HBV Journal Review
September 1, 2011, Vol 8, no 9
by Christine M. Kukka
Diets High in Both Alcohol and Fat Significantly Increase Liver
A diet high in both alcohol and fatty foods is bad for the liver and can cause fibrosis (mild scarring) in the liver, according to a report published in the journal Alcoholism: Clinical and Experimental Research.
Scientists fed mice either water with alcohol, or a high-fat diet, or a combination of the two for six weeks. The high-fat diet produced inflammation in the animals’ liver, more so than when mice were fed just alcohol.
However, the combination of high-fat food and alcohol appeared to act synergistically, significantly increasing inflammation and ultimately leading to liver fibrosis—a precursor to cirrhosis or severe scarring.
The findings should serve as a warning to people whose livers are already taxed by the presence of a hepatitis B virus (HBV) infection.
“….Surprisingly, (a high-fat) diet alone and in combination with alcohol led to a markedly increased hepatic expression of the endotoxin receptor Toll-like receptor 4 (TLR4), which is known to play a crucial role in (causing liver) fibrosis,” the researchers reported.
Tenofovir and Entecavir Deemed Most Effective
A retrospective study, analyzing the evolution of hepatitis B treatment over the past 20 years, assessed the success rates of the best-performing interferon and antivirals. Researchers, writing in the Journal of Gastroenterology and Hepatology, noted that the primary goal of treatment is to lower viral load (HBV DNA), which decreases liver damage and cancer over the long term.
Conventional interferon, the first hepatitis B drug to be licensed in 1991, has been replaced by pegylated interferon (Pegasys), which requires one weekly injection. When treated with interferon, about 33% of patients lose the hepatitis B “e” antigen (HBeAg) and develop “e” antibodies, but only 25% of HBeAg-positive patients achieve undetectable HBV DNA after interferon treatment.
Five antiviral medications have been licensed for hepatitis B since 1998. Lamivudine (Epivir-HBV), the first antiviral approved, is now rarely used because of its high rate of resistance—76% of patients develop drug resistance after 5 years of treatment.
Telbivudine (Tyzeka) is more potent than lamivudine but it also has a high rate of resistance--25% of HBeAg-positive and 11% HBeAg-negative patients develop drug resistance after two years.
Adefovir (Hepsera) is a relatively weak antiviral, but it is effective against lamivudine- and telbivudine-resistant HBV. As a result, it can be added to ongoing lamivudine or telbivudine treatment. Resistance to adefovir develops slowly, rising to 29% for HBeAg-negative patients after 5 years.
Currently, the two standout antivirals that doctors most highly recommend when patients first start treatment are entecavir (Baraclude) and tenofovir (Viread). Entecavir is very potent, with 94% of patients achieving undetectable HBV DNA after 5 years. Resistance develops in only 1.2% of them.
Tenofovir is more potent, and is less likely to cause any kidney damage as a side effect than adefovir. It is effective against lamivudine-resistant HBV. No resistance to tenofovir has been identified in patients who have used it for three years or longer.
“With these current, potent antiviral agents associated with very low rates of resistance, long-term HBV DNA suppression and possibly even reversal of cirrhosis can now be achieved in a proportion of patients,” researchers wrote. “In addition, long-term treatment with these antiviral agents is associated with a reduced risk of development of (liver cancer).”
Protective Boots Worn by Surgeons Don’t
Protect Against Blood Exposure
HBV, because it is such a resilient virus that can even live on hard surfaces for several days, continues to pose an infection risk to health care workers. Recently, researchers writing in the New Zealand Medical Journal report that the virus can penetrate the protective boots (called gumboots) that surgeons wear to protect themselves from liquid and body fluid spills.
Researchers found that blood was able to penetrate nearly 60% of gumboots worn by surgery staff. They checked 94 pairs of gumboots worn by surgery staff and found 55 pairs had blood inside them. About 80 per cent of contaminated boots had blood spots larger than a dime.
The culprit could be too-short surgeon gowns, which allowed liquids to run off the protective gowns into the open neck of the boots.
Researchers noted that universal precautions require health care workers to treat all blood and body fluids as potentially infectious and carrying HBV, the hepatitis C virus, or HIV.
Effective in Liver
A study by Korean researchers, published in the September issue of the Journal of Gastroenterology and Hepatology, finds that entecavir treatment is effective in hepatitis B patients with liver cancer.
The antiviral, which works by meddling with the virus’s genetic material in order to disable its reproductive abilities, was given to 231 hepatitis B patients, 71 of whom also had HBV-related liver cancer. They were treated with 0.5 mg of entecavir daily for at least six months.
Both patient groups responded similarly in achieving undetectable HBV DNA, normal alanine aminotransferase (ALT) levels (which indicate no liver damage), and HBeAg loss after two years of treatment.
In patients with liver cancer and cirrhosis (severe scarring of the liver), 12 months of treatment improved their liver health.
Of the 71 cancer patients, 16 underwent additional treatment, including surgery and radiofrequency ablation to remove tumors, and the other 55 received transarterial chemoembolization to remove tumors.
Sixteen of the liver cancer patients achieved undetectable HBV DNA as a result of entecavir treatment. Those who cleared HBV DNA within 24 weeks of entecavir treatment had better overall survival.
Researchers concluded that entecavir treatment is effective in hepatitis B patients with liver cancer.
Entecavir Effective Over the Long Term
Even when patients don’t appear to respond to entecavir treatment after 48 weeks, over the long term it helps most patients who have never been treated before achieve undetectable viral load, according to a 10-center study in Europe.
European researchers followed 313 patients, enrolled in the European Network for Vigilance against Viral Resistance (VIRGIL) study between 2003 and 2010, treated with entecavir. Patients had HBV DNA exceeding 2,000 IU/ mL, 75% were men, the average age was 43, and 43% were HBeAg-positive. Most had HBV genotype D (48%), followed by genotype A (21%), genotype C (14%), genotype B (9%), and other genotypes (7%).
About three-quarters had never been treated with an antiviral before, and 22% had been previously treated with lamivudine, with 11% developing lamivudine resistance. Fifteen percent had been treated with adefovir, with 4% developing adefovir resistance.
Among the 243 who had never been treated, after 19 months of entecavir treatment researchers found:
- Among HBeAg-positive patients, 48% achieved lower viral load and improved liver health at 48 weeks, 76% achieved that goal at 96 weeks, and 90% achieved it at 144 weeks. HBeAg loss rates were 10%, 21%, and 34% respectively after 48, 96 and 144 weeks.
- Among HBeAg-negative patients, 89% achieved lower viral load and improved liver health at 48 weeks, 98% at 96 weeks, and 99% at 144 weeks.
- A partial response was noted at week 48 in 21% of patients who were previously untreated, however 81% of them achieved a successful response to the antiviral after long-term treatment. Most non- or partial-responders were HBeAg-positive with high viral loads.
- Among patients who had previously been treated, those treated with lamivudine had the poorest response to entecavir, while those previously treated with adefovir fared well on entecavir.
This study shows entecavir is effective up to three years in previously-untreated patients, even if they do not appear to respond by week 48, researchers concluded in the August issue of Hepatology.
Research Suggests the Spice Saffron Protects Against Liver Cancer
A study published in the September issue of Hepatology suggests that the spice saffron provides protection against liver cancer. Researchers administered saffron to rats that had been treated with a toxic chemical to induce liver damage and cancer.
Saffron is a commonly used spice, adding flavor and yellow color to foods.
Researchers from United Arab Emirates University administered saffron to the animals at 75mg/kg, 150 mg/kg, and 300 mg/kg per day for two weeks prior to injecting the rates with the chemical, and then continued the regimen for 22 weeks.
Results showed saffron significantly reduced the number of liver nodules or tumors, with animals receiving the highest dose of saffron showing no signs of tumors. Animals that received pre-treatment with saffron showed the least liver damage, despite exposure to the toxic chemical.
“Our findings suggest that saffron provides an anti-cancer protective effect by promoting cell death (apoptosis), inhibiting proliferation of cancerous cells, and blocking inflammation,” researchers noted.
HBeAg-Negative Patients with Genotype B and Low Viral Load Most Likely to Lose HBsAg
Doctors know patients who lose HBeAg and have low viral load have a better chance of spontaneously losing the hepatitis B surface antigen (HBsAg) and achieving an “inactive” infection status, but what about HBeAg-negative patients who have low viral load?
Many who lose HBeAg often go on to have HBeAg-negative hepatitis B, marked by moderate to high viral load and continued liver damage.
Taiwanese researchers followed 688 HBeAg-negative patients with low viral loads under 2,000 IU/mL and studied the link between HBsAg loss and HBV DNA levels over 11 years.
They reported in the journal Hepatology that the average annual rate of HBsAg loss was 1.6%. They found that patients with the lowest HBV DNA and HBsAg levels, and who had HBV genotype or strain B, which is common in Asia, were more likely to lose the surface antigen.
YMDD Mutations Naturally Occur in 15.5% of
Lamivudine, the cheapest antiviral available around the world, has a low price tag but it also has a high rate of viral resistance. Patients who have YMDD mutations in their HBV are at especially high risk of quickly developing lamivudine resistance.
Historically, researchers assumed this mutation developed only after prolonged lamivudine treatment, however a group of researchers in China have found that this mutation is prevalent even in people who have never been treated with an antiviral.
They found the rate of natural YMDD mutations in western China was 15.56%. These results show that patients’ HBV should be tested for YMDD mutations before lamivudine, which is widely used in China because of its low price tag, is used, according to the report published in the Scandinavian Journal of Infectious Diseases.
Antivirals and HBIG Combination Cut Down Recurrence of Hepatitis B
After Liver Transplantation
As little as 20 years ago, liver transplantation in hepatitis B patients rarely occurred because doctors assumed the infection would recur and the patient would again suffer liver damage from hepatitis B.
Today, according to a study published in the journal Hepatology International, the use of antivirals and low doses of hepatitis B immunoglobulin (HBIG) after surgery make liver transplantation for hepatitis B more widely accepted. Increasingly, successful use of antivirals (which are dramatically less expensive than HBIG) may one day take the place of HBIG treatment after transplant surgery.
In fact, researchers noted that hepatitis B recurs in fewer than 5% of all HBV-infected patients who receive liver transplants.
Weak Vaccine Response During Childhood Leaves Adults Vulnerable to
For how long does the hepatitis B vaccine protect people from hepatitis B? Researchers continue to explore how long the hepatitis B vaccine protects people, especially when they’re immunized as infants, against infection.
In a study, published in the journal Vaccine, researchers in China followed 806 people who were immunized as infants 24 years ago in a region where hepatitis B was prevalent.
The study group was tested for hepatitis B antigens and antibodies at ages 5, 10, and 20 years, and then 402 were screened again at age 24.
Among the 402, 4 (1%) were found to be chronically infected and HBsAg-positive. Another 27 (6.7%) were HBsAg-negative, but they tested positive for the hepatitis B core antibody--indicating they had become infected with the virus at some point despite immunization--but they had ultimately cleared the infection.
About 30% (121) tested positive for only the surface antibody, which means they remained protected against hepatitis B as a result of immunization. The vaccine contains only the surface antigen, which causes the immune system to produce protective surface antibodies.
However, 252 (62.4%) who remained uninfected had no measurable surface antibodies to indicate they were protected against hepatitis B infection. Of this group, 141 received two hepatitis B vaccine booster shots, 30 days apart. As a result, 87% of them ultimately developed protective surface antibodies.
However, researchers noted that those who had responded weakly to the vaccine administered during infancy—when they were tested at age 5 and again at age 24—still had low levels of surface antibodies and these same subjects continued to have low antibody counts into adulthood. Researchers fear this group could be susceptible to infection.
The findings raise more questions about whether screening is necessary, and whether booster shots should be recommended when surface antibody counts are low.
Infants Born to Mothers with High Viral Load and HBV DNA in Their Umbilical Cord Blood
Despite immunization and administration of HBIG (hepatitis B antibodies) to infants born to HBV-infected mothers, about 5% to 10% of newborns will become chronically infected with HBV
Chinese researchers, reporting in the Journal of Viral Hepatitis, studied 869 infants born to HBV-infected mothers between 2007 and 2010. All infants received the identical immunizations, but after 7 to 12 months, 3.1% were found to be HBsAg-positive.
When the mothers’ HBV DNA levels were compared, they found that babies born to mothers whose viral loads exceeded 1 million copies/mL (and who were HBeAg-positive) were much more likely to become infected despite the preventive efforts.
Additionally, all babies with detectable HBV DNA in their umbilical cord blood became HBV-infected.
Presence of Both “e” Antigens and Antibodies Found in 10% of Patients
For the first time, researchers have explored the coexistence of both hepatitis B “e” antigens and antibodies in patients, to see how widespread it is, and what impact it has on patient health.
Chinese researchers screened 1,624 samples from hepatitis B patients, according to their report in the Journal of Viral Hepatitis, and found that 10.4% (169 patients) tested positive for both “e” antigen and antibody. This coexistence of “e” antigen and antibody may result from a mutation in the virus.
These patients tended to be middle-aged, have moderate viral load, higher ALT levels, and more pronounced liver damage compared to patients who were either HBeAg-positive or anti-HBe-positive.
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