HBV Journal Review
March 1, 2014, Vol 11, no 3
by Christine M. Kukka
Tenofovir More Potent Than Entecavir in Patients with High Viral Loads
If you are infected with the hepatitis B virus (HBV) and have a high viral load, which of the two leading antivirals do you choose? Do you opt for tenofovir (Viread) or entecavir (Baraclude)? A team of researchers from Stanford University recommend tenofovir hands down.
The researchers monitored 59 patients treated with tenofovir and 216 treated with entecavir and compared the two drugs’ effectiveness. Antivirals are pills taken daily that make it difficult for HBV to replicate. The patients were treated at four community liver clinics in northern California and monitored over a three-year period.
Among the 72 patients who tested negative for the hepatitis B "e" antigen (HBeAg) and had only moderately elevated viral loads, there was no significant difference in the performance of the two antivirals.
However, among HBeAg-positive patients with HBV DNA levels exceeding 1 million international units per milliliter (IU/mL), tenofovir worked far faster to suppress viral load.
After six months, 18% of tenofovir-treated patients achieved undetectable viral load compared to 11% in the entecavir group.
After 12 months, 51% of tenofovir patients had undetectable HBV DNA compared to 28% of entecavir patients.
And after 18 months, 72% of tenofovir-treated patients were HBV DNA-free, compared to 39% in the entecavir group.
“Tenofovir is significantly more effective than entecavir for achieving complete viral suppression in HBeAg-positive, (never before-treated) chronic hepatitis B patients with HBV DNA greater than 1 million IU/mL,” they wrote in the January issue of the journal of Alimentary Pharmacology and Therapeutics.
Antiviral Treatment After Liver Cancer Surgery Improves Survival Dramatically
A team of researchers from Thomas Jefferson University Hospital reports that antiviral treatment after removal of a liver cancer tumor increased survival from an average 1.3 years to 6.6 years.
The team compared survival in 25 hepatitis B patients who each had similar-sized liver tumors removed through a process known as tumor ablation–involving the removal of liver tumors using heat, cold or chemicals.
None of the patients had ever been treated with antivirals prior to surgery. Nine male patients (average age 53) received no antiviral treatment after surgery while 16 patients (14 male, average age 56) were treated with antivirals.
The average survival rate of untreated patients was 16 months (ranging from three to 36 months). In contrast, patients treated with antivirals survived an average of 80 months or 6.6 years (averaging 15 to 152 months).
Fourteen of 16 antiviral-treated patients are alive today, with two patients living for more than 12 years.
Researchers, writing in the February issue of the journal of Cancer Medicine, concluded that antiviral therapy for patients with liver cancer, "reduces and prevents new/recurrent tumor and improves survival. This novel treatment strategy offers an alternative to liver transplantation in patients with hepatitis B-associated (liver cancer)."
The New "Normal" ALT Levels Are Better at Diagnosing Active Infections
Recently, liver experts lowered what is considered to be "healthy" levels of alanine aminotransferase (ALT) from about 50 international units per liter (IU/L) to 30 IU/L for males and 19 IU/L for women. ALT levels increase when liver cells are damaged by infections such as hepatitis B.
The lower ALT levels have been slow to catch on, many doctors and clinics still use the 50 IU/L benchmark before initiating treatment or more frequent monitoring of hepatitis B patients.
However, a new study by researchers at the University of Southern California in Los Angeles find that the new, lower "healthy" ALT levels are more accurate in identifying patients with active hepatitis B infection.
According to the report published in the February issue of the journal of Digestive Diseases and Sciences, doctors followed 198 Asian-Americans who had never been treated over 21 months. They compared the diagnostic accuracy of using the higher and lower "healthy" ALT levels.
If they had used the higher ALT levels, doctors would have missed liver problems in about 36.6% of the patients. When some of these "missed" patients had liver biopsies, doctors found moderate to severe fibrosis that required treatment.
Using the new, lower ALT levels enabled the doctors to more accurately assess liver health and HBV infection stage in more than 28% of their patients. "Compared with conventional ALT criteria, (the current, lower) ALT criteria is more sensitive in identifying chronic hepatitis B patients in active (infection) phases," they wrote.
Culturally-Adept Program Boosts HBV Screening Among Asian-Americans
About 10% of Asian-Americans have chronic hepatitis B, but few have been screened or treated for the infection that can lead to liver cancer. Most health education and outreach programs have failed to reach this population due to cultural, language and economic barriers.
A recent liver cancer education program in the Baltimore-Washington D.C. area, spear-headed by Johns Hopkins Bloomberg School of Public Health researchers, found that a culturally-adept program that employed native language speakers, a role-playing slide presentation, and a graphic novel increased hepatitis B screening markedly.
The researchers worked with local Vietnamese-, Chinese- and Korean-American community groups to develop education materials that would be suitable to Asian-Americans. The program workers fanned out to recruit potentially at-risk Asian-Americans from Korean Christian churches, Buddhist temples, nail salons, and Chinese language schools.
About half of those recruited (436) were assigned to a control group that received an English language brochure about hepatitis B. The other half (441) participated in a 30-minute education program about hepatitis B and liver cancer in their own language from Asian-American health educators. They watched a role-playing slide presentation that featured Asian-Americans asking doctors about hepatitis B and lab tests, and were given a photo novel about hepatitis B and liver cancer that featured Asian-Americans.
Six months later, both groups were interviewed by phone to see if they had been screened for hepatitis B as a result of the two interventions.
About 34% of the culturally-customized program participants had been screened for hepatitis B. In contrast, only 10% of the control group had been screened.
“In conclusion, this culturally integrated intervention program yielded a substantial increase in screening behavior in under-served, high-risk, Asian minority populations,” researchers wrote in the U.S. Centers for Disease control and Prevention’s February issue of the journal Preventing Chronic Disease.
“We recommend providing culturally and linguistically integrated educational programs as one way to change social norms to increase preventive behavior,” they added, stressing that their program provides a model for large-scale community initiatives that promote hepatitis B and liver cancer prevention among high-risk groups.
Experts Explore Ways to Treat and Monitor HBeAg-Negative Patients
Many adults with chronic hepatitis B eventually develop HBeAg-negative infection as they age, and unfortunately this phase of infection is difficult to monitor and treat.
Over time, HBV in older people are able to replicate without generating HBeAg because of mutations in the HBV's core promoter or precore region. A person with HBeAg-negative hepatitis B often has:
Low or moderate viral load
Undetectable HBeAg and detectable "e" antibodies
Normal or slightly elevated alanine aminotransferase (ALT) levels. ALT levels increase above normal when liver damage occurs.
Varying levels of fibrosis and liver damage, which makes it challenging for doctors to know when to order a liver biopsy.
Current guidelines suggest HBeAg-negative patients with viral loads higher than 20,000 IU/mL or signs of liver damage (elevated ALT levels) should be treated. But when viral loads are teetering just under 20,000 IU/mL and ALT levels are in the upper reaches of normal, it's difficult for doctors to gauge which patient needs treatment or more frequent monitoring.
A study from Iran, published in the February 2014 issue of Hepatitis Monthly, followed viral loads and ALT levels in 243 HBeAg-negative patients for one year to see if viral load could be used to identify which patients had an "active" infection that required treatment.
They found that patients with viral loads ranging between 2,000 and 20,000 IU/mL and persistently normal ALT levels could truly be considered "inactive" carriers who do not need treatment.
However, they stressed that doctors could miss liver damage in these patients if they relied on only one HBV DNA test, "...so appropriate follow-up (using) HBV DNA and ALT levels is recommended to differentiate inactive carriers and patients with (active) HBeAg-negative chronic hepatitis B."(1)
An unrelated study published in the January 2014 issue of the Journal of Clinical Virology tracked hepatitis B surface antigen (HBsAg) levels in patients with varying stages of hepatitis B infection to see if this antigen level could be used as an indicator of staging a hepatitis B infection or when treatment was needed.
Of interest was whether there was a difference in HBsAg levels in the HBeAg-negative patients who had active liver disease or needed treatment.
They found HBsAg levels when combined with ALT levels shed little light on which HBeAg-negative patients needed treatment. "HBsAg is not a suitable marker for evaluating hepatitis activity and distinguishing between cases of HBeAg-negative chronic hepatitis B and inactive (hepatitis B)," they wrote. (2)
1. Source: http://hepatmon.com/?page=article&article_id=15285
2. Source: www.ncbi.nlm.nih.gov/pubmed/24529415
CDC Experts Estimates 6.5 New Hepatitis B Infections for Every One Reported
For every one case of hepatitis B infection that is reported to health authorities in the U.S., researchers predicts there are 6.5 unreported, new infections among adults, which resulted in an estimated 18,730 new hepatitis B infections nationwide in 2011.
New hepatitis B and C infections are notoriously difficult to count. The infections may not cause symptoms or sufficient side effects to prompt a newly-infected person to see a doctor. Even when liver damage symptoms are present, the doctor must diagnose it correctly, confirm the infection through blood tests, and then report it accurately to local health authorities.
Because so many viral hepatitis cases are missed, local health officials can miss outbreaks and they often lack the information they need to design effective prevention and treatment programs.
To try to tackle this information void, researchers from the U.S. Centers for Disease Control and Prevention's division of viral hepatitis crafted a model that incorporated how many new infections would have been:
Symptomatic enough to require a doctor's visit
Evident enough to be correctly diagnosed by a doctor
And, ultimately reported to health officials in 2011.
They used the number of hepatitis cases reported to the National Notifiable Diseases Surveillance System in their estimates. Their formula represents an updated approach to estimating new infections. The last model developed was designed in the 1990s and depended on the experiences of blood transfusion recipients who developed viral hepatitis. These new estimates are lower than what has been used historically by CDC, but may be more accurate.
However, this model does not capture new hepatitis B infections that result from HBV-infected immigrants coming to the U.S.
"...These estimates should be viewed as the best that can be generated at this time to support surveillance, planning and prevention activities until better data sets or more sophisticated models can be developed," researchers wrote in the January edition of the American Journal of Public Health.
Their model also predicted:
2,730 new hepatitis A infections in 2011, with two unreported cases for every reported case
And, 17,100 new hepatitis C virus (HCV) cases annually, with 12.3 new infections for every reported case.
Sperm Washing Successfully Prevents Infection Transmittal During Conception
Using washed or sterilized sperm from HIV, HBV or HCV-infected men and injecting it directly into the egg of an uninfected woman is a safe and effective way for couples to achieve pregnancy when the man has a bloodborne infection, according to a report published in the January 2014 issue of the International Journal of Fertility and Sterility.
A team of Italian researchers followed 62 men, whose sperm was washed (separated from seminal fluid so they were free of any HBV, HCV and HIV molecules) and injected into their partners' eggs.
In total, 38 clinical pregnancies were achieved out of 173 menstrual cycles, resulting in 34 births (16.2% per cycle and 30.1% per couple).
During follow-up, none of the women or infants contracted viral hepatitis or HIV infections.
"Sperm washing and intracytoplasmic sperm injection are shown to be a safe and effective option for reducing the risk of transmission or super infection in serodiscordant or concordant couples who wish to have a child," researchers wrote.
Tenofovir Effective in Patients with Drug Resistance, But Less So with Adefovir-Resistance
The antiviral tenofovir is emerging as one of the most potent and effective antiviral medications, with an extremely low rate of drug resistance. However, the antiviral appears to be less effective in patients who have developed resistance to the antiviral adefovir (Hepsera).
Researchers suggest that HBV with mutations that can "resist" adefovir may also be able to continue to replicate despite tenofovir treatment.
Turkish researchers, reporting in the February issue of the journal of Antiviral Therapy, treated three groups of patients with tenofovir to see what effect adefovir-resistance had on tenofovir's ability to lower viral load. Forty-four of the patients had never been treated with antivirals, 30 had adefovir resistance and the third group of 24 had simply failed to respond well to adefovir treatment.
The 44 previously untreated patients experienced the fastest declines in HBV DNA, with 77.2% achieving undetectable HBV DNA within 12 months.
The two groups, who had previously been treated with adefovir had weaker responses to tenofovir. Only 60% of those with documented adefovir resistance achieved undetectable viral load after 12 months, while 75% of the adefovir nonresponders cleared viral load.
HBV DNA decline is slower in adefovir-experienced patients, researchers noted. "The clinical significance of this slow response may be important in patients with critical liver (disease) and high viral load," they wrote. "Optimal combination treatment (tenofovir plus entecavir) could be considered in these patients."(1)
In a related study published in the January issue of the journal Gut Liver, South Korean researchers studied 17 patients who had developed resistance to other antivirals. Four were treated with tenofovir and 13 were treated with a combination of tenofovir and lamivudine (Epivir-HBV) for 42 months. The doctors monitored viral load, HBeAg status, and kidney function.
After treatment, the average HBV DNA level decreased to undetectable after 48 months. HBeAg loss was seen in two patients. Five patients experienced a resurgence in HBV DNA because they did not take the daily antiviral pills as prescribed. No kidney damage was documented.(2)
1. Source: www.ncbi.nlm.nih.gov/pubmed/24517926
2. Source: www.ncbi.nlm.nih.gov/pubmed/24516703
Hepatitis B Vaccination Still Protects Even When Antibodies Decline
Is someone who has been vaccinated against hepatitis B still protected if their hepatitis B antibody count falls below 10 international units per milliliter (IU/ml)? Some experts fear declining antibodies means a waning of protection while others contend that the immune system continues to remember the virus and can spring into action even if antibodies decline below that level.
To explore this question, Italian researchers followed 571 teenagers 10 and 17 years after they were vaccinated as infants.
When tested in 2003, 10 years after vaccination, 199 children (group A) had antibody levels below 10 IU/ml and 372 teens (group B) had antibody levels exceeding 10 IU/ml. Everyone in group A received a vaccine booster.
Seven years later in 2010, the teens were tested again and researchers found that 67.3% of group A who received boosters had adequate antibodies compared to 75.8% of group B, who did not require boosters.
The researchers, writing in the February issue of the journal of Clinical Microbiology and Infection, reported that the capacity of the teens' immune systems to increase surface antibodies shows that their immune systems "remembered" the virus for hepatitis B and continued to confer protection even when the number of antibodies declined.
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