Bob, you mention screening persons who are candidates for immunosuppressive therapy. I wonder if you could explain why it is important to screen that population for hepatitis B infection.
Slide 10.
Dr Perrillo: In our clinic, we see reactivation in patients who have not been screened for HBV and have undergone immunosuppressive therapy, which allows the virus to replicate unimpeded by the host immune response. We see an immunologic reconstitution effect when immunosuppressive therapy is stopped, and that is often followed by a flare of hepatitis because of aggressive cellular immune attack on hepatocytes that have become more heavility infected. What is particularly dramatic is a flare that is superimposed on severe underlying liver disease and advanced fibrosis, because it can lead to liver failure and death.
The population of patients at risk for HBV reactivation due to immunosuppressive therapy stretches far beyond those undergoing cancer chemotherapy; there are many thousands of patients on other, seemingly more benign immunosuppressive agents, such as tumor necrosis factor-alpha inhibitors, which have also been linked to reactivation. Again, the message is to screen patients before exposure to such drugs and then, if the patient is positive for HBsAg or isolated anti-HBc, you can refer the patient to a specialist who can initiate prophylactic antiviral therapy. The good news is that antiviral therapy, given for a few days to weeks prior to the initiation of immunosuppressive therapy, can prevent the vast majority of these reactivation events from occurring; that is really important to keep in mind.
Dr Ward: Yes, it is an important opportunity to intervene.
Dr Perrillo: John, we have indicated today that hepatitis B is a potentially serious disease both globally and in the United States that is best dealt with by conscientious attention to vaccination, screening those at risk, and linking patients who are HBsAg positive to care. John, can you tell me the health priority plan for hepatitis B, and how are we going to deal with this in the United States in the future?
Slide 11.
Dr Ward: I am happy to report that there has been a lot of attention paid to hepatitis B over the past several years at the policy level here in the United States. In 2010, the IOM released a report calling attention to hepatitis B and to C; the IOM recognized them as underappreciated health problems with missed opportunities of prevention, care, and treatment that resulted in unnecessary loss of life and quality of life.[2] In its report, the IOM issued several recommendations that the US government could take to improve hepatitis prevention, care, and treatment; this led the Department of Health and Human Services (DHHS) to release a plan for viral hepatitis in May 2011. The plan includes a number of activities that the agencies within that department -- including the National Institutes of Health, Food and Drug Administration, and CDC -- could initiate to improve education for providers as well as communities (particularly those experiencing health disparities) in order to improve the opportunities for testing and linkage to care and treatment. Other activities include strengthening surveillance, so that we can better grasp the transmission and burden of disease, and identifying individuals who are not getting preventive services and care services. We have set a goal of eliminating transmission through vaccination, and the plan outlines opportunities to realize that goal, while recognizing particular groups at risk for multiple forms of hepatitis. The plan also recognizes the problem of patient safety and transmission in the healthcare setting. I am happy to report that the plan is available from the DHHS. It is very dynamic, and it really sets hepatitis as a new health priority for the nation.
Slide 12.
Dr Perrillo: It is resoundingly clear, then, that although hepatitis B is a serious clinical and public health issue, it is also something that we can prevent and treat. Treatments have advanced markedly over the past 10 to 15 years, and we now have oral antiviral agents that are very safe and can be given long-term to suppress viral replication. I believe these agents are going to lower the frequency of the complications associated with HBV. It is a very important message, but you can only identify the patients who will benefit most from these therapies through diligent HBV screening.
Dr Ward: Right.
Dr Perrillo: Our message today is that we need to vaccinate patients at risk for HBV, we need to screen those people that we think might be HBV-positive, and we need to link the HBV-positive patients to care. We have to be more active in our surveillance, per the IOM report. The future sounds a bit better because we are beginning to recognize hepatitis B as a serious health priority in this nation and identify where the gaps have been in our surveillance and linkage to care. It is imperative to appreciate the deficiencies in dealing with this serious health issue in order to devise practical and meaningful solutions, wouldn't you agree?
Dr Ward: I could not agree more. We have a good vaccine. We can prevent transmission. We have screening tests and guidelines for direct screening to the populations most in need. People can only benefit from these advances in treatment if we get them screened and into quality care. Both in public health and in clinical medicine, we should realize these opportunities can translate into health benefits for the people in the United States.
Slide 13.
Dr Perrillo: Thank you, John, for your interesting comments and in-depth discussion today, and I want to thank you all for participating in this activity.
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