Hepatitis B
experts met at the 61st annual meeting of the American Association
for the Study of Liver Diseases in Boston recently to share the latest in
hepatitis B treatment and research. News
about promising new treatments, and new information about
the effectiveness of existing antiviral and interferon treatments was shared
with physicians and researchers. Here are some of the studies unveiled at the
conference.
Promising New Treatment
New drug clears infection completely within weeks: Canadian and Bangladeshi
researchers have identified an experimental drug that resulted in the complete
clearance of chronic hepatitis B infection in five of six patients treated with
REP 9 AC.
Research suggests that the hepatitis
B surface antigen (HBsAg), the protein that provides the “cover” of the
hepatitis B virus (HBV), plays a role in suppressing the immune system, which
results in chronic or long-term hepatitis B. Researchers administered REP 9AC,
a DNA-based polymer that stops infected liver cells from producing HBsAg, in
six hepatitis B “e” antigen (HBeAg)-positive patients who had high viral loads
and fibrosis.
Five out of six patients treated
cleared HBsAg and developed surface antibodies—an indication that the patient
has completely cleared the infection. In some patients, this occurred just
seven days after starting treatment. In others, this occurred within 15 weeks
after receiving higher doses of the drug.
Three patients achieved a 3- to
7-fold reduction in HBV DNA after 7-13 weeks of treatment. Additionally, two
other patients cleared HBV DNA, and developed surface antibodies and have
stopped treatment and are now being monitored carefully. One of the patients
remains HBV-free six months after stopping treatment.
“This rapid HBsAg seroclearance appears
to allow the restoration of an effective immune response, as evidenced by
substantial reductions in HBV DNA, seroconversion for HBsAg and HBeAg, and the
achievement of a six-month sustained response in at least one patient to date,”
researchers wrote.
Antiviral Treatment
Tenofovir and emtricitabine (FTC): European researchers tried this antiviral combination, which
has been used extensively against HIV, in 82 patients and monitored them for
its effectiveness and potential antiviral resistance over 15 months.
Six months after starting treatment, viral loads dropped nearly
three-fold, and after 12 months 82% of patients had undetectable viral load. In
a subgroup with HBeAg-positive hepatitis B, many of whom had significant
fibrosis, all had undetectable viral load after 17 months of treatment.
·
403.
Efficacy and
tolerance of tenofovir disoproxil fumarate plus emtricitabine combination in
patients with chronic hepatitis B – A European multicenter study (Updated October 31, 2010)
Long-tenofovir works
well in HBeAg-negative and –positive patients: Researchers, in separate studies, report tenofovir
is highly effective in HBeAg-positive and –negative patients, and causes no
drug resistance even after four years of continuous treatment. It was equally
effective in Asian and non-Asian populations. Even in HBeAg-positive patients
with extremely high viral loads, tenofovir knocked down viral loads to
undetectable in 95% of these patients.
Tenofovir boosts
effectiveness of entecavir: California researchers studied how 42 Asian-Americans (HBeAg-positive)
who did not respond well to entecavir fared when tenofovir or adefovir were
added to ongoing entecavir treatment. They found that adding tenofovir resulted
in a high percentage of patients achieving undetectable viral load, compared to
adding adefovir or replacing entecavir with tenofovir.
Entecavir proves
superior to adefovir (Hepsera): Several studies found entecavir to be more effective than
adefovir in patients who had never been treated. Entecavir proved to be more
effective after 96 weeks of treatment in both HBeAg-positive and –negative
patients.
Entecavir effective: Spanish researchers treated 190
previously untreated patients (both HBeAg-positive and -negative). After 48
weeks, 83% had undetectable viral load (61% among HBeAg-positive patients and
92% among HBeAg-negative). About 82% who had elevated alanine aminotransferase
(ALT) levels (which indicates liver cell damage) developed normal ALTs, 21%
achieved HBeAg seroconversion, and two cleared HBsAg.
·
437. Outcomes of Treatment For Chronic Hepatitis B
with Entecavir Therapy
Benefits from Antiviral Treatment
Reduced fibrosis: A Japanese study showed antivirals
were highly effective in reducing fibrosis, which results in liver stiffness,
in patients. Untreated, fibrosis can develop into cirrhosis and cancer. This
study found that antiviral treatment significantly reduced liver stiffness,
while untreated patients had increased liver stiffness and fibrosis.
·
367. Reduction of liver stiffness of chronic
hepatitis B patients by antiviral therapy
Reducing cancer risk: Antiviral treatment reduced the
5-year risk of liver cancer by 9% to 41%, according to a Japanese study.
Researchers followed 613 HBeAg-positive patients who were screened for liver
cancer over 5.5 years, and compared their outcomes to those of 197 patients who
had been treated with antivirals for several years.
Interestingly, many of the untreated
patients who later developed liver cancer had normal or moderate ALT levels—and
therefore did not qualify for treatment under current guidelines. The 5-year
cancer rate in the untreated group was 12%.
“The current treatment guidelines for chronic hepatitis B
excluded a significant proportion of patients at high risk for liver cancer,”
researchers wrote. If doctors use age, platelet counts, viral load, and
presence of core promoter mutations as criteria, they would identify more than
90% of patients who are at high risk of liver cancer and should be treated.
Antiviral treatment, they noted, “significantly reduced the incidence of liver
cancer among these high risk patients.”
Antivirals effective against cirrhosis: U.S. researchers reviewed numerous studies involving patients with cirrhosis and decompensated hepatitis, which means the liver can no longer function normally. They found that antivirals are effective and safe for treating decompensated cirrhosis. Lamivudine (Epivir-HBV) and entecavir should be avoided if patients have been treated with antivirals previously. Researchers urged more testing of entecavir and tenofovir in these patients, to determine which was more effective.
·
375.
A systematic review
of oral antiviral agents in decompensated HBV cirrhosis.
Side Effects from Antivirals:
Antivirals reduce bone density: Italian researchers followed 319 patients (76% males,
average age 63, 57% with cirrhosis) treated with tenofovir, adefovir, and
lamivudine either alone or in combination for three to four years to see what
impact antiviral treatment had on their reduced bone density.
They found reduced density, which
results in osteoporosis and other weak bone conditions, in 68% of the patients.
The rate was higher (78%) among female patients. The doctors recommended that
patients have a bone mineral assessment performed prior to starting treatment
in order to prevent and treat the condition should it occur.
Pegylated Interferon
More patients should be treated with interferon: Current guidelines recommend that
patients with elevated ALT levels, low viral load, and genotypes A or B have an
increased chance of responding to interferon. U.S. researchers examined 257
patients who received treatment between 2001-2009 to see what
percentage of patients who qualified for interferon actually received it.
Some patients opt not to take interferon because it is costly, has side
effects, and requires injections.
Of the patients in the study, about
half could have qualified for interferon, but only 19% received it. These
patients were likely to be about age 45, male and Caucasian. Among the 12 with
ideal characteristics for interferon, along with genotypes A or B, 42% percent
remained in remission after received interferon treatment. Researchers noted
that interferon, “is underutilized in the population
predicted to have the best response.”
·
396.
Interferon is
Underutilized in Heptitis B (HBV) Patients Most
Likely to Have Favorable Outcomes (Updated
October 31, 2010)
·
451.
Physician Preference
Drives Choice of Oral Hepatitis B Therapy
Extended interferon treatment effective in HBeAg-negative patients with
genotype D:
Increasing the duration of pegylated interferon treatment from 48 to 96 weeks
in genotype D patients improved response. Italian researchers compared the two dose lengths in
103 patients and found that 12 months after treatment ended, 11.8% of those
treated for 48 weeks had HBV DNA under less than 2,000 IU/mL, and 28.8% of
those treated for 96 weeks achieved that outcome. The current 48-week course of interferon
treatment is not recommended for patients with genotype D.
Combination Treatment
Extended treatment with antivirals and interferon combo effective: Forty-one HBeAg-positive patients
with genotypes B or C received pegylated interferon with either lamivudine or
adefovir for 96 weeks (previously the recommended course was 48 weeks).
·
After
48 weeks, 96% of patients achieved undetectable HBV DNA, but after 96 weeks of
treatment 100% had responded.
·
HBeAg
seroconversion: After 48 weeks, 50% of patients treated with interferon and
lamivudine achieved HBeAg seroconversion, after 96 weeks 75% did. Forty-four
percent of the interferon-adefovir group achieved seroconversion after 48
weeks, but 71% did after 96 weeks.
·
HBsAg
clearance: In the interferon-lamivudine group, HBsAg seroconversion rates were
8% after 48 weeks of treatment and 30% after 96 weeks. In the
interferon-adefovir group, HBsAg seroconversion was 4% after 48 weeks and 24%
after 96 weeks.
No additional side effects were reported in those who
received the longer treatment.
Customizing interferon and antiviral treatment effective: Chinese researchers treated 92
HBeAg-positive patients with pegylated interferon, and then measured their HBV
DNA at week 12 in order to try individualized treatment approaches for 76
patients who did not respond. These options included the conventional 48-week
course of interferon, a combination of interferon with either adefovir or
entecavir for 48 weeks, or extended interferon treatment up to 72 weeks.
Patients were then followed for 24 weeks after treatment ended.
The rate of sustained response
(lowered viral load, normalized ALT levels) was 78.3% in the group receiving
extended interferon and 83.3% and 85.7% in the combination groups receiving
entecavir and adefovir respectively. The response rate was 38.1% in the
conventional group that received only 48 weeks of pegylated interferon.
Treating Antiviral Resistance
Antiviral combinations
effective: A study
of 109 patients treated with antiviral combinations after they developed drug
resistance showed the treatment was highly effective and resulted in a rapid
decline in viral load. Most of the Asian-American patients (77%) achieved
undetectable viral load within six months of starting combinations of entecavir
and tenofovir, tenofovir and lamivudine (Epivir-HBV), entecavir and adefovir,
and adefovir and lamivudine.
Safe to switch from
adefovir to entecavir: U.S. doctors followed 106 patients who had responded—or partially
responded—to adefovir and were switched to entecavir. Most were male, in their
40s, and were still HBeAg-positive. Those who had responded to adefovir
continued to respond well to entecavir with normal ALTs and low viral load.
Eight-two percent of patients who had only partially responded to adefovir
eventually responded robustly to entecavir after 24 months of treatment.
·
383. Complete viral suppression (CVS) by entecavir
(ETV) in patients previously treated with adefovir (ADV): Interim report for a
multicenter study (Updated
October 31, 2010)
Pregnancy and HBV
Researchers are examining the safety
and effectiveness of treating HBV-infected pregnant women with antivirals.
Antivirals are used to lower viral load to prevent transmission of infection to
newborns and to treat women who are experiencing liver damage, indicated by
elevated ALT levels. Even when infants are immediately immunized and treated
with HBIG, many born to women with high viral loads still become infected.
Telbivudine (Tyzeka)
Telbivudine proved safe in two studies: Chinese researchers treated 53 pregnant women, in
their second and third trimesters of pregnancy, with telbivudine (600 mg
daily). Their HBeAg status, ALT levels, viral load, and the health of their
infants were evaluated in the study.
At time of delivery, 53% of treated patients had undetectable
viral loads and 62% had achieved undetectable viral load four weeks after
delivery. Only 4% of infants tested positive for the hepatitis B surface
antigen (HBsAg), which indicates infection, compared to 23% of the newborns
born to women in an untreated, control group. All infants born to women treated
with the antiviral during pregnancy were healthy, and the treatment caused no
problems during pregnancy and delivery.
In another Chinese study, 94
HBeAg-positive, pregnant women were treated with telbivudine during their third
trimester. At birth, 6.32% of newborns born to treated mothers were
HBsAg-positive, compared to 30.43% in an untreated control group. Twenty-eight
weeks later, 2.11% of infants born to treated mothers were HBsAg-positive,
compared to 13.04% in the control group.
Tenofovir (Viread): New York doctors treated eight pregnant women with 300 mg daily of
tenofovir during their third trimester of pregnancy. Three were treated due to
ongoing liver damage (elevated ALTs) and four were treated in order to prevent
infection of their newborns.
Tenofovir effectively lowered ALT levels up to four-fold
during four weeks of treatment in all women. Women and newborns alike were all
healthy. Three infants—the only ones for whom test results were
available—tested negative for HBsAg nine months after birth.
·
372.
Outcomes of Eight
Chinese-Americans Pregnant Patients with Chronic Hepatitis B (CHB) Treated with
Tenofovir DF (TDF) During Pregnancy (Updated
October 31, 2010)
Caesarean delivery may
reduce HBV infection:
Chinese researchers monitored 569 infants born to HBeAg-positive mothers and
found HBV infection in 5.94% who were delivered vaginally, 8.51% who were
delivered by emergency Caeserean section, and 2.12%
who were delivered by elective Caesarean section. The researchers suggest elective
Caesarean delivery may be the preferred delivery choice to reduce infection
risk.
Vaccine alone effective in preventing mother-to-child HBV transmission: Currently, the medical practice is
to administer both the first hepatitis B vaccine dose and HBIG immediately when
an infant is born to an HBV-infected mother, followed by a second and third
vaccine dose. HBIG is costly, and often not available in developing countries.
An Indian study found no added benefit from HBIG. They looked
at 170 infants born to infected mothers over 18 weeks and found that equal
numbers were infected in both groups. “Our study clearly documents that vaccine
alone confers equal protection against HBV infection in newborns (born to)
chronic HBV infected mothers,” they wrote. “However, in spite of this
protection, a large number of babies in both the groups developed occult HBV
infection, which may be due to intrauterine transmission of HBV infection.
Trials using antivirals during pregnancy should be done to prevent this immunoprophylaxis failure.”
When to Treat?
AFP test can indicate
when treatment is needed: Many patients have liver damage, but current ALT tests fail to identify
up to one-third of patients who have liver damage and could benefit from
treatment. Taiwanese researchers assessed 152 HBeAg-negative patients who had
never been treated and who had liver biopsies that showed concrete signs of
liver damage. They found that alpha fetoprotein levels greater than 7 ng/mL indicate a patient has liver damage and requires
treatment. The test improved accuracy for assessing treatment needs from 66.7%
to 81%.
Screening for HBV
Primary care providers ineffective in screening
Asian-American patients for HBV. Asian-Americans, who are at high risk of hepatitis B, should
be tested for HBV. A study of 5,143 Asian American patients cared for by
primary care providers affiliated with the Mayo Clinic,
revealed that only 31% were screened for HBV infection between 1994 and 2009.
Of those screened, 8% were HBsAg-positive. Of the remaining 1,474, 70% were
surface antibody positive (showing a resolved infection or immunization, and
30% showed no immunity against HBV.
Asian-Americans who were older tended
to be screened more than those who were younger. One-third of HBsAg-positive patients
had normal ALT levels, which shows that doctors should not depend on abnormal
ALT tests as prompts to conduct HBV screening.
“…HBV screening has been grossly inadequate,” Mayo Clinic
researchers wrote. “In those screened, the prevalence of HBV remained high.
Despite publicity and awareness efforts, HBV remains one of the largest yet
under-diagnosed health disparities in the U.S.”
·
787.
Effectiveness of
Hepatitis B Screening in Primary Care Setting
Knowledge of HBV low among Vietnamese-Americans: Researchers studied infection rates
and knowledge of disease among 698 Vietnamese-Americans living in the San
Francisco area. All were foreign-born and had lived in the U.S. for about 20
years.
They found that 95 (13.6%) were
positive for HBsAg, with higher infection rates in men (16.4% in males vs.
11.3% in females), in those between 30-39, and the
uninsured.
There was a significantly higher
infection rates in those with a family history of HBV and those with prior
occupational exposure to blood.
More education about disease prevention and treatment is
needed, researchers noted, especially among the uninsured.