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HBV Journal Review

HBV Journal Review
September 1, 2012, Vol 9, no 9
by Christine M. Kukka

PDF PDF (download)

Even Insured Adults with Access to Quality Care Aren’t Screened for Hepatitis
Even adults with medical insurance and regular access to doctors are not adequately screened for hepatitis B or C, according to a U.S. Centers for Disease Control and Prevention study published in the journal of Clinical Infectious Diseases.

Researchers examined how many patients enrolled in four private health care organizations across the United States were screened for viral hepatitis over a two-year period. The screening rates were shockingly low, missing an estimated 20% of hepatitis B virus (HBV) infections and half of all hepatitis C infections in this insured patient population.

Nationwide, experts estimate that 65% of people infected with HBV and 75% of those with hepatitis C are unaware of their infections due to poor access to health care and screening. Researchers decided to see how many “missed” hepatitis diagnoses occurred in insured people who enjoyed regular access to quality care.

They studied 866,886 uninfected adults enrolled in health care plans in Pennsylvania, Michigan, the Pacific Northwest, and Hawaii over several years to determine who and how many were screened for viral hepatitis. They then compared the number screened and found to be infected with viral hepatitis against race- and age-matched national data from the National Health and Nutrition Examination Survey (NHANES) to assess the missed diagnoses.

Even with quality health care, only 18.8% (one in five) were tested for HBV infection, with 1.4% testing positive. CDC researchers estimated that at least 21.1% of HBV infections (and 43.1% of hepatitis C infections) in this patient group remained undiagnosed. Bottom line, doctors identified 1,604 hepatitis B infections in their patients, but missed 616 infections due to adequate screening.

Given the low screening rates, which adult patients were flagged for screening and which weren’t?

In compliance with medical guidelines, Asian ethnicity were screened at a higher rate (26.7%) compared to whites (17.9%). But Asian-Americans were screened at a lower rate by doctors than African-Americans, even though they have higher rates of hepatitis B infection.

Older seniors (older than 80) were screened least (9.5%) while those ages 30-39 were screened most (28.2%). Women were screened more often than men.

Elevated alanine aminotransferase (ALT) levels, which can indicate liver damage from liver infections, often failed to trigger screening for hepatitis B or C. Fewer than 45% of patients who had twice the level of ALT that they should were screened for hepatitis B or C. Providers may have thought the liver damage resulted from alcohol abuse or medications instead of viral hepatitis.

A far smaller percentage of patients with only moderately elevated ALT levels were tested for hepatitis. Many patients with hepatitis B have normal ALT levels, which will not serve as a red flag or trigger for screening.

“Even in this population with access to care and lengthy follow-up, only a fraction of expected viral hepatitis infections were identified,” researchers wrote. “Abnormal ALT levels often, but not consistently, triggered testing. These findings have implications for the identification and care of 4-5 million U.S. residents with HBV and HCV infections.”

Despite Immunizations, 28% of Children Born to HBV-Infected Mothers Have “Occult" Infections
Twenty-eight percent of children born to HBV-infected mothers were found to have an “occult” hepatitis B infection (with HBV DNA in the bloodstream, but undetectable hepatitis B surface antigen—HBsAg) despite having been immunized shortly after birth, according to a study published in the Journal of Hepatology.

Researchers screened blood from 75 uninfected (without HBsAg) children in Iran born to HBsAg-positive mothers who had been immunized at birth. The children were screened for both HBsAg and HBV DNA (viral load). The HBV DNA test would pick up on any HBV in the bloodstream, even if the children had mutations in their HBsAg that were able to evade detection by conventional lab tests.

Fifty-five of the 75 tested positive for surface antibodies, which is expected after immunization with just the HBsAg to trigger an immune response. Nine, however, had core antibodies, which indicates past exposure to the virus. Eleven tested negative for surface antigens and surface antibodies and core antibodies.

Occult hepatitis B was diagnosed in 21 children, with HBV DNA levels ranging from 77 to 9,240 copies/mL. All 21 of these patients had surface antibodies, with five testing positive for core antibodies. Among the infected patients, 13 had one or more mutations in their HBV.

“Our study is the first report on the prevalence of (occult hepatitis B) among a selected high-risk group of children born to HBsAg-positive mothers, particularly from a region with low-to-intermediate prevalence of HBV,” the researchers wrote.

They suggested that an absence of HBsAg alone, “ … is not sufficient to completely exclude HBV DNA carriers. (Occult hepatitis B) seems to be relatively frequent in immunized children born to HBsAg-positive mothers.”

They called for additional studies into occult infection, and more research on whether vaccine boosters and/or stronger vaccines are needed to truly vanquish hepatitis B in children born to infected mothers.

Despite Childhood Immunizations, Adult HBV Infections Slowly Increase after Adolescence
Researchers who examined 1,214 blood samples found that despite hepatitis B immunization during infancy and childhood, the number of people with HBV infections, including infections with a strain of HBV with mutations in the surface antigen, increases.

According to the article published in the journal Gastroenterology, Taiwanese children immunized during infancy were protected from infection through adolescence, but beginning at age 18, the number of vaccinated adults with HBV DNA in their blood stream began to slowly increase.

In the study, researchers measured hepatitis B surface antigens and antibodies and hepatitis B core antibodies in Taiwanese ranging from infants to adults older than 87.

HBV DNA levels were measured in HBV-vaccinated patients who tested positive for the core antibody (meaning they had been infected at some point) and those who were infected and tested positive for HBsAg.

Patients born after Taiwan’s HBV vaccination program began in 1984 had significantly lower HBsAg and core antibodies compared to older participants (1% vs. 9.3% for HBsAg, and 2.3% vs. 43.9% for core antibodies.)

However, researchers noted over time that even those who had been vaccinated during infancy had increasing rates of core antibody and limited numbers of surface antibodies.

Core antibodies were found in 0.4% aged 10-14, 1.9% aged 14-18, and 8.1% of those 18-21. HBV infection (evidenced by HBsAg) was found in 2% of those 18-21 compared to a zero infection rates in younger participants.

HBV DNA in the blood was also more common among older patients (3% of those aged 18-21) compared with 0.2% in younger participants.

Among eight fully-vaccinated participants who tested positive for HBV DNA, five had HBsAg mutations. Investigators noted that this increase in surface mutations after adolescence requires careful monitoring, because this “occult” infection can also cause liver damage.

“Universal vaccination effectively controls HBV infection in children and adolescents,” the researchers wrote. “However, after adolescence, there is a significant increase in the seroprevalence of surface antibodies, core antibodies and HBV DNA, indicating that new preventive strategies are needed for adults. Monitoring the prevalence of HBV infection by sensitive HBV DNA assays in subjects beyond adolescence in [the] postvaccination era is mandatory.”

Tattoo Ink Linked to Infection Outbreaks Across the U.S.
The U.S. Food and Drug Administration is encouraging doctors, public health officials, consumers and others to report any tattoo-related infections after numerous clients became infected with nontuberculous mycobacterial infections from contaminated tattoo ink, according to a report in the New England Journal of Medicine.

There is spotty regulation of tattoo parlors and ink manufacturers nationwide, researchers noted. State and local regulators oversee tattoo parlors, but there is weak federal oversight of tattoo inks. According to the article, “…the FDA does not have the authority to require premarketing submission of safety data from manufacturers, distributors, or marketers of cosmetic products, with the exception of most color additives (dyes, pigments, or other substances used to impart color).”

The FDA does have the authority to take other actions to protect the public health, and ask a tattoo ink manufacturer to recall contaminated materials if the FDA is informed about it, which is why the FDA is asking doctors to be on the lookout for outbreaks of tattoo-related infections and report them. They also expressed concern that if contaminated materials can spread bacteria infections, tattoo inks may also spread other harmful pathogens, including hepatitis B.

In the United States, the estimated percentage of adults with one or more tattoos increased from 14% in 2008 to 21% in 2012. In the recent outbreak last January in New York, numerous tattoo clients developed red papules on the gray-colored areas of recently-acquired tattoos.

The FDA collaborated with local, state health officials and CDC to investigate the outbreak. They found similar bacteria outbreaks related to ink-specific tattoos in other areas of the country.

In another report on infection risk from tattooing, researchers reviewed more than 40 observational studies and found an increased infection risk of HBV infection through tattooing. Infection risk was especially high among prison populations and people involved in other high-risk behaviors, according to the report published in the Canadian Journal of Public Health.

Foreign-Born Asian-Americans Have Higher HBV Infection Rates than U.S.-Born
Researchers compared HBV infection rates among U.S.-born and foreign-born Asian Americans enrolled in Kaiser Permanente Hawaii managed care program. According to their report in the journal of Clinical Research and Medicine, foreign-born Asian-Americans had HBV infection rates of 2.6% while U.S.-born Asian-Americans had chronic infection rates of 0.3%.

Of the 513 HBV-infected Asian-Americans in the study, 76% were foreign-born and 24% were U.S.-born. HBV-infected foreign-born participants were significantly younger than the U.S.-born infected group.

Half of the foreign-born participants were in 40-59 years old age group, compared to 32% of the U.S.-born. More of the foreign-born infected participants were women (55%) compared to U.S.-born (50%).

Immunization of children and newborns and safe injection practices by U.S. health care providers probably contribute to the lower infection rate among U.S.-born patients.

Asian Ethnicity Does Not Increase Risk of Liver Cancer
If one has cirrhosis, does Asian ethnicity increase the risk of liver cancer? No, researchers report. Having viral hepatitis does, but Asian ethnicity does not, according to a Stanford University Medical School study published in the journal of Clinical Gastroenterology and Hepatology.

The researchers studied 379 patients with cirrhosis resulting from hepatitis C (68%), hepatitis B (7%), and non-viral causes (25%) who visited the liver clinic at the Stanford University Medical Center over eight years. They reported that 65% were male, 75% white or Hispanic, and 20% Asian. The patients received medical screening every six months for an average 34 months.

Forty-four patients (12%) were diagnosed with liver cancer during the follow-up period. Patients with cirrhosis resulting from viral hepatitis had a statistically significantly higher incidence of liver cancer than those with non-hepatitis causes (such as alcohol abuse.)

However, there was no statistically significant difference in liver cancer incidence between Asian and non-Asian patients.

"In a diverse cohort of patients in the U.S. with cirrhosis, a (diagnosis) of cirrhosis was associated with increased incidence of (liver cancer), but Asian ethnicity was not," researchers wrote. "These findings indicate the importance of cirrhosis ... in determining risk for liver cancer."

Fatty Liver Helps Patients Clear HBsAg, But at a Cost to Liver Health
It has been suggested hepatic steatosis (fatty liver—the collection of excessive fats inside liver cells) somehow contributes to clearance of HBsAg. While clearing HBsAg is sought after, hepatic steatosis in itself may cause more liver fibrosis and cirrhosis than HBV infection, researchers noted in the journal of Digestive Diseases and Sciences.

Researchers followed 150 people who cleared HBsAg, and compared 69 of the patients who had hepatic steatosis to those without fatty liver.

Those with fatty liver had significantly higher body mass, were male, and were about five years younger when they cleared HBsAg, compared to the other group.

However, 30% of those with fatty liver had elevated ALT levels even after losing HBsAg, indicating ongoing liver damage, compared to zero in the other group. Additionally, 10% of those with fatty liver developed cirrhosis (severe liver scarring) while only 3.5% of the other group did.

“In HBsAg carriers with increased body mass index, hepatic steatosis can accelerate HBsAg seroclearance by approximately 5 years,” researchers wrote. “However, the beneficial effects of HBsAg seroclearance should be balanced against the harmful effects of hepatic steatosis.”

Men with Hepatitis B at Higher Risk of Pancreatic Cancer
According to a report in the journal PLoS One, published by the Public Library of Science, a study of 488 Chinese patients with pancreatic revealed that men infected with HBV were at high risk of the cancer.

Researchers analyzed the role of ABO blood type, obesity, diabetes, metabolic syndrome, smoking, alcohol consumption and HBV infection on patient survival. Those with hepatitis B developed pancreatic cancer at a younger age than did other cancer patients, especially among HBV-infected men.

Testing positive for HBsAg and elevated blood sugar (found in diabetes) were associated with lower pancreatic cancer survival rates.

Sleeping Less Than Six Hours Nightly May Lower Vaccine’s Effectiveness
Adults who regularly get more than seven hours of sleep a night are more likely to respond well to a hepatitis B vaccination compared to those who get in less than six hours, according to a study published in the journal Sleep.

People who slept less than six hours on average were 11.5 times more likely to fail to protective sufficient antibodies to protect against hepatitis B infection than those who slept more than seven hours.

Researchers followed 125 adults, aged 40 to 60, who got the vaccine. They monitored their sleep and the number of surface antibodies generated after the three doses of vaccine. About 15% of those vaccinated did not achieve full protection six months after the series ended, and most of those who failed to generate antibodies slept fewer hours.

Researchers speculate that sleep is vital to strengthening the immune system, and substandard sleep may impair the body’s ability to produce antibodies. They recommend adults get a good night of sleep after getting a vaccine.

Excessive Alcohol Use Lessens Entecavir’s Ability to Lower ALT in Patients
Does obesity and alcohol abuse decrease the effectiveness of the antiviral entecavir (Baraclude) in hepatitis B patients? Yes, according to a report in the Journal of Clinical and Molecular Hepatology.

Researchers compared ALT levels, viral load, and HBeAg seroconversion (loss of the hepatitis B “e” antigen and development of “e” antibodies) in 88 patients over a two-year period. They compared the 24 obese patients (defined by their body mass index or BMI) and the 17 who drank alcohol excessively with the moderate drinkers with lower BMIs in the group starting six months after beginning entecavir (0.5 mg daily).

There were no differences in response to entecavir between the obese and normal BMI groups at 3, 6, and 12 months into treatment. Additionally, the rates of seroconversion and undetectable HBV-DNA did not differ significantly between the excessive drinkers and the others. However, after 12 months of treatment only 70.6% of excessive drinkers had achieved normal ALT levels, compared to 91.5% of more moderate drinkers.

“Obesity and hazardous alcohol drinking have no significant impact on the outcome of entecavir treatment,” researchers wrote. “However, the ALT normalization rate at 12 months after initiation of (entecavir) was significantly lower among the hazardous alcohol users.”

Interferon Spurs HBeAg Seroconversion, but Entecavir Achieves Undetectable Viral Load
Which is more effective in HBeAg-infected patients, 92 weeks of entecavir or one year of pegylated interferon (Pegasys)? It depends….Interferon was more effective in helping patients seroconvert and lose HBeAg, but entecavir was more effective in achieving undetectable viral load.

The report, published in the August issue of the journal of Antiviral Therapy, followed 91 patients treated for nearly two years with entecavir and 266 patients treated with interferon for one year and then followed for nearly another year.

Interferon treatment was more effective in spurring HBeAg seroconversion and clearance of HBsAg, compared to prolonged entecavir treatment—but entecavir was better at enabling patients to achieve undetectable viral load.


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