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HBV Journal Review

HBV Journal Review
September 1, 2013, Vol 10, no 9
by Christine M. Kukka

PDF PDF (download)

39.2% of U.S. Newborns Aren't Getting Hepatitis B Vaccine at Birth
Which newborns aren't getting immunized against hepatitis B in the U.S.? The infants who:

  • Do not have health insurance
  • Live in states without a universal hepatitis B vaccine supply policy
  • And have only one provider who administered vaccines.

According to a U.S. Centers for Disease Control and Prevention study, published in the August issue of the journal Preventive Medicine, an alarming 39.2% of newborns missed the first, critical birth dose of hepatitis B vaccination that can protect newborns from hepatitis B even if their mothers are infected.

These results come from data analysis of the 2009 National Immunization Survey of 17,053 U.S. children, aged 19-35 months.

"Children who reside in states without a universal hepatitis B vaccine supply policy, and are not covered by health insurance are two important modifiable risk factors for not receiving the birth dose hepatitis B vaccination, future intervention studies could be needed to help control those modifiable risk factors," CDC researchers wrote.

Source: www.ncbi.nlm.nih.gov/pubmed/23988497

Researchers Suggest Banning or Restricting Lamivudine to Avoid Drug Resistance
A global team of researchers suggest lamivudine (Epivir-HBV) never be used to treat hepatitis B patients because it frequently leads to drug resistance and sets the stage for resistance to other antivirals, such as entecavir (Baraclude).

Lamivudine, the first antiviral approved for hepatitis B treatment, has fallen out of favor in North America and Europe because of its high rate of drug resistance. But because of its low cost, it continues to be commonly used to treat hepatitis B virus (HBV) infection in Asia and Africa, where the majority of the world's hepatitis B patients live.

This report, published in the July 30 issue of PLoS One, examined the molecular make-up of the virus in many patients who had been treated with lamivudine as well as patients who had never been treated. They found the many untreated patients carry a mutation that allows HBV to quickly mutate and develop resistance to lamivudine.

"Our findings strongly suggest that the use of lamivudine will not benefit ...patients," they wrote because of the high risk of lamivudine resistance.

"Finally, since patients can quickly develop drug resistance to entecavir in the presence of lamivudine mutations, the lamivudine mutations can significantly compromise the efficacy of entecavir," they concluded.

They proposed that doctor screen patients for these mutations before ever prescribing lamivudine,"... to most effectively treat chronic hepatitis B patients by selecting only sensitive drugs."

An unrelated article published in the Annals of Medical and Health Sciences Research, also criticized the over-use of lamivudine in hepatitis B patients in Sub-Saharan Africa. Lamivudine was originally developed to treat HIV, but today African providers use it frequently to treat anyone with hepatitis B (when HIV is not present) because it is inexpensive and more effective hepatitis B antivirals, such as tenofovir (Viread) or entecavir, are more costly or unavailable.

But over-prescription of lamivudine for hepatitis B in this region has:

  • Increased drug resistance in African hepatitis B patients
  • Reduced availability of the antiviral to both HIV and HBV patients
  • And driven up the drug’s cost, which reduces its availability for more appropriate HIV treatment.

Critics say a bioethical dilemma has evolved, where doctors prescribe lamivudine to hepatitis B patients without explaining alternative treatment because they assume the patients don’t understand or are too poor to pay for more effective antivirals.

“Implied consent is no justification to embark on a particular treatment course,” researchers from Njala University in Sierra Leone wrote. “To tackle the growing problems of drug resistance and shortages with respect to lamivudine and other antivirals in HIV/AIDS treatment, health care resources should be prescribed with caution, irrespective of whether implied or explicit informed consent has been sought.”

  1. Association of Preexisting Drug-Resistance Mutations and Treatment Failure in Hepatitis B Patients
    Source: ww.ncbi.nlm.nih.gov/pmc/articles/PMC3728369/
  2. Lurking Dangers Behind Overuse of Lamivudine to Treat Non-HIV Hepatitis B Patients in Africa

Knowledge Gap About Hepatitis B Persists Among Asian-Americans
Despite a nationwide campaign to screen, immunize and treat Asian-Americans who are at high risk of hepatitis B, a recent study of 58 HBV-infected Asian-American patients found that most of them did not know how they were infected or whether their family members were also infected months after they were diagnosed.

The survey was conducted by University of California San Francisco researchers. They questioned 58 HBV-infected patients treated at a university liver clinic. The group studied were not hindered by poverty. While 89% were born outside the United States, most had health insurance, their average age was 46, most were married and 55% were male.

Yet they showed little knowledge about hepatitis B, and although they had been diagnosed with hepatitis B and told about the infection, the patients knew little about whether their extended family members (totaling 803) were infected. Among their immediate family members, patients did not know the hepatitis B status of 28% of them.

"This knowledge gap existed despite extensive counseling regarding family testing at every clinic visit," researchers wrote. "In addition, patients, including those with a known family history of liver cancer who have a higher risk of developing (cancer), did not know the serostatus (infection status) of over a quarter (91 of 325) of first-degree relatives or spouses.

"Furthermore, our study suggests that language barriers may play an important role, even with the availability of interpreters, as non-English speakers were less likely to know their family members’ serostatus than English speakers," they noted in their report published in the August issue of the Journal of Immigrant and Minority Health. "It is possible that the language barrier is also a proxy for acculturation; that is, the less English a patient speaks, the less likely that patient may feel comfortable with the specific cultural practices expected in our health care system."

Clearly the health care system must conduct more research to develop a better strategy to reach, educate and screen Asian-Americans for hepatitis B, they noted.

"Focusing efforts on screening family members of individuals with HBV infection will likely increase case finding exponentially and furthermore, improve the efficiency of public health endeavors," they wrote. "The means to achieve this goal, however, remain to be determined."

In an unrelated article published in the journal Gastroenterology & Hepatology, researchers reported a poor response when they tried to screen people at a cultural fair in Miami for hepatitis B and C. Despite the presence of translators and education material, only 2-3% of attendees were screened. "Other strategies will be required to enhance participation in screening programs for viral hepatitis," they wrote.

In a third article on screening Asian-Americans, published in the August issue of the Journal of Viral Hepatitis, researchers followed Los Angeles people who were diagnosed with hepatitis B at community screenings conducted between 2007 and 2010.

About 5.2% of Asian-Americans screened had chronic hepatitis B, nearly all were foreign-born and only 27% could read/write English. Six months after diagnosis, 43% of those interviewed had not received any follow-up care, primarily due to lack of insurance.

  1. "Survey of Asian patients with hepatitis B infection: Limited Knowledge of transmission and screening of family members."
    Source: www.ncbi.nlm.nih.gov/pubmed/23913129
  2. "Screening for hepatitis B virus and hepatitis C virus at a community fair: a single-center experience."
    Source: www.ncbi.nlm.nih.gov/pubmed/23943664
  3. "Demographic and serological characteristics of Asian-Americans with hepatitis B infection diagnosed at community screenings."
    Source: www.medscape.com/viewarticle/807628

Even Liver Specialists Fail to Immunize Patients Against Viral Hepatitis
Hepatologists—physicians who specialize in treating liver disease—fail to recommend hepatitis A and B immunizations to patients with chronic hepatitis C and other liver ailments, according to a study by University of Pittsburgh School of Medicine researchers. The study, published in the July issue of PLoS One, found that even in an academic clinic specializing in liver disease, hepatologists recommended immunization for hepatitis A in only 63% of eligible patients and for hepatitis B in 59.7% of eligible patients.

Appropriate immunization recommendations, which matched current medical practice recommendations, varied from 30% to 98.6% among the liver specialist.

The poor adherence to medical guidelines when recommending immunization did not vary based on patients’ ethnicity, age, gender etc. It instead varied by individual provider, which shows the glaring need for additional training for even physicians whose expertise is liver disease.
Source www.ncbi.nlm.nih.gov/pubmed/23923056

Many Seek Viral Hepatitis Tests Only When Symptoms Appear
About half of patients infected with the hepatitis C virus (HCV) sought testing only after they experienced symptoms or had a lab test indicating liver damage, according to a report in the Aug. 16, 2013, issue of the CDC's Morbidity and Mortality Weekly Report.

Researchers collected data on what factors spurred 4,689 adults with confirmed chronic HCV or HBV infections to be tested.

According to their findings, 60.4% of those who responded said their initial HCV test occurred in a physician's office. Only 22.3% of HCV patients cited injection drug use and hemodialysis--two common risk factors for hepatitis C--as reasons for getting tested. About 45.2% said lab tests, including abnormal liver function tests or liver-related symptoms, prompted them to be tested.

An estimated half of all people infected with hepatitis C in the United States are unaware of their infection status, as are tens of thousands of people with hepatitis B. In 2012, CDC recommended one-time testing for all persons born between 1945 and 1965, as they are at higher risk for infection.

Source: www.cdc.gov/mmwr/preview/mmwrhtml/mm6232a3.htm

After Six Years of Tenofovir Treatment, Still No Signs of Drug Resistance
Tenofovir, one of the leading antiviral drugs for hepatitis B treatment, produced no drug resistance in 585 patients treated for six years.

The report, published in the August issue of Hepatology, followed 347 hepatitis B "e" antigen-negative (HBeAg-negative) patients and 238 HBeAg-positive patients who had been treated with the daily antiviral pill for six years.

They examined the molecular make-up of the virus in 52 patients who still had detectable HBV DNA after lengthy tenofovir treatment to see if any of them had developed drug mutations that enabled the HBV to "resist" tenofovir's ability to block viral replication.

The researchers found that the lingering viral load resulted from failure in some patients to take the antiviral as prescribed. Other patients had HBV with natural mutations (that were not induced by tenofovir treatment) that contributed to the low viral loads.
These two groups of patients either switched to an antiviral combination of tenofovir and emtricitabine or they began taking tenofovir as prescribed. To date, all patients have all achieved undetectable viral load.

Source: www.ncbi.nlm.nih.gov/pubmed/23939953

More Studies Examine Link Between Vitamin D and Liver Damage
Researchers are exploring the link between liver damage and low levels of vitamin D, a vitamin that is critical for the body to absorb calcium and maintain strong bones. This area is of special concern because antivirals may cause some bone loss.

In one study published in the August issue of the journal of Antiviral Therapy, a global team of researchers examined vitamin D levels and liver fibrosis (inflammation) in 158 people coinfected with HIV and HBV who were screened before and after treatment with tenofovir.

They found that vitamin D deficiency in the patients increased from 72.2% before treatment started to 84.2% after five years of tenofovir treatment. Vitamin D deficiency was highest among women. This occurred in a region where there is plenty of sunshine, which helps the body absorb vitamin D. However, researchers found no link between low vitamin D levels and significant liver fibrosis in these treated patients.

"Since HIV-HBV co-infection requires long term use of ... (tenofovir) that can also contribute to bone loss, routine vitamin D assessment and supplementation as necessary should be considered," researchers concluded.

An unrelated study, published in a Chinese journal of hepatology, examined the relationship between vitamin D levels and cirrhosis (severe scarring of the liver.) They compared vitamin D levels in 282 people with cirrhosis and compared it to levels in a healthy control group. They found that the risk of cirrhosis significantly increased as vitamin D levels declined. "Vitamin D might function as a protective factor against development of cirrhosis," they suggested.

  1. "Decline in serum 25-OH vitamin D levels in HIV/hepatitis B virus (HBV) co-infected patients after long term antiretroviral therapy."
  2. "Prospective study on the relation between serum vitamin D levels and liver cirrhosis risk."
    Source: www.ncbi.nlm.nih.gov/pubmed/23967742

Study Examines Which Hepatitis B Patients Relapse with Chemotherapy
Researchers know that chemotherapy drugs used to treat cancer and arthritis weaken the immune system and often cause a reactivation of hepatitis B virus infection, even in people who have undetectable viral load and hepatitis B surface antibodies. In a recent Japanese study, researchers tried to determine which patients with resolved HBV infections were at risk of viral reactivation.

They followed patients with blood cancers who were treated with rituximab chemotherapy. This drug contains manufactured antibodies that attach to defects in cancer cells in order to contain or slow cancer cell reproduction.
They focused on 59 patients who had been infected with HBV (they were positive for the hepatitis B core antibody) but who currently had undetectable viral load and no hepatitis B surface antigen.

Four of the 59 patients (6.8%) had minor HBV reactivation over the 20-plus months of rituximab treatment and follow-up. All of them, researchers noted, had lower levels of protective “peripheral lymphocyte counts” before chemotherapy began, which may predispose them in some way to viral reactivation due to their weakened health.

The four did not experience severe hepatitis B reactivation, and were able to continue their chemotherapy without liver damage.

The study, published in the August issue of the Journal of Medical Virology, underscores the importance of screening all patients for current or resolved hepatitis B infection (including HBV DNA) before starting chemotherapy, and to continually monitor even patients with undetectable viral load during treatment and follow-up.

Source www.ncbi.nlm.nih.gov/pubmed/23926082

Interferon Treatment May Cause Some Hearing Loss
Interferon causes a wide array of side effects, ranging from depression to fatigue and body aches, but Iranian researchers have identified a new malady to add to the list of side effects—hearing loss.

The Iranian researchers followed 24 hepatitis B and C patients treated with interferon and 30 healthy individuals who made up the control group. Their hearing was evaluated through questionnaires and hearing tests one week before treatment began and one month into treatment.

Patients reported minor ringing in their ears, but hearing tests found “progressive decreases in amplitude” in the 1, 2 and 4 frequencies in 41.66%, 18.75% and 32.75% respectfully.

Hearing loss was more common among older males. Researchers, writing in the July issue of the journal Biomedical Research International, suggest doctors monitor hearing during interferon treatment.

Source: www.ncbi.nlm.nih.gov/pubmed/23984336

African-Americans Suffer the Highest Rates of New HBV Infections in the U.S.
According to a study by University of Pennsylvania researchers, African-Americans make up the largest percentage of people who are newly infected with hepatitis B today.

In 2010, African-Americans had the highest rate of acute or new HBV infection with 1.7 cases per 100,000 people. In contrast, Asian-Americans had an acute infection rate of 0.6 per 100,000. Asian-Americans may have higher rates of chronic infection due to infection at birth, but most new infections occurring in the United States are in the African-American community.

In America, being black means you have a 3.9-fold chance of being infected with hepatitis B, compared to whites. According to the study, published in the August issue of the journal of Clinical Gastroenterology and Hepatology, African-Americans tend to be infected with HBV genotype A (84%), which is associated with a 4- to 5-fold increase in liver cancer compared to other genotypes.

To make matters worse, the few hepatitis B studies that have been performed in African-Americans and immigrants from Africa found that liver cancer occurs at a younger age in these populations than in other ethnic groups.

In contrast, among Asian-Americans genotypes B and C are most prevalent. Those genotypes appear not to be less virulent than HBV genotype A.

Additionally, African-Americans may have genetic risk factors that predispose them to developing chronic hepatitis B following exposure to the virus that other ethnic groups do not face. Yet, few doctors screen African-American patients for hepatitis B.

A long-term follow-up study of patients treated with interferon found that African American patients were, "... much more likely to respond to therapy," researchers wrote. "Of note, all African American responders not only cleared the hepatitis B "e" antigen and (achieved undetectable) HBV DNA ... but all cleared HBsAg, a relatively rare milestone with HBV therapy that (usually) occurs in (only) 7.8% of patients on therapy."

Unfortunately, this was a small study and no additional research into African-American's remarkable ability to reportedly clear hepatitis B infection after interferon treatment has been repeated to verify these results.

Few clinical trials have examined the effectiveness of antivirals in this population.

As with Asian-Americans, few African-Americans who qualify for treatment ever receive it. A small study that included patients from an urban medical center found that only 7% of a predominantly African-American and Hispanic population received treatment.

The study cited lack of health insurance, failure to take medication as prescribed and ongoing drug and alcohol use as possible reasons for poor access to treatment. Not surprising, access to liver transplants was also far lower among African-Americans than whites.

Source: www.ncbi.nlm.nih.gov/pubmed/23811241

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