The 60th American Association for the Study
of Liver Disease (AASLD) convened in
A Turkish study that followed 230 patients for five years
after 48 weeks of pegylated interferon treatment ended found that 17% achieved
inactive hepatitis B (low viral load and no signs of liver damage) and 12%
cleared the hepatitis B surface antigen (HBsAg), which indicates a near
clearance of the virus. Patients who benefited most started treatment had
elevated alanine aminotransferase (
· Chinese researchers compared the effectiveness of 48 weeks of pegylated interferon treatment against 72 weeks of the antiviral adefovir (Hepsera) in hepatitis B “e” antigen (HBeAg)-positive patients who had developed viral resistance to the antiviral lamivudine. They found HBeAg seroconversion (loss of HBeAg and development of the “e” antibody) to be much higher in patients treated with interferon (11.6%) versus adefovir (3.8%). The rate of HBeAg seroconversion six months after treatment ended was twice as high in those treated with interferon. Researchers concluded that interferon is an excellent strategy for difficult-to-treat patients with lamivudine resistance.
Another Chinese study found extending interferon treatment
from the currently recommended 48 weeks to 72 weeks produced a higher rate of
HBeAg seroconversion and HBsAg clearance. In one study, 67 HBeAg-positive
patients with elevated
· Greek researchers compared HBsAg loss in untreated patients against HBeAg-negative patients treated with interferon. Untreated patients spontaneously cleared HBsAg at an annual rate of 1.79%, those treated with interferon experienced an 11% clearance rate, and those treated with adefovir over five years had a 33% clearance rate.
· Chinese researchers assessed outcomes among 113 patients treated with either interferon alone, a combination of interferon and adefovir, or adefovir alone for 48 weeks followed by a 48-week follow-up period. Viral load declined more than three-fold in 42% treated with just interferon, 63% treated with the combination, and 23% of those treated with only adefovir. HBsAg clearance and development of surface antibodies at week 96 occurred in 3% of the interferon and adefovir group. None of the patients treated with just adefovir cleared HBsAg.
Combination treatments employing both pegylated interferon and antivirals, which disrupt the viral reproduction process, has yielded inconclusive results to date.
Chinese researchers followed 113 HBeAg-positive patients
treated with either interferon only, adefovir only, or a combination of the
two, to see which group cleared HBeAg and gained the "e" antibody at
week 24, 48, and 96. HBeAg clearance was significantly higher at all time
points in the two groups treated with interferon. At week 96, 42% of
interferon-only, 49% of interferon and adefovir, and 15% pf adefovir-only
treated patients, respectively, cleared HBeAg. Similarly, there was a
significantly greater rate of HBeAg seroconversion at week 96 in the
combination group than in the adefovir-only group, and similarly those
receiving interferon experienced the highest decline in viral load (HBV
Tenofovir continues to do very well in long-term studies worldwide.
One European study of 175 patients who had resistance to
other antivirals found 92% of them achieved undetectable HBV
· The Antiretroviral Pregnancy Registry, which reports birth defects worldwide, followed 942 births to HIV- and HBV-infected women who have been treated with tenofovir between 1989 and 2008. No increase in prevalence of birth defects was reported by the international registry.
· An international team treated 354 patients with either lamivudine or entecavir to see how many cleared HBsAg after 120 weeks of treatment. They also tracked which genotype responded best to antiviral treatment. Patients with HBV strain or genotype A or D had a higher rate of clearing HBsAg (7.7% and 8.1% respectively) than patients with genotypes E or C in both treatment groups. Among those treated with entecavir, 18 or 5.1% lost HBsAg. Only 2.8% of lamivudine-treated patients lost HBsAg. This is among the first studies that explore which HBV genotypes respond best to antivirals.
· An Italian study of 376 mostly HBeAg-negative patients who were treated with entecavir for 72 weeks responded well to the antiviral with no signs of antiviral resistance. However, one fourth of high-viral-load patients showed only a partial response to the drug.
· Meanwhile, a South Korean study found that treating lamivudine- and adefovir-resistant patients with entecavir was ineffective. Most of the patients in the study were male and HBeAg-positive. Only 13% of these patients maintained undetectable viral load after 12 months of treatment.
· German researchers report that a high percentage of patients treated with entecavir develop a side effect called lactic acidosis, which occurs when antivirals prevent mitochondria from using oxygen to effectively convert food into glucose. When this occurs, lactic acid builds up in the bloodstream. The researchers followed 16 patients with liver cirrhosis who were treated with entecavir. Five out of the patients developed lactic acidosis. All patients with lactic acidosis had impaired liver function. Lactic acidosis was lethal in one patient but resolved in the other cases after drug usage stopped. “Our data indicate that lactic acidosis may be observed in patients with chronic hepatitis B and impaired liver function during treatment with entecavir,” they reported. “Thus, entecavir should be applied cautiously in patients with high MELD-Scores (indicating severe liver damage).”
Increasingly, researchers are finding that long-term adefovir treatment can cause kidney damage. Japanese researchers who followed 37 patients treated with adefovir after they developed lamivudine resistance found that 11% of them had kidney problems. They encouraged doctors to track renal function carefully during treatment in order to identify if reducing adefovir dosing was necessary to prevent kidney damage.
Greek researchers followed 213 HBeAg-positive and 185
HBeAg-negative patients treated with telbivudine over four years. They found
79% of HBeAg-positive patients had undetectable viral load and 86% had normal
Chinese researchers found a similar high response to
telbivudine among 213 HBeAg-positive patients. The rate of
· Chinese researchers followed one patient who was treated over 80 months with a succession of antivirals including lamivudine, adefovir, and entecavir. They identified the viral mutations that evolved with the administration of each successive antiviral. They concluded that the evolution of viral mutations that can resist antivirals is a stepwise, selective process and that doctors should be very careful when treating patients with antivirals.
· Japanese researchers made a similar finding when tracking patients treated with lamivudine and adefovir. They found the resulting viral mutations could also resist entecavir. “The risk of multiple drug-resistant strains with long-term therapy must be considered,” they wrote, especially in patients who do not completely attain undetectable viral load.
· A global team of researchers treated 112 people with decompensated liver disease with either tenofovir, the experimental antiviral emtricitabine combined with tenofovir, or entecavir to see if the antivirals were safe in this high-risk population. Through week 48, all treatments were generally well-tolerated with improvement in viral suppression and liver health.
Spanish researchers followed 51 patients who lost HBeAg to
see what impact HBV genotype had on the development of viral mutations and
elevated viral load. They found that patients with
To avoid costly treatment and severe side effects, researchers are searching for ways to determine whether interferon treatment will succeed as early in the treatment process as possible.
· One European study followed 133 HBeAg-negative patients treated with an antiviral and pegylated interferon. They found that reductions in viral load and HBsAg at week 12 indicated if a patient would benefit from continued treatment.
A separate Dutch study similarly followed HBsAg levels and
viral load in 28 HBeAg-positive patients treated with a combination of
pegylated interferon and adefovir for 48 weeks. They found a strong decline in
HBsAg levels during the first 24 weeks of treatment was associated with HBeAg
loss and seroconversion, while high levels of HBsAg and HBV
High caffeine consumption is associated with lower risk of liver inflammation in those with viral hepatitis.
· A Canadian study examined whether caffeine intake from caffeinated cola or tea produced the same beneficial results in 177 patients with viral hepatitis and other liver diseases. They reported that caffeine from two cups of coffee daily lowered the risk of fibrosis far more effectively than when caffeine was derived from other sources.
· A U.S. study found that only 32% of primary care providers adequately treat Asian-American patients for hepatitis B. Fifty-eight percent of the doctors surveyed reported they recommended their HBV-infected patients be monitored three or more times a year, but only 39% of their patients returned for the recommended monitoring. About 62% of doctors were not familiar with current treatment guidelines. Researchers concluded that while most doctors consider hepatitis B to be a serious disease, only one-third adequately screen their Asian-American patients for the infection. More education among doctors about hepatitis B, disease progression, and treatment, is required.
A team of Taiwanese researchers followed 108 patients
coinfected with HBV and the hepatitis C virus (HCV) who were treated with
ribavirin and pegylated interferon, which is the standard of treatment for
hepatitis C. Surprisingly, this treatment was effective against hepatitis B.
Eighteen months after treatment ended, researchers found that 51 patients (47%)
had undetectable HBV
Hepatitis C patients report a higher rate of depression when treated with pegylated interferon and the antiviral ribavirin then hepatitis B patients treated with interferon and different antivirals.
· Taiwanese researchers compared rates of depression among 85 hepatitis B patients and 90 hepatitis C patients treated with interferon and antivirals. After 48 weeks, three hepatitis B patients and 13 hepatitis C patients reported depression. Researchers concluded that ribavirin may be the cause of increased depressive symptoms in hepatitis C patients.
Each year about 24,000 infants are born to women
with chronic hepatitis B infection with a resulting in section rate of 1%.
Indian researchers followed 158 HBsAg-positive pregnant women
and found a surprising number of newborns had “occult” HBV infection despite
immediate immunization and injection with HBIG at birth. Occult infection
occurs when patients test negative for HBsAg but have measurable HBV
· A team of Dutch in Chinese researchers followed 29 patients for 12 months after they stopped antiviral treatment following HBeAg seroconversion to see if this seroconversion represented a safe stopping point for antiviral treatment. There is no medical consensus about when it is safe to stop antiviral treatment. Eight patients had ongoing detectable viral load despite the seroconversion. Ultimately, a sustained response in absence of treatment occurred in only 2 of 9 patients who discontinued therapy after seroconversion. “HBeAg seroconversion induced by (antivirals) was not durable in a majority of cases. These findings may indicate that HBeAg seroconversion, in contrast to what current guidelines suggest, is an imperfect endpoint in assessing antiviral therapy. Treatment with antivirals should thus probably be continued indefinitely or until HBsAg seroconversion,” the researchers noted.