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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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Experts Highlight Under-Treatment of Hepatitis B in the U.S.
Is chronic hepatitis B being undertreated in the United States? Yes says a group of hepatitis B experts, including researchers, specialists, and Hepatitis B Foundation officials, writing in the June 2011 issue of the Journal of Viral Hepatitis.

“Despite the fact that there are between 1.4 and 2 million chronic hepatitis B virus (HBV) infections in the United States, fewer than 50,000 people per year receive prescriptions for HBV antiviral medications,” they noted.

Currently there are now several antiviral medications approved for hepatitis B treatment by the U.S. Food and Drug Administration, and two types of interferon medications.

“Explanations for this incongruence include the potentially large number of infected persons who are unscreened and thus remain undiagnosed,” they noted, “and lack of access, including insurance, education and referral to appropriate medical care, particularly for disproportionately infected populations.”

Only 61.7% of U.S. Health Care Workers Immunized Against Hepatitis B
Because health care workers are at high risk of hepatitis B through exposure to patients’ blood and body fluids, government and medical agencies recommend that all doctors, nurses and other health care workers be immunized against hepatitis.

However, a recent report in the American Journal of Infection Control revealed that only 61.7% have received all three required hepatitis B doses.

The researchers reviewed data from adults in the 2007 National Immunization Survey, and examined the rates of immunization for influenza, tetanus, and hepatitis B among health care professionals.

They found 46.7% had received the flu vaccine, 70.4% had been immunized against  tetanus vaccination in the past 10 years, and 61.7% had received three or more doses of the hepatitis B vaccine. Workers with higher education levels had higher rates of HBV immunization.

The hepatitis B vaccine rates especially were disappointingly low and well below government recommendations for medical workers.

“Innovative strategies are needed to further increase vaccination coverage among health care professionals,” researchers wrote.

Forgetting to Take Your Meds—Not Drug Resistance—May Lead to Treatment Failure
Despite treatment with antiviral medications, many hepatitis B patients experience a resurgence in viral load (HBV DNA) and liver damage. According to an online Hepatology article, drug resistance—when HBV with certain mutations are able to replicate despite treatment—is the reason more than half of patients treated with antivirals experience a rebounding of their infection.

But about 40% of patients who suffer a resurgence of viral load do not have drug resistance. In some of these cases, experts suspect patients are simply not taking their medications as prescribed. “This study underscores the need for patients to take their medicines regularly to derive optimal response,” experts wrote.

But these results also serve as a warning to doctors not to automatically assume drug resistance is the reason for treatment failure. “There is a danger of misdiagnosis of drug resistance and unnecessary modifications to treatment regimen when it could be patients not adhering to their drug regimen," they added.

To determine if drug resistance—as opposed to poor medication adherence—was behind treatment failure, the experts studied 148 patients treated with antivirals by the University of Michigan Health System between January 2000 and July 2010. They found 39 (26%) had at least one incident of a viral rebound.

However, on retesting, 38% of those patients no longer had a breakthrough and 10 of them showed no sign of drug resistance. Overall, the rate of HBV DNA resurgence after 5 years of treatment was 46%. But the rate of a confirmed resurgence (proven by two consecutive blood tests) was only 30% at five years and the probability of drug resistance was actually only 34%.

When the 10 patients who had a viral rebound without any signs of drug resistance continued the same drug regimen, eventually they achieved undetectable viral load, suggesting that missed pills and poor medication adherence may have been behind some of the viral rebound in patients.

Surface Antibodies May Not Completely Eradicate Hepatitis B
Getting rid of the hepatitis B surface antigen (HBsAg) and the emergence of surface antibodies was once considered the “holy grail,” signifying recovery from a chronic hepatitis B infection.

But a study published in the Journal of Viral Hepatitis raises doubt that development of surface antibodies truly constitutes the end of a hepatitis B infection.

Researchers studied two patients who experienced a seroconversion and developed surface antibodies. However they remained positive for the hepatitis B “e” antigen (HBeAg) and continued to have detectable viral load (HBV DNA in their bloodstream) despite the presence of surface antibodies.

A liver biopsy confirmed that one patient’s liver continued to produce HBV proteins (antigens) despite the presence of surface antibodies.

Even though surface antibodies were thought to eradicate the antigens so no new HBV could be created, there were surface antigens remaining that were able to replicate and support continued HBV production, probably due to mutations that masked them from the surface antibodies.

“Thus, neutralizing surface antibodies may appear in chronic HBV carriers for long periods but does not necessarily lead to complete viral clearance,” researchers wrote.

In a similar study published in the April edition of Hepatology, experts found that development of surface antibodies during pegylated interferon treatment may not necessarily indicate the infection has disappeared.

While antiviral medications make it difficult for HBV to reproduce, pegylated interferon strengthens the immune system so it can better fight the infection. In this study, researchers examined the molecular make-up of HBsAg in 245 patients treated with interferon.

Eight patients (3.27%) cleared HBsAg, but two of the eight patients continued to have detectable HBV DNA. Apparently the HBsAg developed a mutation that allowed continued viral replication, even though the HBsAg was not detectable by conventional blood tests.

Emergence of surface antigen mutations is a possibility as the immune system tries to clear the infections, researchers suggest, resulting in “HBsAg-negative hepatitis.”

Monitoring HBsAg During Treatment Could Soon Be Routine Clinical Practice
Measuring surface antigen levels in the bloodstream may soon become a routine test—along with measuring viral load and liver enzymes—to see if treatment is working, according to an article published in Hepatology.

Researchers point out that interferon treatment, which is costly and causes uncomfortable side effects, ideally should result in a rapid reduction in HBsAg levels during the first few weeks of treatment—when it is successful.

If doctors regularly measure HBsAg in the blood stream during the early stages of treatment, they could determine quickly if the medication is working and customize treatment to avoid medication costs and side effects when it’s unsuccessful.

“Early stopping rules being proposed for patients not responding to pegylated interferon, based on lack of HBsAg decline, represent a step towards a response-guided approach,” they wrote.

When it comes to antiviral treatment, “The development of stopping rules for patients treated with (antivirals) would be a desirable step to reduce the burden of a need for life-long therapy,” they added. “However, before stopping rules for antiviral therapy can be applied, there is still more to learn about the kinetics of HBsAg decline, in both natural history and response to therapy, to better define the best timing and relevant HBsAg cut-off levels and how best to apply these in clinical practice.”

Radiation Exposure Increases Liver Cancer Risk More than Viral Hepatitis
A Japanese study finds that exposure to radiation (either through an atomic bomb or exposure from nuclear power plants) increases the risk of liver cancer more than hepatitis B and C.

In their report published in the April edition of Hepatology, researchers describe following 359 people with liver cancer between 1970 and 2002. The liver cancer rates among people who survived the Hiroshima atomic bomb were compared to liver cancer rates among people with hepatitis B and C, and to a control group matched by age, gender, and residence.

The cumulative liver cancer rates were far higher among people exposed to radiation, measured by Gray units or Gy, compared to those infected with HBV or HCV.  The risk of liver cancer for those exposed to 1 Gy of radiation was 1.67 while the liver cancer risks for HBV or HCV infection alone were 63 and 83 respectively.

Researchers found that radiation exposure was a “significant risk” for liver cancer.

Kidney Toxicity Uncommon Among Patients Treated with Tenofovir
Patients taking tenofovir (Viread) for hepatitis B face a moderate risk of kidney damage, according to a report presented to the 46th Annual Meeting of the European Association for the Study of the Liver.

Concerns were raised recently when researchers began finding kidney problems in HIV patients treated with the antiviral tenofovir, which is also used to treat hepatitis B. Researchers wondered if hepatitis B patients faced similar kidney risks from tenofovir or whether HIV infection contributed to kidney impairment.

Researchers followed 675 hepatitis B patients enrolled in three clinical trials involving tenofovir. The first two studies compared tenofovir with the antiviral adefovir (Hepsera), another compared tenofovir with a combination of tenofovir and emtricitabine (Emtriva). Another study looked at HIV-HBV coinfected patients. Most of the study members were male and 30% were Asian. Just over 40% were HBeAg-positive.

When the studies began, fewer than 1% had signs of kidney damage (poor creatinine clearance—less than 50 mL/min), and about 8% had moderate kidney damage (with impaired creatinine clearance of 50-80 mL/min).

Researchers analyzed data collected during 144 weeks and evaluated the patients’ kidney function. Among 426 previously-untreated patients receiving tenofovir, there was a low incidence of kidney problems over 144 weeks of treatment (2 patients had very minor signs of kidney problems).

Among 249 patients who had previously been treated with adefovir before receiving tenofovir, 1 patient (0.4%) had confirmed kidney problems.

Researchers concluded, “Tenofovir over 144 weeks was safe and well tolerated without clinically relevant changes in renal (kidney) function across a broad range of patient populations including those with co-morbidities typically associated with renal impairment.”

HBV Infection Appears to Contribute to Bone Loss
An international team of investigators looked into risk of bone loss in 250 hepatitis B patients who were evaluated before enrolling in the above-mentioned tenofovir clinical trials. They screened the patients’ bone density because tenofovir has been linked to bone loss.

Some had previously been treated with other antivirals. The researchers found many of the patients already had reduced bone mineral density, 6 had osteopenia, or low bone density, while 4 had more severe osteoporosis before treatment began.

Past antiviral treatment appeared to have had no impact on bone density, they noted. They did find that males and Asians have greater reductions in bone mineral density compared to females and non-Asians.

“Our data demonstrate a higher prevalence of baseline bone disease among patients with chronic HBV,” they concluded. “Duration of chronic HBV but not duration of treatment appears to [have an] impact [on] bone mineral density.”

Genotype A Patients More Likely to Seroconvert on Tenofovir
Another study presented at the European Association for the Study of the Liver conference showed that patients with HBV genotype or strain A and low levels of HBsAg were more likely to lose HBeAg and develop “e” antibodies (called HBeAg seroconversion) than patients with other genotypes.

In the study, 259 patients were assigned to take either tenofovir or adefovir for 48 weeks, and then adefovir-treated patients could switch to tenofovir for the next two years. Most were male, one-third were Asian, and more than half had advanced fibrosis or cirrhosis (severe liver scarring).

Seventy percent who were treated with tenofovir for 192 weeks maintained undetectable HBV DNA, with 104 patients (40%) experiencing at least one episode of HBeAg seroconversion during treatment, including 72 who stayed on tenofovir the whole time and 32 who switched from adefovir to tenofovir.

Patients with genotype A were most likely to experience HBeAg seroconversion, followed by genotype B and C. Patients with genotype D were 72% less likely to experience seroconversion than patients with genotype A. Those with lower HBsAg levels were also more likely to seroconvert.

There were no significant links between HBeAg seroconversion and race/ethnicity, gender, viral load, or liver health.

Asians Coinfected with Hepatitis B and C Have “B” as Their Dominant Infection
Asian-Americans who are infected with both HBV and HCV are more likely to have HBV infection as their dominant liver infection, compared to coinfected non-Asians, according to a U.S. study published in Hepatology.

Stanford University researchers followed a multi-ethnic group of patients and analyzed their HBV DNA, HCV RNA, and alanine aminotransferase (ALT) levels (which increase when liver cells are damaged and die). They compared 115 coinfected patients with 115 patients infected with only HBV.

The number of patients with elevated ALT levels, indicating liver damage, was similar in both groups. However, dual-infected Asian-Americans tended to have more HBV DNA and less HCV RNA. However, only 23% of this coinfected group (where HBV was dominant) received treatment for hepatitis B, compared to 43% of the HBV-only group.

“Our findings may suggest that … Asian ethnicity is an independent predictor for HBV-dominated dual infection,” researchers wrote.

Copper in Aquariums Destroys Bacteria That Threatens Those with Infected Livers
According to an article in the journal Biology & Nature, placing a brass or copper plate in aquariums that house seafood or shellfish that is to be eaten raw could kill off the dangerous seafood bacteria Vibrio. The bacteria can be especially lethal to people with hepatitis infections.

In Korea, about 12% of food poisoning cases are attributed to Vibrio. Researchers found that copper ions that diffuse from a brass plate in a fish tank filled with seawater kills nearly all Vibrio bacteria within 40 hours.

The copper is absorbed by the bacteria, causing them to die and fall off the gills and skin of the fish. Vibrio are even flushed from the internal organs of the fish, sinking to the bottom of the tank.

Koreans have claimed that food served in a traditional bowl called a bangzza is safer to eat and food researchers have proved the science behind the myth. The 78% copper and 22% tin mixture used to make the traditional bangzza kitchenware allows enough copper ions to escape into the food to kill Vibrio bacteria.

In countries with many people suffering from poor sanitation and hygiene, where cholera and other Vibrio bacteria are rife, it appears this traditional cookware may save lives.



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