HBV Journal Review
May 1, 2010, Vol 7, no 5
by Christine M. Kukka
Indefinite Antiviral Treatment Required to Sustain HBeAg Seroconversion
Should antivirals be continued after a patient seroconverts and loses hepatitis B “e” antigen (HBeAg) and develops “e” antibodies? Researchers are struggling to determine how long antiviral treatment, which disrupts the hepatitis B virus (HBV) reproductive cycle, should be continued after seroconversion.
Dutch researchers followed 42 patients, who seroconverted, for an average 59 months and concluded that antivirals must be continued indefinitely in order to sustain HBeAg seroconversion.
Of the 42 patients, 33 (79%) continued therapy after HBeAg seroconversion, and of these, 22 (67%) had viral recurrence of HBV despite continued treatment, usually due to viral resistance to the antiviral lamivudine (Epivir-HBV). Nine of the 42 (21%) discontinued therapy after HBeAg seroconversion and only two of them sustained the seroconversion after treatment ended.
Researchers concluded that HBeAg seroconversion occurring during antiviral treatment is almost always temporary and that long-term treatment appears necessary, according to their report published in the April 2010 issue of Gastroenterology.
Researchers Call for Re-Examination of What Healthy ALT Levels Are in Children
U.S. researchers have found that alanine aminotransferease (ALT) tests used to screen children for liver disease are often interpreted incorrectly and are ineffective in identifying which children have liver damage, according to the SAFETY study (Screening ALT for Elevation in Today’s Youth) report published in the April issue of Gastroenterology.
ALT is an enzyme released by injured or dying liver cells. When ALT levels rise above normal, doctors know liver damage is occurring. Recently, researchers have lowered what is considered to be “healthy” ALT levels in adults from about 50 IU/L to 30 IU/L for men and 19 IU/L for women. But to date, 50 IU/L has been used as upper normal for children.
Researchers affiliated with the San Diego School of Medicine sampled pediatric ALT levels from national health agencies and found that average ALT levels in 1,000 healthy children was 22 IU/L for girls and 25 IU/L for boys. However, most children’s hospitals in the U.S. continue to use 50 IU/L as the healthy upper ALT range for children.
The researchers compared children with normal livers and those with liver damage from HBV and hepatitis C virus (HCV) infection, to see which ones would be identified as having liver damage by the 50 IU/L ALT assessment and the new, lower ALT scores.
They reported that only one-third to one-half of children with chronic liver disease would be detected by the current tests that use the 50 IU/L levels. In addition to failing to identify children with liver damage, the high ALT levels are currently used by pharmaceutical companies when conducting clinical trials on new drugs, which may result in misleading information. Also, medical organizations currently use the 50 IU/L to indicate when liver damage is occurring in pediatric patients and treatment is needed.
The researchers called for more research in order to accurately establish “healthy” ALT levels in children in order to guide treatment and medical research decisions.
Hepatitis B Vaccine Effectively Protects Against Infection Over 20 Years
For how long does hepatitis B immunization, when administered at birth, protect against infection? Thai researchers followed 222 infants born to hepatitis B-infected mothers who were vaccinated at birth with the required recombinant hepatitis B vaccine series, over 20 years. One hundred of the vaccinated infants also received a booster dose at age 5.
Over the next 20 years, the individuals were followed with a focus on the hepatitis B core antigen and antibody. When vaccinated, only the surface antigen is injected in order to spur production of surface antibodies, which are usually the only HBV antibodies present in vaccinated individuals. When the core antigen or antibody is present, it means the person was also exposed to the virus.
None of the subjects acquired an active acute or chronic HBV infection. However, during the first decade, 12.2 percent developed core antibodies—meaning they had been exposed to the virus and fought off infection. All of these youth were born to mothers who tested positive for HBsAg and HBeAg, which usually indicates a high viral load.
During the second decade, HBV infections were detected in 12.8% of subjects born to both HBeAg-positive and -negative mothers. Increases in surface antibodies unrelated to additional HBV vaccination or infection were detected in approximately 10% of subjects.
Researchers , writing in the April issue of the Journal of Viral Hepatitis, concluded that immunization at birth with a recombinant hepatitis B vaccine, “confers long-term protection against clinical disease and new chronic hepatitis B infection despite confirmed hepatitis B exposure.”
Antiviral Entecavir Proves Effective in Previously-Untreated Patients
Japanese researchers evaluated the effectiveness of entecavir (Baraclude) at varying doses in 167 HBV-infected adults who were treated with daily doses of 0.01mg, 0.1mg or 0.5mg for 24 to 52 weeks, and then treated with 0.5mg daily doses for several more months. None of the patients had been treated with an antiviral previously.
After an average 96 weeks of entecavir treatment, 88% of patients had undetectable HBV-DNA, 26% achieved HBeAg seroconversion, and 90.1% had normal ALT rates.
After three years, 3.3% of patients had developed viral resistance to the drug. The researchers, writing in the March 2010 issue of the Journal of Hepatology, reported that long-term entecavir treatment produced high rates of viral control and reduced liver damage.
- In a different study, Chinese researchers, writing in the Journal of Viral Hepatitis, also found entecavir to be highly effective in 160 patients who took the antiviral for 144 weeks. Of the patients, 89% achieved undetectable HBV DNA, 86% had normal ALT levels, 20% reported HBeAg loss and 8% had HBeAg seroconversion.
- Another entecavir-related study found that the antiviral worked well in patients who developed resistance to the antiviral adefovir (Hepsera), but it is not effective in patients who have developed lamivudine resistance, according to a European study published in the April 2010 Journal of Hepatology. Those lamivudine-resistant patients who developed resistance to entecavir, however, were effectively treated with the antiviral tenofovir (Viread).
“Entecavir should not be used in patients with previous lamivudine resistance, yet it may still be an option in lamivudine-experienced patients in case lamivudine resistance never developed,” researchers noted.
More Studies Needed to Assess if Needle-Exchange Programs Really Work
Needle-exchange programs designed to decrease transmission of HBV, HCV, and HIV among injecting drug users to date have shown little impact on lowering transmission of blood-borne infections, according to a review of studies by United Kingdom researchers in the March 2010 issue of Addiction.
Needle-exchange programs are controversial, with opponents arguing that they sustain people's addictions and promote drug use, so supporters are eager for studies that confirm their effectiveness in preventing new infections. Recently, the U.S. repealed a ban on federal funding for needle-exchange programs.
One World Health Organization report, which reviewed several studies, concluded there is “compelling evidence” for these programs. But U.K. researchers reported that several of the studies that WHO focused on had weaknesses that compromise their findings. The research team found the evidence supporting the programs was “modest.” When it came to hepatitis C, researchers found there was insufficient evidence to say whether the programs were effective or not.
This remains a difficult issue to examine scientifically. Many of the needle-exchange programs studied had strict limits on the number of syringes and needles distributed, so while they might have reduced users' needle sharing and reuse, they might not have been adequate. It is also not known what amount of injecting equipment given to clients actually results in lower infection rates.
“The main public health implications of the findings are that a higher level of coverage of interventions, including (needle and syringe programs), is likely required to reduce blood-borne virus transmission,” researchers noted.
HBeAg Seroconversion from Interferon Is Sustained Years after Treatment Ends
Approximately 30% to 40% of patients with HBeAg-positive hepatitis B treated with pegylated interferon achieve HBeAg seroconversion within six months after treatment ends.
The “durability” of this seroconversion was studied in 85 HBeAg-positive patients who were treated with peginterferon alfa-2b 1.5 mug/kg/week for 32 weeks and lamivudine for 52 or 104 weeks and followed for about six years.
Twenty-five (29%) of all patients retained the “e” antibody and undetectable HBV DNA after five years. The rate of HBeAg seroconversion rose progressively from 37% at the end of treatment to 60% at 5 years.
Among those who responded by the end of treatment, 82% and 57% and sustained HBeAg seroconversion and virologic response at 5 years. Only two patients of the 85 patients had advanced fibrosis after five years.
Indicators of successful treatment included viral load status at Week 16 of treatment, whether they seroconverted and had undetectable HBV DNA at the end of treatment.
The addition or duration of lamivudine treatment had no impact on any long-term response, according to the report by Hong Kong researchers published in Hepatology.
Many Substance Abuse Treatment Centers Don't Offer Viral Hepatitis Screening
Fewer than half of all substance abuse treatment facilities surveyed nationwide reported that they conduct on-site infectious disease screening, according to a new study sponsored by the Substance Abuse and Mental Health Services Administration (SAMHSA).
Rates of HIV, tuberculosis, sexually transmitted diseases, hepatitis B and C are high among drug users. This study was based on data from the 2007 National Survey of Substance Abuse Treatment Services (N-SSATS), an annual census of all known facilities in the United States, both public and private, that provide substance abuse treatment.
The facilities that were most likely to provide infectious disease screening were operated by the federal government, followed by a state government. More than half of the approximately 1,100 treatment programs provided on-site screening for hepatitis B (62.1 percent), hepatitis C (64.1 percent), HIV (69.8 percent), sexually transmitted diseases (67.8 percent), or tuberculosis (93.3 percent).
Facilities that provided hospital inpatient treatment were more likely than facilities providing outpatient or non-hospital residential treatment to offer screening for hepatitis B. Where available, the most common types of on-site screening were for tuberculosis, (34.3 percent), and HIV (29.7 percent).
Operating-room Needlesticks and Sharps Injuries Rise Despite Efforts to Reduce Them
After passage of the Needlestick Safety and Prevention Act of 2000, hospitals' injury rates dropped 31.6% in nonsurgical areas but have increased 6.5% in surgical settings, according to a report in the April issue of the Journal of the American College of Surgeons.
Suture needles appear to be the major culprit, with most injuries occurring when the needles are used or passed between providers. This risk prevents HBV-infected providers from performing surgical practices and places surgeons and nurses at risk when patients are infected.
The results suggest surgical teams have been unresponsive to implementing occupational safety measures despite their high risk. The law required health care employers to provide safety-engineered needles and sharp instruments designed to reduce risk, and it applied equally across hospital settings.
The reason for the increase in operating room injuries is unclear since there have been a number of changes in surgery, including greater use of less risky laparoscopic techniques and more outpatient procedures.
But the surgical culture of resistance to change and the poorly safety-designed devices available for surgery until recently may be reasons that surgery hasn't kept up with other surgical settings in injury reduction.
In the operating room, just three devices account for most injuries: suture needles (43.4%), scalpel blades (17.1%), and disposable syringes (12.1%). Focusing on suture needles may present the greatest opportunity for improving operating room safety, researchers wrote.
Substituting blunt suture needles for sharp ones when suturing less-dense tissues could reduce the injury rate by 29.2%, researchers suggested, based on a prior study's finding of 59% reduced risk with blunt suture needles.
Longer Period of Interferon Treatment Needed for HBV Genotype D Patients
Treating patients who have HBeAg-negative hepatitis B, genotype D, with pegylated interferon for twice as long as is currently recommended produced vastly better results than treating them for just the currently-recommended 48 weeks, according to a report presented by Italian researchers at the 45th Annual Meeting of the European Association for the Study of the Liver, held in April in Vienna.
The findings are important because to date patients with genotype D have not responded well to interferon, and are often not considered candidates for this treatment.
While both groups had similar responses when their treatments ended, one year later 29% of 52 genotype D patients treated for 96 weeks had undetectable HBV DNA, compared to 12% of 51 genotype D patients treated for 48 weeks. Additionally, 6% of the longer-treated patients cleared HBsAg. Both groups had similar rates of normal ALT levels at the end of treatment.
Researchers Find Tenofovir Effective for Adefovir- and Lamivudine-Resistant HBV
Another round of research into how lamivudine- and adefovir-resistant patients fare when treated with tenofovir found the antiviral to be highly effective in those patient groups, according to a report released at the European Association for the Study of the Liver conference.
The majority of patients achieved undetectable HBV DNA at the following rates:
- 75% of 141 patients with no mutations responded to tenofovir with undetectable viral load and normal ALT rates.
- 83% of 12 patients with adefovir resistance responded to tenofovir.
- 86% of 7 patients with lamivudine resistance mutations responded.
- The number of HBeAg-positive patients experiencing HBeAg seroconversion increased after two years of tenofovir treatment.
Current Liver Transplant Allocation System Leaves Women at a Disadvantage
Women with end-stage liver disease in need of liver transplantation are less likely to get liver transplants and are more likely to die while awaiting transplants, according to a report presented at the European Association for the Study of the Liver conference.
The researchers suggest that the current transplant allocation system needs to be re-examined and refined to reduce gender disparities.
Women awaiting transplants tended to have lower serum creatinine (SCr) values, due to smaller size and muscle mass, despite worse renal (kidney) function when placed on the waiting list. As a result, they were not considered to be at high risk of death and were not placed at the top of the wait list. Consequently, they were significantly less likely to undergo transplantation and had higher death rates after three months on the list,
In earlier studies, 65% of cirrhotic women had increases in their transplant ranks when their SCr values were corrected for gender.
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