HBV Journal Review
May 1, 2014, Vol 11, no 5
by Christine M. Kukka
Adding Interferon to Ongoing Antiviral Treatment Is Highly Successful
Adding pegylated interferon to ongoing antiviral treatment produced remarkable rates of hepatitis B "e" antigen (HBeAg) loss and even hepatitis B surface antigen (HBsAg) loss, according to a study presented at the International Liver Congress held in London in April.
Eighty-three HBeAg-positive patients in China, who had been on antivirals for more than two years, had 48 weeks of interferon treatment added to their treatment regimen. A control group continued on only antivirals:
- 60% of the group treated with add-on interferon lost HBeAg and their viral loads dropped below 2,000 IU/mL. In contrast, only 13.8% of patients treated with only antivirals achieved those benchmarks.
- 27.7% of patients in the combination treatment group lost HBsAg. No one in the antiviral group lost HBsAg.
- All patients who had low HBsAg levels (less than 1,000 IU/mL) at the start of interferon treatment achieved HBeAg loss and 91% cleared HBsAg.
" Sequential combination therapy of (antivirals) and pegylated interferon effectively resulted in high rates of complete response and HBsAg loss in patients with prior long-term exposure to (antivirals)," researchers wrote. (Abstract 0117)
Another study exploring the benefits of sequential antiviral and interferon treatment found that HBeAg-positive patients who had been on antivirals for three years or longer also experienced high rates of HBeAg loss and development of "e" antibodies (HBeAg seroconversion) when their antivirals were replaced with pegylated interferon.
At week 48, the HBeAg seroconversion rate in the interferon-treated group was 66.67% compared to 2.5% in the antiviral group. (Abstract P1071)
A third study from India also found notable improvements when pegylated interferon was added to ongoing tenofovir treatment. Sixty patients were treated with tenofovir for 12 weeks (300 mg daily), then:
- One group had pegylated interferon added to the ongoing tenofovir regimen for 24 weeks, and then were followed for another 28 weeks.
- The other half continued their tenofovir treatment for 52 weeks.
Sixty percent of the interferon-plus-tenofovir group achieved healthy liver health, with normal alanine aminotransferase (ALT) levels, compared to 30% in the tenofovir-only group. The combination-treatment group also experienced greater viral load (HBV DNA) declines and HBeAg seroconversion (53.3% vs. 23.3% in the antiviral-only group).
"Sequential therapy using tenofovir and pegylated interferon may provide rapid and high biochemical and virological response in selected HBeAg-positive patients," researchers noted. "Long-term clinical trials are needed to assess (the) sustained durable response." (Abstract P1092)
Vitamin E Helps HBV-Infected Children Lose HBeAg, Reducing Liver Damage
A small study, presented at the 2014 Liver Congress found that HBeAg-positive children who were treated with vitamin E (15 mg/kg/daily) for 12 months achieved higher rates of HBeAg conversion, lower viral loads and normal ALT levels than did untreated children.
The Italian study followed 46 children treated with vitamin E for 12 months and six children who were not for a total of 24 months, including 12 months of monitoring after treatment ended.
"A complete response (normal ALT levels and HBV DNA under 2,000 IU/mL) was achieved in eight of the 23 children treated with vitamin E (33%) compared to only one of 23 children who were not treated (4%).
HBeAg seroconversion was also higher in the vitamin E-treated group, however specific numbers were not included in the abstract's description of the study. (Abstract P1088)
Common Chinese Toad May Hold the Key to Preventing and Treating Liver Cancer
The glandular secretions and skin of the common Chinese toad (Bufo bufo gargarizans), found in rice fields, wetlands and ponds across China, may be a potent medicine in treating liver inflammation and preventing liver cancer in patients with hepatitis B-related liver disease.
Extracts from this frog have been used for hundreds of years in traditional Chinese medicine. "One of the most widely used commercial preparation is Huachansu (Cinobufacini), which is a sterilized hot water extract of dried toad skin," researchers noted in a review of current studies analyzing the effectiveness of toad extracts in treating inflammation and cancer.
"Since 1991, Cinobufacini has been officially approved by the Chinese Food and Drug Administration as a regimen for treating patients with HBV and several types of cancer including liver, lung, colon, and pancreatic cancer," they wrote. Lab tests show Cinobufacini slowed the growth of lung cancer cells in mice and prolonged their lives. Other clinical trials in China have demonstrated the anticancer effect of Cinobufacini injection in liver and lung cancer patients with response rates of 10% and 16% respectively, and other studies showed higher concentrations of the drug could yield even better results.
Also noteworthy, when Cinobufacini was used in combination with drugs such as chemotherapy or radiation, the drug appeared to lessen those treatment's toxic side effects while protecting healthy liver tissue and improving outcomes.
The Australian researchers, writing in the March issue of the journal of Evidence-Based Complementary and Alternative Medicine, stressed that additional clinical trials are needed to full identify how the compound works. "... Toad glandular secretion and skin extraction have a real potential as resources for the development of therapeutical agents for preventing or treating human cancers by inducing apoptosis (cancer cell death), sensitizing cancer cells to conventional cancer therapies, or protecting host cells from any side effects," they wrote.
Even at Top Hospitals, Doctors Fail to Treat Hepatitis B Patients Properly
Harvard Medical School researchers found physicians at the prestigious Massachusetts General Hospital in Boston repeatedly failed to monitor hepatitis B patients properly in compliance with medical guidelines defined by the American Association for the Study of Liver Diseases - AASLD.
In an indicting report, published in the April issue of the American Journal of Gastroenterology, researchers wrote that doctors working at Harvard's teaching hospital, "... show remarkably poor adherence to AASLD guidelines, particularly in the areas of liver biopsy, timely liver cancer and ALT (liver damage) monitoring, and testing for co-infection."
Harvard researchers evaluated the charts of 962 adult hepatitis B patients treated at Mass General to see whether doctors complied with AASLD medical guidelines in:
- Monitoring ALT levels. When liver cells are damaged or die, these liver enzymes rise above normal.
- Measuring patients' viral load to determine how active the HBV infection was
- Performing liver biopsies when needed to guide treatment decisions
- Treating patients when liver damage was evident
- Screening for liver cancer
- And testing HBV-infected patients for hepatitis A (to see if vaccination was needed), HIV and hepatitis C.
They discovered that 60% of patients did not have liver biopsies, despite clinical signs of liver damage that should have triggered biopsies. "Eighty-nine percent of these missed biopsies were needed to further assess possible HBeAg-negative chronic hepatitis B," they wrote.
Most patients who needed treatment received it, but 121 patients who had unclear symptoms did not receive liver biopsies, which would have clarified whether treatment was merited.
Additionally, 45% of patients did not undergo timely liver cancer screening and 29% did not have timely blood tests to assess liver health and hepatitis B status.
Patients treated by liver experts – gastroenterologists – had slightly better rates of proper monitoring than those treated by primary care physicians, but 35% of the patients were not tested for hepatitis A, 24% weren't tested for hepatitis C, and 54% were not tested for HIV.
"These findings call for greater efforts to meet physician knowledge gaps, incorporation of decision support tools, and improved communication among providers," they wrote in the April issue of the American Journal of Gastroenterology. (1)
An unrelated study, published in the April issue of the journal of Digestive Diseases and Sciences, evaluated the quality of care given to 12,016 hepatitis B patients treated by the Northern California Kaiser Permanente Medical Care Program (KPNC) from July 2009 to December 2010 and found it lacking.
About 51% of the patients visited doctors during the study period, 14% saw gastroenterologist or infectious disease specialists and 37% saw primary care providers.
Fewer than 40% had both viral load and ALT testing done, as recommended by medical guidelines, and only 56% of eligible patients received screening for liver cancer.
Liver doctors tended to comply with current guidelines better than primary care providers, with 90% of specialists properly screening patients versus 47% of primary care providers.
"Most patients initiated on HBV treatment met eligibility, and very few patients with evidence of needing treatment were left untreated," researchers from Kaiser Permanente noted. "However, monitoring of ALT and HBV DNA levels, as well as liver cancer surveillance, were not frequent, underestimating the proportion of patients that warranted HBV therapy."(2)
1. Source: www.ncbi.nlm.nih.gov/pubmed/24732869
2. Source: www.ncbi.nlm.nih.gov/pubmed/24728968
Study Finds Doctors More Likely to Treat Hepatitis B in Men Than Women
A Stanford University-Pacific Health Foundation study of 862 hepatitis B patients treated at four U.S. health centers over a 12-month period found that men were more likely to be treated than women, even though both qualified for treatment under current medical guidelines.
The study, presented at the Liver Congress, followed the 862 patients (53% male, average age 42) most of whom qualified for treatment due to liver damage. However, only 46% were treated.
According to the report, 95 were seen by primary care doctors, 566 went to community gastroenterology clinics, and 201 were seen by university hepatologists. Men and patients over age 50 were more likely to be treated than women and younger patients.
Primary care providers failed to follow guidelines the most, while gastroenterology clinicians and liver specialists more accurately followed medical guidelines and prescribed treatment.
"Further studies are needed to examine potential causes for the observed gender disparity and to improve access to antiviral therapy in different care settings," the researchers wrote. (Abstract 031)
Study Confirms Doctors Frequently Fail to Screen and
Vaccinate Those at Risk
Another study that asked 400 Wisconsin primary care providers whom they screened for hepatitis B found few of them followed medical guidelines and screened and vaccinated high-risk patients.
The doctors reported poor screening of patients at risk of sexual transmission of hepatitis B, with 61% stating that they screened patients who had more than one sex partner in six months and 86% reporting they screened patients with a history of sex with prostitutes. Screening rate for persons with a history of intravenous drug use was 94%.
Only 65% of doctors reported screening children of immigrants for hepatitis B, only 73% reported screening patients on hemodialysis and only 69% screened prison inmates.
Screening increased when providers had experience and training about hepatitis B. Vaccination rates were similarly substandard. Doctors reported they failed to screen and vaccinate patients because of:
- Cost to patients
- They thought someone else had screened and vaccinated the patient
- Time constraints
- Lack of knowledge
"Without improved education and practices of primary care providers about HBV screening and vaccination, the goals of Healthy People 2020 regarding HBV will not be met," researchers noted in the March issue of the journal of Hepatitis Research and Treatment.
"Barriers to screening and vaccination need to be addressed," they added. "Cost-effectiveness of alternative strategies such as universal vaccination under the age of 50 should be explored."
Antiviral Treatment Dramatically Improves Liver Cancer Test Accuracy
When hepatitis B patients are treated with antivirals, a common liver cancer test that measures alpha fetoprotein (AFP) levels in the blood suddenly becomes much more accurate, according to a study published in the April issue of the Journal of Gastroenterology and Hepatology.
AFP screening is a relatively inexpensive and easy way to screen for liver cancer, but it is notoriously inaccurate in people with hepatitis B, with many results showing false positives for liver cancer.
South Korean researchers performed AFP screening on 207 hepatitis B patients before and after they were treated with antivirals to see if detection of liver cancer improved during treatment.
Before treatment began, 22.2% of the patients had elevated AFP levels (exceeding 20 ng/ml). After six months of treatment, only 5.5% of patients had above-normal AFP levels, and after 12 months that number declined to 1.3%.
"All patients who did not suffer from liver cancer exhibited normal AFP levels at 12 months," researchers wrote. "The cumulative incidence of liver cancer was 9.5% during 36 months of follow-up. If AFP levels were over 20 ng/ml after 12 months of antiviral treatment, the probability of liver cancer development approached certainty."
Bottom line: After 12 months of antiviral treatment, 100% of patients with elevated AFP levels (more than 12 ng/ml) had liver cancer.
$50 Cash Incentive Increases HBV Immunization 12-Fold
A small cash incentive, totalling about $50 U.S. (30 British pounds) in grocery vouchers, dramatically increased hepatitis B immunization among 210 heroin addicts undergoing methadone treatment in London.
Historically, injection drug users have low vaccination rates despite the fact that 22% of them become infected with the hepatitis B virus (HBV). This initiative, described in the April issue of The Lancet, offered the injection drug users the following options:
- No financial incentive to be immunized
- A 10-pound payment in grocery vouchers for each of the three vaccine injections
- Or escalating payments of 5 pounds, 10 pounds and then 15 pounds for the third and last dose
Only 9% of drug users who received no incentives were immunized with all three doses. However, 45% of those receiving 10 pounds at each visit were fully immunized and 49% of those receiving increasing payments were immunized.
The fact that payments increased compliance did not surprise researchers at the National Addiction Center at King's College, however the scale of the increased participation did.
Also, the paid patients tended to be on time for their appointments, which saved the program money.
A commentator on the study, writing in the same edition of The Lancet, noted, "Health care policy makers might be wise to consider traditional market forces when designing and delivering prevention strategies. The findings ... suggest that contingent financial incentives might be as or more important in the disease prevention marketplace as they are in commercial markets."
Hepatitis B and C Cause Ten-Times More Deaths Than HIV in Europe
Deaths from viral hepatitis far exceed deaths from HIV/AIDS across Europe, according to results from the recent “The Global Burden of Disease Study 2010” that were presented at the International Liver Congress.
The study, funded by the Bill and Melinda Gates Foundation and coordinated by the University of Washington, found that there were 10 times more deaths from hepatitis B and C than from HIV. The study estimates 57,000 deaths from hepatitis C and 31,000 deaths from hepatitis B in 2010, compared to 8,000 deaths from HIV/AIDS.
While HIV/AIDS remains a key global health priority, the higher death rates from viral hepatitis means that hepatitis B and C, "must clearly now be counted among the top global and local priorities for health," officials said.
They called for additional resources to prevent, detect and treat hepatitis B and C in order to address the funding and resource shortages for these major preventable diseases.
Globally, deaths from viral hepatitis and HIV increased from 1990-2010 with HIV/AIDS ranking 6th (causing 1.47 million deaths worldwide over the study period) and viral hepatitis B and C combined ranking 9th, causing 1.29 million deaths.
JOURNAL OF HEPATOLOGY
VOLUME 60, SUPPLEMENT 1,
The International Liver Congress™ 2014
49th annual meeting of the
for the Study of the Liver
April 9–13, 2014, London,
Back to News Review