Hep B Blog

Tag Archives: Research

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Nucleoside Analogues’ Benefits in HBV Vary

UnknownThis informative article from Internal Medicine News, July 1, 2014, analyzes two studies from the July issue of Gastroenterology, and looks at the impact of antivirals on the incidence of liver cancer, the need for liver transplantation and the risk of death in chronic HBV patients.  The potency of the antiviral made a significant difference and supported current practice guidelines recommending the use of entecavir and tenofovir as first line drugs for the treatment of chronic HBV. Be sure to also read the accompanying editorial by Dr. George Papatheodoridis. 

Internal Medicine News Digital Network, July 1, 2014, article written by DENISE NAPOLI.

Nucleoside analogues are effective at preventing hepatocellular carcinoma in hepatitis B, but all are not equal when it comes to overall mortality and liver transplant, according to two new studies in the July issue of Gastroenterology.

In the first study, Dr. Chun-Ying Wu of the National Yang-Ming University, in Taipei, Taiwan, and his colleagues examined the long-term protective effects of nucleoside analogue therapy among chronic hepatitis B patients (doi.org/10.1053/j.gastro.2014.03.048).

They conducted a retrospective nationwide cohort study using data from Taiwan’s National Health Insurance Research Database, collecting records from 1997 through 2010 on patients with chronic hepatitis B.

Click here to read Internal Medicine News article and editorial in its entirety. 

Hepatitis B Treatment, Liver Cancer

HBV Journal Review – July 2014

ChrisKHBF is pleased to connect our blog readers to Christine Kukka’s monthly HBV Journal Review that she writes for the HBV Advocate. The journal presents the
 latest in hepatitis B research, treatment, and prevention from recent academic and medical journals. This month, the following topics are explored:

  • Ground-Breaking Study Finds Antiviral Treatment Does Reduce Cancer Risk
  • Sequential Treatment of Antivirals Followed by Interferon Spurs HBeAg Seroconversio
  • Is the Current Recommended Dose of Entecavir Too Low for Some Patients?
  • Measuring Liver Stiffness, Spleen Size and Platelets Can Predict Cancer Risk
  • Tenofovir Effective in Patients with Lamivudine Resistance
  • Entecavir and Adefovir Combo Works Best in Lamivudine-Resistant Patients
  • When Is It Safe to Stop Antivirals? Experts Still Not Sure
  • Liver Stiffness Test Identifies Which Patients Develop Liver Damage After Treatment Stops
  • Study Suggest Hepatitis B Immunization Could Cut Diabetes Risk by Half
  • Herbal Medication Treatment Linked to Liver Failure in Patient with Hepatitis B

HBV Journal Review

July 1, 2014
Volume 11, Issue 7
by Christine M. Kukka

Ground-Breaking Study Finds Antiviral Treatment Does Reduce Cancer Risk

For the first time, an authoritative study has found that antiviral treatment appears to reduce the risk of hepatitis B virus (HBV)-related liver cancer. Even though treated patients had more liver damage, their cancer rates were similar to untreated, healthier patients.

Researchers from the U.S. Centers for Disease Control and Prevention examined the health records of 2,671 hepatitis B patients treated at four health centers across the U.S. between 1992 and 2011. Half of the patients were Asian-American and about 31% (820) had been treated with antivirals. The treated patients tended to have more liver damage, were older, male and less likely to be Asian-American than untreated patients in the study.

Researchers, reporting in the June issue of the journal ofClinical Gastroenterology and Hepatology, found that 67 (3%) of the 2,671 patients developed liver cancer over the study period. Twenty of the 820 patients treated with antivirals developed cancer, compared to 47 of the 1,851 untreated patients.

Treated patients with viral loads less than 20,000 IU/mL had a significantly lower risk of cancer than untreated patients with similarly low viral loads.

Antivirals appeared to confer some protection against liver cancer even in patients with fibrosis (liver inflammation) and cirrhosis (liver scarring), suggesting that viral loads may be the primary culprit behind liver cancer. By suppressing viral load, liver cancer was avoided in many of these high-risk patients with serious liver damage.

Researchers wrote, “…We found that antiviral treatment had a beneficial effect across a spectrum of viral load levels (and disease severity.)”

Source: www.ncbi.nlm.nih.gov/pubmed/24107395

Sequential Treatment of Antivirals Followed by Interferon Spurs HBeAg Seroconversion 
Chinese researchers found that hepatitis B “e” antigen (HBeAg)-positive patients who were treated first with the antiviral entecavir (Baraclude) and then with pegylated interferon achieve a higher rate of HBeAg seroconversion (loss of HBeAg and development of “e” antibodies) than patients treated with only entecavir.

Continue reading the HBV Journal Review…

 

Hepatitis B Treatment, Liver Cancer

Antiviral Therapy May Lower Risk of Liver Cancer – MedicalResearch.com Interview with Dr. Stuart Gordon MD

UnknownThank you MedicalResearch.com for this interview and insights by Dr. Stuart Gordon, MD, Gastroenterologist, Henry Ford Hospital, Detroit, MI.

 

 

MedicalResearch: What are the main findings of the study?

Dr. Gordon: In a large American cohort of Hepatitis B patients, those who took antiviral therapy had a significantly lower risk of developing liver cancer than those who did not take such therapy.

MedicalResearch: Were any of the findings unexpected?

Dr. Gordon: Similar findings have been noted in other parts of the world, but not in american populations. In addition, this report showed that the protective effect of antiviral therapy (against developing primary liver cancer) was found not just among patients with cirrhosis, who are at greatest risk, but also among those with lesser degrees of liver fibrosis. This finding was rather unique.

MedicalResearch: What should clinicians and patients take away from your report?

Click to read interview in its entirety 

Hepatitis B Treatment, Liver Cancer, Living with Hepatitis B

Antiviral Therapy May Prevent Liver Cancer in Hepatitis B patients

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Useful confirmation of what we already thought was true. Good news…

(HealthNewsDigest.com) – DETROIT, June 9, 2014  —

Researchers have found that antiviral therapy may be successful in preventing hepatitis B virus from developing into the most common form of liver cancer, hepatocellular carcinoma (HCC).

That was the finding of a study published in the May issue of Clinical Gastroenterology and Hepatology. Investigators from Henry Ford Health System in Detroit, Geisinger Health System in Danville, Pa., and Kaiser Permanente in Honolulu, Hawaii and Portland, Ore. participated in the study, along with investigators from the Centers for Disease Control and Prevention in Atlanta.

According to the first-of-its-kind analysis of more than 2,600 adult participants with hepatitis B, those treated with antiviral therapy had a significantly lower occurrence of HCC during a five-year follow up period. Overall, 3 percent of patients developed HCC during the study’s timeframe. But patients who received antiviral therapy were 60 percent less likely to develop HCC than untreated patients.

“The results of this study allow us to reassure our patients that we are not just treating their viral levels, but that antiviral therapy may actually lessen their chance of developing liver cancer,” said the study’s lead investigator, Henry Ford Health System’s Stuart C. Gordon, M.D., who worked closely with Henry Ford Senior Scientist Mei Lu in Detroit. Continue reading here.

 

Uncategorized

HBV Journal Review – June 2014

ChrisKHBF is pleased to connect our blog readers to Christine Kukka’s monthly HBV Journal Review that she writes for the HBV Advocate. The journal presents the
 latest in hepatitis B research, treatment, and prevention from recent academic and medical journals. This month, the following topics are explored:

  • Belatedly, National Panel Recommends Screening At-Risk Patients for Hepatitis B
  • Genotypes and Mutations Define the Course of Hepatitis B Infection
  • Older Patients Who Lose HBeAg After Treatment May Relapse
  • Tenofovir Proves Ineffective in Patient with Multiple Drug Resistance
  • Nearly All HBeAg-Negative Patients Relapse After Antiviral Treatment Stops
  • Studies Find Hepatitis Infection Does Not Increase Pancreatic Cancer Risk
  • Screening Pregnant Women for High Viral Loads Is Cost Effective
  • Hepatitis B Appears to Impede Fertility
  • Despite Low Viral Load, Infected People Can Still Infect Family Members
  • Good News: HBV Infection Rates Lower Than Expected Among Korean-Americans
  • Green Tea May Be an Effective Antiviral

HBV Journal Review

June 1, 2014
Volume 11, Issue 6
by Christine M. Kukka

Belatedly, National Panel Recommends Screening At-Risk Patients for Hepatitis B

Ten years after it recommended against screening the “general population” for hepatitis B, an independent national task force that creates prevention guidelines for primary care providers has finally recognized that certain high risk groups in the U.S. should be screened for hepatitis B.

Their recommendations, recently published in the Annals of Internal Medicine, come after numerous studies faulted primary care providers for failing to screen patients for hepatitis B and missing opportunities to treat patients for liver disease and immunize family members against hepatitis B virus (HBV) infections.

Other health care organizations, including the U.S. Centers for Disease Control and Prevention (CDC), the Institute of Medicine, and the American Association for the Study of Liver Disease, have been recommending for years that primary care doctors screen high-risk patients for hepatitis B, which has infected up to 2.2 million Americans.

The U.S. Preventive Services Task Force (USPSTF) recently issued clinical guidelines recommending that doctors screen the following patients for hepatitis B:

  • People from countries that have hepatitis B rates exceeding 2% (which includes Asia, Africa, Central Europe and parts of Central and South America).
  • U.S.-born people whose parents immigrated from countries with high rates of HBV infection.
  • HIV-positive people, injecting drug users, men who have sex with men, and
  • Household contacts of people infected with HBV.

The task force’s guidelines suggest that because an effective vaccine to protect against the infection and effective treatments for hepatitis B are now available, they decided to issue these recommendations. However, both the vaccine and effective treatments have been available for more than a decade.

“In the 2004 recommendation, the USPSTF focused only on the general population,” the authors wrote in the recommendations. “In the current recommendation, the USPSTF focused on high-risk populations as it considered new evidence on the benefits and harms of antiviral treatment, the benefits of education or behavior change counseling, and the association between improvements in intermediate and clinical outcomes after antiviral treatment.” The task force noted that it, “…found inadequate evidence that education or behavior change counseling reduces disease transmission.”

Source: www.uspreventiveservicestaskforce.org/uspstf/
uspshepb.htm

Genotypes and Mutations Define the Course of Hepatitis B Infection
Researchers are increasingly finding that HBV genotypes or strains—and the mutations that they generate—can determine the severity of a patient’s infection.

Each of the world’s 10 genotypes and their mutations have different characteristics that can increase risk of cirrhosis and liver cancer, determine whether an infection becomes chronic, and basically determine a patient’s destiny, according to a recent study, published in the May issue of the World Journal of Hepatology …

Continue reading the HBV Journal Review… 

Hepatitis B Treatment

Alnylam Discloses HBV Program, Shows 2 Log HBSAG Knockdown with Research-Grade SNALP Tech

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HepatitisBVirus-1

Harnessing the Power of RNAi Gene Silencing in Quest of a Cure for Chronic Hepatitis B, and the HBV KnockDown blog written by Dirk Haussecker, who believes it’s about time everyone got serious about a functional cure for hepatitis B. 

Following cryptic remarks during a conference call earlier this year, Alnylam today officially announced its entry into the cure-HBV race.  In impressive data presented at the ongoing TIDES meeting, the company showed that up to 0.5mg/kg SNALP-siRNA was able to knock down HBsAg by ~2 log (99% knockdown) in infected chimpanzees.  The data had been generated by Merck from which Alnylam acquired the RNAi assets in January.  The goal is now to apply some of the learnings generated with Merck’s research-grade SNALP LNP technology and come up with a new candidate based on Alnylam’s GalNAc delivery platform (IND to be filed end of 2015).
In addition to the impressive HBsAg knockdowns, 3-4log knockdowns of viral DNA in serum were seen in the 4 chimpanzees.  In the most viremic chimp, the 4log lowering of viral load was able to normalize liver enzyme (ALT) levels that had been elevated by ~5x ULN.  Intriguingly, in 2 chimps with normal ALTs at the time of treatment, liver enzymes started to increase after dosing had finished (ruling out SNALP LNP as the culprit) and in 1 case also well after viral DNA had started to recover following cessation of RNAi dosing.
Intriguingly, while viral DNA recovered in this short study involving the administration of 3 doses (for every chimp 0.125mg/kg, then 0.25mg/kg, then 0.5mg/kg) over a span of 40 days, there were indications of a desired immunological response similar to that seen withARC520 in the chimp study, most notably an elevation of interferon gamma accompanied by ~2x increases in ALT in 2 of the chimps.
The competition
 
With Tekmira, ISIS/GSK and now Alnylam (and possibly more to come) following on the heels of Arrowhead Research and ARC520, the competitive landscape is starting to look quite complex.  How it will play out will likely depend on the degree of HBsAg knockdown required (in relative and absolute terms) and who will run the right combination studies with other HBV agents, especially immune boosters such as interferon and possibly RT inhibitors (note: Alnylam speculates that RT inhibitor co-treatment will be beneficial and thereby justified its use of a single RNAi trigger).
If a deep multi-log HBsAg knockdown were required, it would favor Tekmira’s candidate which will be based on a 3rd gen SNALP LNP which can be considered superior to what came out of Merck’s copy-cat efforts subject of today’s presentation.  If lesser knockdowns were able to achieve comparable cure rates, then the power would shift to the subcutaneous versions by Alnylam and ISIS/GSK (esp. the likely GalNAc-based follow-up version).
For ARC520, especially at 2mg/kg and Tekmira probably just 6 months behind, the competition may prove too much, not least because in the 2-dose study in the chimpanzee, the HBsAg knockdown was less than a log (80%).  Granted it was an extremely viremic chimp and one of the RNAi triggers was a mismatch, but still.  If Arrowhead and/or Tekmira demonstrate increased cure rates in 2015, Arrowhead should waste no time and push a single-molecule DPC into development to potentially once again take the lead.
The big question is how far along the way to clinical translation is single-molecule DPC?  Tomorrow may provide an answer.

Hepatitis B Treatment, Living with Hepatitis B

HBV Journal Review – May 2014

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ChrisKHBF is pleased to connect our blog readers to Christine Kukka’s monthly HBV Journal Review that she writes for the HBV Advocate. The journal presents the
 latest in hepatitis B research, treatment, and prevention from recent academic and medical journals. This month, the following topics are explored:

  • Adding Interferon to Ongoing Antiviral Treatment Is Highly Successful
  • Vitamin E Helps HBV-Infected Children Lose HBeAg, Reducing Liver Damage
  • Common Chinese Toad May Hold the Key to Preventing and Treating Liver Cancer
  • Even at Top Hospitals, Doctors Fail to Treat Hepatitis B Patients Properly
  • Study Finds Doctors More Likely to Treat Hepatitis B in Men Than Women
  • Study Confirms Doctors Frequently Fail to Screen and Vaccinate Those at Risk
  • Antiviral Treatment Dramatically Improves Liver Cancer Test Accuracy
  • $50 Cash Incentive Increases HBV Immunization 12-Fold
  • Hepatitis B and C Cause Ten-Times More Deaths Than HIV in Europe

HBV Journal Review
May 1, 2014
Volume 11, Issue 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)

Source: www.hbvadvocate.org/EASL_2014_
Abstracts.pdf

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.

Continue reading the HBV Journal Review… 

 

Hepatitis B Treatment

Three New Studies Help Clarify Optimal Use of Combination Therapy in Chronic Hepatitis B Patients

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EASLThree new studies presented today at the International Liver Congress 2014 have helped clarify the optimal use of combination therapy with peginterferon and nucleoside analogues (NUCs) to achieve the best treatment outcomes in patients with chronic hepatitis B (CHB).

“Together these ground-breaking data will go a long way to influencing future CHB  guidelines,” said EASL’s Educational Councillor Professor Cihan Yurdaydin from the Department of Gastroenterology, University of Ankara, Turkey.

In the first study , CHB patients who had failed on prior long-term exposure to one of the nucleoside analogue (NUC) antivirals demonstrated high rates of complete response and HBsAg loss when prescribed a sequential combination of peginterferon and NUC.

In the second study , adding peginterferon to the nucleoside analogue entecavir was shown to enhance response rates and viral decline in HBeAg-positive CHB patients with compensated liver-disease, was generally safe and well tolerated, and may facilitate the discontinuation of entecavir.

Finally, data from a third study suggested that adding on a NUC for six weeks to PegIFNalfa-2a does not enhance treatment response, with no increase in HBeAg seroconversion rates beyond that achieved by PegIFNα-2a alone after 24 weeks follow-up.

Continue reading more…

Hepatitis B Treatment, Liver Cancer, Living with Hepatitis B

HBV Journal Review – April 2014

ChrisKHBF is pleased to connect our blog readers to Christine Kukka’s monthly HBV Journal Review that she writes for the HBV Advocate. The journal presents the
latest in hepatitis B research, treatment, and prevention from recent academic and medical journals. This month, the following topics are explored:

  • Despite Antiviral Treatment, Liver Cancer Risk Persists
  • Vitamin D Appears to Help Prevent Liver Cancer
  • Dandelions May Be the Next Best Herbal Treatment for Hepatitis B
  • Kidney Problems Are Prevalent with Hepatitis B Even Before Treatment Starts
  • HBV Genotype H Appears to Cause Immediate Chronic Infection in Adults
  • HBV Genotype E Has the Worst Response to Pegylated Interferon
  • Cancer-Causing YMDD Mutations Found Frequently in HBV Genotype C
  • High Iron Levels Found in Patients with Liver Failure
  • Vietnamese-Americans at High Risk of Undiagnosed Hepatitis B and C
  • Entecavir Performance Is Mediocre in Lamivudine-Resistant Patients
  • A Simple Platelet Count Test Could Be Best Indicator of Fibrosis

HBV Journal Review
April 1, 2014
Volume 11, no 4
by Christine M. Kukka

Despite Antiviral Treatment, Liver Cancer Risk Persists
Researchers have hoped that treating hepatitis B patients with antivirals would reduce both their viral loads and their liver cancer risk. However, a new study that followed 1,378 treated and 1,014 untreated patients over five years found antivirals did not reduce liver cancer rates as hoped.

The study tracked new liver cancer cases among patients infected with the hepatitis B virus (HBV) (average age 47, 65% male) who had been treated primarily with entecavir (Baraclude) for their high viral loads and liver damage. They compared that group’s liver cancer occurrence to those of patients whose “inactive” HBV infection did not require treatment.

Among the treated group, 70 patients (6.2%) developed liver cancer during the study period compared to only 11 (1.1%) in the untreated group. Notwithstanding  the ability of antivirals to reduce viral load, a life-long history of HBV infection and liver damage appeared to increase cancer risk, despite the reduction in viral load later in life.

What is especially disappointing is that liver cancer developed even in treated patients who had no history of cirrhosis (severe liver scarring) which increases cancer risk. Among the antiviral-treated patients:

  • • 20 of 223 HBeAg-negative patients who had cirrhosis at the start of treatment developed liver cancer.
  • • 15 of 316 HBeAg-negative patients who had no cirrhosis also developed liver cancer.
  • • Among the treated patients who developed liver cancer, 30 were positive for the hepatitis B “e” antigen (HBeAg) and 30 were HBeAg-negative.

How well the antiviral worked in patients also determined who remained cancer-free. Of the 246 patients who failed to achieve low or undetectable viral loads as a result of treatment, 36 (18.8%) patients developed liver cancer over the five-year study.

The risk of cancer was increased overall by male gender, underlying cirrhosis and older age in the treated group. Curiously, having high viral loads (HBV DNA) at the start of treatment did not appear to increase liver cancer risk.

The key message for doctors is that liver cancer risk remains despite a dramatic reduction in viral load, researchers noted. “…Patients on (antiviral) treatment that effectively suppressed viral replication are still at higher risk of liver cancer compared with patients with inactive stage chronic hepatitis B,” they concluded in the study published in the March issue of the journal Gut.

Persistent liver damage before the start of antiviral treatment, evidenced by elevated alanine aminotransferase (ALT) levels, may predispose patients to liver cancer, they also noted.

“The inactive group may have more intact immune response to HBV and therefore may also have entered the inactive stage early in life, with a shorter period of high viral replication and active hepatitis,” they wrote.

Source: www.ncbi.nlm.nih.gov/pubmed/24615378

Vitamin D Appears to Help Prevent Liver Cancer
Recent studies show a diet rich in vitamin D can improve liver health in patients with hepatitis B. A new study from Emory University in Atlanta finds that people with high vitamin D levels have lower rates of liver cancer.

The researchers examined vitamin D levels and liver cancer risk among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition between 1992 and 2010.

Continue reading this review and additional HBV related reviews for March

Hepatitis B Diagnosis & Monitoring, Hepatitis B Prevention, Hepatitis B Treatment, Liver Cancer, Living with Hepatitis B

The World’s Second Deadliest Cancer Is …Preventable

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bandages

Liver cancer is the world’s second leading cause of cancer deaths, according to the latest World Cancer Report 2014 released by the International Agency for Research on Cancer (IARC), which is the specialized cancer agency of the World Health Organization (WHO). About 800,000 deaths per year are related to liver cancer. Continue reading "The World’s Second Deadliest Cancer Is …Preventable" →

Baruch S. Blumberg Institute