Hepatitis B in Immigrant Populations: Breaking Barriers and Improving Outcomes
Including proceedings of a national series of lunch and learn meetings
Activity Date: December 2009  — Activity Info: Volume 9, (3)
 

HEPATITIS B IN IMMIGRANT POPULATIONS: BREAKING BARRIERS AND IMPROVING OUTCOMES
Ahmet Gurakar, MD*

First discovered in 1965, hepatitis B is a double-stranded DNA virus that is known to infect 350 to 400 million people worldwide, generating 50 million new cases and resulting in 520 000 deaths annually.1-3 Although the rate of infection with the hepatitis B virus (HBV) has decreased significantly as a result of successful vaccination programs, chronic HBV remains the leading cause of cirrhosis and hepatocellular carcinoma (HCC) in endemic areas, including much of Europe, Asia, Africa, the Middle East, and the Pacific Islands, where the regional prevalence of hepatitis B surface antigen (HBsAg) positivity ranges from 2% to 8%.4

In general, the frequency of HBV infection and patterns of HBV transmission vary dramatically in different parts of the world. Approximately 45% of the world’s population lives in areas where the prevalence of chronic HBV infection is high (>8% of the population is HBsAg-positive), 43% live in areas of intermediate prevalence (2%–7% of the population is HBsAg-positive), and only 12% of the world’s population lives in areas of low endemicity (<2% of the population is HBsAg-positive). In highly endemic regions, the lifetime risk of HBV infection is more than 60%.5 These areas include most of Asia (except Japan and India), most of the Middle East, the Amazon Basin of South America, most Pacific Island Groups, Africa, and regions with certain populations (eg, Native Alaskans, Australian Aborigines, and Maoris in New Zealand).5 In these parts of the world, most infections occur at birth (perinatally) or during early childhood, when the risk of acquiring chronic infection is the greatest. There is little recognition of acute disease because most early childhood HBV infections are asymptomatic. In areas of intermediate endemicity, the lifetime risk of HBV infection ranges from 20% to 60% and infections occur in all age groups. Acute disease is commonly recognized because many infections occur in adolescents and young adults. In areas of low endemicity (eg, the United States), the lifetime risk of infection is less than 20% and most infections occur among adults in well-defined risk groups (eg, injection drug users and men who have sex with other men).5

In the United States, a marked decrease in the prevalence of chronic HBV infection among younger, vaccinated, foreign-born US residents is contrasted by an increasing rate of liver cancer deaths among certain foreign-born populations, particularly Asian/Pacific Islanders. Clearly, the prevalence of HBsAg (indicator of chronic HBV infection) in the United States appears to be impacted by migratory trends from regions of high endemicity. From 1996 (when the data were gathered for the HBsAg prevalence) to 2002, approximately 1.9 million, 933 000, 337 000, and 401 000 persons immigrated from Asia, Europe, Africa, and South America, respectively. 6 The prevalence of HBV among Asian Americans ranges from 10% to 15%, and HCC ranks as the first, second, and fourth leading cause of death among Asian American men living in California, Vietnamese and Cambodian Americans, and Chinese and Korean Americans, respectively.7 Among persons immigrating to the United States from the Middle East and Africa, the prevalence of chronic HBV is 5% to 15%, and is higher in men than in women.4 Alarmingly, 25% of these immigrants are women are of reproductive age, a factor that increases the risk of perinatal transmission of HBV. The prevalence of chronic HBV among immigrants from Eastern European counties (except Hungary) is 2% to 7%.4 In the past, the Centers for Disease Control and Prevention recommended screening only persons born in geographic regions with HBV endemicity of 8% or higher (Figure 1), but the agency recently updated screening recommendations to include all persons born in geographic regions with HBV prevalence of 2% or higher (Figure 1).4,8

figure 1


RISK OF VERTICAL TRANSMISSION

Hepatitis B virus is present in body fluids, including blood, saliva, sweat, breast milk, tears, urine, vaginal secretions, semen, and menstrual blood.9 Viral transmission may occur via mother-to-child (vertical or perinatal transmission) or percutaneous or mucosal exposure to infectious bodily fluids (horizontal transmission). In areas with a low prevalence of HBV, horizontal transmission (eg, sexual contact, injection drug use, or occupational exposure to blood or blood products) is more common. In regions of high endemicity, which is particularly relevant to this discussion, perinatal transmission remains the predominant mode of HBV acquisition. If a pregnant woman contracts acute HBV infection during the first or second trimester, HBV rarely infects the infant. However, if infection occurs in the third trimester or in the postpartum period, it will likely lead to infection in the infant.1 Infants born to mothers who are both hepatitis B envelope antigen (HBeAg) (+) and HBsAg (+) have a 70% to 90% risk of developing chronic HBV infection by 6 months of age (in the absence of postexposure prophylaxis), whereas those born to HBeAg (-) and HBsAg (+) mothers have a considerably lower risk of infection (10%).10 Because immediate postnatal vaccination with both passive and active immunoprophylaxis of at-risk infants born to HBsAg (+) mothers significantly reduces the risk of transmission, current guidelines recommend that infants born to infected mothers receive the HBV vaccine and HBV immune globulin within 12 hours of birth. Infants born to mothers whose HBsAg status is unknown should receive the HBV vaccine within 12 hours of birth and the mother should have blood drawn immediately. If the mother is determined to be HBsAg (+), her infant should receive HBV immune globulin at no later than 1 week of age.10

HBV DISEASE PROGRESSION

As illustrated in Figure 2, progression of HBV infection is variable. Acute HBV infection is usually selflimiting and benign, but in a proportion of patients, it may progress to chronic HBV infection, leading to more serious complications, including cirrhosis, liver failure, and HCC.11-14 Initially, acute infection (shortterm infection) causes the body to mount an immune response, which essentially involves eradicating the virus by destroying HBV-infected liver cells. In some patients (ie, adults or adolescents), the immune response succeeds and the patient experiences a complete recovery (resolution). In other HBV-infected individuals (ie, infants), however, the immune response is insufficient in eliminating the virus acutely, and thus the immune system perseveres and may eventually (over months, many years, or indefinitely) lead to mass destruction of infected liver cells as the virus spreads (ie, long-term infection). This slow, persistent destruction of liver cells by the immune system can lead to fibrosis, cirrhosis, and HCC. Patients infected with HBV whose immune systems cannot eliminate the virus are referred to as chronic HBV carriers, and these individuals can transmit the virus to others. The reason why chronic infection cannot be cured may be related to the ability of the HBV virus to enter the nucleus of liver cells and produce covalently closed circular (ccc) DNA, which is essentially a permanent blueprint for the virus. Each time the virus reproduces, it replenishes the supply of cccDNA and, although currently available treatments can reduce HBV DNA to undetectable levels, they cannot eliminate the cccDNA.

figure 2


Hepatitis B virus-related morbidity and mortality is alarming and, at times, difficult to detect early, as evidenced by cases in which HCC developed in relatively young patients and in the absence of any previous liver disease. In those who develop cirrhosis, the 5-year life expectancy drops substantially. One study found the 5-year survival in 130 patients with cirrhosis (27% of whom had ascites; mean serum bilirubin was 1.6 mg/dL and mean albumin 3.5 g/dL) was 55%.15 In another study of 21 patients with cirrhosis and hepatic decompensation (determined by presence of ascites, jaundice, encephalopathy, and/or a history of variceal bleeding) the 5-year survival was 14%.16

The relationship between chronic HBV infection and HCC has become increasingly clear in recent years, with one major study correlating serum HBV DNA levels with the risk of developing the malignancy.17 In this prospective trial of 3653 HBsAg (+) patients (aged 30–65 years) in Taiwan, the incidence of HCC increased with serum HBV DNA levels in a dose-response relationship, ranging from a 1.3% rate for an HBV DNA level of less than 300 copies/mL to a 14.9% rate for an HBV DNA level of 1 million copies/mL or more. Participants with persistent elevations in serum HBV DNA levels during follow- up had the highest risk of HCC. This study underscores both the importance of determining viral load and utilizing current treatment regimens to achieve undetectable viral levels.

This issue of Johns Hopkins Advanced Studies in Medicine is based on the proceedings of a national series of “lunch and learn” meetings, which were held from August to October 2009. This monograph is dedicated to educating primary care physicians, nurses, nurse practitioners, and physician assistants on screening for and managing chronic HBV infection in at-risk immigrant populations within the United States. Tarek Hassanein, MD, explores the life cycle of HBV as it relates to perinatal or early childhood- acquired infection, and reviews the various phases of HBV infection. He also discusses diagnostic and screening strategies (including the recently updated recommendations from Morbidity and Mortality Weekly Report), along with public health implications of treating HBsAg (+) individuals.

In discussing management of chronic HBV infection, Norman L. Sussman, MD, focuses on US Food and Drug Administration-approved regimens, treatment duration and end points, and therapeutic monitoring. He also addresses management of chronic HBV infection in special populations, specifically in pregnant patients and in those undergoing chemotherapy for solid organ or hematologic malignancies.

REFERENCES

1. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507-539.
2. Hoofnagle JH, Doo E, Liang TJ, et al. Management of hepatitis B: summary of a clinical research workshop. Hepatology. 2007;45:1056-1075.
3. Hu KQ. Hepatitis B virus (HBV) infection in Asian and Pacific Islander Americans (APIAs): how can we do better for this special population? Am J Gastroenterol. 2008;103:1824-1833.
4. Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57(RR-8):1-20.
5. World Health Organization. Geographic prevalence of HBsAg. Available at: http://www.who.int/vaccines-surveillance/ graphics/htmls/hepbprev.htm. Accessed July 8, 2009.
6. US Citizenship and Immigration Services. 2002 Yearbook of Immigration Statistics. US Department of Homeland Security Web site. Available at: http://uscis.gov/graphics/shared/ aboutus/statistics/yearbook/2002.pdf. Accessed July 8, 2009.
7. Asian Liver Center. Stanford University School of Medicine Web site. Available at: http://liver.stanford.edu. Accessed June 4, 2009.
8. Traveler’s Health—Yellow Book. Centers for Disease Control and Prevention. Available at: http://wwwn.cdc.gov/travel/ yellowbook/ch4/hep-b.aspx. Accessed June 5, 2009.
9. Boag F. Hepatitis B: heterosexual transmission and vaccination strategies. Int J STD AIDS. 1991;2:318-324.
10. Centers for Disease Control and Prevention. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP); Part 1: Immunization of Infants, Children, and Adolescents. MMWR Morb Mortal Wkly Rep. 2005;54(RR-16):1-31.
11. Torresi J, Locarnini S. Antiviral chemotherapy for the treatment of hepatitis B virus infections. Gastroenterology. 2000;118(2, suppl 1):S83-S103.
12. Moyer LA, Mast EE. Hepatitis B: virology, epidemiology, disease, and prevention, and an overview of viral hepatitis. Am J Prev Med. 1994;10(suppl):45-55.
13. Fattovich G, Giustina G, Schalm SW, et al. Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis. Hepatology. 1995;1:77-823.
14. Perrillo RP, Wright T, Rakela J, et al. A multicenter United States-Canadian trial to assess lamivudine monotherapy before and after liver transplantation for chronic hepatitis B. Hepatology. 2001;33:424-432.
15. Weissberg JI, Andres LL, Smith CI, et al. Survival in chronic hepatitis B: an analysis of 379 patients. Ann Intern Med. 1984;101:613-616.
16. De Jongh FE, Janssen HL, de Man RA, et al. Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver. Gastroenterology. 1992;103:1630-1635.
17. Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65-73.

*Associate Professor of Medicine, Division of Gastroenterology and Hepatology, Medical Director, Liver Transplantation, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Address correspondence to: Ahmet Gurakar, MD, Associate Professor of Medicine, Division of Gastroenterology and Hepatology, Medical Director, Liver Transplantation, The Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite # 429, Baltimore, MD 21205. E-mail: aguraka1@jhmi.edu.

The content in this monograph was developed with the assistance of a medical writer. The authors made substantial contributions to the intellectual content of the articles by conceiving and designing the original presentations, researching references and studies, drafting the manuscripts, reviewing and revising the manuscripts, and/or providing supervision.

     
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