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HBV Journal Review

HBV Journal Review
March 1, 2013, Vol 10, no 3
by Christine M. Kukka

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Few Ethnic Minorities at Risk of Hepatitis B Are Screened for Infection
The U.S. Centers for Disease Control and Prevention (CDC) recommend that all people immigrating from countries with hepatitis B virus (HBV) infection rates above 2% should be screened.

However, a recent study of 28 ethnic communities across the nation finds the U.S. falls far short of that goal despite the CDC recommendation and the inherent cost effectiveness of screening immigrants at risk of hepatitis B, and immunizing uninfected family members.

A recent CDC study, published in the journal Hepatology, scoured survey data collected from the 2009-2010 Racial and Ethnic Approaches to Community Health study that tracked access to health care and HBV screening in ethnic communities.

Of 53,896 people surveyed, only 21,129 (39.2%) had been tested for the hepatitis B surface antigen (HBsAg–which indicates a current infection.) The survey found the following percentages of ethnic minorities had been tested for hepatitis B:

  • 40.4% of African-Americans
  • 35.6% of Hispanics
  • 42.5% of Asian-Pacific Islanders. (Testing was higher in foreign-born Asian-Americans than U.S.-born–48% vs. 31%.)
  • And, 39.1% of Native Americans/Alaska natives.

As expected, younger people with higher incomes, a college education, and health insurance had higher rates of HBV screening. The most common venue for HBV testing was a doctor's office or lab.

Of all people tested, 5.8% were HBV-infected. Asian-Americans had the highest infection rate of 12.7%.

Males and those with health insurance had the highest rate of receiving treatment for hepatitis B after screening revealed infection (37% vs. 21%.)

Researchers faulted primary care providers for failing to screen immigrants for HBV infection, despite the medical practice guidelines.

“Awareness and screening campaigns for physicians and the public should be implemented widely to promote hepatitis B testing and facilitate access to care,” researchers wrote.

An unrelated study published in the Journal of Immigrant and Minority Health confirmed the gaps in HBV screening among Laotian immigrants in the Minneapolis-St. Paul area. A study of 167 adult Laotian immigrants by the University of Minnesota School of Public Health found that more than half did not know about hepatitis B or how it is transmitted. Only 14 (8.4%) had been vaccinated against HBV infection, and only 2 of the 14 had received all three recommended vaccine doses.

“This study outlines gaps in knowledge and resources that could address the staggering HBV disparity in this community,” public health researchers wrote.

Even Asian-American College Students Unaware of Hepatitis B Risk
Considering Asian-Americans are at high risk of hepatitis B, how aware are Asian-American college students about hepatitis B? How many have been immunized? Not many according to a recent study, underscoring the knowledge gap in hepatitis B even among at-risk college students.

The study, conducted by the University of Massachusetts College of Nursing and Health Services, screened 66 U.S.-born students and 142 foreign-born students for hepatitis B.

None of the U.S.-born students were infected, one had a resolved HBV infection, and 68% had been immunized.

Among foreign-born students, 4% had chronic infection, 62% had been immunized, and 19% had resolved infections.

The Asian-American college students showed very little knowledge about hepatitis B immunization–half did not know if they had been vaccinated.

“The lack of awareness of their HBV-infected status points out the importance of routine HBV screening of high-risk populations such as Asian students," researchers wrote in the February issue of the Journal of American College Health.

Vaccine's Effectiveness May Wane Over Time Unless Surface Antibodies Remain
A CDC study of college students suggests that even if people have very low levels of surface antibodies, the immunization they received during infancy may still protect them against hepatitis B.

Recently, some reports have raised doubts whether vaccines administered during infancy continue to confer protection against hepatitis B into adulthood. Other studies have found slight increases in HBV infection in young adults who had been vaccinated during infancy.

The vaccine contains only the surface antigen (HBsAg), in order to spur production of protective surface antibodies. Scientists assume that antibody levels exceeding 10 IU/L should confer protection against infection.

In the study, reported in the journal of Clinical and Vaccine Immunology, researchers administered a single vaccine dose to 153 students–called a challenge dose–to see how many students generated surface antibodies, which would prove their immune systems recognized the antigen from the infant vaccine and were ready to fight the infection.

Before receiving the challenge vaccine, 130 students (85%) had surface antibodies less than 10 IU/L and of these 72 had undetectable levels of surface antibodies.

They found that students with low levels of residual surface antibodies (between 1-9 IU/L) were more likely to respond to the challenge dose and generate more surface antibodies (83%) compared to those with undetectable surface antibodies. Only half of students with undetectable antibodies before the challenge dose generated a protective quantity of antibodies afterwards.

“The presence of any detectable (surface antibodies) among persons vaccinated in the remote past may indicate the persistence of immune memory,” they wrote.

Remaining unresolved is the issue of whether the childhood vaccine loses its effectiveness as people reach adulthood and whether booster vaccine doses are needed.

Sexually Transmitted Infections Affect Young Adults and Carry High Costs
The CDC conducted a study of the number of sexually transmitted infections in 2008, including chlamydia, gonorrhea, syphilis, herpes, human papillomavirus, hepatitis B, HIV, and trichomoniasis, and found that adolescents and young adults bear the brunt of these infections.

Of 19.7 million infections in 2008, nearly 50% (9.8 million) were in young women and men aged 15 to 24 years. Officials argue that this young population clearly needs to be the focus of more education and prevention efforts, according to the article in the journal of Sexually Transmitted Diseases.

In another article in the same journal, researchers estimated the cost, per lifetime, of these eight STIs, using cost estimates from 2002 to 2011.

They found that the total lifetime direct medical cost of the 19.7 million cases of STIs in 2008 was $15.6 billion.

Total costs were as follows:

  • chlamydia ($516.7 million)
  • gonorrhea ($162.1 million)
  • hepatitis B ($50.7 million)
  • HIV ($12.6 billion), human papillomavirus ($1.7 billion)
  • herpes simplex virus type 2 ($540.7 million)
  • syphilis ($39.3 million)
  • and trichomoniasis ($24 million).

"Sexually transmitted infections continue to impose a substantial cost burden on the payers of medical care in the United States," researchers wrote. "The burden of STIs would be even greater in the absence of STI prevention and control efforts."

Declining HBsAg Levels During Interferon Treatment Forecasts Success
Increasingly, researchers are finding that declines in surface antigen (HBsAg) and volume of HBV DNA in the bloodstream during interferon treatment can predict if a patient will respond to treatment, which spurs the immune system to fight infection.

A recent study, published in the February issue of the European Journal of Gastroenterology and Hepatology, found that patients who experienced declines in HBsAg between treatment weeks 12 and 24 had the best treatment success.

The Chinese study followed HBsAg levels in 70 hepatitis B "e" antigen (HBeAg)-positive patients who received three weekly injections of interferon (5 MU of IFNα-1b) over 48 weeks.

They found viral load (HBV DNA) and HBsAg levels declined at similar rates between weeks 12 to 48, but those with lower HBsAg levels (down to 6109.01 IU/ml at week 24) responded best.

An unrelated study published in the Journal of Hepatology, found another clue that predicts if interferon treatment will be a success. Dutch researchers found that patients with identifiable levels of interferon-gamma inducible protein 10 (IP-10) in their bloodstream have an increased chance of responding to treatment.

When present, IP-10 indicates an immune system primed to fight infection.

They followed 210 HBeAg-positive patients treated with pegylated interferon for 52 weeks and reported that those with higher IP-10 levels when starting treatment achieved higher rates of HBeAg loss.

Patients with higher IP-10 levels, and no precore or core promoter mutations in their HBV at start of treatment had better chances of clearing HBsAg (48% of those with high IP-10 levels lost HBeAg and HBsAg).

Entecavir and Tenofovir Safe in Patients with Severe Cirrhosis
Hepatitis B patients with cirrhosis, including those with severe liver damage (decompensated cirrhosis) can safely take either entecavir (Baraclude) or tenofovir (Viread), according to a Spanish study published in the Annals of Hepatology.

The study followed 48 patients with either compensated or decompensated cirrhosis treated for three years with either antiviral. Eight of the patients had decompensated cirrhosis, which means severe scarring in the liver has damaged the organ's ability to function and liver failure was imminent.

The average age was 55, most were Caucasian, male, and eight patients were HBeAg-positive.

As expected, patients who began the study with "compensated" functioning livers fared better on treatment. After 12 months more than 80% of them achieved normal ALT levels, indicating no liver damage. However, only 71.4% of those with decompensated cirrhosis achieved normal ALT, but many decompensated patients did slowly improve over time.

However, the cirrhosis took its toll on both groups. During follow-up, seven patients died, four received liver transplants and five developed liver cancer. Among those with decompensated cirrhosis, three died during the first six months of treatment.

Survival among the compensated vs. decompensated cirrhotic patients at 24 months was 88.2% vs. 57.1%, respectively. “In conclusion, in compensated and decompensated cirrhotic patients, entecavir and tenofovir were effective and well tolerated," researchers wrote.

Adding Tenofovir to Telbivudine Boosts Its Effectiveness in Hard-to-Treat Patients
Thai researchers tried adding tenofovir to ongoing telbivudine (Tyzeka) treatment in 105 HBeAg-positive patients and found the antiviral combination was highly effective in hard-to-treat patients who did not respond to the telbivudine alone.

According to their report in the journal PLoS One, patients received a 600-mg telbivudine pill daily for 24 weeks. Forty-five patients continued to have detectable viral load and they had a 300 mg tenofovir pill added to their daily telbivudine regimen.

At Week 52, 84% of those receiving the combined treatment had undetectable HBV DNA and 64% had normal ALT levels.

HBeAg clearance occurred in 16% of the hard-to-treat group, and HBeAg seroconversion (appearance of the HBeAG antibody) occurred in 11% of the antiviral combination group.

“Telbivudine therapy with tenofovir intensification at Week 24, where indicated .... appears effective and well tolerated for the treatment of chronic hepatitis B," researchers wrote.

Some Infants Are Infected with HBV Prior to Birth
Doctors know that infants born to women with high viral loads are at high risk of infection—even when they are immediately immunized at birth and given hepatitis B antibodies (HBIG) at birth.

Now doctors are finding that some of these infants may have been infected before they were born due to the presence of the virus in their mother’s ovaries or placenta.

If HBV stays outside the placenta, doctors believe the child has a better chance of avoiding infection. A Chinese study examined what happens when HBsAg cross the placenta and are present in the ovary. They retrieved samples of ovarian and placental tissue during Caesarian births from HBV-infected pregnant women.

According to their report published in the journal PLoS One, HBsAg was detected in 15 of 33 (45%) placental tissue samples. Of these 15 infants, three became HBV-infected.

HBsAg was also found in seven (21%) of 33 ovarian tissue samples. Among the seven, two infants became HBV-infected as a result of intrauterine exposure. “HBsAg expression in cells of the ovarian follicle or placental capillary endothelium signal a higher risk for intrauterine HBV infection,” researchers wrote.

Breastfeeding Does Not Increase Risk of Mother-to-Child HBV Infection
Chinese researchers, reporting in the journal PLoS One, confirmed that infants who breastfeed are not at higher risk of contracting hepatitis B from their infected mothers than infants who are bottle-fed.

The researchers followed 546 children born to 544 HBV-infected mothers, with 397 breastfed and 149 formula-fed. They reported that 137 were born to HBeAg-positive mothers. All children had been vaccinated but only 53.3% received the hepatitis B immune globulin (HBIG).

Only 2.4% of the infants became HBV-infected–1.5% of breast-fed children and 4.7% among formula-fed children.

The difference in infection rates had more to do with the mothers' HBeAg-positive rate and high viral load at birth than with feeding styles. Most of the HBeAg-positive mothers chose to bottle-feed their children.

"Breastfeeding is not a risk factor for mother-to-child transmission of HBV," they wrote. "Therefore, clinicians should encourage HBV-infected mothers to breastfeed their infants."

Tenofovir Effective After Lengthy Treatment in Those With Drug Resistance
Turkish researchers compared the effectiveness of tenofovir in two groups of patients–those who had never been treated and patients who had drug resistance to the antiviral lamivudine (Epivir-HBV)–to see if tenofovir was more effective in any group.

Of 197 patients (mostly male, average age 43), 105 patients had never been treated and 65 were HBeAg-positive. They were treated with tenofovir for about 29 months. A second group of 71, who had not responded to lamivudine, had tenofovir added to their treatment.

Similar percentages of patients in both groups achieved undetectable HBV DNA and normal ALT levels, indicating no liver damage, over 36 months of tenofovir treatment. However, patients who were HBeAg-positive with high viral loads took longer to achieve low viral loads, according to the report published in the journal of Antimicrobial Agents and Chemotherapy.

An unrelated study published in the journal Hepatology came to a similar conclusion, finding that tenofovir was effective in HBeAg-positive patients with high viral loads, though it took two years or longer for the antiviral to finally tamp down viral loads to less than 400 copies/mL.

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