HBV Journal Review
April 1, 2010, Vol 7, no 4
by Christine M. Kukka
Innovative Treatment Reduces Viral Load in Four Patients
For years, researchers have tried to use dendritic cells in cancer patients to help their immune systems identify, target, and destroy cancer cells. Recently, researchers from Belarus successfully used dendritic cells in four hepatitis B patients to spur their immune systems to attack the hepatitis B virus (HBV) infection.
Dendritic cells are special immune cells that help infection-fighting T- or B-cells identify and zero in on certain antigens or viral proteins. Researchers believe that people with chronic hepatitis B do not produce mature or adequate numbers of dendritic cells and therefore cannot eradicate the viral infection.
At a presentation at the 2010 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting, researchers reported using dendritic cell therapies, similar to what has been developed to fight cancer, in four men (ages 30 to 60) infected with HBV.
The dendritic cells were prepared using blood from the patients. The cells were then injected in the men three times over a two-month period.
All patients responded with significant decreases in viral load (HBV DNA) and alanine aminotransferase (ALT) levels one month after the injections. Elevated ALT levels can indicate that the hepatitis viral infection is damaging liver cells.
Three of the four patients had an increase in T-cells and other infection-fighting cells after the dendritic cell injection. One month after the study ended, HBV viral loads were undetectable in two patients, and two others had significant reduction.
Researchers urged larger and more long-term studies to assess the sustained impact of this treatment.
HBeAg Level Changes Predict Which Patients Respond to Pegylated Interferon
Thai researchers tracked patients’ hepatitis B surface antigen (HBsAg) and hepatitis B “e” antigen (HBeAg) levels, and viral load in 30 HBeAg-positive patients treated with pegylated interferon for 48 weeks to determine which patients responded best to treatment.
According to their report published in a recent issue of Hepatology Research, the patients who responded best had consistent decreases in HBsAg, HBeAg and HBV DNA levels during treatment. However, a two-fold decrease in HBeAg levels after 24 weeks of treatment was the best predictor of which patients seroconverted (lost HBeAg and developed the “e” antibody), and developed lower viral loads.
One patient who cleared HBsAg after treatment ended had exhibited a more rapid decline in HBsAg during treatment than those who responded without losing HBsAg.
The one-third of the patients who seroconverted and achieved undetectable viral load had lower levels of HBsAg, HBeAg, cccDNA and viral load than non-responders.
Measuring HBeAg during treatment may be a better indictor of who will successfully respond to the costly treatment, which can also cause serious side effects, than measuring HBsAg and HBV DNA levels, the researchers suggested.
HBsAg-Positive Women Face Higher Death Rates from Liver Disease and Certain Cancers
Most hepatitis B-related survival studies have focused on men. Recently, researchers from Taiwan and the U.S. evaluated survival rates in women chronically infected with hepatitis B.
About 2.1 million Taiwanese women, who had been screened for hepatitis B during pregnancy, were tracked for more than 11 years to determine if HBsAg-infected women experienced higher death rates than uninfected women.
Researchers concluded that the infected women had a slightly higher death rate than uninfected women for all causes, and a six-fold higher death rate from liver disease than uninfected women. In addition to liver disease, infected women had higher death rates from non-Hodgkin lymphoma, and gallbladder and extrahepatic bile duct cancers, according to the report published in The Journal of Infectious Diseases.
65% of Those Infected with Hepatitis B Are Unaware of Their Infection
A recent report by the Institutes of Medicine (IOM) on hepatitis B and C faulted health care providers, social service professionals, and the public for a lack of awareness about the infection and lack of screening for hepatitis B.
The full IOM report is available online and was recently published in Hepatology. Studies indicate that up to 1.4 million people have chronic HBV infections and approximately 65% of them are unaware they are infected.
Abigail Mitchell, study director of the IOM report, said the lack of public and provider awareness has contributed to the limited resources to control and prevent HBV and HCV infections in the United States. There are three- to five-times more people living with chronic viral hepatitis infections than with HIV infection, but just 2% of the fiscal year 2008 budget of the CDC NCHHSTP (National Center for HIV/AIDS, Viral Hepatitis, Sexually Transmitted Disease, and Tuberculosis Prevention) was allocated for viral hepatitis while 69% was allocated for HIV/AIDS.
The report recommended that the CDC should develop specific cooperative viral-hepatitis agreements with all state and territorial health departments to support surveillance for acute and chronic hepatitis B and C.
The IOM report also focused on improvement to viral hepatitis services through improved outreach and awareness, prevention of new infections, identification of infected people, social and peer support, and medical management of infected people.
Saliva of Children Who Have High Viral Loads May Transmit Hepatitis B
Researchers suggest that HBV-infected children who have high viral loads could transmit the infection to other children. Currently, experts contend that the saliva of HBV-infected people does not transmit HBV unless it contains blood.
In this study, a team of European researchers investigated the relationship between HBV DNA in saliva and blood from 46 children with chronic hepatitis B.
They found high levels of HBV DNA in the saliva of HBeAg-positive children, who also had high levels of HBV DNA in their blood.
The researchers, writing in the March 2010 issue of the Pediatric Infectious Disease Journal, suggest saliva could be a vehicle for horizontal transmission of HBV among children.
Puberty May Spur HBeAg Seroconversion in Some Boys
A report by Taiwanese researchers presented at the 17th Conference on Retroviruses and Opportunistic Infections revealed that some boys may spontaneously lose HBeAg and develop “e” antibodies (called seroconversion) and develop a reduced viral load when they reach puberty.
The study, also published in the March 2010 issue of the journal Gastroenterology, is one of several attempts to understand why many males experience more severe disease progression and liver damage than females from hepatitis B. Researchers have suspected that the female estrogen hormone and the male hormone testosterone may affect disease progression differently.
Researchers followed 100 HBeAg-positive boys, enrolled when younger than age 10, for more than 10 years. They tracked testosterone levels and compared outcomes among 87 boys who reached puberty at around age 13 with boys who reached puberty at around age 15.
Boys who reached puberty sooner experienced significantly earlier HBeAg seroconversion than those who reached puberty later, and they had higher ALT levels, which indicate liver cell damage, during the time they when were HBeAg-positive.
The early puberty group also experienced a greater decline in viral load between ages 10 and 20 years than did the late puberty group.
The researchers concluded that earlier-onset puberty is associated with earlier HBeAg seroconversion, higher ALT levels, and a greater viral load reduction. However, these findings did not shed much light on why men experience more severe liver disease over their lifetimes.
Many Patients with ALTs in the High-Normal Range Have Liver Damage
Historically, researchers have assumed that HBV-infected people who have normal ALT levels have little or no liver damage and do not require treatment. However, recently the “healthy range” of ALT levels has been markedly reduced, and now Australian and Chinese researchers have found that many HBV-infected people with reportedly “normal” ALT levels have significant liver damage.
The researchers, writing in the March 2010 issue of the Journal of Viral Hepatitis, compared liver biopsy results, age, viral load, and HBeAg status in 252 patients with normal ALT levels and 270 with elevated ALT levels.
They found 38.5% of people with normal ALT levels had healthy livers, 25.4% had significant inflammation and/or fibrosis, and 8.4% had severe liver scarring–cirrhosis. There were significantly higher rates of liver damage in “healthy” patients whose ALT levels were near the high-normal range (40%) than those in the low-normal group (16.6%).
Based on their results, researchers recommended biopsies and treatment in patients age 40 or older, especially if their ALT levels were in the normal/high range.
Milk Thistle Supplements, Taken Orally, Appear Ineffective
Silymarin, found in milk thistle supplements and believed to help prevent liver damage, appears not to be effective when taken orally, but may help damaged livers heal when it is injected intravenously in high doses, according to a Los Angeles Times article that featured Leonard B. Seeff, a hepatitis expert and recently retired senior scientific officer for the National Institute of Diabetes and Digestive and Kidney Diseases
In high doses, silymarin appears to be good for the liver, Seeff said. Studies show that taking large amounts of the compound intravenously can help slow the virus that causes hepatitis C.
But according to experts, when taken orally, silymarin breaks down extremely quickly. In a 2009 study, researchers gave high, 700-mg oral silymarin oral supplements to 32 patients with hepatitis C every eight hours for seven days, which was 10 times more silymarin than most people would get from herbal supplements.
Despite the high dose, the blood levels of silymarin fell far short of levels achieved during intravenous treatment and the treatment had no effect on liver function or health.
If people still want to try a liver supplement, experts recommended a pure milk thistle product without any other herbal additions.
One in Five At-Risk Babies in the U.S. Aren’t Vaccinated against Hepatitis B
About one in five babies born to mothers infected with HBV are not immunized within 12 hours of birth, which effectively prevents transmission of infection in 85% to 95% of births.
Researchers from the U.S. Centers for Disease Control and Prevention reviewed medical records of 4,762 mothers and 4,786 infants. The records represented about 25 consecutive live births from 190 U.S. hospitals, each of which was surveyed about their hepatitis B prevention policies in their labor and delivery departments.
Records showed that 18 women tested positive for hepatitis B at the time of admission to the hospital. While 62 percent of their newborns received the hepatitis B vaccine and immunoglobulin, nearly 14 percent left the hospital unvaccinated and nearly 20 percent did not receive hepatitis B antibodies (HBIG), which also helps prevent infection after exposure, before discharge.
Of 320 women whose hepatitis B status was unknown, meaning they may or may not have been infected, only about 52 percent of their infants were vaccinated within 12 hours of birth. About 20 percent of these babies left the hospitals without immunizations.
Hospitals must institute immunization policies to prevent hepatitis B, which is almost entirely preventable through vaccination, researchers noted in the April 2010 issue of Pediatrics.
About 90 percent of children who contract hepatitis B during infancy and early childhood develop chronic infections and face a high risk of liver disease and cancer.
The CDC recommends infants receive the hepatitis B vaccine at birth, and then receive booster shots at one and six months, and it recommends that pregnant women should be tested for hepatitis B as part of their prenatal care. If screening has not occurred during prenatal visits, women should be tested upon admission to the hospital, but not all hospitals do so routinely.
Only 67 percent of hospitals had a policy in place requiring newborns to be immunized, and only 63 percent of hospitals screened women upon admission if there was no documentation of a hepatitis B test. Nearly 81 percent of hospitals said they would give exposed infants the hepatitis B vaccine within 12 hours and about 77 percent said they would give HBIG within 12 hours.
“The fact that only about 73 percent of hospitals even look at the results of the hepatitis test is pretty atrocious,” authors noted. “That means 27 percent of hospitals don't even look." In addition, researchers noted documentation errors in medical records, such as those that failed to note that the mother reported having hepatitis B.
Each year, about 40 to 90 cases of perinatal hepatitis B are reported to the CDC, although the true number may be 10 to 20 times that, according to researchers.
Children born in hospitals that had policies in place requiring universal immunization had the best chance of being immunized, experts noted.
Vietnamese-Americans Had High Rates of HBV Infection and Low Rates of Vaccination
Experts screened 322 Vietnamese-Americans for hepatitis B and C and found 2.2% tested positive for hepatitis C and 9.3% tested positive for HBsAg. Forty-eight patients (15.5%) reported a family history of liver disease, but 68.8% of them reported they had never been immunized against hepatitis B and 77.1% reported none of their family members had been immunized.
Among those without a family history of liver disease, 156 (85.2%) reported no vaccination and 168 (91.8%) reported no family members had been vaccinated.
Most of those infected with HBV had seemingly normal ALT levels, so it is unlikely that their infection–and resulting immunization of their family members–would have been identified by health care providers, unless the providers knew that they should screen all Asian-Americans for HBsAg because of their high risk of infection, according to the report published in the February 2010 issue of the Journal of Viral Hepatitis.
Experts Recommend Pegylated Interferon to Spur HBeAg Seroconversion
A multinational team of hepatitis B experts, writing in the March 2010 Journal of Digestive Diseases and Sciences, identified HBeAg seroconversion as an important goal in managing and treating hepatitis B patients.
“Patients with HBeAg-positive chronic hepatitis B should consider pegylated interferon if they are younger than 40 years (especially women), have lower HBV DNA levels, can afford this treatment, and have a lifestyle that would support adherence to injection therapy,” they wrote. This type of interferon treatment requires weekly injections.
Alternatively, they recommended antivirals in patients with ALT levels greater than twice the upper limit of normal, HBV DNA levels less than 1 million IU/ml, and compensated hepatitis B. Entecavir (Baraclude), telbivudine (Tyzeka), and tenofovir (Viread) may be used as first-line therapy, the experts noted, and the antivirals can be administered indefinitely in HBeAg-positive patients who seroconvert. Telbivudine and tenofovir should be considered in women of child-bearing age, they added.
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