HBV Journal Review
November 1, 2014, Vol 11, no 11
by Christine M. Kukka
Experts Say Breastfeeding While Taking Antivirals Is Safe
Women infected with the hepatitis B virus (HBV) face a medical conundrum. If they have high viral loads they are encouraged to take antivirals during pregnancy to reduce their HBV DNA levels to avoid infecting their newborns–but then they're told not to take antivirals if they want to breastfeed.
A fetus is exposed to far higher levels of an antiviral in utero if the mother takes a daily antiviral pill than through breast milk. And to date, no medical studies have found any harm to babies from exposure to the miniscule amounts of antivirals found in breast milk, according to a provocative study published in the October issue of the journal of Clinical Infectious Diseases.
In fact, the World Health Organization recommends that HIV-infected women continue antiviral treatment (which includes some of the same drugs used to suppress viral load in HBV-infected women) while breastfeeding.
According to the international study spearheaded by Johns Hopkins Bloomberg School of Public Health researchers, breast milk from tenofovir-treated women contains 20% of the levels found in the woman's blood stream after a 600 mg-pill was taken.
This topic is important because many women need to stay on antivirals after giving birth to prevent "flares" or sudden increases in viral load that can cause liver damage. Also, breastfeeding is far healthier for babies than bottle milk, especially in resource-poor populations.
The researchers suggest antivirals should not be prohibited in nursing mothers, and that current recommendations should be re-evaluated given the lack of proof of any harm posed to babies.
In an editorial accompanying the report, pediatric hepatitis B expert Philip Rosenthal, director of Pediatric Clinical Research at the University of California San Francisco, wrote that the current ban against breastfeeding while on antivirals appears to pit a fetus' health against that of the mother and newborn.
"The authors (of the study) clearly provide proof that fetal exposure to (antivirals) are much higher than the exposure associated with breastfeeding," he writes. So what is a doctor to do?
Do you allow the mother to risk a flare of her hepatitis B when you discontinue the drug ... so that she can breastfeed her infant? he asked. Do you rely on HIV research that found these drugs can be safely continued while breastfeeding? Do you just ignore the recommendations and allow the mother to breastfeed, or do you prohibit breastfeeding and continue her on antivirals?
He noted that no drug company is going to spend the money or time required to run clinical trials to confirm the safety of antivirals during breastfeeding. So it falls on doctors and advocates to request drug agencies to re-examine the facts, he suggests.
"In the interim, I suspect that each individual physician will need to have a frank conversation with (a) patient prior to delivery," he writes, to explore the pros and cons of antivirals and breastfeeding so together they can make a decision that benefits both mother and child.
Source: www.ncbi.nlm.nih.gov/pubmed/25313254
Doctors Fail to Adequately Treat HBV-Infected Women After Childbirth
While health officials have campaigned long and hard to vaccinate infants born to HBV-infected women within hours of birth to prevent infection of newborns, doctors appear to forget the mothers' infections after they give birth, according to a blistering report published in the September issue of the American Journal of Obstetrics and Gynecology.
A Massachusetts study followed 291 HBV-infected women enrolled in the Partners HealthCare system who gave birth between 2002 and 2012. These women were treated at two of the best hospitals in the country, but they found only 19% of the women received adequate follow-up care for hepatitis B after childbirth. Their average age was 31, nearly all spoke English and had private insurance, so access to health care was not an issue. If these women failed to get adequate care, poor women with inadequate insurance and language barriers probably fare even worse, doctors suggest.
Researchers reported only 47% of the women enrolled in the study had follow-up with an HBV specialist after giving birth. Of this group, only 19% were then tested for hepatitis B "e" antigen (HBeAg), the hepatitis B "e" antibody, viral load (HBV DNA) or had their liver enzymes tested to determine if they had liver damage within one year of their HBV diagnosis, which medical guidelines recommend.
Mothers who had adequate medical follow-up were more likely to have tested positive for HBeAg and had signs of liver damage. This suggests doctors, including liver specialists, followed guidelines only when they thought the infection was causing liver damage based on superficial indicators, researchers noted.
"Having a primary care provider and being HBeAg-positive, a marker of more aggressive HBV, were associated with postpartum HBV specialty follow-up," they wrote. "This finding suggests that nonpatient factors, such as obstetrician knowledge of HBV, may play an important role in adherence to postpartum HBV follow-up care. Future studies are needed to confirm our findings in other health care settings and to evaluate physician and system-related factors affecting postpartum follow-up care."
Source: www.ncbi.nlm.nih.gov/pubmed/25281364
Doctors Continue to Fail to Screen Asian-Americans for Hepatitis B
A study by University of California San Francisco researchers found that doctors often fail to adequately screen and immunize their Asian-American patients for hepatitis B–especially female patients–even though this population is at high risk for HBV infection.
Researchers scoured the medical records of 20,574 Asian-American patients treated by primary care providers. The average patient age was 52 and 63.4% were female.
They discovered only 61.5% were screened for hepatitis B and only 47.4% of HBV-susceptible patients were vaccinated.
While 148 (44.8%) doctors reported they were knowledgeable and "had a favorable attitude" toward hepatitis B screening, 43.2% were unfamiliar with HBV guidelines that require screening and immunization.
Female patients were less likely to be screened and vaccinated, as were patients of doctors with busy, high-volume practices.
"Rates of HBV screening and vaccination of (Asian-American) patients in this safety-net system are suboptimal, and provider factors play a significant role," researchers wrote in the October issue of the Journal of General Internal Medicine. "Efforts to cultivate positive attitudes among providers and expand healthcare system resources to reduce provider barriers to HBV care are warranted."
Source: www.ncbi.nlm.nih.gov/pubmed/25324148
Statins Protect Hepatitis B Patients Against Heart Disease and Liver Cancer
For years, doctors refrained from prescribing statins–cholesterol-lowering drugs–to hepatitis B patients for fear they might worsen liver damage. Statins reduce cholesterol by blocking a chemical in the liver that is needed to produce cholesterol.
But new studies find statins not only effectively prevent high cholesterol in hepatitis B patients, they also protect these patients against liver cancer.
According to a report published in the September/October 2014 online journal, Dr. Robert Gish's hepaHealth, not only do statins safely reduce the risk of cardiovascular disease in patients with viral hepatitis, but a study of 1.4 million patients with 4,298 cases of liver cancer found that statins reduced liver cancer by 37%.
Additionally, when statins were added to ongoing chemotherapy to treat liver cancer, they prolonged survival. However, researchers are not sure how statins lower cancer risk, and Gish called for additional research into these drugs.
"Future research should include substantiating the preventative role of statins in liver cancer so that the use of these drugs can be incorporated into current practice guidelines for the prevention and treatment of this aggressive cancer, especially in those with mild liver disease who may benefit the most from such therapeutic intervention," he wrote.
Source: www.scribd.com/doc/237571687/Effects-of-Statins-on-the-Risk-of-Hepatocellular-Carcinoma
New Study Finds Antivirals Lower Liver Cancer Risk
A large Canadian study, reported in the journal of Alimentary Pharmacology & Therapeutics, found that several years of antiviral treatment reduced liver cancer risk in patients with hepatitis B.
In this study, 549 high-risk hepatitis B patients were treated with antivirals–primarily entecavir (Baraclude) and tenofovir (Viread)–for more than three years. Their average age was 46, 65% were male, 32% were HBeAg-positive, and 20% had cirrhosis (severe liver scarring).
Over 3.2 years of follow-up, 11 (3.2%) developed liver cancer. Their cancer rates were "significantly" lower than similar patient groups who did not receive antiviral treatment. The drop in cancer incidence became most apparent after four years of treatment, researchers noted.
Source: www.ncbi.nlm.nih.gov/pubmed/25312649
Studies Find Tenofovir Lowers Viral Load Faster Than Entecavir
Researchers analyzed numerous studies to compare the effectiveness of tenofovir and entecavir–currently the two most potent antivirals on the market–and found tenofovir to be more potent, especially in previously untreated patients.
The study, published in the October issue of the Journal of Clinical Pharmacology, reviewed two clinical trial results and nine studies involving 1,656 patients treated with the two drugs.
Nearly all of those treated with entecavir had never been treated before, nor had 481 of the 664 treated with tenofovir.
After 48 weeks of treatment, tenofovir proved to be the faster-acting antiviral. Both groups achieved similar rates of normal alanine aminotransferase (ALT) rates, which indicates no liver damage.
"These results suggest that tenofovir is a better choice to treat chronic HBV patients than entecavir as it is better able to suppress HBV viral load and has a similar safety profile," researchers wrote. (1)
An unrelated study by Turkish researchers published in the October issue of the International Journal of Infectious Diseases, also compared the two antivirals and found that tenofovir induced a faster decline in viral load than entecavir. Also, 7% of entecavir-treated patients eventually developed resistance to the antiviral.
Their study compared outcomes in 90 tenofovir-treated patients and 105 patients treated with entecavir. Most patients were male (72%), average age was 43, and all were treated for about 30 months.
Both groups had similar HBeAg seroconversion rates and similar rates of ALT normalization. However the average time it took patients to achieve undetectable viral load levels was 11.5 months in the tenofovir group and 12.9 months in the entecavir group. (2)
Source 1: www.ncbi.nlm.nih.gov/pubmed/25293471
Source 2: www.ncbi.nlm.nih.gov/pubmed/25286184
Liver Transplants Safe in Older Hepatitis B Patients
For many people with hepatitis B, serious liver disease does not develop until they are in their 60s, but are older patients good candidates for a liver transplant?
Doctors in China found they are. According to a report published in the October issue of the journal of Hepatobiliary & Pancreatic Diseases International, doctors compared survival in 60 transplant patients who were age 60 and older against 305 transplant patients who were younger than 60.
Survival at 1, 3, 5 and 8 years were 81.6%, 71.6%, 66.7% and 63.3% respectively for the older group and 84.9%, 77.7%, 70.8% and 65.6% for the younger group. Only when the older patients had kidney damage did they fare worse than the younger patients following transplant surgery.
"Liver transplantation is safe and feasible for patients with HBV-related end-stage liver disease aged over 60 years," they wrote. "Older patients with renal insufficiency should undergo transplantation earlier than younger patients."
Source: www.ncbi.nlm.nih.gov/pubmed/25308360
Scientists Develop Micro Weapon to Disable HBV's Cancer-Causing X Protein
Researchers in New Zealand may have found a way to disable HBV's X-protein–the culprit that enables HBV to integrate into liver cells and causes liver cancer. Scientists developed a micro weapon called a PROTAC (proteolysis targeting chimeric molecule) that targets and disables the X-protein.
According to their report published in the October issue of the journal of Biochemistry and Biophysical Research Communications, the cell-penetrating PROTAC they developed simultaneously disables the X-protein's functionality and causes it to degrade.
To date researchers have experimented with the PROTAC only in a laboratory setting. Researchers are now calling for preclinical studies of PROTAC to test its ability to prevent or treat HBV infection and liver cancer in human patients.
Source: www.ncbi.nlm.nih.gov/pubmed/25305486
Foreign-Born U.S. Residents Less Likely to Be Immunized
In a study published in the October issue of the American Journal of Preventive Medicine, a Centers for Disease Prevention and Control finds that foreign-born residents in the U.S. have far lower immunization rates than do U.S.-born residents.
They reviewed immunization rates in adults reported in the 2012 National Health Interview Survey for a variety of diseases and found large discrepancies.
Native residents had significantly higher vaccination rates than foreign-born respondents:
- Influenza rates were 40.4% vs. 33.8% in foreign-born residents
- Pneumonia vaccine rates were 62.6% vs. 40.5% in the elderly,
- And hepatitis B rates were 37.2% vs. 28.4%, even though foreign-born residents generally are at higher risk of HBV infection.
"It is important to consider foreign birth and immigration status when assessing vaccination disparities and planning interventions," CDC officials recommend.
Source: www.ncbi.nlm.nih.gov/pubmed/25300733
Antivirals Can Safely Replace HBIG Following Liver Transplantation
A new review of recent studies into liver transplants for hepatitis B finds that antivirals can effectively replace hepatitis B immune globulin (HBIG) to prevent a recurrence of infection.
HBIG, which is very expensive, is made up of surface antibodies harvested from donors who have overcome the infection and have high levels of antibodies in their blood. Historically, HBIG was the only drug available to help hepatitis B patients fight off a recurrence of HBV infection after they received new livers.
In this latest study published in the October issue of the World Journal of Gastroenterology, researchers conclude, “…it is now rational and cost-effective to decrease and, perhaps, cease altogether, the routine use of HBIG during and following liver transplantation for HBV infection.”
Source: www.ncbi.nlm.nih.gov/pubmed/25339803
All Hepatitis B Patients Appear at Risk from Chemotherapy
Even when a hepatitis B infection is “inactive” or a patient has cleared the hepatitis B surface antigen (HBsAg), patients risk a dangerous reactivation of infection when they are treated with chemotherapy for lymphoma, breast or other cancers, according to a new study on chemotherapy-related reactivations.
Researchers argue that all hepatitis B patients must be monitored and treated with new, potent antivirals to prevent a deadly reactivation.
Researchers, reporting in the October issue of the World Journal of Gastroenterology, reviewed recent studies to find out who exactly was at risk of hepatitis B reactivation.
Is someone who has normal ALTs and undetectable viral load at risk? Or is someone who has cleared the infection and has low levels of surface antibodies at risk?
They experts assert that anyone who has ever been infected is at risk of reactivation when treated with immune-suppressing chemotherapy, especially the drug rituximab, used to treat non-Hodgkin’s lymphoma.
People with prior HBV infections treated with chemotherapy have:
- A 24% risk of reactivation if they are treated with rituximab
- A 14%-21% rate if they are treated for solid tumors
- And a 41%-56% rate if they are treated for breast cancer.
Reactivation can occur even if patients have cleared HBsAg and have surface antibodies. Those at higher risk of HBV reactivation during chemotherapy treatment include males and young patients, and of course those who have "active" hepatitis B with elevated liver enzymes, which indicate ongoing liver damage.
Researchers noted that new antivirals, including entecavir, are far more effective at preventing reactivation than lamivudine (Epivir-HBV).
The most successful preventive treatment, researchers noted, uses entecavir before chemotherapy begins and continues for several months after chemotherapy ends.
Source: www.ncbi.nlm.nih.gov/pubmed/24002804
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