HBV Journal Review
August 1, 2010, Vol 7, no 8
by Christine M. Kukka
Steroid Treatment for Asthma or Lung Disease Increases Risk of Hepatitis B Reactivation
Taiwanese researchers tracked the impact of steroid medications used to treat asthma and chronic obstructive pulmonary disease (COPD) – including chronic bronchitis and emphysema – in people infected with the hepatitis B virus (HBV).
The doctors were particularly interested in whether the steroid treatments would lead to reactivation of HBV infection, resulting in increased viral load (HBV DNA) and liver damage.
They followed 198 patients with asthma or COPD who were positive for the hepatitis B surface antigen (HBsAg) and treated with either inhaled steroid or steroids delivered in pills or injections.
They found the group that received steroids in pills or injections had a higher rate of HBV reactivation than the group who used only inhaled steroids.
HBV reactivation occurred in 11.1% of patients in the pill or injected-treated group. Their reactivation rates were higher even when treatment was sporadic and was not a high-dose.
“These results suggest that addition of injected or pill-form steroids to inhaled steroid treatment increases the risk of HBV reactivation, especially when steroids are administered continuously or at high doses,” they wrote in the July 2010 issue of the journal Respirology.
Concurrent “e” Antigen and Antibody Can Indicate High Risk of Liver Damage
Some patients with chronic hepatitis B test positive for the hepatitis B “e” antigen (HBeAg) and the “e” antibody simultaneously in the same lab test. Chinese researchers closely monitored 169 patients who had both the “e” antigen and antibody to see what the concurrent “e” antigen and antibody status had on their health.
Writing in the July 2010 issue of the Journal of Viral Hepatology, researchers reported that the dual appearance of “e” antigen and antibody occurred most frequently in patients of medium age who had elevated viral load (HBV DNA in their bloodstream) and above-normal alanine aminotransferase (ALT) levels, which increase when liver cells are damaged or die.
The viral load and liver damage were more pronounced than in comparison patients who had either the “e” antibody or the “e” antigen.
In patients who had never been treated with an antiviral, concurrent “e” antigen and antibody status tended to indicate the presence of liver disease, researchers concluded.
Two Adult Hepatitis A and B Vaccine Doses as Effective as Three Pediatric Doses in Children
Two adult doses of a combined hepatitis A and B vaccine appear to be as effective as three doses of pediatric-dosed vaccine when used in children, according to a study by Czech researchers published in the July 2010 issue of the journal Vaccine.
The researchers followed 300 adolescents, aged 12-15, half of whom received two doses of the adult vaccine formula, and the other half received three doses of the pediatric combined hepatitis A and B vaccine.
After 10 years, both groups had adequate hepatitis A protection, and about 85% of subjects in both groups had adequate hepatitis B antibody protection. No adverse side effects were reported.
“…The two-dose schedule of the combined hepatitis A and B vaccine (in) adult formulation is an effective alternative to the conventional three-dose schedule of the pediatric formulation in adolescents,” they wrote.
Adefovir-Lamivudine Combination Much More Effective than Entecavir in Lamivudine-Resistant Patients
Korean researchers compared the effectiveness of entecavir (Baraclude), adefovir (Hepsera) or the addition of adefovir to ongoing lamivudine (Epivir-HBV) treatment in patients who developed resistance to the antiviral lamivudine and who experienced an increase in viral load and ALT levels.
Twenty-four patients were treated with the antiviral entecavir, 44 were switched to adefovir, and 36 had adefovir added to their ongoing lamivudine treatment.
After six months, ALT levels normalized in 75%, 65.9%, and 74.3% of patients receiving just entecavir, adefovir alone, and adefovir and lamivudine combination respectively.
A significantly higher decline in HBV-DNA occurred in the group treated with the adefovir-lamivudine combination, than in the entecavir group.
Undetectable HBV DNA was noted in 33.3% of the entecavir group, 27.3% of the adefovir-only group, and 68.6% of the adefovir-lamivudine combination group. HBeAg seroconversion (loss of HBeAg and development of the “e” antibody) was significantly higher in the combination adefovir and lamivudine group.
Viral breakthrough and viral resistance were detected in 25% of the entecavir group and 13.6% of the adefovir-only group. No viral resistance was identified in the combination lamivudine-adefovir group.
“Adefovir add-on treatment in patients with lamivudine resistance suppresses HBV replication more effectively than entecavir or adefovir monotherapy,” researchers wrote in a recent issue of the Journal of Gastroenterology and Hepatology.
Tenofovir and Entecavir Are Most Effective During the First Year of Treatment
Canadian researchers compared the effectiveness of the first 12 months of various drug treatments used to treat hepatitis B patients who had never been treated before. They included lamivudine, pegylated interferon, adefovir, entecavir, telbivudine (Tyzeka), and tenofovir (Viread).
They reviewed a variety of studies and databases recording treatments in both HBeAg-positive and HBeAg-negative patients published prior to October 2009.
In HBeAg-positive patients, tenofovir was most effective in inducing undetectable levels of HBV DNA (in 88% of cases), normalization of ALT levels (66%), HBeAg seroconversion (20%), and HBsAg loss (5%). Tenofovir also ranked third in liver health improvement (53%).
Entecavir was most effective in improving liver health (56%), second for inducing undetectable HBV DNA (61%), and normalization of ALT levels (70%), and third in loss of HBsAg (1%).
In HBeAg-negative patients, tenofovir was the most effective in inducing undetectable HBV DNA (94%) and improving liver health (65%). It ranked second for normalizing ALT levels (73%).
“In the first year of treatment for chronic hepatitis B, tenofovir and entecavir are the most potent oral antiviral agents for HBeAg-positive patients; tenofovir is most effective for HBeAg-negative patients,” researchers wrote in the June 2010 issue of Gastroenterology.
Tenofovir Alone or Combined with Emtricitabine Equally Effective for Adefovir-Resistant Patients
An international team of researchers compared the effectiveness of an emtricitabine (FTC) and tenofovir combination against tenofovir alone in 105 patients with resistance to the antiviral adefovir. Many had also developed resistance to lamivudine.
By week 48, 81% in both groups had experienced HBV DNA declines down to 400 copies/mL. Adherence to taking the medications appeared to be the primary factor associated with HBV DNA levels below 400 copies/mL, according to the report in Gastroenterology.
Elevated ALT Levels and Low Platelet Counts Are Risk Factors for Fibrosis
U.S. researchers followed 964 patients with liver disease, resulting from hepatitis B and C infections and non-alcoholic fatty liver disease (NAFLD), to see what characteristics signaled the presence of fibrosis.
Compared with HCV and HBV patients, NAFLD patients were more obese, diabetic, hypertensive, and had high cholesterol. Significant fibrosis occurred in 55%, 43% and 20% of HCV, HBV and NAFLD patients respectively. Factors independently associated with fibrosis in NAFLD included diabetes and elevated ALT levels.
Among hepatitis patients, risk factors for development of fibrosis included low platelet counts, older age for hepatitis B patients, and elevated ALT in hepatitis C patients.
Ninety-six of these patients were followed for an additional four years. Those who developed fibrosis or worsening fibrosis had HCV infection, higher ALT levels, and lower platelet counts.
Researchers, writing in the journal Alimentary Pharmacology & Therapeutics, concluded that diabetes was a risk factor for fibrosis only in patients with NAFLD, while elevated ALT levels and/or low platelet counts were risk factors for fibrosis in viral hepatitis patients.
Taiwanese Study: Hepatitis B Does Not Increase Risk of Diabetes
Taiwanese researchers followed 1,233 adults who were examined in 1997-1998, and then again in 2000-2001, to determine if people with chronic but asymptomatic hepatitis B had a higher risk of diabetes. Of that group, 483 subjects were examined a third time in 2006-2008.
The prevalence and incidence of diabetes between asymptomatic HBV carriers and a control group without hepatitis B were studied over the 10-year period to see if HBV infection increased the risk of diabetes.
They found no significant correlation between asymptomatic HBV infection and diabetes in patients examined in 1997-1998, 2000-2001, or 2006-2008 when adjusted for age, gender, and body mass index, according to their report in the journal Journal of Gastroenterology and Hepatology.
22.8% of Unvaccinated U.S. Adults Aged 18-44 Engage in High-Risk Behaviors
Hepatitis B vaccination rates among adults remain stagnant, even though about 20% of adults aged 18 to 44 report engaging in high risk behaviors, according to a report presented at the 2010 International Conference on Emerging Infectious Diseases in July 2010.
Most of the new 43,000 HBV infections in 2007 occurred in unvaccinated adults with multiple sex partners, men who have sex with men, and injecting drug users.
To investigate the prevalence of these high-risk behaviors, researchers reviewed national data on sexual behaviors and drug use from population-based surveys conducted between 2000 and 2008, and applied it to 2009 U.S. Census data to determine the percentage of the population engaging in high-risk behaviors for HBV. Analysis showed the following for adults 18-44 during the past year:
16.5% to 19.3% had at least two sexual partners
0.2% to 0.4% used illicit drugs by injection
5% to 6% of men had ever had a male sex partner
Estimates showed 19.3% to 22.8% of U.S. adults in this age group engaged in risky behaviors that required hepatitis B immunization protection.
This information should underscore the importance of promoting hepatitis B immunization in this age group, according to U.S. Centers for Disease Prevention and Control researchers.
Chinese Researchers Find Transmission of Drug-Resistant HBV
Researchers in China have documented transmission of drug resistant-HBV in 14 cases of newly-transmitted, acute hepatitis B. To date, researchers have not found much evidence of transmission of drug-resistant HBV from someone who has been treated and developed drug resistance to another.
Researchers in Beijing collected samples from 201 patients with acute hepatitis B, who had never been treated with an antiviral. They identified 14 new hepatitis B cases (7% of samples) that had drug-resistant mutations that result from treatment with the antivirals lamivudine, adefovir, and entecavir.
“Drug-resistant HBV strains, including those not resistant to (just) lamivudine, are transmissible and can cause acute hepatitis B in China,” they wrote in the June 2010 issue of the Journal of Clinical Virology.
Donated Blood with High Levels of Surface Antibodies Offers an Affordable Alternative to HBIG
Researchers tried substituting donated blood that had high levels of hepatitis B surface antibodies for hepatitis B immune globulin (HBIG) in liver transplant patients to see if the much more affordable blood donation was as effective as preventing HBV infection recurrence after surgery.
The cost of one single unit of donated blood with surface antibodies is $140, and the average annual cost of treatment after a liver transplant would be about $1,148 per patient. The annual cost of treatment with HBIG, meanwhile, ranges from $25,000 to $100,000.
According to a report in the July 2010 issue of the journal BMC Gastroenterology, researchers used fresh frozen plasma obtained from blood donors that contained at least 4,500 international units of surface antibodies.
Twenty-one HBV-related liver transplant patients received the treatment in addition to long-term antivirals, and were followed for 4.5 years. Each patient received on average 8.2 treatments per year, and the antibodies in each treatment remained effective for about 20 days, similar to HBIG treatments.
All 21 patients remained free of HBV recurrence during follow-up and no transfusion-transmitted infection or other serious complication was documented. Researchers concluded that the donated plasma, “may be a useful and economical approach for the prevention of HBV recurrence …if used in combination with antivirals.
The Liver Harbors Drug-Resistant HBV, though HBV in Blood Samples Show No Such Resistance
Because the HBV has a weak genetic blueprint, mutations are common as the virus rapidly replicates, especially when antiviral treatment kills off the “wild” or natural virus without mutations and leaves the drug-resistant HBV untouched.
Canadian and U.S. researchers compared the number of mutated HBV in patients’ bloodstreams with the HBV in their livers to see if there was any differences between the two.
They focused on patients who had liver transplants. Most had been treated with antivirals and all appeared to have very low quantities of HBV DNA in their bloodstream.
Writing in the July issue of the Journal of Viral Hepatitis, researchers reported that when the patients’ HBV was closely examined, they found no mutated or drug-resistant HBV in the patients’ bloodstream, but two-thirds of the HBV from the patients’ livers had drug-resistant mutations.
“Despite apparent HBV suppression (from antivirals), the liver continues to support HBV replication,” they noted.
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