HBV Journal Review
October 1, 2013, Vol 10, no 10
by Christine M. Kukka
Study Finds Only 21% of Hepatitis B Patients Are Treated Correctly
A new study, examining how well San Francisco primary care providers care for their patients infected with the hepatitis B virus (HBV), finds most fail to screen them for liver cancer or regularly evaluate their viral load or hepatitis B "e" antigen (HBeAg) status, though medical guidelines require annual or semi-annual testing.
The study, published in the September 2013 issue of the journal Digestive Diseases and Sciences, surveyed doctors who provide care through a safety net program to many uninsured patients. They were asked how well they thought they followed current medical guidelines, and then patient medical records were analyzed to assess the true quality of care.
Of the 148 doctors surveyed, 79% claimed to follow medical guidelines and monitor patients' liver health every 6 six 12 months. However, patient medical records covering the last 12 months showed substandard care.
Only 75% of patients had their alanine aminotransferase (ALT) levels, which shows liver damage, tested in the past year.
Only 51% had their viral load (HBV DNA) tested.
Only 51% had been screened for liver cancer (either with an alpha fetoprotein test or some type of liver imaging). This test should be performed annually, and doctors are at risk of medical malpractice if they do not screen patients for cancer.
HBeAg tests were performed in only 29% of patients.
Only 32% of the hepatitis B patients had been immunized against hepatitis A, another guideline requirement, to protect them from another liver infection.
Bottom line, researchers found that only 21% of patients had been monitored properly in compliance with current hepatitis B guidelines. Forty-three percent of doctors were not familiar with medical guidelines for hepatitis B management and only 73% answered all questions about hepatitis B correctly.
There was also a racial bias regarding which HBV-infected patients were screened for hepatitis C and HIV. Doctors tended to test African-American and Latino patients for hepatitis C (48% and 44% respectively) at a higher rate than they tested whites and Asian-American patients (34% and 31%.)
The study suggests that fear of malpractice—more than knowledge of current practice guidelines—may drive doctors to perform the required liver cancer screenings each year. Also, the researchers suggest that hepatitis B public education initiatives, spearheaded by the San Francisco Hepatitis B Free Campaign, may have contributed to better monitoring of Asian-Americans because it raised awareness among the public and their providers.
"These findings highlight the importance of targeted provider education to improve overall care," for hepatitis B, the researchers from the University of California, San Francisco, suggest.
Combination of Chinese Herbs Plus Antiviral Entecavir Proves Effective
An increasing number of research studies are starting to scientifically evaluate the effectiveness of herbal remedies.
The latest study, published in the August issue of the journal of Evidence-Based Complementary and Alternative Medicine (eCAM), found that a compound of six Chinese herbs, called the Lingmao Formula, combined with the antiviral entecavir (Baraclude) was more effective than entecavir alone in reducing viral load and spurring loss of HBeAg.
The study treated 301 HBeAg-positive patients with mildly elevated elevated ALT levels for 52 weeks with either 0.5 mg of entecavir daily or the same entecavir dose combined with Lingmao Formula—a pre-measured compound of six herbs dissolved in warm water and drank twice daily.
22.8% in the combination group lost HBeAg, compared to 12.6% in the entecavir-only control group.
21.3% lost HBeAg and achieved undetectable HBV DNA in the combination group, compared to 8.9% in the control group.
14% seroconverted and developed "e" antibodies and achieved undetectable viral load, compared to 8.1% in the control group.
The percentage of patients achieving normal ALT levels, indicating no liver damage, was similar in both groups.
Full study text can be accessed at:
Caesarians Reduce Infection of Newborns When Mothers Have High Viral Loads
A study published in the journal Clinical Gastroenterology and Hepatology finds that Caesarean deliveries reduce the risk of hepatitis B infection in babies born to mothers with high viral loads.
Currently, immediate immunization and treatment with hepatitis B antibodies (HBIG) at birth prevents mother-to-child infection in more than 90% of cases. However, about 6% to 7% of infants—especially those born to mothers with high viral loads exceeding 1 million copies/mL—become infected despite preventive measures.
While doctors are starting to treat these pregnant women with high viral loads with antivirals during the last trimester of pregnancy to reduce HBV DNA, this treatment is new and does not yet have U.S. Food and Drug Administration approval.
Also, some HBV-infected women may experience a sudden surge in HBV DNA during the last few months or weeks of pregnancy because of the stress of the pregnancy, which provides little opportunity to use antivirals.
A global group of researchers studied 1,409 infants born to HBV-infected mothers and zeroed in on infants born to mothers with high viral loads. They looked at the delivery modes to see what impact normal vaginal delivery, elective Caesarean delivery or emergency Caesarean delivery (with higher risk of ruptured membranes and contact with infectious fluids) had on HBV infection in babies.
They found babies born to highly-infectious mothers had lower rates of infection when they were delivered by elective Caesarean (2.9%) as opposed to vaginally (6.3%) or by emergency Caesarean (7.6%).
An editorial about the study published in the journal observed, "...Given the potential long-term benefits of preventing mother-to-child transmission of HBV, the reassuring safety profile of elective Caesarean section for both mother and fetus, the absence of long-term safety data for antiviral therapy in pregnant chronic patients, the possibility of unexpectedly high HBV DNA levels close to delivery in some mothers precluding timely administration of antiviral therapy ... elective Caesarean section may be a suitable complement," to (immunization and HBIG) in mothers with viral load exceeding 1 million copies/mL.
Combined Antiviral and Interferon Treatment Effective in Those Under Age 30
After nearly two years of treatment with a combination of antivirals and pegylated interferon (Pegasys), 41.1% of patients lost HBeAg and developed "e" antibodies (seroconversion), and 18.9% lost the hepatitis B surface antigen (HBsAg).
The combination treatment was more effective, according to the study, than treatment with just an antiviral alone. Only 33.3% of those receiving 96 weeks of either lamivudine (Epivir-HBV) or adefovir (Hepsera) experienced HBeAg seroconversion and none of them lost HBsAg, according to a recent report published in the Chinese journal of hepatology (PMID 24021787).
These Chinese researchers treated 135 HBeAg-positive patients for a lengthy period—most recommendations call for up to 48 weeks of interferon but these researchers extended treatment to nearly two years. Forty-five patients received just the antiviral and 90 received the interferon and antiviral combination.
During treatment and 24 weeks after treatment stopped, researchers analyzed the patients' response to see how many seroconverted and achieved normal ALT levels (indicating no liver damage) and undetectable viral load (less than 1,000 copies/ml of HBV DNA.)
In the group receiving the combination treatment, those age 30 and younger responded best with higher rates of clearing HBsAg.
"Prolonged (antiviral plus interferon) combination therapy can significantly improve the rate of HBsAg seroconversion in HBeAg-positive-patients, and this treatment regimen is especially efficacious in patients under the age of 30," they wrote (1). This study is also notable because there are now far more potent antivirals available for use than lamivudine and adefovir.
A similar study, published in the Chinese journal of experimental and clinical virology (PMID: 24044216), followed the effectiveness of varying combinations of pegylated interferon and entecavir in 60 HBeAg-positive patients with high viral loads.
Three groups were treated with either just interferon, just entecavir, or a sequential treatment of interferon for 12 weeks followed by interferon and entecavir for 12 weeks and ending with just interferon for 36 additional weeks.
Twenty-four weeks after the treatments ended, the combination group and the entecavir-only group had similar rates of undetectable HBV DNA and normal ALT levels, which were far higher than the interferon-only group. HBeAg levels declined most markedly in the combined treatment group.
New Tenofovir Formula May Lead to Less Bone Loss and Kidney Problems
A new formulation of the antiviral tenofovir (Viread), which has proven highly effective against both hepatitis B and HIV infection, appears to be successful even at lower doses in a recent clinical trial in HIV-infected patients.
A lower dose afforded by the new formulation means a reduced risk of side effects such as kidney problems or bone loss. These side effects have surfaced in some HBV- and HIV-infected patients who were treated with tenofovir over several months and years.
The new formulation, called tenofovir alafenamide, is absorbed more effectively by cells so it requires lower dosing, according to a report on a Phase II trial presented at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (1.) When tested in HIV patients, the drug was found to be highly effective, producing five-fold higher concentrations of tenofovir in HIV-infected cells, but the lower dose resulted in reduced tenofovir concentration in the blood.
Phase III trials in HIV patients are currently underway. There are no reports yet when Gilead will begin trials in hepatitis B patients.
In an unrelated study (2), published in the September issue of the journal Gastroenterology, New Zealand researchers reported that the antiviral telbivudine (Tyzeka) surprisingly improved kidney function in hepatitis B patients with cirrhosis.
Each antiviral is unique and appears to have different effects on kidney function and health. "In global trials of patients with compensated and decompensated cirrhosis, long-term telbivudine(treatment) was associated with a sustained improvement of renal (kidney) function—particularly among patients with increased risk of renal impairment. The mechanisms of this renal protective effect remain to be determined," they wrote.
HBV Mutation Found Only in Men May Explain Their Higher Rates of Liver Damage
Why do men suffer more severe liver damage from HBV infection than women? Korean researchers may have found a clue. They isolated a mutation in the outer covering of the HBV called W4P/R that occurs only in male patients.
They followed 247 patients with W4P/R who all had HBV genotype C and found these male patients had higher rates of HBV-related liver disease, including cirrhosis and liver cancer, than patients who did not have the mutation.
"The W4P/R mutation may in part provide the likely explanation for the relatively high ratio of male to female incidence in liver cancer generation in Korean chronic patients," they concluded in their report published in the September issue of the Journal of Clinical Microbiology.
Sumo Wrestlers Found to Transmit HBV Infection
After two students on a high school sumo wrestling team were hospitalized with acute (new) hepatitis B infections in Japan, doctors tracked the infections to their HBV-infected wrestling coach who had a high viral load.
The HBV DNA from the two wrestlers and coach were analyzed and found to have similar patterns, indicating a similar infection source.
Sumo players are more likely to get injured with exposure to cuts, bleeding and body fluids, compared with players of other sports because of the close body contact of this wrestling style. There have been some reports, though unverified, that sweat from people with high levels of HBV DNA may transmit the virus if it gets into open cuts and wounds.
"In our cases, percutaneous HBV transmission through the bleeding wounds was the most probable infection route," researchers wrote in the journal of Hepatology Research. "We conclude that a universal HBV immunization program should be introduced urgently in Japan, similar to those implemented in other countries worldwide."
Taiwan's Hepatitis B Immunization of Infants Reduces Hepatitis B by 90%
Taiwan's comprehensive program that has immunized nearly all newborns against hepatitis B beginning in 1984 has lowered hepatitis B and liver cancer rates, and liver failure deaths in infants by about 90% (1).
According to a research letter published in the Sept. 4, 2013 issue of the Journal of the American Medical Association, from 1977-1980 to 2001-2004, chronic hepatitis B in those aged 5 to 29 decreased by more than 90% and liver cancer declined by more than 80%. The death rate for infants with hepatitis B-related liver failure declined more than 90%.
By 2010, Taiwan had an immunization rate of 96.9% among newborns.
In contrast, the U.S. has achieved a hepatitis B immunization rate in newborns of only 71.6% as of 2012. (2)
Tenofovir Reverses Severe, Decompensated Cirrhosis
Indian researchers found that the antiviral tenofovir was highly effective in treating hepatitis B patients with high viral loads and decompensated cirrhosis—a life-threatening condition where the liver is so severely scarred that it cannot function.
Researchers treated 96 patients with decompensated cirrhosis with tenofovir for 24 months. The treatment reversed decompensated cirrhosis and remarkably improved liver health as it knocked down viral replication, according to the report published in the September issue of the journal of Antiviral Research.
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