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HBV Journal Review
September 1, 2014, Vol 11, no 9
by Christine M. Kukka
New Study Finds HBV Genotype E Responds Poorly to Entecavir
Experts know some hepatitis B virus (HBV) strains called genotypes respond better to interferon treatment than others, but now scientists are discovering that genotypes respond differently to antiviral treatment too.
HBV genotypes are found in different regions of the world and each evolved over centuries to have slightly different molecular make-ups with unique traits. Some carry a higher risk of liver damage and cancer, while other genotypes are less virulent.
In a recent study, Italian researchers compared how well patients with genotypes A, D and E fared after three years of treatment with the antiviral entecavir (Baraclude). All of the patients tested negative for the hepatitis B "e" antigen (HBeAg-negative). The scientists measured hepatitis B surface antigen (HBsAg) levels and HBV DNA (viral load) every three months during the first year of treatment and then every six months over the study period.
They found the rates of HBsAg declines resulting from antiviral treatment varied markedly between genotypes. They extrapolated how many years of entecavir treatment each genotype required before a patient would clear HBsAg and achieve undetectable viral load.
HBV genotype A: It would take on average 15.6 years of entecavir treatment for an HBeAg-negative patient with HBV genotype A to lose HBsAg. This genotype is found in northern Europe, North America, India and southern Africa.
HBV genotype D: It would take 17 years for genotype D patients to lose HBsAg. This strain is found primarily in Russia, the Middle East, the Mediterranean region, and India.
HBV genotype E: This genotype, found in Central Africa, responded the most poorly to entecavir. Scientists estimated it would take 24.6 years for these patients to lose HBsAg, according to the report published in the August issue of the Journal of Medical Virology.
Source: www.ncbi.nlm.nih.gov/pubmed/25131947
HBV Genotypes Help Tell the Human Story of Slavery in the Americas
Because HBV genotypes develop in specific regions around the world, their distribution around the world today can help tell the story of mass human migrations, including the enslavement and forced migration of millions of Africans to Brazil since the 1500s.
In a unique study published in the August edition of the journal PLoS One, a global team of researchers examined the molecular make-up of HBV in Brazilians today in order to trace the infection's geographic source during the slave trade.
Surprisingly, their study shows that hepatitis B may be a relatively "new" disease in some parts of Africa, and may not have appeared there until the 1800s.
Brazil has a moderate rate of hepatitis B infection, and nearly all of those infected have HBV genotype A, (subgroup 1). Curiously, this genotype and its subgroup originally developed in Bangladesh, India, Japan, Nepal, the Philippines and United Arab Emirates–far from the Central and Western African countries of Congo, Kenya, Malawi, Rwanda, South Africa, Tanzania, Uganda and Zimbabwe, where most of Brazil's 5 million slaves came from between 1551 to 1840.
If the people who came to Brazil during this period had no hepatitis B in their home countries, how did an HBV genotype subgroup that originated in Asia and the southern tip of Africa come to dominance in Brazil?
History has the answer. Brazil was the last nation in the Americas to outlaw the slave trade. To avoid global laws and treaties that banned the transatlantic slave trade, in a last ditch effort to import slaves, Brazil brought in between 300,000 to 400,000 captives, primarily from southeast Africa (Mozambique) between 1837 and 1856. This coastal country has been visited by Asian and Indian traders for centuries and researchers suspect this HBV genotype was introduced here through Asia in the mid-1800s.
The researchers surmise that hepatitis B did not arrive with the millions of African people brought into Brazil between the 1500s and early 1800s, but with the later importation of a smaller group of captives from Asian-influenced Mozambique.
Comparing HBV genotypes in people of African descent in the Americas to those of today's African residents also tells the story of HBV's migration within Africa.
For example, today genotype E is the dominant genotype in the African country of Angola, which was home to many people captured and sold as slaves in South America more than 200 years ago. But HBV genotype E is rarely found in South Americans today. This means that hepatitis B genotype E was recently introduced to Angola, probably over the last 150 years.
Similarly, the absence of HBV genotypes of African origin in Brazil today show this genotype, "did not circulate, at least endemically, in western-central Africa, from where originated the great majority of the slaves between the 16th and the 19th century," researchers wrote.
Source: www.ncbi.nlm.nih.gov/pmc/articles/PMC4133366/
Researchers Find Tenofovir Increases Hip Bone Loss in Older Patients
Hepatitis B patients treated with the front-runner antiviral tenofovir (Viread) run a risk of reduced bone mass in their hip area, according to a recent report in the August issue of the Journal of Infectious Diseases. The risk of weaker hip bones resulting from tenofovir treatment is more pronounced in older patients who smoke, are thinner with lower body mass, and have advanced liver disease.
Loss of bone mineral density (bone mass) has been documented in HIV-infected patients treated with tenofovir long-term. British researchers decided to monitor 122 tenofovir-treated hepatitis B patients to see if they also lost bone mass, and compare them to a control group of 48 untreated-patients.
Both the control group and treated patients were scanned by X-rays to measure bone mass. Tenofovir-treated patients had reduced bone mineral density, but it was limited to the hip area, researchers noted. "Age and advanced liver disease are additional contributing (risk) factors, underlining the importance of multifactorial fracture risk assessment," they wrote, recommending that doctors perform bone density tests when starting patients on tenofovir in order to identify those at risk of hip injuries.
Source: www.ncbi.nlm.nih.gov/pubmed/25156561
Decline in HBV RNA Indicates Who Loses HBeAg During Antiviral Treatment
Researchers may have found a simple blood test to determine which patients are going to lose HBeAg during antiviral treatment.
German researchers measured the levels of HBV RNA in 50 patients treated with antivirals and found those who had the greatest RNA declines during antiviral treatment were the most likely to lose HBeAg and develop "e" antibodies, called HBeAg seroconversion.
Unlike HBV DNA, which sits in a cell's nucleus and issues genetic instructions to create more HBV, it is the HBV RNA's job to transfer those instructions from the nucleus to ribosomes so DNA never has to leave the safety of the nucleus.
Increasingly, researchers are looking at HBV RNA to see if they can manipulate these messenger RNA in order to impede HBV reproduction.
In this study, researchers monitored HBV RNA in 50 HBeAg-positive patients treated with antivirals over 30 months. They found the patients who had the greatest decline in HBV RNA after three to six months of treatment were the ones who ultimately lost HBeAg and developed "e" antibodies. When HBeAg seroconversion occurs, viral load and risk of liver damage usually decline.
Researchers noted that HBeAg-negative patients, who had already lost HBeAg, already had low levels of HBV RNA.
Measuring HBV RNA was a more accurate indicator of which patients would lose HBeAg than measuring viral load, the liver enzyme alanine aminotransferase (ALT) or HBsAg levels, researchers concluded in their report published in the August issue of the journal Hepatology.
Source: www.ncbi.nlm.nih.gov/pubmed/25132147
Shortened Vaccination Schedule May Get More Drug Users Immunized
A study of three U.S. needle-exchange programs finds that an on-site, fast-track hepatitis B immunization dosing schedule may get more injecting drug users protected against infection, according to a report published in the August edition of BMC Public Health.
Many injecting drug users are at high risk of this blood-borne infection, but they are notoriously hard to reach and immunize. First, the hepatitis B vaccination requires three doses, the second delivered 30 days after the first and the third delivered six months later. Secondly, few users are willing to be screened and then return to a clinic for vaccination, even when financial incentives are offered; so researchers hope needle exchange sites could be effective venues for immunizations.
This recent study followed drug users who used needle exchange programs in Chicago and Hartford and Bridgeport, Conn. When the usual vaccination schedule was used among 271 participants, only 141 (52%) returned for the second and third doses.
However when an accelerated vaccination schedule was used (second dose one month after the first and third dose two months later instead of six months later) in 324 participants, 206 (63.6%) returned for all three doses.
Drug users who were older and frailer were more likely to return for immunization. Researchers noted that vaccination rates remain low among younger drug users. "Thus, special attention should be paid to recruiting and retaining younger participants," they wrote.
Source: www.ncbi.nlm.nih.gov/pmc/articles/PMC4138371/
Primary Care Doctors Rarely Screen Patients for Cirrhosis
A study by doctors from the University of North Carolina Liver Center finds that less than half of primary care doctors who treat patients with cirrhosis (severe liver scarring) actually screen patients for liver damage and cancer.
Current medical guidelines require doctors to screen cirrhotic patients for liver damage and cancer by using ultrasound and alpha fetoprotein tests. However, according to the study published in the August issue of the journal of Clinical Gastroenterology and Hepatology, many physicians in North Carolina fail to monitor their at-risk patients for liver damage and cancer.
Researchers mailed a survey asking about their liver cancer monitoring practices to 1,000 North Carolina providers. Of the 391 who responded, 89% indicated they saw patients with cirrhosis, but only 45% of them screened for liver cancer.
Of the doctors who did not screen patients:
84% indicated they referred patients to gastroenterologists (liver specialists) to perform the screening.
24% were unaware of the recommendations that mandated screening.
8% were uncertain there was any benefit to screening for cancer.
And 8% were concerned about costs.
While a little more than half of the doctors knew about liver transplantation and tumor removal as treatment options, very few knew about newer surgeries to remove liver tumors.
Most doctors see patients with cirrhosis, but only a minority screen for liver cancer, researchers wrote. "Primary care provider knowledge of effective liver cancer therapy options is suboptimal. Efforts to enlist (doctors) in liver cancer surveillance may be best served by increasing their knowledge of effective therapies," they concluded.
Source: www.ncbi.nlm.nih.gov/pubmed/25117773
Tenofovir or Telbivudine Recommended for Pregnant Women with High Viral Loads
A comprehensive overview of ways to prevent mother-to-newborn hepatitis B infection recommends the use of either tenofovir or telbivudine (Tyzeka) in pregnant women who have high levels of HBV.
While treating HBV-infected pregnant women with antivirals has not yet been approved by the U.S. Food and Drug Administration, increasingly doctors are treating women with high viral loads (with HBV DNA exceeding 10 million international units per milliliter–IU/mL) in order to prevent infection of newborns.
Current medical guidelines call for screening all pregnant women for hepatitis B and immediate immunization and use of hepatitis B immune globulin (HBIG) in babies born to infected mothers.
This approach works to prevent infections in about 97% of births, but according to a recent study in the International Journal of Women's Health, about 3% of babies born to women with a 1 million IU/mL viral load will still become infected. That percentage increases to 9% among babies born to women with viral loads exceeding 100 million IU/mL.
Since 1989, antivirals have been safely used in pregnant, HIV-infected women to prevent infection of newborns, and doctors use some of those same antivirals to treat hepatitis B. So starting about five years ago, doctors began treating HBV-infected women with antivirals to tamp down their viral load before delivery.
Today, researchers recommend telbivudine and tenofovir for use in pregnant women. There is no risk of fetal toxicity with those two drugs, while animal studies have found embryo or fetal toxicity associated with lamivudine (Epivir-HBV), entecavir, and adefovir (Hepsera). Additionally, lamivudine has been found to be a weak antiviral when used during pregnancy and has caused drug resistance.
Early studies have found no transmission of HBV infection to infants when mothers are treated with either telbivudine or tenofovir.
Researchers stressed the importance of a collaborative approach by all doctors involved in a pregnant woman's care to screen for hepatitis B, immunize newborns and administer HBIG, and treat women with high viral loads with antivirals.
Source: www.ncbi.nlm.nih.gov/pubmed/?term=vertical+transmission+of+
hepatitis+B+virus%3A+challenges+and+solutions
Access to Healthy Food Vital for HBV Patients, but Many Live in Food "Deserts"
In the first study of its kind, researchers have documented that people with liver disease who have easy access to fresh, healthy food markets and avoid fast foods have healthier eating habits and better health than those whose only options are fast food outlets or convenience stores, according to a report in the September-October issue of the Annals of Hepatology.
Researchers surveyed 267 people with hepatitis B, hepatitis C or non-alcoholic fatty liver disease (NAFLD) living in the greater Washington DC area about their eating and shopping habits. Using Geographic Information Systems (GIS) technology they also plotted what food sources–ranging from fast food places, ethnic groceries, convenience stores, restaurants, and fresh food groceries–were near their homes in these heavily developed urban and suburban areas.
Not surprisingly, people who live close to fresh food markets have healthier diets than those who must depend on convenience stores or fast food restaurants for meals. Healthy diets, low in salt and fats, are critical for people living with viral hepatitis. NAFLD patients ate more prepared food and less fresh food, probably because of geographic distance from healthier food sources.
Based upon these findings, it is important for health care providers serving a chronic liver disease population to investigate a patient’s food environment, fresh food consumption, and primary food source choices and “aggres-sively refer patients for dietetic services for effective life-style change management," researchers from George Mason University reported.
Source: www.annalsofhepatology.com/revista/numeros/2014/
HP145-09-Survey%20%28F_070814J%29_PROTEGIDO.pdf
Scientists Create Viable Liver Cells in a Lab for HBV Research
A new technique for studying the lifecycle of HBV could help researchers develop a cure for the disease. In a report published in the Proceedings of the National Academy of Sciences, researchers describe using microfabricated cell cultures to sustain HBV in human liver cells in a lab, which allows them to study how the HBV-infected liver cells respond to drug treatments.
To develop new drugs, researchers need to study how infected liver cells respond to experimental treatments. Until now, researchers have been unable to maintain HBV-infected liver cells in a lab setting. The cells are unstable and need the entire liver to sustain them.
Using a process researchers developed when studying the hepatitis C virus, the researchers developed a system that uses liver cells from livers donated for transplant plus stem cells derived from human skin samples and introduced into the liver-like cells.
Researchers will now use these liver cells to investigate new treatments for HBV.
Source: www.yumanewsnow.com/index.php/news/health/7469-model-of-viral-
lifecycle-could-help-in-finding-a-cure-for-hepatitis-b
Nerve Damage Prompts Warning Against Telbivudine-Interferon Combo Treatment
A drug trial that combined the antiviral telbivudine and pegylated interferon was found to cause nerve damage in seven of 50 patients treated with the combination, according to a report published in the August issue of the Journal of Hepatology.
The high rate of peripheral neuropathy, which causes damage to the nerves that transmit information from the brain and spinal cord to other parts of the body, prompted the study's global team to caution against the use of this drug combination.
Investigators compared outcomes in three groups of hepatitis B patients treated with the drug combination (50), only interferon (54) and only telbivudine (55). After 24 weeks, peripheral neuropathy occurred in seven of the 50 patients receiving combination treatment, in one of the telbivudine-treated patients and in none of the interferon-treated group.
However, 71% of the combination group achieved undetectable HBV DNA during the study period, compared to 35% in the telbivudine-only group and 7% of the interferon-treated group.
"Despite the rapid and profound reductions in HBV DNA levels, combination therapy with telbivudine and PegIFN should not be used," researchers cautioned.
Source: www.ncbi.nlm.nih.gov/pubmed/25152207
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发表于 2014-9-2 12:50
