HBV Journal Review
July 1, 2012, Vol 9, no 7
by Christine M. Kukka
In the U.S., Many with Hepatitis B Lack Health Insurance
A lack of health insurance prevents many U.S. residents who are infected with the hepatitis B virus (HBV) from getting the screening, monitoring, and treatment that they need to prevent liver disease, according to an advocacy brief published by the National Viral Hepatitis Roundtable.
According to a June 2012 analysis of uninsured Americans by Health Management Associates, people with HBV are less likely to have health insurance than the general population. As a result, they miss out on care that could lessen the impact and spread of the disease.
According to the study, provisions in the Affordable Care Act that are scheduled to take effect in 2014 will extend health insurance coverage to up to 70% of people diagnosed with HBV who now lack insurance--providing coverage to nearly 150,000 HBV-infected Americans.
Over a 20-year period, the HMA projects that increases in access to health coverage could lead to a 20% reduction in premature HBV-related deaths and a 58% reduction in the need for HBV-related liver transplants.
Cost savings from liver transplants could be reinvested in HBV screening, with each 5% reduction in transplantation financing more than 420,000 screenings.
Psoriasis Treatment Can Reactivate Hepatitis B
Hepatitis B patients who have psoriasis run the risk of reactivating their viral hepatitis if they are treated with tumor necrosis factor-alpha inhibitory agents such as etanercept, adalimumab and infliximab.
Autoimmune diseases, which can cause inflammation including the skin irritation psoriasis, can be subdued by drugs that inhibit tumor necrosis factor. However, these same medications that inhibit the immune system's inflammatory response often allow HBV DNA to rebound as the immune system lets down its guard. Liver damage can recur, even in people who have inactive hepatitis B infections.
Baylor University Medical Center researchers reviewed all available studies involving hepatitis B and tumor necrosis factor inhibitors and found that these drugs indeed can trigger a resurgence in hepatitis B, even when patients test negative for the hepatitis B surface antigen HBsAg), and appear to have a resolved infection.
"Infliximab has been associated with more reactivation cases than the other two agents and fatalities have been reported with this agent," Baylor researchers wrote in the June issue of the Journal of the American Academy of Dermatology.
Researchers suggest careful screening of patients before initiating this psoriasis treatment and use of antiviral treatment if tumor necrosis factor agents are used.
Screening Everyone for Hepatitis B Before Chemotherapy Is Cost-effective
Screening every patient before beginning chemotherapy for lymphoma (cancer of the lymph system) is the most cost-effective approach to preventing accidental reactivation of hepatitis B, according to a report published in the Journal of Clinical Oncology.
University of Toronto researchers developed three models to assess the cost of screening lymphoma cancer patients for HBV prior to chemotherapy. Chemotherapy suppresses the immune system and people with active or inactive HBV infection can experienced a life-threatening reactivation of infection when treated with chemotherapy.
Researchers compared screening all patients for HBsAg (which indicates a current infection), screening only patients considered at high risk for hepatitis B (using ethnicity, sexual history etc. as criteria), or screening none of the patients, with the expectation that those whose HBV reactivates will be treated with antivirals.
The screen-all-patient strategy cost $32,589 (Canadian), the screen those reportedly at risk was $32,598, and the cost of screening no one was $32,657.
Screening everyone, while providing a slight economic edge, also delivered the highest one-year survival rate for patients (84.99%), compared to the other options (84.96% and 84.86%).
"In patients receiving (chemotherapy) for lymphoma, screening all patients for HBV reduces the rate of HBV reactivation (10-fold) and is less costly than screening only high-risk patients or screening no patients," the authors wrote.
Which Backup Drugs Should Be Used When Antiviral Resistance Develops?
Antivirals–drugs that attack viral DNA so HBV cannot reproduce easily–have now been used for more than a decade to suppress HBV reproduction and reduce liver damage.
The downside to these drugs is that HBV mutate rapidly and over time are able to "resist" some of these antivirals within months or years.
For example, it only takes one or a few mutations in HBV for the antivirals lamivudine (Epivir-HBV), adefovir (Hepsera), or telbivudine (Tyzeka) to stop working effectively. More encouraging, it requires numerous mutations in HBV before the newer antivirals–tenofovir (Viread) and entecavir (Baraclude)–lose their effectiveness.
Because many patients have developed resistance to lamivudine and adefovir, researchers are trying to find the best back-up antiviral or antiviral combination to help them when their treatment loses effectiveness. What follows are some recent recommendations and findings in medical journals:
- Best treatment for lamivudine resistance? Chinese researchers, reporting in the June issue of Internal Medicine, compared the effectiveness of adefovir alone, adefovir plus lamivudine, and adefovir plus entecavir in 91 lamivudine-resistant patients over 24 months. The adefovir-entecavir combination produced the most significant declines in HBV DNA, with 78% achieving undetectable viral load after six months of treatment.
- AASLD and EASL guidelines: However, the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) recommend switching lamivudine-resistant patients to tenofovir or adding adefovir to ongoing lamivudine treatment. Researchers note that replacing lamivudine with entecavir has not proven highly effective.
- Treating lamivudine-resistant children: Korean researchers, writing in the Journal of Pediatric Gastroenterology and Nutrition, reported on a 24-week study where 27 lamivudine-resistant children and adolescents were treated with either adefovir, adefovir and lamivudine, or just entecavir. Children treated with the lamivudine-adefovir combination or with just entecavir responded better than receiving only adefovir.
- Treatment for adefovir resistance: AASLD suggests adding either lamivudine or entecavir to ongoing adefovir treatment, or switching to a combination of tenofovir and emtricitabine. In contrast, EASL guidelines recommend a swap to either entecavir or tenofovir if the patient has only been treated with adefovir. If the patient had lamivudine resistance prior to their adefovir treatment, EASL recommends switching to tenofovir plus another antiviral.
- Telbivudine resistance treatment: AASLD recommends adding tenofovir or adefovir to telbivudine, or switching to tenofovir plus emtricitabine. EASL suggests switching to or adding tenofovir, or adding adefovir to ongoing telbivudine treatment if tenofovir is not available.
- Entecavir resistance: AASLD says to switch to tenofovir or tenofovir plus emtricitabine. EASL agrees to adding or switching solely to tenofovir, or adding adefovir to ongoing treatment if tenofovir is not availble.
- Tenofovir resistance: To date, there has been no viral resistance identified in patients treated with tenofovir for more than five years, so AASLD has no recommendations. However, EASL suggests adding any of the other available antivirals if resistance ever occurs.
Most Infected at Birth Lost HBeAg during the Second and Third Decades of Life
How long does it take children infected with HBV at birth to finally lose the hepatitis B e antigen (HBeAg), develop "e" antibodies, which usually results in the much sought-after lower, healthier viral load?
Iranian researchers followed 139 HBeAg-positive children over nearly two decades to see when children seroconverted (losing HBeAg and developing "e" antibodies). Most of the children in the study were infected despite being immunized and treated with hepatitis B immune globulin (HBIG) at birth. Others had never been immunized.
Every six months, the participants' HBsAg, HBeAg, surface antibodies and "e" antibodies were tested. Over the 19-year study period, 82 (59%) of the children seroconverted and developed "e" antibodies, according to the study published in the June issue of the Journal of Clinical Virology.
The seroconversion rates were 25% in the first decade, of those remaining 63.4% seroconverted during the second decade, and 70.5% seroconverted in the third decade. Children born to mothers who were HBeAg-negative had higher seroconversion rate than those born to HBeAg-positive mothers (75% vs. 33.9%). Children who received the hepatitis B vaccine and HBIG seroconverted earlier than those who had not been immunized.
Study Explores When It May Be Safe to Stop Adefovir
Researchers followed 33 HBeAg-negative patients who had undetectable viral load and normal alanine aminotransferase (ALT) levels (indicating no liver damage) for nearly six years after they stopped taking adefovir to see what happened. The patients had been taking adefovir for a long period–about five years.
During the first few months after stopping adefovir, all patients experienced a resurgence in their HBV DNA and 25 (76%) had marked increases in viral load. But during the six-year follow-up period, 18 patients (55%) achieved sustained levels of low viral load and persistently normal ALT levels.
Among this group, 13 (72%) even cleared HBsAg. Fifteen patients (45%) who had a marked rebound in their viral load were retreated with antivirals (11 during the first 18 months and four after the third year), without evidence of liver damage. Only one lost HBsAg.
Study participants who had higher ALT levels before treatment began and after treatment stopped (indicating an active immune response to the infection) had higher rates of HBsAg clearance after treatment stopped.
"In HBeAg-negative patients ... it is safe and effective to discontinue adefovir therapy after four or five years;" researchers wrote in the journal Gastroenterology, "55% of patients have sustained responses and 39% lose HBsAg."
Only Half of Birthing Clinic Nurses Educate Mothers About Their HBV Infection
Researchers assessed how well 518 nurses in eight birthing hospitals in Santa Clara County, California–where hepatitis B prevalence is among the highest in the nation–provided information about HBV to infected mothers.
Sadly, few of the nurses surveyed between 2008 and 2010 provided education information about hepatitis B infection, prevention, monitoring and treatment to new mothers.
According to the report in the June issue of the Journal of Obstetrical and Gynecological Neonatal Nursing, 80% of nurses had provided care to a pregnant woman with chronic hepatitis B, but only 51% routinely provided patients with educational information about hepatitis B. While 75% routinely informed patients about effective methods to prevent mother-to- child transmission, only a small minority (17-34%) educated infected women about how they could protect themselves from liver disease through monitoring and treatment, and prevent infecting other household members.
Fewer than 25% correctly answered most questions about hepatitis B prevalence, risks, and symptoms. However, after educational seminars, knowledge increased significantly.
The knowledge gap researchers found in these nurses, who can play a pivotal in educating new mothers, "represents a noteworthy gap and an opportunity for targeted training and education to improve perinatal hepatitis B prevention and medical management of infected mothers," they wrote.
Immunization in Taiwan Comes Close to Eradicating Hepatitis B
Every five years, since universal infant immunization for hepatitis B began in Taiwan in 1984, researchers have surveyed its youth to measure the decline of HBV infection in Taiwan.
In 1984, Taiwanese children had a 10% chronic infection rate. Twenty-five years after the vaccine was mandated at birth to stop mother-to-child infection, the chronic infection rate has dropped to 0.9% in those younger than age 30, according to the report in the Journal of Hepatology.
In this latest study, researcher screened 3,332 youth under age 30 (representing all ages) to assess the decline of HBV infection. In addition to the low levels of active infection, they found only 7% of the study population tested positive for the hepatitis B core antibody, indicating a past infection. Back in 1984, 28% of this population had at some time been infected with hepatitis B (with most clearing the infection.)
"The continued decrease in HBsAg prevalence (chronic infection) suggests that the elimination of HBV infection is becoming a reality," researchers wrote.
96% of Patients Treated with Entecavir for Four Years Achieve Undetectable HBV DNA
Japanese researchers followed 474 HBeAg-negative and -positive patients who were treated for four years with entecavir and found that by the fourth year:
- 96% achieved undetectable HBV DNA
- 42% cleared HBeAg and developed "e" antibodies
- And 84% had normal ALT levels, indicating no liver damage from the infection.
According to the report in the Journal of Hepatology, only five of the 474 patients did not respond to entecavir, with two (0.4%) developing resistance to the antiviral.
Entecavir-Tenofovir Combination Generates Few Treatment Advantages
University of Michigan researchers tried treating 379 patients with just entecavir or a combination of entecavir plus tenofovir for 100 weeks to see if the drug combination was more powerful or effective than entecavir alone. These two antivirals are considered among the best and most effective of all available antivirals currently.
The study group included 264 HBeAg-positive patients and 115 HBeAg-negative patients--none of whom had been treated previously.
Both treatment groups had similar success in achieving undetectable HBV DNA (83.2% vs. 76.4%).
Among HBeAg-positive patients, those receiving the drug combination therapy achieved slightly higher levels of undetectable HBV DNA than those receiving just entecavir (80.4% vs. 69.8%). However, this advantage was seen only in patients who had high viral loads when they began treatment, not in HBeAg-positive patients with lower viral loads.
Rates of HBeAg loss and seroconversion were similar in both groups, however more patients in the entecavir-only group achieved normal ALT rates.
None of the patients in the study developed viral resistance.
"The combination therapy could provide an incremental benefit to HBeAg-positive patients," with high HBV DNA levels, researchers noted in their report in the journal Gastroenterology.
Study of Medical Students Shows Immunization Remains Effective
Researchers from the U.S. Centers for Disease Control and Prevention screened 2,481 medical, dentistry and other health care graduate students who had received all three hepatitis B vaccine doses during childhood or adolescence to see if they remained protected against the infection.
Most in the study were women (64.6%), U.S.-born (85.6%), and white (63.2%), and the majority had been immunized during adolescence (age 14).
About 93% had surface antibody levels exceeding 10 IU/L, which confirms protection against infection. (The vaccine contains only HBsAg, to spur creation of surface antibodies.)
However, students who were younger when they were immunized (with more years passing since vaccination) had lower surface antibody levels.
Ninety-eight percent of students who had less than 10 IU/L of antibodies quickly generated the adequate number of protective antibodies after receiving one booster shot of the vaccine, according to the report published in the July issues of the journal, Infection Control & Hospital Epidemiology.
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