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HBV Journal Review

HBV Journal Review
May 1, 2011, Vol 8, no 5
by Christine M. Kukka

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HBV Infection Rate in the United States Drops from 5.1% to 4.6%
A national study to determine the incidence of hepatitis B virus (HBV) infection nationwide estimates that 0.27% of the U.S. population has chronic hepatitis B, according to a report in the March 2010 issue of the Annals of Internal Medicine.

The study focused on a representative population of 39,787 enrolled in a National Health and Nutrition Examination Survey conducted between 1999 and 2008. Participants were considered chronically infected if they were age 6 and older and tested positive for the hepatitis B surface antigen (HBsAg).

About 4.6% of those surveyed (representing approximately 12 million people nationwide) had been exposed to the virus, with the vast majority clearing the infection and developing surface antibodies. About 0.27% (represent-ing about 704,000 people nationwide), were found to have chronic hepatitis B by testing positive for HBsAg.

In contrast, between 1988 and 1994, experts estimated the chronic HBV infection rate to be 0.42% and the previously infected rate at 5.1%.

The current infection rates are lower, especially among those ages 6 to 19, who have been vaccinated under government-mandated childhood immunization programs that began in 1992. While children age 2 had the highest rates of immunity (ranging from 68.6% to 73.2%) due to immunization, adults–including those at high infection risk of infection–had much lower rates of immunity from vaccination.

Unfortunately, the study did not include incarcerated and homeless people, who can be at high risk of HBV infection, nor did it include undocumented immigrants, who have high rates of infection if they are from countries with high HBV prevalence.

Cancer Expert Promotes Screening All Chemotherapy Patients for Hepatitis B
Every cancer patient receiving chemotherapy should be tested for HBV, according to a presentation at the recent National Comprehensive Cancer Network’s 16th Annual Conference.

Chemotherapy, which suppresses the immune system, can cause a rebound in HBV DNA (viral load) and liver damage because the immune system can no longer keep it in check, according to experts from the Memorial Sloan-Kettering Cancer Center in New York City.

If patients are tested, those with “inactive” chronic hepatitis B can be treated with antivirals, which make it hard for HBV to replicate even when the immune system is weakened by the chemotherapy. If not treated with antivirals, HBV-infected chemotherapy patients risk an HBV reactivation, and between 5% to 40% of them will die of liver failure.

Currently, leukemia and lymphoma cancer patients treated with rituximab (Rituxan and MabThera) are routinely screened for HBV. But doctors often fail to identify those at risk of hepatitis B, including those of Asian and African descent, as well as sexually active people, men who have sex with men, and injecting drug users. An estimated one-third of the world has been exposed to HBV and about 350 million have chronic infection.

Despite this prevalence, the network does not recommend universal testing for patients undergoing chemotherapy. Instead, the network says in its Prevention and Treatment of Cancer-Related Infections guideline, that, "in patients undergoing intensive immunosuppressive therapy, evaluation of HBV surface antigen, core antibody, and surface antibody should be considered at baseline."

Some medical centers go farther and routinely test all chemotherapy patients for HBV, including Sloan-Kettering and Stanford Comprehensive Cancer Center in Palo Alto, Calif.

Preventing HBV reactivation is far more effective than treating a reactivated infection, experts noted. One study found that patients who had reactivated hepatitis B during chemotherapy and weren’t treated with antivirals until after chemotherapy started experienced a 47% rate of liver damage or failure.

While many organizations endorse universal screening for immunosuppressive therapy, surprisingly the American Society of Clinical Oncology does not recommend universal screening. It contends that additional “randomized controlled trials” are needed to establish the need for universal screening.

“There are no randomized controlled trials to show that parachutes work," the presenters argued during their presentation. Since instituting screening at Memorial Sloan-Kettering in 2006, the center has had only 3 HBV reactivations, all of which resulted because patients did not take the prescribed antiviral medications.

Experts Examine Connections between Hepatitis B and Diabetes
Experts continue to explore the impact on the endocrine system of HBV infection in the liver and diabetes, which can impair the immune system.

  • The incidence of acute hepatitis B is nearly twice as high in adults with diabetes, according to new data from the Centers for Disease Control and Prevention (CDC) that was presented to a recent meeting of the CDC’s Advisory Committee on Immunization Practices. The data was based on 12 million people in Connecticut, Colorado, Oregon, and New York City who participated in the CDC’s Emerging Infection Program.

    When experts examined the hepatitis B rates in the study population, they found that the diabetes rate among the hepatitis B patients was nearly double that of the entire study population (15% vs. 8.4%).

    The Advisory Committee on Immunization Practices is currently weighing whether to recommend hepatitis B vaccination for all people with diabetes. This proposal has been gaining momentum as a result of hepatitis B outbreaks traced to improper re-use and sharing of blood glucose testing and insulin injection devices in nursing homes and health care settings.

  • A report in the journal of Alimentary Pharmacology & Therapeutics examined the impact of diabetes on dialysis patients who were immunized against hepatitis B. Because of the medical procedures involved in dialysis, these patients can be at high risk for medically-contracted hepatitis B. They found a clear association between diabetes and poor response to hepatitis B immunization in individuals on long-term dialysis.


Biopsy and Treatment Recommended in HBeAg-negative Patients above 30, Even When ALT Is Normal
Chinese researchers, writing in the March 2011 issue of the journal Liver International, recommend a liver biopsy in all patients who are hepatitis B “e” antigen (HBeAg)-negative and age 30 or older even if they have normal alanine transaminase (ALT) levels.

ALT levels rise above normal when liver cells are damaged or die, but these researchers found there was an elevated risk of liver inflammation and fibrosis in HBeAg-negative patients even when ALT levels were normal or only slightly elevated.

Over a three-year period, researchers followed 499 chronic hepatitis B patients and divided them into groups with normal and above normal ALT levels.

They found that even when ALT levels were normal, 66 (23.1%) of HBeAg-negative patients had inflammation and 31 (10.8%) had fibrosis. Those rates were lower among HBeAg-positive patients.

The HBeAg-negative patients with even slightly elevated ALT levels also had far higher rates of liver damage than HBeAg-positive patients. Among those who were HBeAg-negative, 34 (30.6%) had moderate-to-severe fibrosis and 38 (34.2%) had fibrosis when their ALT levels were only 1.5-times the normal rate.

Additionally, patients who were age 30 or older had significantly higher rates of liver inflammation and fibrosis.

“We recommend liver biopsy in HBeAg-negative patients over 30 years of age regardless of ALT level and starting treatment [when] ALT is 1.5 times normal instead of twice the upper normal limit,” they wrote.

HBV Immunization at Birth Reduces Infection, but Parents May Still Transmit Infection
Since 1984, Taiwan has mandated universal hepatitis B immunization at birth to prevent mother-to-child transmission of HBV. But how effective has this vaccine been in preventing infection after immunization–when the mother and/or father are infected?

Researchers, writing in a recent issue of the Journal of Medical Virology, followed 18 children born to HBsAg-positive parents.

Of these 18, four (21.4%) became infected. Three of them were born to HBsAg-positive mothers and one was born to an HBsAg-positive father.

“In conclusion, this small study showed that both maternal and paternal transmissions are important in the intrafamilial spread of HBV infection,” researchers wrote. “In addition, the introduction of HBV vaccination has resulted in a reduction of intrafamilial transmission, but a study of a large population is needed.”

A separate Chinese study into HBV infection at birth, also published in the Journal of Medical Virology, examined whether immunization or treatment with hepatitis B immune globulin (HBIG- hepatitis B antibodies) could prevent mother-to-child infection.

The scientists studied blood samples taken from the infants and mothers before the vaccine or HBIG were administered to determine if the infants had been exposed to the virus in the uterus, during birth, or after, during regular mother-to-child contact. They followed 214 infants born to HBsAg-positive mothers over three years.

They found that mother-to-child transmission occurred in 4.7% (10 of 214) of the infants; the perinatal transmission rate was 3.7% (in 8 of 214), and the intrauterine transmission rate was 0.9% (2 of the 214).

The risk of mother-to-infant transmission increased in mothers who were HBeAg-positive and had high HBV DNA levels.

After 36 months, all perinatal cases became HBsAg-negative, but all infants infected while in the uterus developed chronic hepatitis B. “These results indicate that infants infected via intrauterine transmission cannot be effectively protected by HBIG and the hepatitis B vaccine,” they wrote.

Antiviral Effective in Preventing Liver Failure in Acute Hepatitis B Cases
A small number of people develop a severe, life-threatening form of hepatitis B, called fulminant hepatitis, when they are infected. Researchers, writing in the April issue of Liver International, report that using an antiviral commonly used to treat chronic hepatitis B can quickly reduce the patient’s viral load and improve survival markedly.

A review of a hospital’s database of fulminant hepatitis patients found that the 38 who received the antiviral lamivudine (Epivir-HBV) had a far lower death rate (63.2%) compared to untreated patients (84.6%).

HIV-HBV Coinfected Face Higher Death Rates than HIV-HCV Coinfected
HIV-positive gay and bisexual men in the long-running Multicenter AIDS Cohort Study (MACS) coinfected with HBV and HIV face twice the risk of death than those coinfected with the hepatitis C virus (HCV) and HIV, according to a report presented at the 18th Conference on Retroviruses and Opportunistic Infection.

The study followed 229 men who were HIV-HBV coinfected and 243 men who were HIV/HCV coinfected over a seven-year period.

Liver-related death rates were nearly twice as high for the hepatitis B group than the hepatitis C group. The liver-related death rate was 14.5 per 1,000 person-years in the HIV-HBV coinfected group, compared with 8 per 1,000 person-years in the HIV-HCV coinfected group.

Researchers did note that the death rate for HBV-HIV coinfected men began to decline after tenofovir (Viread) became available for treatment of hepatitis B. Tenofovir is effective against both HIV and HBV.

The findings underscore the need to screen and immunize those at risk of both HBV and HIV infections, and for treating coinfected patients with antiviral drugs that are effective against both viruses.

Hepatitis B X Protein Holds the Key to HBV Reproduction
Researchers have for years tried to figure out what role the hepatitis B X protein (HBx) played in the virus’s life cycle.

Recently, German scientists were able to study livers cells infected with HBV that lacked the “x” protein. They found that cells “inoculated” with HBx-deficient HBV particles, “did not lead to productive HBV infection,” while liver cells inoculated with normal HBVs (that had the HBx) did lead to infection, according to their report published in the March 2011 edition of the Journal of Hepatology.

“Our results demonstrate that HBx is required to initiate and maintain HBV replication,” they wrote, “and (they) highlight HBx as the key regulator during the natural infection process.”

Entecavir Reverses Advanced Fibrosis and Cirrhosis
U.S. researchers followed 10 patients with advanced liver fibrosis and scarring (cirrhosis) who were treated with the antiviral entecavir (Baraclude) for six years to see if the treatment was effective in reversing their advanced liver damage.

Writing in the March issue of the journal of Clinical Gastroenterology and Hepatology, researchers reported that all 10 patients showed marked improvement in liver health, even among the four patients who had cirrhosis when treatment began, over the six-year treatment period.

Tenofovir Highly Effective, with No Resistance, after 144 Weeks
An international team of researchers, conducting an eight-year study into tenofovir, report that at Week 144, the more than 600 patients in the study have done well on the antiviral and showed no signs of developing antiviral resistance.

According to the report published in the March issue of Hepatology, only 0.8% (5) of the 641 patients receiving tenofovir continued to have detectable HBV DNA (greater than 400 copies/mL).


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