HBV Journal Review
February 1, 2015, Vol 12, no 2
by Christine M. Kukka
Quality of Care for Women with Hepatitis B Varies Dramatically Across U.S.
A U.S. Centers for Disease Control and Prevention study, published in the journal Infectious Diseases in Obstetrics and Gynecology, found a large discrepancy in medical treatment for women with hepatitis B-related liver disease.
While scientific evidence shows antivirals are safe in pregnant women and effectively lower the risk of mother-to-child infection, American doctors prescribed antivirals to only 12.6% of pregnant women infected with the hepatitis B virus (HBV). In contrast, they prescribed antivirals to 20% of non-pregnant women.
The important study examined prescription records of 17 million, privately-insured women in 2011. Researchers identified 6,274 women in the study group who were HBV-infected and examined what drugs were prescribed to treat their liver disease.
Pregnant women were most commonly prescribed the antivirals tenofovir (Viread) (73.4%) and lamivudine (Epivir-HBV) (21.9%). The high rate of lamivudine usage is surprising–lamivudine has a high rate of drug resistance and is no longer recommended as a first-line treatment for any patient.
Currently tenofovir and entecavir (Baraclude) are the top two recommended antivirals because of their safety, potency, and low rates of drug resistance.
Among 48 treated pregnant women:
- 16 (33.3%) were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery. Many women with HBV experience liver-damaging "flares" after childbirth and monitoring and treatment is important during the post-partum period.
- 14 (29.2%) started treatment during the third trimester of their pregnancy–probably to lower viral load to avoid infecting their newborn–and continued antiviral treatment for at least one month after delivery.
Nonpregnant women were most commonly prescribed tenofovir (50.2%) and entecavir (41.3%), as is recommended by current medical guidelines. Surprisingly, these female patients with liver disease had a better chance of getting treatment if they lived in the South, compared to patients living in the Northeast region of the U.S.
"Among this insured population, pregnant women with chronic hepatitis B received an antiviral significantly less often than nonpregnant women," researchers wrote. The results show the need to examine doctors' treatment of female patients nationwide, the CDC officials concluded, and to increase antiviral use in pregnant women to prevent infection of newborns.
Source: www.ncbi.nlm.nih.gov/pmc/articles/PMC4274824/
One-third of HBeAg-negative Women Experience "Flares" After Childbirth
Nearly one-third of HBV-infected women experience liver-damaging "flares" within six months of giving birth, according to a study published in the January 2015 issue of the World Journal of Gastroenterology.
The doctors in Greece followed 27 hepatitis B e antigen (HBeAg)-negative pregnant women from pregnancy through several years after childbirth. They measured the women's alanine aminotransferase (ALT) levels (which rise when liver cells are damaged or die) and HBV DNA levels (viral load) every three months in the first year after childbirth and then every six months in the ensuing years.
Of the 27 women who completed the study, flares occurred in eight (29.6%) women, all within six months of delivery. Women who had viral loads exceeding 10,000 international units per milliliter (IU/mL) during their pregnancies were at higher risk of post-partum flares. The risk of flares was moderately increased in women with viral loads exceeding 2,000 IU/mL.
Because these women were HBeAg-negative, their viral loads were probably lower when they gave birth compared to HBeAg-positive patients who have high viral loads.
Experts concluded that HBeAg-negative women with HBV DNA levels at or exceeding 10,000 IU/mL were at higher risk of hepatitis B reactivation following childbirth.
Viral load during pregnancy far more accurately predicted which woman would experience postpartum flares than ALT levels during pregnancy.
Source: www.ncbi.nlm.nih.gov/pubmed/25632200
Immunizing Newborns Is an Effective Tool in Preventing Cancer
Immunizing infants at birth against hepatitis B reduces risk of infection and liver cancer and is far more effective in preventing the viral infection than waiting to immunize children when they're 10-14, according to a report published in the journal PLOS Medicine.
The study followed 17,204 newborns in rural China who were immunized at birth and 17,395 who were not immunized (serving as the control group) between 1996 and 2012.
Researchers surveyed the children twice, once in the 1996-2000 period and again in 2008-2012, for hepatitis B-related liver disease and cancer. They reported that:
- Liver cancer rates were 84% lower in the vaccinated group than the control group.
- Death rates from liver disease were 70% lower in the vaccinated group than in the control group.
- And, infant fulminant hepatitis was 69% lower among immunized children.
Two-thirds of the children in the control group were later immunized when they were 10 to 14 years-old. However this later vaccination was not as effective. Only 21% of the older children were protected against hepatitis B by the vaccine, compared to 72% of infants vaccinated as newborns.
Source: www.ncbi.nlm.nih.gov/pubmed/25549238
Experts Warn: Don't Delay Treatment in Patients with HBV Genotype C
Current medical guidelines suggest doctors wait three to six months before prescribing antivirals to patients with high ALT levels, which indicate liver damage. The delay is suggested because sometimes spontaneous HBeAg seroconversion (loss of HBeAg and development of "e" antibody) occurs during these ALT spikes.
However, a new study published in the December 2014 issue of the journal Clinical and Molecular Hepatology finds that seroconversion is unlikely to occur when patients have HBV strain or genotype C. Experts say doctors should treat these patients immediately to avoid more liver damage.
Researchers in South Korea followed 90 HBeAg-positive patients with elevated ALT levels for six months without initiating treatment. During that time, only one patient (1.1%) achieved spontaneous HBeAg seroconversion. In the meantime, half of the patients experienced deteriorating liver health with one requiring a liver transplant due to liver failure.
Instead of waiting, researchers noted, "Immediate antiviral therapy should be considered, especially in patients with high ALT and HBV DNA levels in endemic areas (with) genotype C infection."
Source: www.ncbi.nlm.nih.gov/pubmed/25548741
Antivirals Help Patients with Cirrhosis, If Started Early Enough
A new study finds that antivirals help prolong survival and improve liver health even in patients with severe liver damage and scarring (decompensated cirrhosis) who qualify for liver transplants.
A study in Japan, reported in the January 2015 issue of Hepatology, found that antiviral treatment improved five-year survival, enabled 49.1% of those treated to lose HBeAg and develop "e" antibodies, and allowed 33.9% of patients to get off liver transplant wait lists because of their improved liver health.
The study followed 707 patients with decompensated cirrhosis, including 284 untreated patients and 423 patients treated with antivirals.
Despite their poor liver health and prognosis, the antiviral-treated patients needed fewer transplants and 59.7% survived beyond five years, compared to 46% of untreated patients.
Patients treated early with antivirals had better outcomes than those with delayed treatment, researchers noted.
"Antiviral therapy significantly modifies the natural history of decompensated cirrhosis, improving liver function and increasing survival," they wrote. "The results underscore the importance of promptly administering potent antiviral drugs to patients under consideration for liver transplants."
Source: www.ncbi.nlm.nih.gov/pubmed/25627342
Entecavir Effective at Clearing HBV's cccDNA from Liver Cells
An article in the World Journal of Gastroenterology reports that the antiviral entecavir works better than lamivudine to rid the liver of covalently closed circular HBV DNA (cccDNA)–the viral "seed" that stubbornly embeds in liver cells and remains ready to churn out more virus.
The cccDNA can persist in liver cells for years even after interferon or antiviral treatment clears HBV DNA from the bloodstream. To date, researchers assumed this cccDNA disappeared only after individual infected liver cells were killed by the immune system.
In this study, researchers measured cccDNA in the liver cells of HBeAg-positive patients before and after they were treated with antivirals for at least 52 weeks. They treated 159 patients with entecavir (0.5 mg daily) and 146 with lamivudine (100 mg daily).
After 48 weeks, entecavir produced significantly greater reductions in cccDNA in liver cells examined by liver biopsy than lamivudine.
Entecavir was also more effective at lowering viral load and improving liver health.
"Forty-eight weeks of entecavir resulted in greater reductions in cccDNA and total hepatic HBV DNA than lamivudine, but long-term therapy may be needed for (complete) cccDNA elimination," researchers wrote.
Source: www.scribd.com/doc/253634882/Covalently-Closed-Circular-Hepatitis-B-Virus-DNA-Reduction-With-Entecavir-and-Lamivudine-ccDNA-Manuscript
Older Age and a Weakened Immune System Can Cause HBV to Reactivate
Doctors know that an immune system weakened by chemotherapy can cause even a resolved or dormant hepatitis B infection to reactivate, but new information shows old age, other diseases, or surgery can also cause HBV to rebound.
According to a study published in the January 2015 issue of the Journal of Medical Virology, two elderly men had spontaneous reactivation of hepatitis B following surgery and development of diabetes.
Both had resolved hepatitis B infections and one even had hepatitis B surface antibodies, indicating he had cleared the infection.
In one case, a 73-year-old male had surgery in 2008 and at the time tested positive for surface antibodies, which should indicate he had cleared the infection. However, in 2009 he redeveloped HBsAg, HBeAg and a high level of HBV DNA, along with elevated ALT levels due to a weakened immune system.
In the other case, reported in the journal, a 76-year-old male who had been operated on for esophageal cancer in 2002, was diagnosed with diabetes in 2009. At that time he tested negative for HBsAg.
However, he tested positive for HBsAg in September 2012 just before he underwent another round of surgery for recurrent esophageal cancer. In the ensuing months, his viral load increased greatly as the infection reactivated as a result of his weakened immune system.
"Aging, surgical stress and complication of diseases associated with compromised immunity, such as cancer, arteriosclerosis and diabetes may trigger spontaneous HBV reactivation," the researchers reported.
Source: www.ncbi.nlm.nih.gov/pubmed/25612181
Survey Shows Doctors Fail to Adequately Screen forLiver Cancer
A survey of 177 doctors from three academic centers, sponsored by the Cleveland Clinic Foundation, found most of them use unreliable alpha fetoprotein (AFP) blood tests to screen for liver cancer instead of using more accurate ultrasounds.
Current medical guidelines call for doctors to use ultrasounds or imaging technology to screen patients at high risk of liver cancer, including those with HBV-related inflammation or cirrhosis.
Ultrasound has a sensitivity for identifying liver tumors that range from 65% to 80%, depending on the operator. Obesity and cirrhosis can often make tumors or lesions harder to find. (1)
AFP tests are performed on a blood sample, and above-normal AFP readings can indicate the presence of liver cancer. However, AFP's accuracy is much lower than ultrasounds, running under 60%. Additionally, AFP tests have even lower accuracy in certain patient populations. (1)
Despite these medical guidelines, many medical faculty members and residents relied on AFP tests for semi-annual cancer screenings instead of ultrasound technology.
Among those who performed liver cancer screening in patients with hepatitis B and C-related cirrhosis every six months, 35% of them used AFP tests and only 22% used ultrasound imaging tests.
"Further, 22 physicians (12.4%) did not check for serum AFP levels and 33 (18.6%) never used imaging to screen for liver cancer," researchers reported in the January 2015 issue of Gastroenterology Reports. (2)
"The majority of the participating physicians screen high-risk patients for liver cancer," they concluded. "However, the most appropriate modality of screening (i.e. imaging) is not employed by most physicians and there is greater reliance on AFP levels."
Source 1: www.clinicalcorrelations.org/?p=4530
Source 2: www.ncbi.nlm.nih.gov/pubmed/25563577
Innovative Venues Increase Hepatitis B Screening Among Asian-Americans
Despite the high rate of hepatitis B among Asian-Americans, public health officials struggle to screen, immunize and treat this population and many remain undiagnosed and unvaccinated due to economic and cultural barriers to healthcare.
However, an initiative by the Asian Health Coalition and University of Chicago that screened Asian-Americans in non-clinical settings–such as street fairs and churches–was able to reach twice the number of people who were screened at area clinics.
The Asian Health Coalition and community partners conducted screenings at health fairs organized by churches and social service programs, and they followed up with clients to link them to care in both clinical and nonclinical settings.
As a result of this initiative, twice as many Asian-Americans were screened in these nonclinical settings than at local clinics. The participants in both settings were similar in gender, health insurance status, years of residence in the U.S., education and how many tested positive for HBV infection.
Additionally, equal numbers of people from both groups were successfully referred to medical care.
"Nonclinical settings were as effective as clinical settings in screening for HBV, as well as in making treatment options available to those who tested positive," the researchers reported in the December issue of the Journal of Multidisciplinary Healthcare.
Source: www.ncbi.nlm.nih.gov/pubmed/25609976
Study Finds Waste Collectors at High Risk of Hepatitis B
While patients are supposed to dispose of needles and other injection equipment in sturdy containers, many do not, which leaves people who collect municipal waste at risk of accidental needle sticks and bloodborne infections.
A recent study from Attica, Greece, found that 15% of waste collectors had been exposed to HBV compared to a 2.5% infection rate among white-collar workers.
The researchers screened 50 waste collectors, who reported frequent exposure to needle-stick injuries at work, and a similar number of office workers who are not exposed to waste. In the study, only one worker tested positive for hepatitis C exposure.
"Our study corroborates previous results of an increased prevalence of hepatitis B infection among municipal waste collectors," researchers wrote in the Greek journal (PMID: 25551841).
"Vaccination against HBV among municipal solid waste collectors and promotion and use of safer methods for the collection of non-hospital medical waste could represent potential measures for the prevention of hepatitis B infection among municipal waste collectors," they concluded.
Source: www.ncbi.nlm.nih.gov/pubmed/25551841
Study Comparing Four Antivirals Finds All Appear Effective
Chinese researchers tried four different types of antivirals in 155 previously-untreated patients (all HBeAg-positive) to see which antiviral worked best. After one year of treatment, they found all antivirals worked equally well.
After 52 weeks of treatment, surprisingly there were no marked differences between the antivirals, which included entecavir, lamivudine, telbivudine (Tyzeka) and a combination of lamivudine and adefovir (Hepsera).
According to the report published in the January 2015 issue of the Saudi Journal of Hepatology, after 52 weeks of treatment the mostly-male patients experienced these results:
- Lamivudine-treated group: 36% lost HBeAg and 83% achieved undetectable viral load.
- Entecavir-treated group: 39% lost HBeAg and 96% achieved undetectable viral load.
- Telbivudine group: 48% lost HBeAg and 91% achieved undetectable viral load.
- Lamivudine plus adefovir group: 35% lost HBeAg and 89% had undetectable viral load.
Source: www.healio.com/hepatology/chronic-hepatitis/news/online/%7B0992611c-1b44-4389-a39e-7fa2a8494f54%7D/various-regimens-effective-in-treating-chinese-patients-with-hbv
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发表于 2015-2-2 12:18