HBV Journal Review
January 1, 2014, Vol 11, no 1
by Christine M. Kukka
Amniocentesis Increases Risk of Hepatitis B Infection in Infants
Chinese researchers compared the rates of hepatitis B virus (HBV) infection in infants born to HBV-infected women who underwent amniocentesis to women who did not and found that the procedure increased HBV infection in infants.
Amniocentesis is the sampling of amniotic fluid using a hollow needle inserted into the uterus. The fluid is used to screen for developmental abnormalities in a fetus.
According to the report published in the November 2013 Journal of Hepatology, researchers found that women with high viral loads who underwent the procedure had higher rates of infecting their infants (6.35%) than those who did not (2.53%).
The scientists compared infection rates in 63 infants whose mothers had amniocentesis against 198 infants whose mothers did not. However, when the mothers' viral loads were moderate, amniocentesis did not increase mother-to-child (vertical) infection rates. Significant increases in vertical infection occurred only when women had high viral loads, greater than about 7 million copies per milliliter.
"Hepatitis B surface antigen (HBsAg-positive) women who plan to have amniocentesis should be evaluated for the risk of vertical transmission and (assessed) according to their HBV DNA levels," researchers wrote. They called for more studies to be performed to confirm their findings.
Tenofovir Alone Effective in Treating Adefovir-Resistant Hepatitis B
The antiviral tenofovir (Viread) by itself is as effective as the combination of tenofovir plus emtricitabine (Truvada) in treating hepatitis B patients who have developed resistance to the antiviral adefovir (Hepsera).
European researchers treated 46 adefovir-resistant patients with just tenofovir and 39 with tenofovir plus emtricitabine for 168 weeks.
Long-term suppression of HBV DNA to low levels (less than 400 copies/mL) occurred in 84% of the tenofovir-treated group and 82% of the emtricitabine plus tenofovir group.
No signs of tenofovir resistance occurred during the three-year study period, and there were no notable side effects in either treatment group.
"Tenofovir monotherapy is as effective as emtricitabine/tenofovir combination therapy in maintaining long-term viral suppression in patients with a suboptimal response to adefovir," researchers wrote in the November issue of the Journal of Hepatology, "and is well tolerated in this population."
Another Study Confirms Increased Pancreatic Cancer Risk in People with Hepatitis B
Scientists continue to investigate reports that chronic hepatitis B or hepatitis C infections may increase a patient's risk of pancreatic cancer.
Chinese researchers evaluated 10 studies that compared pancreatic cancer rates in people with current or resolved hepatitis B infections and those with current hepatitis C infections.
According to their report published in the December 2013 issue of the journal Hepatobiliary and Pancreatic Diseases International, Hepatitis B and C infection significantly increased risk of pancreatic cancer by more than 20%.
Meanwhile, the presence of the hepatitis B surface antibody (indicating immunization or a resolved infection) was linked to a decreased risk of pancreatic cancer.
Uncover the Strengths and Weaknesses of the Antiviral Entecavir
Entecavir lowers viral load, but not HBsAg levels: Chinese researchers followed 222 patients who were treated with entecavir (Baraclude) for up to five years and found that while the antiviral was very effective in lowering viral load, there was a disappointingly slow decline in HBsAg over the course of treatment.
Clearing HBsAg is an important treatment goal and it greatly reduces the risk of liver damage from the infection.
The researchers, reporting in the December issue of the Journal of Gastroenterology and Hepatology, found that viral load rapidly declined in all patients with entecavir treatment, with 97.1% achieving undetectable viral load after five years. Only two patients (representing 1.2% of those studied) developed resistance to entecavir.
However, "In contrast to the profound HBV DNA suppression, long-term entecavir treatment only achieved a slow decline in serum HBsAg," they wrote. "...Additional therapeutic agents are needed to increase the chance of HBsAg clearance in chronic hepatitis B."
One-third of patients who respond quickly to entecavir clear HBeAg: About 31% of hepatitis B "e" antigen (HBeAg-positive) patients who achieve undetectable HBV DNA after six months of entecavir treatment will lose HBeAg after two years of treatment, according to a Taiwanese study published in the December 2013 issue of the Journal of the Formosan Medical Association.
Researchers followed 68 HBeAg-positive patients (75% male, average age 46) and found that 30.9% of them lost HBeAg after two years of treatment. Patients who responded well to the antiviral after just six months of treatment and achieved undetectable HBV DNA usually went on to clear HBeAg within two years.
Study finds genetics—not drug resistance—is why some patients don't respond to entecavir: While entecavir is recommended as one of the top, first-line treatments for hepatitis B, a small percentage of patients respond slowly to the antiviral.
Researchers have suspected that some people may harbor virus with mutations that are able to "resist" entecavir's ability to halt viral replication. However, a study published in the November 2013 journal Antiviral Therapy, finds that a weak immune system may be the culprit.
Italian researchers analyzed HBV from five people who responded quickly to entecavir and five who responded slowly. They found no entecavir-resistant virus in patients who failed to respond, instead they found a weak immune response that... "might be at odds in rapidly clearing infected cells from the liver."
Antiviral Telbivudine Appears to Protect Kidney Health
The antiviral telbivudine (Tyzeka), may not be as potent as other hepatitis B antivirals, but it appears to have a unique quality—it appears to “protect” the kidneys against damage usually linked to antiviral treatment, according to an article in the December issue of the Journal of Viral Hepatitis.
Some antivirals, including adefovir (Hepsera), cause kidney damage, but in an unusual twist, telbivudine appears to somehow protect kidneys.
To evaluate how much kidney protection telbivudine confers, researchers monitored kidney (renal) function in 831 hepatitis B patients who received a combination of antivirals for 96 weeks, including:
- Telbivudine and adefovir
- Adefovir plus lamivudine
- Adefovir plus entecavir
- Adefovir alone
- and entecavir alone
Among the five treatment groups, significant improvements in kidney function was observed in the adefovir plus telbivudine and adefovir plus lamivudine groups over the study period. Improvements were most significant in patients who began telbivudine when their kidney function was not up to par.
“In conclusion, our results suggest that the combination therapy of telbivudine and adefovir is significantly associated with renoprotective effects in chronic hepatitis B patients when compared with other adefovir-based combination or single (antiviral) therapies,” the researchers wrote.
Experimental Treatment Would Help Immune System Attack HBV Infection
Iranian researchers are developing a ground-breaking "monoclonal antibody" that would help the immune system identify and destroy the hepatitis B surface antigen to eradicate the infection.
In the case of chronic hepatitis B, the immune system fails to identify the HBsAg as part of a harmful, viral invasion. Normally, the "epitope" on the HBsAg antigen should serve as a red flag to the immune system, indicating that T-cells and antibodies should attack it. But in the case of HBsAg, its epitope has a mutation, involving a single amino acid, that allows it to remain hidden from the immune system.
According to a report published in the December issue of the journal of Gastroenterology and Hepatology, Iranian researchers are developing a monoclonal antibody therapy that neutralizes these cloaked epitopes so the immune system would recognize and eradicate them. To date, their research has been conducted only in laboratories.
"Our results indicate that antibodies against different epitopes of the 'a' determinant of HBsAg are able to neutralize HBV," they wrote. "These results have important implications for the development of antibody-based therapies against HBV."
Study Shows Antiviral Treatment Helps Liver Function
Albumin, produced by the liver, is an essential protein that promotes growth and repair of body tissue. A new study shows that antiviral treatment in people with hepatitis B improves liver health and quickly restores production of this vital protein.
Mexican researchers, reporting in the December issue of the journal of Medical Molecular Morphology, followed changes in albumin levels in 12 hepatitis B patients who were treated with antivirals.
Albumin levels in patients' blood, "...significantly increased very soon after the treatment was started." Within 12 months, liver tissue and function had been restored, leading to healthy production of albumin levels.
Is There a New Normal for Healthy ALT
Alanine aminotransferase (ALT) is an enzyme produced by liver cells. When liver cells are damaged by HBV infection, ALT levels in the blood increase above normal—but what really is normal?
Several years ago, researchers discovered they had pegged “normal” ALT levels too high, and established new, healthy ALT normal levels at up to 30 international units per liter (IU/L) for men and 19 IU/L for women. But a report published in the December issue of Hepatology Research, suggests that figure should be tweaked.
Japanese researchers analyzed ALT levels in 11,404 healthy adults and then weeded out subjects whose ALT levels could be affected by older age, weight, diabetes, and high cholesterol.
When only the healthiest adult subjects were evaluated, the new “healthy” ALT was 29 IU/L for men and 23 IU/L for women.
Obesity May Decrease Hepatitis B Vaccine Effectiveness, But Old Age Does Not
South African researchers who are working on developing an effective vaccine against HIV infection, examined other factors that could render vaccines ineffective and found that obesity may hinder the performance of the hepatitis B vaccine.
According to their report in the December issue of the journal PLoS One, researchers conducted a follow-up study of women who had been recently immunized against hepatitis B. None of the women were HIV-infected.
They found that obese women with a high body mass index (BMI) often failed to develop adequate hepatitis B antibodies after immunization, which are needed to protect them against infection.
Obese individuals (BMI index at or greater than 30kg/m(2)) were significantly more likely to be vaccine non-responders following two HBV vaccine doses, they reported.
"There was no observed association between vaccine responses and age, method of contraception or time from vaccination to antibody measurement," they wrote, suggesting that obesity may limit the vaccine's effectiveness.
An unrelated article in the December issue of the journal Vaccine found that old age does not decrease the effectiveness of the hepatitis B vaccine in the elderly. U.S. Centers for Disease Control and Prevention researchers reported that 22 out of 27 residents in an assisted living facility responded well to the vaccine and generated adequate protective antibodies after immunization.
The residents had been vaccinated against both hepatitis A and B following an outbreak of hepatitis B resulting from improperly re-used medical devices. Of the 27 residents who were screened for hepatitis B surface antibodies after their three-dose immunizations, 22 (81%) achieved protection. The vaccine protected even elderly residents age 75 and older.
"Adult vaccine recipients of all ages, even those over 60 years of age, demonstrated a robust capacity for achieving hepatitis B seroprotection in response to the combined hepatitis A/B vaccine," they wrote. "The role for vaccination in interrupting HBV transmission during an outbreak remains unclear, but concerns about age-related response to hepatitis vaccine may be insufficient to justify foregoing vaccination of susceptible residents of assisted living facilities."
High Rates of Coinfections Underscore Need for Coordinated Care
Between 2000 and 2010, New York City health officials reported 840,248 people were reported to be infected with HIV, tuberculosis, hepatitis B, hepatitis C, chlamydia, gonorrhea, and/or syphilis. Thirteen percent of the 840,248 had two or more of these infections.
- 64% of those with syphilis had another infection/s
- 52% of those with gonorrhea had another infection/s
- 31% of HIV-infected people had another infection/s
- 23% of people with tuberculosis had another infection/s
- 20% of people with hepatitis C had another infection/s
- 16% of those with chlamydia had another infection/s
- and 11% of those with hepatitis B had another infection/s
The high number of coinfections reported in the study published in the December issue of the Journal of Public Health Management and Practice underscored the importance of coordinating infectious diseases programs across the city, according to researchers.
"Conducting the match brought surveillance programs together to work collaboratively and has resulted in ongoing partnerships on programmatic activities that address multiple diseases," they reported.
More Evidence: Lamivudine Should Not Be Used in Pregnant Women
Treating pregnant women who have high viral loads with antivirals safely lowers their viral load and reduces the risk of infecting newborns. However, a study by Australian researchers finds that the antiviral lamivudine (Epivir-HBV) should not be used in these women.
Lamivudine was the first antiviral sanctioned for hepatitis B treatment, as a result it is the cheapest antiviral drug available but it is also the least effective and quickly leads to drug resistance.
Because it is commonly used and inexpensive, researchers studied how well lamivudine performed when it was administered in 21 mothers with high levels of HBV DNA during their third trimester of pregnancy. Five infected women were not treated and used as the control group.
The lamivudine-treated women achieved only moderate declines in viral load, however none of their children became HBV-infected. In contrast, one of the children born to the five untreated women became infected with HBV.
However, four (19%) of the lamivudine-treated women developed varying levels of lamivudine-resistance. "Lamivudine therapy during late pregnancy only reduced maternal (viral load) moderately, and drug-resistant viral variants emerged," they noted in the December issue of the Journal of Viral Hepatitis.
Currently, doctors prefer to use tenofovir or entecavir in pregnant women because the drugs are potent and have very low rates of drug resistance.
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