Category Archives: Hep B Treatment

HBV Journal Review – July 2014

Posted on June 30, 2014 | Leave a comment
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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:

  • 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…

 

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

Posted on June 16, 2014 | Leave a comment
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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 

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Posted in Hep B Treatment, Liver cancer, liver cancer prevention, Research

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Antiviral Therapy May Prevent Liver Cancer in Hepatitis B patients

Posted on June 10, 2014 | Leave a comment
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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.

 

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Posted in Hep B Treatment, liver cancer prevention, Living with Hep B, Research

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

Posted on May 13, 2014 | Leave a comment
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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.

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HBV Journal Review – May 2014

Posted on April 30, 2014 | 2 Comments
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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… 

 

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