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HBV Journal Review

HBV Journal Review
October 1, 2010, Vol 7, no 10

by Christine M. Kukka

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Vitamin D Deficiency Nearly Universal Among People with Liver Disease
U.S. researchers reported in the September 2010 journal Digestive Diseases and Sciences that 92 percent of people with chronic liver disease suffer vitamin D deficiency, and one-third of them, especially those with cirrhosis, suffer severe vitamin D deficiency.

Researchers followed 118 patients (43 with hepatitis C-related cirrhosis, 57 with hepatitis C without cirrhosis, and 18 with nonhepatitis-related cirrhosis) and measured their vitamin D levels. They found that 109 (92.4%) had some degree of vitamin D deficiency.

  • In the hepatitis C with cirrhosis group of 43 patients, 16.3% had mild deficiency, 48.8% had moderate deficiency, and 30.2% had severe vitamin D deficiency.
  • In the hepatitis C group without cirrhosis, 22.8% of the 57 had mild deficiency, 52.6% had moderate deficiency, and 14% had severe deficiency.
  • In the cirrhotic group without hepatitis, 38.9% of the 18 had mild deficiency, 27.8% had moderate deficiency, and 27.8% had severe vitamin D deficiency.

African-American women and people with cirrhosis were at the highest risk of vitamin D deficiency.

HBeAg-Positive Patients with High ALT Levels Respond Well to Telbivudine 
Chinese researchers compared the effectiveness of the antiviral telbivudine (Tyzeka) in 40 hepatitis B “e” antigen (HBeAg)-positive patients with extremely high alanine aminotransferase (ALT) levels—10 to 20 times the upper limit of normal—with a group of 40 HBeAg-positive patients with moderately elevated ALT levels (2- to 10-times the upper limit.) Above-normal ALT levels indicate that liver cells are damaged or dying.

After 52 weeks of telbivudine treatment, the average decrease in HBV DNA levels was 7-fold in the high ALT group and 6-fold in the lower-ALT group.

The percentage of patients with undetectable HBV DNA (viral load) after a year of treatment was 72.5% in the high ALT group and 60% in the moderate-ALT group. Additionally, 45% of high ALT patients and 27.5% of the other group became HBeAg-negative, and 37.5% of the high baseline group and 22.5% of the moderate group lost HBeAg and developed “e” antibodies.

Ten percent of the high ALT group lost hepatitis B surface antigen, and three developed surface antibodies. Only 1 patient in the moderate ALT group became HBsAg-negative.

Equal numbers in both groups achieved normal ALT levels after a year of treatment.

“High baseline ALT level is a strong predictor for optimal results during telbivudine treatment,” researchers wrote in the August 2010 issue of the World Journal of Gastroenterology.

The Chinese researchers focused on telbivudine in this study, even though it has a high rate of viral resistance, because other recommended antivirals, such as tenofovir (Viread), are costly and not widely available in China.

Survival After Liver Cancer Surgery Increases When Fibrosis Is Minimal
Fibrosis and severe liver scarring—cirrhosis—contribute to the development of liver cancer. But once cancerous tumors are removed from the liver, what role does fibrosis play in recurrence of liver cancer?

Taiwanese researchers compared the outcomes of 76 cancer patients who had either minimal fibrosis or advanced fibrosis after one small liver tumor was removed surgically.

They followed 14 patients with minimal fibrosis and 62 with advanced fibrosis over 77 months. Survival was significantly higher and cancer recurrence markedly lower among patients with minimal fibrosis.

Researchers concluded in the September 2010 issue of Hepatology International, “… minimal fibrosis is associated with a lower incidence of (cancer) recurrence and with better survival.”

Faulty Pediatrician Practices Result in Low Childhood Immunization Rates
Researchers, using data covering 5.9 million U.S. children in the 2004-2006 National Immunization Survey, found that just over 80% of the children had received their recommended immunizations by 36 months of age.

The goal of the study was to assess the success of pediatricians’ immunization practices. The investigators evaluated whether children received the full range of childhood vaccines, including the three recommended hepatitis B doses.

Writing in the Journal of Pediatrics, the researchers noted that patients of providers who administered the first hepatitis B vaccine at birth had a higher rate of immunizations at 36 months of age. Mothers with a high school education or higher tended to have children with higher rates of immunization.

African-American children had the lowest rate of immunization, as did children living in poverty. Also, vaccination rate declined when children received immunizations from more than one provider.

The investigators concluded that a medical practice’s vaccine policies can greatly influence immunization rates among children.

“It seems incredible that with so many potential opportunities to deliver hepatitis B vaccines (7 health maintenance visits before age 19 months) the practitioners could not deliver 3 hepatitis B vaccinations,” researchers wrote. “This observation raises the real question, unable to be answered by the current study, of whether the problem is that practitioners assume that the first hepatitis B vaccination was given in the nursery, so the children receive, on average, only 2 more doses, forever leaving them deficient for the hepatitis B series.”

New Studies Confirm Liver Damage Even When HBV Infection Is Inactive
New studies of patients who have “inactive” hepatitis B virus (HBV) infection confirm that even patients with normal ALT levels and low viral load experience liver damage from the infection and may require treatment.

Bangladeshi researchers, reporting in a recent issue of the Journal of Medical Virology, performed liver biopsies on 141 “inactive” hepatitis B patients whose viral load was less than 10,000 copies/mL and who tested negative for HBeAg.

They found that 26% of the patients (36 of 141) had mild to moderate inflammation, 17 had severe fibrosis, and 10 patients had both severe inflammation and fibrosis.

All of the 10 patients were male and older than 25 years. However, all were HBeAg-negative and had low levels of HBV DNA and normal ALT levels.

This study, like recent ones into the true health of “asymptomatic” hepatitis B patients, reveals that liver damage is present in a considerable number of seemingly “healthy” patients, and that they may require treatment despite their low viral load and normal ALT levels.

A different study, this one exploring normal ALT levels in HBeAg-positive patients, published in the August 2010 issue of the Journal of Viral Hepatology, reviewed the liver health of 193 patients who underwent liver biopsies over a 10-year period. Among those studied, most were HBeAg-positive, had elevated ALT levels, 55.7% were Asian-American, 56.4% were men, and the average age was 43.

“Significant” liver disease was observed in 14% of those with normal ALT at the time of biopsy (but who had elevated viral load) and in none of the patients with persistently normal ALT.  “Significant liver disease is rare in patients with chronic HBV and persistently normal ALT,” the researchers concluded.

Hepatitis B Virus Origins May Be Millions of Years Old
Genetic fragments found in songbirds today are identical to viral fragments found in today’s hepatitis B-like viruses—which proves that hepatitis-like viruses were circulating about 20 million years ago.

Viruses trick a cell into reproducing their genetic codes in order to create more viruses, and some even insert their RNA into the host cell's genome or blueprint in order to reproduce. Sometimes these viral parts are passed on to their host's offspring, and the viral particles are passed from generation to generation.

University of Texas researchers examined song bird fossils from a variety of evolutionary periods and ultimately found 15 identical fragments from the hepatitis B family. These fragments still survive today in the genome of the zebra finch of Australia, and in the dark-eyed junco of North America.

These two species diverged from each other millions of years ago, indicating that the virus had infected one of their common ancestors and its viral DNA particles have been handed down to both species.

Up to 75 percent of the ancient viral fragments were identical to currently circulating viruses, which had previously been estimated to be less than 6,000 years old. However, the new results suggest the origin of hepatitis viruses may go back much farther, according to the report in LiveScience.

Declines in HBsAg and HBeAg After 12 Weeks of Pegylated Interferon Indicate Long-Term Treatment Success
Researchers compared declines in HBsAg and HBeAg among patients treated with either conventional interferon (requiring three weekly injections) or pegylated interferon (requiring one weekly injection) at weeks 12 and 24, and then for 24 weeks after treatment to see if the antigen levels predicted treatment success.

Chinese researchers, writing in the September 2010 Journal of Gastroenterology and Hepatology, reported that pegylated interferon was the more successful treatment of the two. Additionally, those who achieved an HBsAg decline down to 1,500 IU/mL at week 12, and who then achieved a drop of HBsAg to 2,890 by week 24 had a far higher chance of losing HBeAg and developing “e” antibodies 24 weeks after treatment ended.

During the follow up period, patients with HBeAg seroconversion remained HBeAg-negative and none of them progressed to cirrhosis. But patients who did not seroconvert had a higher rate of developing cirrhosis.

Widespread Drug Resistance Found in Chinese Patients Treated with Antivirals
Researchers followed 1,803 Chinese hepatitis B patients, who had previously been treated with the antivirals lamivudine, adefovir, or telbivudine to see what impact their HBV strain or genotype had on the development of drug resistance—when HBV with certain mutations are able to “resist” the antiviral treatment and continue reproducing.

Drug-resistance was detected in 560 of the 1,803 patients, including:

  • 214 of 490 patients treated with lamivudine
  • 35 of 428 patients treated with adefovir
  • Five of 18 patients treated with telbivudine
  • And 306 of 794 patients treated with more than one antiviral, either sequentially or in combination.

Adefovir mutations were detected in 36 of 381 patients treated first with lamivudine and then switched to adefovir, in contrast to only one of 82 patients who had adefovir added his ongoing lamivudine treatment.

Entecavir resistance was detected not only in patients previously treated with lamivudine and/or entecavir, but also in lamivudine-treated patients who had never been treated with entecavir.

Double mutations were more common in patients with genotype C than in genotype B, and patients infected with this double mutation had higher ALT levels, indicating liver damage, than those infected with single mutations.

Multidrug-resistant HBV strains were identified in eight patients, including two new mutations that had not been identified before, according to the report published in the September issue of the Journal of Viral Hepatitis.

HBV Patients Who Smoke Have Higher Rates of Diabetes
Between 1997 and 2004, Taiwanese researchers studied the link between smoking and diabetes in 3,539 people infected with hepatitis B or C. None of the groups had diabetes when the study began. Among the 423 people who eventually developed diabetes, most were age 65 or older, frequently consumed alcohol, had a higher body mass index, and had been infected with hepatitis C and/or B.

The higher the smoking levels, the greater the incidence rate of diabetes among HBV-infected participants.

Obesity and hepatitis B increased the risk of diabetes in smokers, according to the study published in the Journal of Viral Hepatitis.

Laotian- and Hmong-Americans Suffer Highest Rates of Liver Cancer Among Asian-Americans
Asian-Americans are known to have high rates of liver cancer due to the prevalence of hepatitis B infection, but a new report found that Laotian-Americans and Hmong-Americans have higher rates of hepatitis B infection and are more than twice as likely as other Asian-Americans to die from hepatitis B liver disease and cancer.

These two groups’ liver cancer tends to be diagnosed at later stage when it has already spread and it is difficult to treat, according to the report published in the journal Cancer Epidemiology, Prevention and Biomarkers. Only 3% of Laotian- and Hmong-Americans with liver cancer undergo surgery or liver transplantation, compared with 22% of other Asians, the researchers reported.

According to the National Cancer Institute, in the U.S., 24,120 people are expected to be diagnosed with liver cancer this year, often resulting from HBV infection, and 18,910 will die.

Deaths from liver cancer in the United States are the fastest rising group of cancer deaths because the disease is so difficult to treat. The rise is due, in large part, to immigration from Asia. The rates of liver cancer are highest in male Asian Americans and Pacific Islanders, almost 12 times the rate for non-Hispanic whites. The problem is particularly severe in California, where 5 million Asian Americans account for 14% of the state's population.

The University of California Davis study used data from the California Cancer Registry to identify 6,068 Californians of Asian descent diagnosed with liver cancer between 1988 and 2007. The data provided information about Chinese, Filipino, Vietnamese, South Asian, Korean, Japanese, Laotian/Hmong, Cambodian and Thai ethnic groups. The Hmong are an ethnic group from the mountainous regions of China, Vietnam, Laos and Thailand. Thousands of them were enlisted by U.S. forces during the Vietnamese war to fight Communist insurgents, and many were resettled in the United States afterward.

The researchers found that the Laotian/Hmong group were 2.08-times as likely to die from liver cancer as other Asian groups, while Cambodians were 26% more likely to do so.

The average survival for Laotian/Hmong patients in the study was one month after diagnosis, compared with three months for Cambodians; four months for Thais and Filipinos; six months for Chinese, Japanese and Vietnamese; and seven months for Koreans and South Asians.

Liver cancer survival rates are substantially higher for whites, especially when the disease is detected early enough for surgical removal or a liver transplant. For those who receive a transplant, the five-year survival rate is 75%. Many Hmong- and Laotian-Americans are low-income and unlikely to receive care until their cancer is advanced and often inoperable.

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