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HBV Journal Review

HBV Journal Review
April 1, 2012, Vol 9, no 4
by Christine M. Kukka

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For Older Adults, Health Care Procedures Pose Higher Hepatitis Risk Than Sex and Illicit Drugs
What poses the highest risk of hepatitis B or C infection to adults age 55 and older? Unprotected sex with more than one partner? Illicit drug use? Or visits to the doctor?

Faced with an increase in the number of viral hepatitis outbreaks due to re-used medical devices among older adults, U.S. Centers for Disease Control and Prevention (CDC) researchers decided to find out what practices and behaviors posed the highest hepatitis transmission risk.

They examined new hepatitis B virus (HBV) and C (HCV) cases reported to three health departments in New York and Oregon over two years to see how they were infected. Investigators focused on behaviors and health care visits that occurred within six months before symptoms were reported—the usual "incubation period" for viral hepatitis. They compared the hepatitis patients' histories to that of an uninfected, control group.

Researchers tracked 37 hepatitis B and 11 hepatitis C cases and found 21% of them reported one or more risky behavior, including sexual or household contact with an HBV- or HCV-infected person, more than one sex partner, illicit drug use, or incarceration. The control group, in comparison, had a 4% risky behavior rate.

Then they compared what medical procedures the two groups had experienced. They found hepatitis patients had far higher rates of hemodialysis (8%), injections in health care settings (58%), and surgeries (33%) than did the control group.

When these various risk factors were analyzed for the 48 patients, researchers calculated that:

  • High risk behaviors (sex, illicit drug use) posed a 17% "attributable" risk of hepatitis
  • Injections in a health care setting posed a 37% risk
  • And hemodialysis posed an 8% risk

Health care exposures clearly pose a higher risk of hepatitis than risky behaviors. "Health care exposures may represent an important source of new HBV and HCV infections among older adults," researchers wrote the March issue of Hepatology.

Pegylated Interferon and Adefovir Combination More Effective Than Interferon Alone
Researchers are trying to determine if a combination of pegylated interferon (Pegasys, which boosts the immune system) and antivirals (which hinder the virus' ability to replicate) is more effective than interferon alone.

In this study, published in the March 2012 issue of the journal Hepatogastroenterology, researchers treated 160 patients with either pegylated interferon alone (which requires a weekly injection) or with a combination of the interferon plus the antiviral adefovir (Hepsera).

At week 24, the percentage of patients who achieved normal alanine aminotransferase (ALT) levels (which indicate no liver damage) and undetectable viral load (HBV DNA) were higher in the combination group (57.50% and 43.75% respectively) than in the interferon-only group (40% and 27.5%).

After 96 weeks of treatment, 46—25% of the patients treated with both interferon and adefovir—cleared the hepatitis B “e” antigen (HBeAg) and developed "e" antibodies (called seroconversion) compared to 30% in the interferon-only group.

"Furthermore, there was no statistically significant difference in relapse rates and adverse events between the two groups," researchers noted.

Researchers concluded that the combination therapy, "... can accelerate undetectable HBV DNA and elevate HBeAg clearance/seroconversion rates to a greater degree," than with just interferon.

Many Younger Patients with Liver Cancer Don't Experience Cirrhosis, So Diagnoses Are Delayed
Current practice guidelines do not call for aggressive liver cancer screening in young adults (age 40 or younger) who do not have cirrhosis (severe liver scarring), which is considered a precursor to liver cancer.

But a multinational team of researchers decided to study hepatitis B patients were who recently diagnosed with liver cancer to make sure the current screening guidelines were effective in finding liver cancer early through alpha fetoprotein (AFP) tests and ultrasounds.

According to their report published in the April Journal of Digestive Diseases, doctors assessed 93 patients admitted to Bellevue Hospital Center with liver cancer.

Eighteen of the cancer patients were younger than 40, and only 12 (66.7%) of them had cirrhosis.

"Current guidelines for liver cancer screening in patients with HBV may lead to a delay in diagnosis in non-cirrhotic patients under 40 years," researchers noted.

"Consideration should be given to modifying current recommendations to advocate entering HBV patients into a cancer-screening program at young age."

Doctors May Miss HBV in HIV-Infected Patients
Doctors, writing in the International Journal of STD and AIDS, reported on a case of a missed hepatitis B infection in an HIV-infected man who had tested negative for the hepatitis B core antibody (anti-HBc). This test is commonly used to identify past and current HBV infections.

After he tested negative for the core antibody, he was immunized with the three doses of hepatitis B vaccine. However, doctors noticed that his ALT levels remained above normal. During this period, he received antiviral treatment for his HIV infection. These antivirals are not always effective against hepatitis B, and one—lamivudine—can quickly cause drug resistance.

Another round of hepatitis B testing finally revealed he was positive for the hepatitis B surface antigen (HBsAg) and HBV DNA. He was switched to tenofovir (Viread), an antiviral that is effective against both HIV and HBV.

Researchers cautioned doctors to perform more thorough screening for hepatitis B among those infected with HIV, beyond the core antibody test, in their report in the International Journal of STD and AIDS.

In an unrelated study, researchers presenting at the 19th Conference on Retroviruses and Opportunistic Infections reported success in treating HIV-HBV coinfected patients with tenofovir. About 17% of HBeAg-positive patients cleared HBeAg after one year and 47% cleared it after six years of treatment. About 23% lost HBeAg and developed "e" antibodies after six years of tenofovir.

Five (8%) of the HBeAg-positive patients lost HBsAg during treatment, as did three HBeAg-negative patients.

Researchers noted that 71% of HBeAg-positive coinfected patients with HBsAg levels below 100 IU/mL cleared HBsAg after six months of treatment.

Low Levels of HBsAg and HBV DNA Could Predict Viral Clearance
Researchers closely followed people who were HBeAg-negative and who eventually lost HBsAg to see what characteristics could predict loss of HBsAg. Knowing these attributes may be valuable to doctors who are trying to decide when to stop treatment or when treatment is needed.

They compared 203 HBeAg-negative patients who spontaneously cleared HBsAg without treatment with 203 other HBeAg-negative patients of similar age and gender. They screened the patients' HBsAg and HBV DNA levels and found that average HBsAg levels were:

  • 23.5 IU/mL in patients three years before HBsAg clearance
  • 3.51 IU/mL two years before clearance
  • 0.524 IU/mL one year before clearance
  • and 0.146 IU/mL six months before clearance.

Those who cleared HBsAg consistently had lower HBsAg and HBV DNA levels compared to those in the control group who did not clear HBsAg. While HBsAg levels did decrease slightly over time in the control group, HBV DNA levels remained constant and did not decline.

Researchers reported in the March issue of Hepatology that patients who had HBsAg levels less than 200 IU/mL, and who had regular reductions in HBsAg of 50% annually may clear HBsAg within three years.

Hepatitis B Patients May Need Selenium Supplements
Pakistani researchers discovered that people experiencing hepatitis B-related liver damage may have deficiencies in selenium—an essential trace mineral that strengthens the immune system. Selenium contributes to the creation of antioxidants that help protect people from cancer and heart disease.

They measured selenium levels in 150 patients infected with HBV and HCV and compared those levels with 26 healthy people. They found selenium levels higher in healthy individuals than in those with viral hepatitis. The more liver disease patients had, the lower were their selenium levels.

"Based on findings of this study, it is proposed that selenium should be supplemented in such patients in order to optimize nutritional support and to get better treatment response," they wrote in the March issue of the Saudi Journal of Gastroenterology.

HBV Infection in Women Does Not Affect Gender of Offspring
Does the presence of hepatitis B infection increase the chance that a woman will give birth to a son? No say Taiwanese researchers, writing in the March issue of American Journal of Human Biology.

They studied the hepatitis B status of 90% of 3 million women who gave birth in Taiwan between 1988 and 1999.

Five percent of the women who gave birth were HBeAg-positive, and they were "slightly" more likely to have a son (on average they gave birth to 108 sons compared to 106 daughters). Age, birth order, mother's age, birth year and area of residence had no impact on this ratio, nor apparently did hepatitis B status.

Lamivudine May Be Effective for Some, If Carefully Monitored
Lamivudine is the cheapest and most widely available antiviral available worldwide, but current guidelines do not recommend this drug due to its high rate of drug resistance. But are there some patients for whom lamivudine is an inexpensive and effective option?

Researchers followed 369 patients over 10 years and zeroed in on 47 patients (36 male, average age 44) who were treated with lamivudine and carefully monitored over several years.

Lamivudine worked in 45 (96%) patients, with 88% achieving undetectable viral load after four years, along with a decrease in liver damage. Seven of 13 HBeAg-positive patients seroconverted and developed “e” antibodies. Treatment was ineffective in only 11% of the patients.

Based on these researchers concluded that lamivudine could still be used in patients, but only if the patients were monitored every six to 12 months to identify treatment failure, according to their report in the March issue of the Canadian Journal of Gastroenterology.

Testing All Patients with Elevated ALTs May Identify Hepatitis
Health care providers often do not screen at-risk patients for hepatitis B and C, which is why 70% of people infected with HCV and about 60% of people infected with HBV do not know they are infected and remained untreated.

One indication of viral hepatitis infection is elevated ALT levels. These liver enzymes increase above normal when liver cells are damaged and die.

Dutch researchers decided to see if would be worthwhile to screen primary care patients with elevations in ALT for viral hepatitis.

They screened 750 blood samples from patients whose ALT levels were mildly elevated (30-50 IU/l), moderately elevated (50-70 IU/l, and critically elevated (70-100 IU/l). They then tested the samples for HCV and HBV.

They found that people with ALT levels of 50-100 IU/l, had a hepatitis C infection rate that was ten-fold higher than in the general population. An above-normal rate of HBV was not identified in patients with elevated ALT levels.

As a result, according to researchers writing in the British Journal of General Practice, “…follow-up for HCV is indicated in these patients, even when other explanations for ALT elevation are present.”

Only 34% of Elderly Can Be Successfully Immunized Against Hepatitis B
Recently, epidemiologists have identified outbreaks of hepatitis B in long-term care facilities due to improper re-use of diabetes testing equipment.

To determine how effective immunization would be, CDC researchers immunized seniors (average age 79.5, 56% female, 51% African-American) against hepatitis B, and then screened them to see if they had enough antibodies to fight off infection.

According to their report published in the March issue of the journal Vaccine, only 29 (34%) of 86 residents who received all three vaccine doses responded successfully and developed enough hepatitis B surface antibodies to prevent infection.

"There were no significant differences in vaccine response by age, gender, race, diabetes status, body mass index, or current smoking status," they wrote. "Our findings indicate that a low proportion of skilled nursing facility residents achieved a seroprotective response after hepatitis B vaccination."

Surface Antigen Declines with Onset of Cirrhosis and Liver Cancer
Ironically, the amount of HBsAg circulating in the bloodstream of hepatitis B patients decline as they develop cirrhosis and liver cancer, according to a report published in the Chinese medical journal Zhonghua Gan Zang Bing Za Zhi.

HBsAg and HBV DNA levels were monitored in 47 chronic hepatitis B patients, 72 patients with cirrhosis, and 54 liver cancer patients.

The average HBsAg levels:

  • Decreased from 2,361.10 IU/ml in chronic hepatitis B patients to 1,001.64 IU/ml in cirrhotic patients and down to 594.35 IU/ml in liver cancer patients.
  • Among HBeAg-positive patients, HBsAg decreased from 3259.83 IU/ml in the chronic patients to 1,077.30 IU/ml in the cirrhotic group and then to 789.72 IU/ml in the liver cancer group.
  • Among HBeAg-negative patients, HBsAg declined from 1,669.00 IU/ml in the chronic group to 1,001.64 IU/ml in the cirrhotic group and 582.05 IU/ml in cancer group.

Elevated ALT Levels Do Not Accurately Predict Liver Damage
Between 1994 and 2008, Hong Kong researchers performed liver biopsies on 319 untreated hepatitis B patients to study the relationship between ALT levels and liver damage.

In the study, 211 patients were HBeAg-positive and 108 were HBeAg-negative, with an average age of 31 and 46 years respectively.

Nine of 40 (22.5%) HBeAg-positive patients who had normal ALT (30 U/L for men, 19 U/L for women) had significant liver damage.

Age, aspartate aminotransferase (another enzyme that indicates liver health) and platelet count were all good indicators of who had significant fibrosis among HBeAg-positive patients with elevated ALT levels.

Among HBeAg-negative patients, viral load and platelet count were better predictors of liver damage.

What was significant was that an elevated ALT level did not always accurately predict the presence of liver damage or significant fibrosis among either HBeAg-positive or -negative patients.

In fact, there was no significant difference in fibrosis among patients with moderately elevated ALT (one to two-times the upper limits of normal) and those with more than twice the upper level of normal for both HBeAg-positive and -negative infections, according to Hong Kong researchers' report published in the journal PLoS One.

They concluded that, "an elevated ALT does not accurately predict significant liver injury." Doctors should consider more than just ALT when making decisions about initiating treatment, they noted.

One-Third of Hepatitis B Patients Forget to Take Their Daily Antivirals
A recent article in the World Journal of Hepatology suggests that many hepatitis B patients often forget to take their daily antiviral pills. It is important to take antiviral medications regularly, because poor adherence can lead to development of antiviral resistance.

Australian researchers asked 80 patients about their antiviral adherence in a survey and discovered that only 66% took the pills as prescribed while 25 (33.8%) reported they often forgot their medications. The most common reason cited by patients was forgetfulness, running out of medications, being too busy, and recent changes in daily routines.

"Adherence rates were much less than that expected by the physician and has potential adverse affect on long term outcome," doctors noted.

New MicroRNA Test Very Effective in Identifying Liver Cancer
Today, an alpha fetoprotein (AFP) tests performed on a blood sample is the most common test used to identify liver cancer--but it fails to identify cancer in nearly half of all patients.

A new test using microRNAs (miRNAs)—small RNA molecules that can signal the presence of tumors--appears to be more accurate and could eventually replace AFP tests, according to a report in the online journal BMJ Open.

Researchers measured and compared miRNAs in 57 liver cancer patients, 29 hepatitis B patients, and 30 healthy people in China.

The miRNAs were an effective biomarker for liver cancer, and markedly declined after patients had liver tumors removed surgically, confirming that the tumors produce the miRNAs.

The miRNA test found cancer in 96.7% of cases, while AFP tests are only 50% effective. The new test found very early-stage cancers that were completely missed by AFP tests.



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