Invited Commentary: Screening for hepatitis B in the immigrant population and individuals who are in need of immunosuppressive drug therapy

Abstract

Chronic hepatitis B (CHB) afflicts approximately 300 million people in the world. Hepatitis B virus (HBV) is a known carcinogenic virus and continues to be the leading cause of hepatocellular carcinoma (HCC) (1). Approximately 70% of hepatitis B surface antigen (HBsAg) carriers reside in intermediate (>2% prevalence) to high-risk (>8% prevalence) areas such as Asia, the Pacific Islands, Africa, India, and parts of Southern Europe (1). There is a common misperception that this disorder is not very common in the United States. However, 63% of the nearly 28 million immigrants who entered the US between 1974 and 2008 were born in countries of intermediate or high prevalence (2). The Immigrant Refugee and Migrant Health Branch of the Centers for Disease Control and Prevention (CDC) estimated that an average of 53,000 CHB cases were imported to the US yearly from 2004 to 2008. Forty percent of these cases originated from China, Vietnam, and the Philippines (2). The CDC has recently revised its prevalence estimates and concluded that 2.2 million US residents are likely to have chronic HBV infection, of which 1.3 million are judged to be foreign-born individuals. Even these figures are likely to be too low, however, because the estimates do not take into account illegal immigrants and other socially disadvantaged patients. Importantly, HBsAg testing is not required as part of the process of immigrating into the United States (3). This lack of a requirement for HBV screening is an important missed opportunity to programmatically diagnose this condition.

The CDC has long recommended that patients born in intermediate to high prevalence countries undergo testing for HBsAg and antibody to hepatitis B core antigen (anti-HBc), with the primary purposes being to identify susceptible household members of HBsAg carriers who would benefit from vaccination but with the added advantage of uncovering individuals with active underlying liver disease who would benefit from antiviral therapy. Conscientious attention to this screening recommendation would provide a possible fail safe for the lack of detection during the entry process into the US. However, a recent report by the Institute of Medicine has concluded that 65% of individuals with CHB in the US are unaware of their infection (4). Hepatitis B is now seen as a major health disparity affecting many foreign-born populations. This is primarily due to poor patient self-awareness of infection, lack of understanding about long-term complications, language barriers, cultural attitudes toward illness, and oftentimes limited access to health care. A lack of provider awareness about who to test and how to interpret the findings of screening are additional contributing factors (4).

To improve viral health prevention services, the US Department of Health and Human Services released a comprehensive plan outlining a set of actions for reducing health disparities among populations disproportionately affected by viral hepatitis, such as foreign-born persons. Several large community-based efforts for screening have been undertaken and described in conjunction with these efforts (5). These have generally been done in large cities where there is a known high density of foreign-born immigrants from endemic regions. Unfortunately, these community-based programs for patient education and screening are not part of a coordinated national network and are not governmentally funded.

In this issue of Baylor Proceedings, two articles from Baylor Scott and White Health in Temple touch upon some of these issues and provide new insights into how to improve screening efficiency in two very different populations. In one article by Hasan and colleagues, the authors tested 96 Korean Americans for HBsAg, anti-HBs, and anti-HCV (6). None of the individuals was positive for anti-HCV, but 53% had evidence of past hepatitis B infection and 5 were found to be HBsAg carriers and were offered care at the medical center. What makes this HBV screening study relatively unique is that it was done in central Texas, an area not normally considered to have a high density of immigrants with hepatitis B. Patients were tested on their knowledge of hepatitis B both before (pretest) and after (posttest) an educational session, and the authors were able to demonstrate significant improvement in knowledge of viral transmission, complications, and importance of screening. The authors also wisely presented the educational material in a culturally sensitive manner with presentations in Korean and/or English.

The objectives of HBV screening should be to ensure that HBsAg carriers undergo routine HCC surveillance when appropriate, to offer treatment to those with active underlying liver disease, and to ensure vaccination of susceptible household contacts. To accomplish these objectives, screening must always be linked to care in private or public health care settings. This can be a challenge and requires dedication, personnel resources, and the cooperation of community providers and health leadership.

The second paper in this issue by Ramirez and colleagues deals with another area in which HBV screening often makes a major difference in the well-being of individuals with unsuspected CHB (7). It is clear that a failure to screen patients for HBV who are about to undergo immunosuppressive drug therapy can result in hepatitis B reactivation and associated flares of hepatitis (8, 9). This is most often discussed in the context of cancer chemotherapy and organ transplantation but has been observed less frequently in patients treated with biologic agents for chronic inflammatory disorders (9). Rates of occurrence during cancer chemotherapy vary from 10% to 70% depending in large part on the HBV serologic status of the patient and immunologic potency of the chemotherapy. HBsAg carriers, particularly those with detectable serum HBV DNA, have the highest risk of reactivation, but episodes can occur in patients with resolved infection (HBsAg negative, anti-HBc positive) when treated with highly aggressive immunosuppression (9). Unfortunately, several large studies have shown that only a small minority (20%) of oncologists in the United States and elsewhere in the world routinely screen for HBV before initiating cancer chemotherapy, and even fewer patients are placed on prophylactic antiviral therapy (10). This practice is discordant with the recommendations of the major international liver organizations, the CDC, and the US Preventive Services Task Force (1, 9). Once HBV reactivation occurs, hospitalization is needed in 40% of patients, chemotherapy is interrupted in 40% to 50% of patients, and death due to liver failure may occur in as many as 25% of cases (8). Several randomized controlled trials in patients with lymphoma, breast cancer, or HCC have demonstrated that antiviral prophylaxis can prevent reactivation in more than 85% of cases when initiated before or early in the chemotherapy cycle (9).

An important finding to come from the current study in the Baylor Proceedings by Ramirez is that a simple measure such as a checkbox on the order form for rituximab, a B-cell–depleting agent frequently used with CHOP therapy to treat lymphoma, led to significantly higher rates of HBV screening (3.7% screening rate for a historical cohort and 68.7% for a second cohort after the checkbox order sheet was implemented). Other centers have reported even higher rates of screening when orders for immunosuppressive drug therapy are flagged and the provider is then given the information that HBV screening remains to be done; in one study, a 94% screening rate was observed using a computer-generated ordering system for HBV markers in individuals who had no prior testing followed by Hepatology staff review of the results (11, 12).

CHB is a potentially serious and relatively common disorder. Without intervention, up to 25% of individuals with CHB die of late complications, including cirrhosis and liver cancer. Fortunately, HBV infection is preventable through vaccination, and safe and effective antiviral therapies are available that forestall disease progression, prevent viral reactivation, and reduce the incidence of HCC in HBsAg carriers with advanced fibrosis (1). However, HBV screening is the critical first step in taking action to ensure that this occurs. We in the hepatology and gastroenterology community need to continue to broaden efforts to educate providers who may be less sensitive to these issues. Inroads into increasing the awareness and importance of CHB in the immigrant populations where the disease is most prevalent also are greatly needed if we are to make the most headway in the future.

Robert Perrillo, MD
Hepatology Division, Baylor University Medical Center at Dallas, (e-mail: roberper@baylorhealth.edu)