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HBV Journal Review

HBV Journal Review
November 1, 2011, Vol 8, no 11
by Christine M. Kukka

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Lab Tests Unable to Detect Hepatitis B in Patients Infected with Genotype G

Researchers, studying the rare hepatitis B virus (HBV) strain called genotype G, found that current lab tests are unable to detect hepatitis B in patients with this genotype, according to their report published in the November issue of the Journal of Viral Hepatitis.

HBV Genotype G infects fewer than 1% of people with hepatitis B worldwide and is found primarily in Europe and the U.S. Because of its unique molecular make-up, HBV genotype G can replicate without producing the hepatitis B surface antigen (HBsAg) or the hepatitis B “e” antigen (HBeAg)—two antigens that are required by every other HBV genotype to reproduce.

Lab tests used to detect HBV infection in people and blood donors specifically look for HBsAg. Additionally, people with HBV Genotype G often have low levels of HBV DNA (viral load), which also escape detection.

The threat of an undetectable HBV genotype is just now coming to light because most people with HBV genotype G are also coinfected with HBV genotype A, which does produce HBsAg and HBeAg when reproducing, so researchers assumed genotype G would also generate those antigens during its reproductive cycle.

But in this recent study, scientists studied blood samples from a patient who was newly infected with only HBV genotype G infection. Over the course of his infection, the patient showed the presence of HBV DNA, and hepatitis core antibodies (which develop after initial exposure to the virus), but he produced neither surface nor “e” antigens or antibodies.

“Our findings demonstrate that HBV genotype G mono-infection occurs and that routine serology (blood tests are) unsuitable for its detection,” the researchers wrote.

Hepatitis B Vaccine Less Effective in Seniors Over Age 60

The U.S. Centers for Disease Control and Prevention (CDC) screened 48 residents living in assisted living facilities who were recently vaccinated with all three doses of the hepatitis B vaccine to see how effective the vaccine was in older Americans.

Health officials are concerned about protecting this population against blood-borne infections because there have been several hepatitis B outbreaks in nursing homes and other senior residential facilities after blood glucose monitoring equipment was improperly reused.

The Epidemic Intelligence Service of the CDC’s Division of Viral Hepatitis immunized residents, who were found to be susceptible to hepatitis B, with one dose of the Engerix-B vaccine administered at O, 1 and four months. Blood samples were collected 90 days after the last vaccine shot and analyzed to assess how effective the vaccination was.

Of the 48 people screened, only 16 (33.3%) had adequate numbers of hepatitis B surface antibodies to protect them from infection. The older the resident, the less effective the vaccine was. Researchers reported that 88% of residents age 60 and younger achieved immunity, while only 12% of those age 90 and older developed adequate antibody protection.

“These findings highlight that hepatitis B vaccination is of limited effectiveness when administered to older adults,” CDC researchers wrote in the October issue of the journal Vaccine. “Improvements in infection control and vaccination at earlier ages might be necessary to prevent spread of infection in assisted living facilities.”

Hepatitis B Vaccine Recommended for Diabetics Under Age 60

The CDC’s Advisory Committee on Immunization practices has “strongly recommended” that diabetic patients under age 60 be vaccinated against hepatitis B.

Up to age 60, people with diabetes have twice the risk of becoming infected than those without diabetes, however only 17% of those with diabetes and 26% of those without diabetes have been fully vaccinated against hepatitis B.

The agency made the recommendation because diabetes patients in nursing and assisted living facilities have been infected recently due to reused glucose monitoring equipment. The recommendation was not extended to those older than 60 because, as noted earlier, the immunization is not as effective in older seniors.

More Drugs Found to Reactivate Hepatitis B in Patients with Current and Resolved Infections

While chemotherapy, which suppresses the immune system, is known to cause a resurgence of hepatitis B in patients with current or resolved infections, researchers are now finding that tumor necrosis factor-α (TNF-α)-targeted therapies (called anti-TNF) used to treat rheumatic, digestive, and skin diseases also cause hepatitis B to recur.

Spanish researchers, writing in the October issue of the Baltimore Journal of Medicine, followed 89 patients who were HBsAg-positive and 168 patients who were hepatitis B core-antibody positive (indicating a resolved hepatitis B infection) who were treated with this class of immune-suppressing drugs.

Even when infections are resolved and surface antibodies are generated, small quantities of HBV are believed to linger in the liver, and may rebound if the immune system is weakened by illness or immune-suppressing drugs.

  • Among HBsAg-positive patients: HBV reactivation occurred in 35 (39%). The percentage was higher in patients who had been previously treated with the immune-suppressing drugs, and lower in those who simultaneously received antivirals to suppress HBV replication. Liver failure occurred in 5 patients, 4 of whom died. The drug Infliximab caused the highest rate of HBV resurgence and liver damage, compared with the drug etanercept in this group.
  • Among core antibody people, with resolved infections: Reactivation occurred in 9 (5%) cases, including 1 patient who died due to liver failure.

In summary, anti-TNF agents caused significant liver damage in HBsAg-positive patients, including elevated alanine transferaminase (ALT) levels in 42% (indicating liver cell injury or death), reappearance of HBV-DNA in 39%, and death from liver failure in 5%.

The rate of reactivation in people with resolved HBV infections was 7-fold lower than in HBsAg-positive patients.

The results show that preventive measures, including use of antivirals to suppress the infection, are needed in people treated with TNF-targeted drugs, according to the report published in the October issue of the Baltimore Journal of Medicine.

Adefovir-Telbivudine Combination Effective in Lamivudine-Resistant Patients

With several antivirals now available, researchers are trying to determine which combination will be most effective in patients. Each antiviral targets a different region of the virus, and combinations may be especially effective in people who have developed resistance to some antivirals, such as lamivudine (Epivir-HBV), which has a high rate of resistance.

In a recent study reported in the journal Hepatology International, researchers studied the effectiveness of the antiviral adefovir (Hepsera) used alone or in combination with telbivudine (Tyzeka) over 48 weeks  in patients who had developed resistance to lamivudine.

Declines in HBV DNA were greater in the group received the antiviral combination (viral load drops were 7.4-fold in the combination group, compared with 4.9-fold in the group treated with only adefovir.) Additionally, 38.5% of the group receiving both antivirals achieved undetectable HBV DNA compared to the group treat with only adefovir.

Two adefovir-only patients developed a viral breakthrough due to the drug’s ineffectiveness. None of the combination-treated patients experienced a resurgence of viral load.

HBeAg loss occurred in 3 patients in the combination group and one patient in the adefovir group.

Other Antiviral Combinations Appear Highly Effective in Hard-to-Treat Patients

A team of U.S. researchers followed 109 Asian-American patients with hepatitis B treated at a northern California clinic to see if antiviral combinations were more effective in patients who had not previously responded to treatment or had developed drug resistance.

According to the report published in the Journal of Clinical Gastroenterology, the antiviral combinations appeared to be highly effective. Between 2004 and 2009, combination treatment was given to:

  • 29 patients who had developed antiviral resistance to one or more antivirals
  • 60 who had not responded to single antiviral treatment to date
  • And 20 others.

Combination treatments used over a two-year period included lamivudine, adefovir, telbivudine, entecavir (Baraclude), tenofovir (Viread), and emtricitabine (an antiviral used to treat HIV that has not yet been approved by the U.S. Food and Drug Administration for hepatitis B.)

The majority (77%) achieved undetectable viral load after 6 months of various treatment combination regimens: 80% were treated with tenofovir and entecavir, 76% with tenofovir and lamivudine, 75% with entecavir and adefovir, and 69% with adefovir and lamivudine. After six months, undetectable viral load was achieved by 73% of all patients, including those who had developed antiviral resistance.

Despite their previous treatment failures, high rates of complete viral suppression were rapidly achieved, researchers noted. The outcomes did not vary based on which drug was used or if there was a history of drug resistance.

Tenofovir Effective in Treating Patients with Entecavir Resistance

While entecavir and tenofovir are considered the best available antivirals and are recommended as first-treatment options, 3% of patients treated with entecavir don’t respond to treatment.

Researchers tried treating 14 of the patients who had not responded to entecavir with tenofovir to see if that drug would be effective in these patients. The patients were Chinese, predominantly male, HBeAg-positive, and infected with either genotype C (71%) or B (29%). 

After 65 weeks of treatment with tenofovir, all 14 patients achieved undetectable HBV-DNA and normal ALT levels. Two of 12 HBeAg-positive lost HBeAg and developed “e” antibodies over 80 weeks of treatment. None of the tenofovir-treated patients failed to respond to treatment.

“In conclusion,” researchers wrote in the Journal of Viral Hepatitis, “suboptimal response to entecavir is rare (approximately3%). Tenofovir is safe and very effective in the management of HBV patients with (poor response) to entecavir.”

No Increased Risk from Hepatitis B Results from Wrestling

An Iranian research team studied the risk of transmitting HBV or hepatitis C virus (HCV) infection among male wrestlers in Iran and found there was no increased risk of blood-borne infections from the sport, according to a report published in the Journal of Athletic Training.

The researchers compared the prevalence of HBV and HCV among 420 male wrestlers, and compared it to a control group of athletes who participated in low- to moderate-contact sports, such as volleyball (205 players) and soccer (205 players).

The prevalence of hepatitis B core antibodies, which shows past infection, was 13.4% in wrestlers and 10.9% in the control group. The prevalence of HBsAg (indicating current HBV infection) was 1.2% in wrestlers and 0.5% in the control group.

The prevalence of HCV antibodies was 0.5% in wrestlers and zero in the control group. Researchers noted there were more risk factors for blood-borne infections (such as sexual activities etc.) among wrestlers than in the control group.

“Within the limits of our study, we found no evidence that participation in Tehranian wrestling increased HBV or HCV transmission when compared with transmission in athletes participating in low- to moderate-contact sports,” they wrote. “Prevention of blood-borne infections in Tehranian wrestlers should be focused not only on appropriate care for bleeding injuries, but also on general risk factors for these conditions.”

New York City Project Greatly Increases HBV Awareness Among Asian Immigrants

Despite high rates of hepatitis B among Asian immigrant groups, the medical establishment has not been effective in educating and screening this population about the infection.

Between 2004 and 2008, a New York City pilot program called B free NYC, provided hepatitis B community education and awareness, free screening and vaccinations, and free or low-cost treatment primarily to immigrants from Asia, and to other racial and ethnic minority groups.

The program was the largest citywide screening program in the United States, reaching nearly 9,000 people, and the only one providing comprehensive care to those with HBV.

During the program, new hepatitis B cases reported from predominantly Asian neighborhoods in the city increased 34% annually. More than 2,000 people were vaccinated, and 1,162 of the 1,632 people who tested positive for hepatitis B received care from the program's clinical services.

According to the report published in the October journal of Health Affairs, the program was found to be highly effective in reaching the target population and providing care, and may, “serve as a useful prototype for addressing hepatitis B disparities in communities across the United States.”

Doctors Unaware HBV Is Spread Primarily Through Heterosexual Activity Among Adults

A study by Emory University researchers found that health care providers lack awareness that hepatitis B is primarily transmitted among adults through heterosexual activity in the U.S., according to a report in the October issue of the journal of Digestive Diseases Sciences.

The study sampled 1,000 physicians, including internists, primary care providers, and gastroenterologists to determine this group’s knowledge about hepatitis B, and their capability to effectively assess patients’ risk for hepatitis B and immunize and screen them.

Researchers created a survey featuring four fictional case histories that described patients at high risk for contracting HBV, followed by questions regarding knowledge, attitudes, and beliefs of HBV screening and vaccination.

Researchers found practitioners often did not ask about such risk factors as heterosexual activity, and therefore did not promote immunizations as recommended by CDC for certain high-risk groups.

On average, providers endorsed 71% of the CDC’s HBV vaccination guidelines. Those who did not effectively screen patients were younger and were not aware that adult HBV is contracted primarily through heterosexual sex.

“Future efforts to improve adherence should target trainees, emphasize the importance of obtaining sexual histories in high-risk patients, and inform that HBV is predominantly a heterosexually transmitted infection,” researchers wrote.


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