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HBV Journal Review
August 1, 2011, Vol 8, no 8
by Christine M. Kukka
Flares during Antiviral Treatment Rarely Lead to Viral Clearance
A team of Dutch and Chinese researchers followed 227 patients, who were treated with antivirals to see what impact flares—marked by sudden rises in viral load (HBV DNA) and/or increases in liver damage—had on these patients.
They wanted to see if flares showed that the patients’ immune systems were fighting the infection and whether they resulted in clearance or suppression of the hepatitis B virus (HBV) infection. When the immune system battles HBV infection, it attacks the infected liver cells, and alanine aminotransferase (ALT) levels rise, indicating that liver cells are damaged or dying.
Unfortunately, they discovered that flares that occur during or after antiviral treatment almost never lead to improvement, and they sometimes resulted in severe liver damage.
According to the report published in the July issue of the Journal of Viral Hepatitis, researchers documented 27 flares over a total of 9,779 antiviral treatment months. The rate was about 3.2% per 100 person years.
Patients treated with lamivudine (Epivir-HBV), which has a high rate of drug resistance, had the most flares (4.9 per 100 person years). When drug resistance occurs, HBV that have mutated so that they can “resist” the antiviral are able to replicate freely, and viral loads rebound. Twenty (74%) of 27 flares that occurred during treatment were due to development of lamivudine-resistance.
Seventeen flares occurred after patients stopped taking an antiviral.
No flares were documented in patients who switched to a new antiviral, with lower rates of drug resistance, when their first antiviral appeared not to be effective in suppressing the virus.
None of the flares led to clearance of the infection. Seven flares resulted in severe (decompensated) liver disease.
Liver Cancer Rates Increase as Hepatitis-Infected Populations Age
Australian researchers followed liver cancer rates between 1992 and 2007 to see what impact immunization against hepatitis B and other health care initiatives had on the cancer rates resulting from HBV and hepatitis C virus (HCV) infections.
They reported in the Journal of Viral Hepatitis that between 1992 and 2007, of 1,201 people with liver cancer, 556 had HBV infection, 592 had hepatitis C, 45 were coinfected with HBV and HCV, and 8 also had HIV co-infection.
They found a minor decline in liver cancer rates, from 148 in 1995 to 101 in 2007, among the HBV-infected group, but they noted a significant increase in cancer rates from 75 to 152 in the HCV-infected group.
Researchers noted that despite declines in the age-adjusted incidence rates of liver cancer, the actual number of cases increased due to the aging of the infected population and an increasing prevalence of both hepatitis B and C in Australia.
Most HBeAg-Negative Patients with Normal ALTs and High Viral Loads Have Fibrosis
Another study has found that even people with no signs of liver damage (with normal ALT levels) can still have significant fibrosis from hepatitis B, and that viral load may be the truer indicator of liver damage among people who have hepatitis B e antigen-negative (HBeAg) hepatitis B.
Researchers compared 203 HBeAg-negative patients who had a viral load of 20,000 IU/mL or higher with a group who had lower viral loads. Liver biopsies, in which a small slice of liver tissue is examined for fibrosis, were conducted on all of them.
The patients were divided into four groups:
- Group I had HBV DNA levels exceeding 20,000 IU/mL and persistently high ALT levels, which indicates dying or damaged liver cells. Fibrosis was detected in 72.7% of them.
- Group 2 had HBV DNA levels exceeding 20,000 IU/mL and normal ALT levels, appearing to indicate no liver damage. Fibrosis was detected in 52.9%.
- Group 3 had HBV DNA levels less than 20,000 IU/mL and elevated ALT levels. Fibrosis was detected in 57.5%.
- And Group 4 had HBV DNA levels less than 20,000 IU/mL and normal ALT levels. This group had a fibrosis rate of only 18.9%.
Researchers, reporting in the Journal of Viral Hepatitis, concluded that significant fibrosis was present in a large percentage of HBeAg-negtive patients with viral loads that exceeded 20,000 IU/mL even when they had normal ALT levels. Most of the patients had HBV strain or genotype D.
Only the combination of normal ALTs and low viral load could safely predict a low risk of fibrosis, they concluded.
In a separate article in the same issue, Japanese researchers reported monitoring 104 HBeAg-negative patients with persistently normal ALTs to see what impact their viral load had on their liver health.
During the sixth year of the study, 5 patients (4.8%) had liver cancer and 14 (13.5%) had reactivation of their hepatitis—marked by increased viral load and ALT levels. At year 10, the liver cancer rate was 13.7% and the hepatitis infection reactivation rate was 15.5% in this group.
Patients with high HBV DNA levels, exceeding 100,000 IU/mL, were at most risk of cancer and infection reactivation. Surprisingly, ALT levels appeared to play no role in predicting who was at risk of liver damage.
Researchers noted that HBV DNA levels did not appear to change dramatically over the years, and their levels at the beginning of the study served as a predictor of who would develop cancer and liver damage.
“As the baseline HBV DNA level reflects the future level (of the patient’s viral load), appropriate clinical management (based on the patient’s) viral level is expected to decrease future risk,” they wrote.
Pregnant Women Infected with Hepatitis Face More Risks during Delivery
A research team found that women infected with HBV or HCV face more risks during delivery.
The researchers assessed gestational diabetes mellitus, premature births, intrauterine growth restriction (IUGR), pre-eclampsia, hemorrhaging, cholestasis (when bile flowing from the liver is blocked), and caesarian delivery in the Nationwide Inpatient Sample from 1995 to 2005 in the U.S. that followed 1,446 women infected with both or either virus.
Women with HBV had an increased risk for premature delivery, but a decreased risk for caesarean delivery. Individuals with both HBV and HCV co-infection had an increased risk for hemorrhaging following birth. There was no link between viral hepatitis with IUGR or pre-eclampsia.
“Women with hepatitis have an increased risk for complications during pregnancy,” researchers reported in the July Journal of Viral Hepatitis. They recommended counseling infected women about potential risks.
Antiviral Telbivudine Safe in Preventing Mother-to-Child HBV Infection
The antiviral telbivudine (Tyzeka) appears safe to use in HBV-infected pregnant women, who have high viral loads to prevent them from infecting their newborns.
Chinese researchers, writing in the Journal of Hepatology, reported treating pregnant women with 600 mg daily doses of telbivudine starting at pregnancy week 20 until birth. The women were all HBeAg-positive with high viral loads. Women with high viral loads have a much higher rate of transmitting hepatitis B to their newborns, even when the infants are immediately immunized and injected with hepatitis B immune globulin (HBIG), which contains hepatitis B antibodies.
Telbivudine treatment during pregnancy resulted in a marked reduction in HBV DNA and HBeAg levels in the women.
Forty-four (33%) of the 135 telbivudine-treated mothers had undetectable viral loads at time of delivery, while none of the untreated women had undetectable HBV DNA.
Seven months after delivery, none of the babies born to telbivudine-treated mothers had HBV infection, while 8% of infants born to untreated mothers became infected.
There were no adverse effects reported to either mothers or their infants from the telbivudine treatment.
What Happens if a Newborn’s Parents Refuse the Hepatitis B Vaccine?
A clinical ethics advisory committee explored medical risks to infants born to HBV-infected mothers when the parents refuse to allow the newborn to be vaccinated.
Writing in the June 29, 2011 issue of Vaccine, the researchers recounted the high risk of infection posed to newborns of infected mothers.
After birth, a 12-hour window of opportunity exists to immunize the newborn and also treat the child with HBIG to reduce the risk of infection.
- If the mother is HBeAg-positive, the infant faces a 75.2% risk of becoming infected. This is reduced to 6% when the vaccine and HBIG are administered at birth.
- If the mother is HBsAg-positive but HBeAg-negative, the transmission risk is 10.3%, which is reduced to 1% by giving the vaccine and HBIG.
“If the vaccine is accepted but HBIG is refused, as for example by some Jehovah's Witnesses, the risk to babies (born to) HBeAg-positive mothers is reduced to 21% and to babies of HBeAg-negative mothers to 2.6%.
“These figures can be used to inform parents and as a possible basis for child protection proceedings if parents decline vaccine and/or HBIG,” the Australian researchers wrote. “We argue from the perspective of the best interests of the child that the severity of the condition justifies initiating child protection proceedings whenever a baby is born to a hepatitis B carrier mother and, despite concerted attempts to persuade them, the parents refuse vaccine and/or HBIG.”
How Long Is Antiviral Treatment Needed Before Patients Clear the Virus?
Dutch researchers created a theoretical model to predict how long antiviral treatment would be needed before patients could finally clear the infection and loose the hepatitis B surface antigen (HBsAg). The surface antigen is the last antigen to disappear when the body clears the infection.
They followed 75 patients who responded successfully to treatment using the antivirals entecavir (Baraclude) and tenofovir (Viread) over several years.
Researchers noted that HBsAg decline was most pronounced in patients who were HBeAg-positive when they started treatment.
Age, ALT levels, and HBeAg loss were all linked to marked declines in HBsAg.
Based on the data, researchers extrapolated that it would take on average 36 years for HBeAg-positive patients to lose HBsAg, and 39 years for HBeAg-negative patients to lose HBsAg as a result of antiviral treatment.
“Thus, most patients treated with entecavir and tenofovir will probably need decades of therapy to achieve HBsAg loss,” they wrote in the Journal of Infectious Diseases.
Researchers Document the Spread of Hepatitis B Following Explosion
For the first time, researchers tracked transmission of HBV among people exposed to blood during a ship explosion that caused numerous casualties. HBV is easily transmitted through exposure to blood, and is 50- to 100-times more infectious than HIV.
According to a report in the Journal of Infectious Diseases, in 2009, a boat carrying 49 exploded off Australia. Twenty-three people suffered significant burns and were transferred to Royal Perth Hospital in Perth.
One of the patients was chronically infected with HBV. Over the following months, three other patients were diagnosed with acute hepatitis B—indicating new infections—and an additional four patients showed they had recently been exposed to HBV.
Molecular testing found that the HBV strain from the original HBV patient was similar in the other cases. Researchers suggest that transmission occurred at or around the time of the boat explosion.
This is the first report of confirmed transmission of HBV following a disaster, and it underscores the importance of treating all people who have potentially been exposed to HBV during a disaster with HBIG, to prevent infection.
Liver Cancer Stem Cells with High Levels of CD24 Resist Treatment
Some virulent cancerous liver tumors are embedded with a “super cancer stem cell” that makes them resistant to chemotherapy and allows them to spread to other body parts and even stage a comeback after tumors are removed, according to a report in the journal Cell Stem Cell.
These stem cells have a unique surface protein called CD24 and patients with high levels of CD24 in liver cancers have poor survival rates. CD24 apparently activates a protein in the cell called STAT3 that goes into the nuclei of cells and helps them form tumors, spread, and resist chemotherapy.
If researchers develop a way to inhibit STAT3, they will be able to block the function of cancer stem cells.
Stem cells are found throughout the body and are special because they can transform into different cell types and multiply.
In their experiment, researchers searched human liver cancer cells and found that those with high concentrations of CD24 had a 67% chance of cancer recurrence in the first year after surgical removal of tumors, compared to a 21% recurrence in those whose tumors had low CD24 counts.
Those with high CD24 count had a 80% chance of their cancer spreading to other body parts, compared to 32% chance of spreading in patients with low D24 count.
Researchers Find Hepatitis B Vaccination Inadequate Among U.S. Health Care Students
A study in the August issue of Infection Control and Hospital Epidemiology finds that hepatitis B immunization of health care students is falling short of current recommendations.
Health care workers are at high risk of becoming infected if they are exposed to blood or body fluids containing HBV.
U.S. Centers for Disease Control and Prevention researchers analyzed hepatitis B immunization records of 4,075 health care students at one university between 2000 and 2010 and found that only 59.8% had received all three of the recommended hepatitis B vaccine series.
They also found that only 83.8% of those vaccinated were protected against hepatitis B infection when tested for antibodies, which was below the recommended vaccine coverage rate of 90%. Vaccine booster shots are recommended when hepatitis B antibodies are not adequate following immunization to confer protection against the virus.
The study also found that very few of these students had been vaccinated during their childhood, despite national medical recommendations in place at the time. The majority of these students with documented vaccination were only recently vaccinated, either during or a few years prior to attending college.
More Than Two-Thirds of Injecting Drug Users Exposed to Hepatitis B and C
The first study to assess hepatitis B and C infection worldwide among injection drug users found that two-thirds have been exposed to HCV, while HBV rates vary from country to country. Researchers examined HCV data from 77 countries and HBV data from 59 countries.
HCV infection rates among drug users ranged from 60% to 80% in 25 countries, including United States (73%), China (67%) and Canada (64%). Twelve nations had infection rates exceeding 80%, including Mexico with a 97% HCV infection rate.
While HBV is more easily transmitted through body fluids than HCV, due to higher concentrations of viruses, hepatitis B rates were lower among drug users globally, perhaps due to immunization. There is no vaccine that protects against hepatitis C.
Hepatitis B ranged from 5% to 10% in 21 countries, and exceeded 10% in 10 countries, including 12% for the United States. Vietnam had the highest rate (20%), followed by Estonia (19%), Saudi Arabia (18%), and Taiwan (17%).
Worldwide, an estimated 10 million drug users have HCV and 1.2 million have HBV.
In the report published in The Lancet, the Australian researchers urged public health officials to increase awareness of how HBV and HCV are transmitted to prevent these costly, blood-borne infections.
Hepatitis A and B Vaccinations of People with Liver Disease and Diabetes Far Below Recommendations
In a related report published in the July issue of Hepatology, U.S. researchers found that immunization against hepatitis A and B among adults with other liver diseases and diabetes was also inadequate.
Medical guidelines recommend all people with hepatitis C, and non-alcoholic fatty liver disease, and other liver diseases be vaccinated against hepatitis A and B to protect their livers from additional injury. But data from the National Health and Nutrition Examination Surveys conducted in 1999-2008 showed that hepatitis A vaccination in people with liver disease increased from 13.3% to 20% during that time period and hepatitis B immunizations increased from 23.4% to 32.1%.
While the rates are increasing, they remain low, researchers noted. “Given the public health implications of acute hepatitis A and hepatitis B in patients with chronic liver disease, better implementation of the vaccination recommendations for these populations is warranted.”
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