HBV Journal Review
January 1, 2013, Vol 10, no 1
by Christine M. Kukka
Can Hepatitis B Patients Ever Stop Taking Antivirals? Researchers Say No
Can people infected with the hepatitis B virus (HBV) expect to clear the virus as a result of antiviral treatment? Can they expect to one day stop taking the daily antiviral pills? French researchers say no. The drug is very effective in impeding viral reproduction, but only as long as it is taken.
Researchers followed patients who took a variety of antivirals for 8.5 years to see if the drug would knock down the hepatitis B surface antigen (HBsAg) sufficiently to clear the infection. (Undetectable HBsAg and development of surface antibodies indicates a patient has cleared the infection.)
They found antivirals produced a slow but consistent reduction of HBsAg as the antiviral drugs did their work in suppressing the HBV DNA (viral load) circulating in the body. But the decline was so slow, on average it would require most patients to take antivirals for 52.2 years to totally rid their bodies of HBsAg.
They concluded that clearing HBsAg as a result of antiviral treatment, "...is unlikely to occur during a patient's lifetime, even if HBV replication is well controlled," they reported in the December 2012 issue of the Journal of Hepatology. "Thus, lifetime therapy is required in the vast majority of HBV-infected patients."
Tenofovir Found Effective in White Teens with Genotypes A and D
The antiviral tenofovir (Viread), which has already proven very effective in adults, was found equally effective in 51 HBV-infected teens in a recent clinical trial. The antiviral, which is approved by the U.S. Food and Drug Administration (FDA) for use in adults, proved equally effective in stopping replication of the virus in youths ages 12-18.
The study, published in the December issue of Hepatology, compared the effectiveness of tenofovir in primarily white, male teens treated with 300 mg of tenofovir daily over 72 weeks with 50 untreated HBV-infected teens. Nearly all participants were hepatitis B “e” antigen (HBeAg) positive and had high levels of HBV DNA.
Tenofovir dramatically suppressed HBV in the treated teens, with 89% achieving HBV DNA levels under 400 copies per milliliter and 74% achieving normal alanine aminotransferase (ALT) levels, indicating no liver damage, after 72 weeks. In contrast, none of the teens in the placebo group achieved undetectable viral load.
Among tenofovir-treated, HBeAg-positive patients, 21% lost HBeAg and one even cleared the virus—losing HBsAg and developing surface antibodies.
Also significant in the study was that tenofovir was effective in teens who had already developed drug resistance to the antiviral lamivudine (Epivir-HBV).
No side effects, such as bone density loss or neuropathy (nerve damage), were reported over the 72-week study period. Those side effects have been reported in adults treated long-term with this drug. It remains unclear if longer treatment with tenofovir in teens would cause these side effects.
While the study endorses tenofovir, and may lead to FDA approval of the drug in teens, many questions remain about whether early treatment during childhood will decrease liver cancer risk, and how long children should be treated with an antiviral. Also, because the study was based in the U.S. and Europe, the majority of those enrolled were white patients with HBV genotypes or strains A and D. Additional studies are needed to determine if the drug will be effective in Asians and those with other genotypes.
Tenofovir Effective in Patients with Advanced Fibrosis and Cirrhosis
A new study of 348 hepatitis B patients—many of whom had advanced liver inflammation (fibrosis) and scarring (cirrhosis)—found that five years of tenofovir treatment improved liver health and caused no drug resistance, according to the report in the December issue of Lancet.
The patients had liver biopsies at the start of treatment and five years later, which revealed that 87% had improvements in liver health. Fifty-one percent had reduced fibrosis. Of the 96 patients with cirrhosis at the beginning of treatment, 74% no longer had cirrhosis after five years.
"In patients with chronic HBV infection, up to 5 years of treatment with tenofovir was safe and effective," researchers noted. "Long-term suppression of HBV can lead to regression of fibrosis and cirrhosis."
Entecavir Reduces Liver Cancer by 10%, Compared to No Treatment
To find out if antiviral treatment prevents liver cancer in chronically-infected hepatitis B patients, Japanese researchers compared liver cancer rates in 316 entecavir (Baraclude)-treated patients with 316 untreated patients with similar age, gender, and disease progression.
Over five years, they found the entecavir group had a liver cancer rate of 3.7%, while the untreated group had a cancer rate of 13.7%, according to the report published in the journal Hepatology.
"Long-term entecavir treatment may reduce the incidence of (liver cancer) in HBV-infected patients," they concluded. "The treatment effect was greater in patients at higher risk of liver cancer," they added, including those who had fibrosis, cirrhosis and other signs of liver damage.
Impact of Hepatitis B on Pregnancy
• Role of HBV Genotype: Japanese researchers followed 21 pregnant women through childbirth to see what impact their HBV viral strain or genotype had on pregnancy. They reported in the journal of Internal Medicine, that women with genotype C had higher viral loads, some liver damage (evidenced by elevated ALT levels) and low platelet counts at time of delivery.
While all women in the study delivered healthy babies, four of six women with genotype C were HBeAg-positive and had high viral loads. It has been reported that people with genotype C lose HBeAg later in life, and so may still be HBeAg-positive during their child-bearing years. As a result, women with this genotype may be more likely to infect their newborns, unless preventive treatment is used, and be at risk is liver damage from prolonged years of high viral load.
• Role of Male Partner's Genotype: Another study from Japan, reported in the journal Microbiology and Immunology, found that men with HBV genotype A may be more prone to infect their pregnant partners.
This genotype may be more resilient and has been showing up more frequently among sexually active men with new hepatitis B infections. "There are concerns that horizontal transmission of HBV from these men to pregnant partners could increase," researchers noted. "These data suggest ... the possibility that the increase of genotype A may (then consequently) influence vertical (mother-to-infant) transmission of HBV."
• Lamivudine treatment safe throughout pregnancy—Researchers followed 92 women who were treated with lamivudine throughout their pregnancy to see if the antiviral had any impact on the health of their newborns. According to the report published in the World Journal of Gastroenterology, the antiviral caused no abnormalities or "adverse effects" in either mothers or infants.
"Lamivudine treatment is safe for chronic HBV-infected pregnant mothers and their fetuses with a gestational age of less than 12 weeks or throughout the entire pregnancy," they reported. The antiviral also helped reduce viral load and prevent mother-to-infant infection in 97.1% of cases.
Studies Find Hepatitis B Vaccine Protection May Wane in Late Adolescence
Two studies in Hong Kong, where universal hepatitis B immunization began in late 1983, suggest that hepatitis B vaccination protection may weaken as teens reach late adolescence.
According to a report in the journal Epidemiology and Infection, researchers monitored HBsAg status of teenage mothers treated between 1998 and 2008. All of the women should have been immunized at birth.
They found the following HBsAg-positive rates:
- Between 2 to 5% in those age 16
- Between 2 to 7% in those age 17
- And about 8% in those ages 18 and 19.
This shows that as the young women aged, their risk of hepatitis B infection increased, suggesting, "... the protective effect of the vaccine declined in late adolescence."
A second study from Hong Kong, published in the journal Infection, found that first-year university students in that city also had higher HBV infection rates as they aged. Of 2,688 students enrolled in the study, 2.9 % were HBsAg-positive.
What is significant is the infection rates increased significantly from 0.9% in students under age 18 to 5.5 % in those age 21 or older.
"Among the university students enrolled in our study, the overall prevalence of HBV infection before and after the introduction of HBV vaccination was lower than the 10 % found in the general population," researchers noted. "There was, however, a significant progressive increase with age at testing from 18 to 21 years, suggesting a previously overlooked contribution of horizontal transmission to the high prevalence of HBV infection found in our adult population."
Silymarin Appears Beneficial in Drug Combinations
Silymarin, derived from the milk thistle plant, is an herbal supplement that is believed to help protect the liver from infection and other diseases, but researchers do not know in detail how effective this herb is and at what dose.
A recent Chinese study, published in the European Journal of Clinical Microbiology and Infectious Diseases, examined 12 studies that involved placebo, control groups that examined the effectiveness of silymarin when combined with antiviral treatments.
"Silymarin was equivalent to antiviral drug or protection liver drugs in serum transaminases, viral load and hepatic fibrosis markers," they found. "But silymarin combined with antiviral drug or antiviral drug and protection liver drugs significantly reduced the level of serum transaminases, hepatic fibrosis markers and serum TGF-β1, TNF-α, IL-6 versus antiviral drug or protection liver drugs."
They concluded that the herbal supplement, when combined with antiviral drug or antiviral drug and protection liver drugs, "may have potential therapeutic value." But they added that the data is still too limited to result in a full recommendation of the herbal supplement until additional trials and studies are conducted.
U.S. Doctors Play Key Role in Screening Asian Immigrants for Hepatitis B
Asian immigrants and their offspring have high rates of chronic hepatitis B in the United States—reaching up to 10%. So what's the best way to promote screening, immunization, and treatment in this culturally diverse, at-risk population?
The family doctor is the most powerful influence in this group, according to a report published in the Journal of Immigrant Minority Health. Researchers from Johns Hopkins Bloomberg School of Public Health in Baltimore and the Maryland Asian American Liver Cancer Education Program surveyed 877 Asian immigrants to help identify the most powerful source who could most influence screening and treatment.
Those surveyed were almost evenly split among Korean, Chinese and Vietnamese immigrants. The average age was 44, most were women, 58% were college-educated (only 34.9% claimed to speak English well) and 59.2% had lived more than 25% of their lives in the U.S. Sixty-two percent were employed, 60.1% regularly saw a physician and 67.8% had health insurance.
Despite their education and access to health care, only 16.4% knew of a family history of HBV infection.
The most commonly reported sources for hepatitis B information among those surveyed were newspapers (especially among older respondents), physicians, friends, television, and the Internet (among younger, college-educated respondents). About 80% of respondents had heard of HBV from one of these sources.
Interestingly, among Vietnamese immigrants, community health fairs were the third most popular source of HBV information.
Across all groups, physicians were the most important sources of hepatitis B information and had the strongest impact on whether patients were screened. But unfortunately, health care providers often fail to screen Asian-American clients for hepatitis B despite clear practice guidelines on this topic that call for screening.
This study is the first of its kind and is expected to affect how experts develop a national HBV education campaign spear-headed by the U.S. Department of Health and Human Services in 2013.
Hepatitis and Alcohol Abuse Contribute to Increase in Liver Deaths Among Addicts
An Australian study published in the journal Drug, Alcohol Dependence finds that death from liver disease—often resulting from viral hepatitis and alcohol abuse—is increasing among heroin-addicted people.
In their study, they found deaths from liver disease occurred at 9.8-times the rate in heroin-addicted people than among the general population and have been increasing over time. Viral hepatitis contributes to 76% of these deaths, and alcohol plays a role in 43% of them.
"Increased uptake of treatment for hepatitis C virus infection is crucial to reducing the burden of liver-related mortality in this population," they wrote. "Hepatitis B vaccination, and screening of (addicted) patients for alcohol use disorders and delivery of brief interventions as clinically indicated may also be of benefit."
Formula Proposed to Treat and Monitor HBV Patients When They Receive Immune-Suppressing Drugs
Japanese researchers have crafted a formula when to treat people with current or resolved hepatitis B infections with antivirals if they receive immune-suppressing drugs for diseases such as osteoarthritis or rheumatoid arthritis.
Recently, doctors have discovered that inactive hepatitis B infections can rebound and become active when people are treated with immune-suppressing drugs. As a result, medical organizations worldwide have been trying to establish an algorithm for when to test these patients for hepatitis B, and at what point to treat them with antivirals in order to prevent a dangerous rebound in HBV infection.
The proposal promoted by Japan's College of Rheumatology (in a country where HBV infection was common) and published in the journal Modern Rheumatology makes the following recommendations:
- All patients starting immunosuppressive therapy should be screened for HBsAg (which indicates a current infection.)
- Those negative for HBsAg should be screened for hepatitis B core antibody (HBcAb) and hepatitis B surface antibody (HBsAb) as well (which would indicate a resolved infection.)
- Patients who are HBsAg-positive and have HBV DNA in their bloodstream should receive antivirals before starting immunosuppressive therapy.
- If patients are HBsAg- and HBV DNA-negative with resolved infections, they should have their ALTs and HBV DNA monitored monthly during treatment and for at least 12 months after finishing immunosuppressive treatment.
- If HBV DNA becomes positive, patients should immediately receive antivirals while continuing immunosuppressive therapy to avoid liver damage. "To facilitate proper management of patients with HBV infection, collaboration between rheumatologists and hepatologists is strongly encouraged," they recommended.
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