Hep B Blog

HBV Journal Review – December 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:

  • Twenty-five Percent of HBV-Infected Women Have Liver “Flares” after Childbirth
  • Experts: Do Not Treat Patients in the Immune-Tolerant Stage of Infection
  • Entecavir and Tenofovir Equally Effective in HBeAg-positive Patients and Cirrhotics
  • Tenofovir Effective in Patients with Adefovir- and Lamivudine-Resistance
  • Adding Interferon to Ongoing Antiviral Treatment Effective in HBeAg-positive Patients
  • Antivirals Improve Survival Among Hepatitis B Patients
  • Interferon Effective in HBeAg-negative Patients, Early HBsAg Declines Predict Success
  • Study Finds Asian Immigrants, Especially Chinese, at High Risk of Hepatitis B
  • Immunization Continues to Protect Against Hepatitis B Decades Later
  • Doctors Fail to Vaccinate Hepatitis Patients Against Other Hepatitis Infections
  • Study Confirms HBV Patients Have Higher Kidney Disease Rates

Continue reading "HBV Journal Review – December 2014"

AASLD 2014 Liver Meeting – HBV Coverage

Unknown-5Get HBV Advocate’s Christine Kukka’s take on the top HBV related, published reports from the AASLD Liver Meeting as she provides her Top Ten List! 

 

Top Ten Reports from the 65th Annual Liver Meeting
By Christine M. Kukka, HBV Advocate 

Hepatitis B experts from around the world met at the 65th annual American Association for the Study of Liver Diseases (AASLD) conference in Washington D.C. this week to share the latest in hepatitis B treatment and research.

  1.  Which combination of antivirals and interferon works best against hepatitis B
  2. Tenofovir continues to excel with no signs of drug resistance after eight years
  3. Tenofovir treatment is safe over an entire pregnancy for both mother and child
  4. Tenofovir and entecavir combination successful against drug-resistant HBV
  5. Who remains at risk for hepatitis B in the U.S.?
  6. Antivirals appear to lower liver cancer risk
  7. But antivirals don’t reduce cancer risk in older patients with cirrhosis
  8. How long do patients have to keep taking antivirals after they lose HBeAg and achieve undetectable viral load?
  9. Liver cancer risk remains, even after HBsAg clearance in older, male patients
  10. Experts say treatment is needed when ALT levels are only moderately elevated

Continue reading "AASLD 2014 Liver Meeting – HBV Coverage"

HBV Journal Review – November 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:

  • Experts Say Breastfeeding While Taking Antivirals Is Safe
  • Doctors Fail to Adequately Treat HBV-Infected Women After Childbirth
  • Doctors Continue to Fail to Screen Asian-Americans for Hepatitis B
  • Statins Protect Hepatitis B Patients Against Heart Disease and Liver Cancer
  • New Study Finds Antivirals Lower Liver Cancer Risk
  • Studies Find Tenofovir Lowers Viral Load Faster Than Entecavir
  • Liver Transplants Safe in Older Hepatitis B Patients
  • Scientists Develop Micro Weapon to Disable HBV’s Cancer-Causing X Protein
  • Foreign-Born U.S. Residents Less Likely to Be Immunized
  • Antivirals Can Safely Replace HBIG Following Liver Transplantation
  • All Hepatitis B Patients Appear at Risk from Chemotherapy

Continue reading "HBV Journal Review – November 2014"

Fighting the Doom and Gloom: Prevention Works!

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Hepatitis B vaccination event in Laos.

In recognition of Liver Cancer Awareness Month, Liver Cancer Connect is highlighting some of the advances in prevention, screening, and treatment that are leading to increased survival among people with liver cancer. Continue reading "Fighting the Doom and Gloom: Prevention Works!"

Arrowhead’s HBV Candidate Requires Further Dose Escalation

It should be noted while numerically the improvement in knockdown from 1mg/kg to 2mg/kg was only 12%, this is likely the result of the apparent high variability at the lower dose level with the increased tightness of the knockdown range at 2mg/kg indicating that the RNAi mechanism is starting to be solidly engaged with the expectation of a steepening dose response going forward.
It should be noted while numerically the improvement in knockdown from 1mg/kg to 2mg/kg was only 12%, this is likely the result of the apparent high variability at the lower dose level with the increased tightness of the knockdown range at 2mg/kg indicating that the RNAi mechanism is starting to be solidly engaged with the expectation of a steepening dose response going forward.

Sadly, we read that Phase 2a data presented by Arrowhead fell short of expectations for their ARC-520 drug to treat chronic hepatitis B. Hopefully dose escalation to 4mg/kg will result in both effective and safe results. However, there are others in the race for the cure, and may the most effective and safe drug soon result in a functional cure for chronic HBV.
~ hepbtalk

 

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.  Be sure to visit Dirk Haussecker’s blog !  

Today, we learned about some hard HBsAg knockdown numbers from the phase IIa Hong Kong study of ARC520 in chronically infected HBV patients.  The data relate to the first 2 cohorts in this ongoing dose escalation trial.  Accordingly, the mean HBsAg knockdown at nadir for the starting dose of 1mg/kg was 39% within a range of 22-57%(n=6) while it was 51% within a range of 46-59% for the 2mg/kg cohort (n=6).

ARC520 was given as a single dose to patients already stably on polymerase inhibitor entecavir.

While clearly missing the company’s own guidance of a 1 log reduction at 2mg/kg, the good safety profile-no SAEs at all in the study with all AEs rated to be unrelated to ARC520- in addition to the steepening dose-response curve following 2mg/kg means that ARC520 is far from being out of the HBV knockdown race.  Still, the stock market over-reacted, punishing ARWR stock with a percent decrease that matched the reported knockdowns.

Although even I ended up willing myself into believing that a 70-80% knockdown was possible following a single ARC520 dose of 2mg/kg, revisiting the chimp study which involved 2 doses of ARC520 (first one at 2mg/kg then one at 3mg/kg), it should be noted that at the time the 3mg/kg dose was administered, the HBsAg levels had only declined by 50%…about the same as achieved in the phase IIa study.  It is thus possible that Arrowhead gave the 2nd dose just as HBsAg levels were about to go up again, consistent with the already rebounding levels of HBV DNA and HBeAg in that study.

As a result, my expectations for the single 3mg/kg dose are now 70-75% based on the ~75-80% peak HBsAg knockdown in the chimp study following the 2mg/kg and 3mg/kg doses.  This also means that in order to reach that 1log knockdown goal the company had set for itself, 4mg/kg will most likely be needed.  Importantly, in the concurrent phase I dose-escalating study in healthy volunteers, this quite large amount of drug seemed to be well tolerated and the company is awaiting approval to adopt this dose in the Hong Kong study.

This projection is not much off the 90% knockdown achieved in the ARC-AAT program at 3mg/kg in non-human primates.  The improvement of this 2nd DPC-based candidate about to enter the clinic is possibly explained by progress in the potency of 2-molecule DPC delivery technology.  I add this as today many were confused about what the interim phase IIa results meant for the platform and the value of the company.

Overall, as long as 4mg/kg is an acceptable dose from a tox point-of-view, ARC520 is still in the game to be first-in-class in HBV knockdown.  It would have been much worse if say a 70% knockdown had been reported, but worrisome safety signals emerged.  On the other hand, the continued need for a dose escalation would seem to delay Arrowhead’s broad-based phase IIb study plans, meaning that the competition, in particular Tekmira’s TKM-HBV is coming closer.

At a market cap of ~$400M, the market has almost fully discounted the potential of ARC520 given the $150M+ in cash as well as the IND-ready, first-in-class ARC-AAT for which we can expect solid knockdowns in the clinic.  Interestingly, data for this candidate were selected for an oral presentation at AASLD while the ARC520 data will be in less prestigious poster form. Finally, should the single-molecule DPC which got me excited about the Arrowhead RNAi platform in the first place finally reach the clinic, it would necessitate an upward revision of the value of the company.
Disclosure: Long ARWR.  I sold most of my holdings at $11 and change given the underwhelming results and increasingly negative market reaction, but got back in below $6 when I considered the sell-off to be a gross over-reaction and imminent 3mg/kg data having the potential to surprise the market to the upside from now much lowered expectations.  Add to this ARC-AAT, the platform…

HBV Journal Review – October 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:

  • Chronic Hepatitis B Remains Public Health Challenge in U.S.
  • Epidemiologists Become Molecular Detectives to Investigate HBV Outbreaks
  • Telbivudine Effectively Prevents Infection of Newborns Born to Infected Mothers
  • GGT Blood Test Reveals Fibrosis and Cirrhosis in Hepatitis B Patients
  • Early Research Combining Antivirals with a Protein “De-activator” Shows Promise
  • Diabetes Dramatically Increases Liver Cancer Risk in Cirrhotic Patients
  • Tenofovir Linked to Higher Rates of Bone Loss than Entecavir
  • Tenofovir Equally Effective against Hepatitis B in Asians and Non-Asians
  • Liver Cancer Risk Factors Do Vary Between Racial Groups
  • Even Liver Specialists Fail to Screen Chemotherapy Patients for Hepatitis B
  • European Study Confirms Coffee Dramatically Lowers Liver Cancer Risk

HBV Journal Review

October 1, 2014
Volume 11, Issue 10
by Christine M. Kukka

Chronic Hepatitis B Remains Public Health Challenge in U.S.

A new U.S. Centers for Disease Control and Prevention report on hepatitis B prevalence finds that while new infections have declined markedly, treating chronic hepatitis B infection remains a public health challenge.

New hepatitis B virus (HBV) infections have plummeted since 1990 due to comprehensive immunizations. The CDC report estimates only 18,760 people were infected with HBV in 2012.

In 2012, the highest rates of new infections were among those aged 30–39 years (2.17 cases per 100,000 population), and the lowest were among children under age 19 who had been immunized at birth.

Many of the new infections were transmitted sexually or through injecting drug use.

However, an estimated 700,000 to 1.4 million U.S. residents are chronically infected. According to the report, Viral Hepatitis Surveillance United States, 2012, about half of those chronically infected were either born in Asia or were born to HBV-infected mothers in the United States.

In 2011, the death rate from chronic hepatitis B was 0.5 deaths per 100,000 population. The highest mortality rates were among people aged 55–64 years, Asian and Pacific Islander, and male.

“Identifying these chronically infected persons and linking them to care remains a challenge,” the authors reported.

Source: www.cdc.gov/hepatitis/Statistics/
2012Surveillance/

Epidemiologists Become Molecular Detectives to Investigate HBV Outbreaks

While new HBV infections have declined dramatically since the early 1990s due to effective immunizations, public health officials continue to examine where new infections are coming from and who is getting infected.

Read the HBV Journal Review in its entirety here. 

 

Hepatitis B Positive Speakers Discuss HepB with Geraldine Doogue

Heartfelt discussion with the “Hepatitis B Positive Speakers Group”, led by Australia’s Geraldine Doogue, ABC TV and Radio. Join Yvonne, David, Trevor, Linh and “Tina”, as they discuss their personal hepatitis B experiences -living with the stigma, and discrimination you can both see and “not quite put your finger on”, and their willingness to give back, and to increase community awareness.

If you’re on the Hepatitis B Information and Support Listserve, you may recognize Yvonne, one of the list moderators who mentions the emotional support she gets from her her cyber friends. 

Thank you Hepatitis Australia for sharing this discussion! 

 

HBV Journal Review – September 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:

  • New Study Finds HBV Genotype E Responds Poorly to Entecavir
  • HBV Genotypes Help Tell the Human Story of Slavery in the Americas
  • Researchers Find Tenofovir Increases Hip Bone Loss in Older Patients
  • Decline in HBV RNA Indicates Who Loses HBeAg During Antiviral Treatment
  •  Shortened Vaccination Schedule May Get More Drug Users Immunized
  • Primary Care Doctors Rarely Screen Patients for Cirrhosis
  • Tenofovir or Telbivudine Recommended for Pregnant Women with High Viral Loads
  • Access to Healthy Food Vital for HBV Patients, but Many Live in Food “Deserts”
  • Scientists Create Viable Liver Cells in a Lab for HBV Research
  • Nerve Damage Prompts Warning Against Telbivudine-Interferon Combo Treatment

HBV Journal Review

September 1, 2014
Volume 11, Issue 9
by Christine M. Kukka

New Study Finds HBV Genotype E Responds Poorly to Entecavir
Experts know some hepatitis B virus (HBV) strains called genotypes respond better to interferon treatment than others, but now scientists are discovering that genotypes respond differently to antiviral treatment too.

HBV genotypes are found in different regions of the world and each evolved over centuries to have slightly different molecular make-ups with unique traits. Some carry a higher risk of liver damage and cancer, while other genotypes are less virulent.

In a recent study, Italian researchers compared how well patients with genotypes A, D and E fared after three years of treatment with the antiviral entecavir (Baraclude). All of the patients tested negative for the hepatitis B “e” antigen (HBeAg-negative). The scientists measured hepatitis B surface antigen (HBsAg) levels and HBV DNA (viral load) every three months during the first year of treatment and then every six months over the study period.

They found the rates of HBsAg declines resulting from antiviral treatment varied markedly between genotypes. They extrapolated how many years of entecavir treatment each genotype required before a patient would clear HBsAg and achieve undetectable viral load.

HBV genotype A: It would take on average 15.6 years of entecavir treatment for an HBeAg-negative patient with HBV genotype A to lose HBsAg. This genotype is found in northern Europe, North America, India and southern Africa.

HBV genotype D: It would take 17 years for genotype D patients to lose HBsAg. This strain is found primarily in Russia, the Middle East, the Mediterranean region, and India.

HBV genotype E: This genotype, found in Central Africa, responded the most poorly to entecavir. Scientists estimated it would take 24.6 years for these patients to lose HBsAg, according to the report published in the August issue of the Journal of Medical Virology.

Source: www.ncbi.nlm.nih.gov/pubmed/25131947

HBV Genotypes Help Tell the Human Story of Slavery in the Americas
Because HBV genotypes develop in specific regions around the world, their distribution around the world today can help tell the story of mass human migrations, including the enslavement and forced migration of millions of Africans to Brazil since the 1500s.

Read the HBV Journal Review in its entirety here. 

‘Think Again’ About Hepatitis – World Hepatitis Day Events in Ghana

imagesTheobald Owusu-Ansah of the Theobald Hepatitis B Foundation works tirelessly to raise the profile of hepatitis B in Ghana, where the HBV prevalence is approximately 30% in blood donors. Through collaboration with others, and heightening awareness with Ghanaian celebrities, Theobald and others were able to raise viral hepatitis awareness, and provide free screening and HBV vaccination during their World Hepatitis Day event this year. Read his account below and check out Theobald and the work he and his foundation are doing at the www.theobaldhepb.org or find THBF on Facebook

Viral hepatitis is the leading cause of liver cancer, which is the second most common cause of cancer deaths in Africa. On World Hepatitis Day, we urged the government to take actions ASAP to improve hepatitis awareness, monitoring, prevention and treatment.
 ASAP is a blue print framework for Global action, developed by the WHO to guide national government on the effective ways to prevent and control the transmission of viral hepatitis. This framework has four axes:

1.  Awareness raising, partnership promotion and resource mobilization,
2.  Scientific evidence that drives policies and actions,
3.  Access to immunization and information to prevent transmission,
4.  Provision of screening, care and treatment.

Thousands of Ghanaians live with viral hepatitis. About a third of Ghanaians living with viral hepatitis are unaware of their status and are not receiving care and treatment for the condition. It is estimated that hepatitis B kills over 1 million people each year, and an estimated 1 in 12 persons are currently infected and have to face life with chronic liver disease.

Ghana belongs to one of the areas where the prevalence of chronic HBV infection is high (≥8%), and that of hepatitis C is from 5-10%. There is high prevalence in approximately 30% among blood donors.
 In the year ending 2010, the incidence of viral hepatitis in Ghana was 43/100,000 population, with 102 deaths, which represents a 30% increase as compared to the year 2006 incidence of 30/100,000 population. (Source: www.theobaldhepb.org)

Ghana is rated a high-risk country for hepatitis B & C with between 10 and 15 percent prevalence rate. Out of every 100 Ghanaians, 13 may test positive for hepatitis B, which is far more prevalent than HIV/AIDS.

On the 20th July 2014, Celebrities in Ghana united to raise funds to support free Hepatitis B screening and vaccination. The program was under the theme “Celebrities Car Wash”.  Celebrities including Okyeame Kwame, Ghana Rap Doctor, former national black stars captain Stephen Appiah, Ghanaian actor Van Vicker and others volunteered to wash public cars for a fee to raise funds to support the programme.

The staff of Theobald Hepatitis B Foundation, Okyeame Kwame Foundation and other medical officials joined the celebrities for the car washing fundraising event. Members of the public took advantage of the celebrities’ car wash to bring their cars to be washed by their favorite’s celebrities. Celebrities expressed their interest in becoming viral hepatitis ambassadors in Ghana.

The event showed that you don’t need a big bank account to be able to make a difference, but with a bit of vision, one can create awareness.

On that day, we are calling on the government to develop and implement coordinated national action plans to fight viral hepatitis. The Theobald Hepatitis B Foundation in collaboration with the Hepatitis Coalition of Ghana, Okyeame Kwame Foundation together with MDS Lancet Laboratories, Roche and Ridge Hospital RPD on Saturday 26th July, 2014, offered free hepatitis B screening and vaccination to hundreds of people at James Town – Mantse Abgona in Accra. Out of 359 people screened, 49 people tested positive and they received counseling on what to do and what not to do, in terms of treatments and other biochemical tests they needed to undergo.

The Rapper observed that the youth turned out for the screening this year and expressed appreciation for the turnout. “I am really glad to see most of the young people come for the screening. This is to say that the youth is giving attention to health and this also indicates that we are moving in the right direction as a people,” says Okyeame Kwame.

The president of the Theobald Hepatitis B Foundation, Mr. Theobald Owusu Ansah delivered his speech for the occasion on the theme: “HEPATITIS: THINK AGAIN”, calling on the government to give much attention to Hepatitis B.

Thank you to all World Hepatitis Day supporters, sponsors and the media who volunteered their time, supplies, and/or funds to support this year’s events, and raising the profile of viral hepatitis in Ghana.

 

Perspective on the Liver Biopsy – “The Gold Standard”

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Have you noticed fewer patients living with chronic HBV seem to get liver biopsies to assess liver damage?  Here is a perspective on the Liver Biopsy, known as the “gold standard”, by William Carey, MD, Division of Gastroenterology and Hepatology of the Cleveland Clinic.

Published in Healio , July 14, 2014 

Liver biopsy is referred to as the “gold standard” in assessing both the activity and degree of fibrosis in many chronic liver diseases including hepatitis B. It is not likely to retain this lofty status much longer. Liver biopsy has several important drawbacks. Among them are cost, risk for complications, need for additional health care resources, patient and physician aversion to the procedure, inadequate specimen size and the lack of specific findings.

Liver biopsy adds between $2,500 to $3,500 to the cost of an evaluation (even higher for transvenous liver biopsy). Approximately 20% of patients will experience significant pain following percutaneous liver biopsy. More severe complications include pneumothorax, major bleeding, inadvertent biopsy of the kidney or colon, and perforation of the gallbladder. Death, most often due to uncontrolled bleeding, may occur in up to 1 in 1,000 biopsies. Underappreciated is the risk of no-representative sampling, either because of the small size of biopsy specimen or patchy distribution of fibrosis.

Noninvasive measures to assess hepatic fibrosis have been around for a generation and are increasingly used as a substitute for liver biopsy. The 2014 medley of noninvasive estimates of hepatic fibrosis includes FibroTest/FibroSure, APRI, FIB-4, other serum based test combinations, and elastography (either ultrasound- or MRI-based). Noninvasive tests have potential both for determination of current liver damage and for monitoring disease progression. They can be done at a fraction of the cost of a liver biopsy. Salkic and colleagues have reported the results of an exquisitely performed meta-analysis of peer reviewed published reports and confirmed the value of FibroTest/FibroSure in hepatitis B — mainly in excluding the diagnosis of cirrhosis. The findings of this review are restricted to hepatitis B, but others have shown similar findings in hepatitis C and alcoholic liver disease.

While there is growing consensus that noninvasive markers provide valuable information, allowing the clinician to make important decisions about treatment, screening for varices and hepatocellular carcinoma, it is essential to understand limitations of FibroTest, including distortions in results in individuals with Gilbert’s syndrome and in those with hemolysis. This study reiterates the relative insensitivity of noninvasive tests in discriminating between lesser degrees of fibrosis (F0, F1, and F2).

Data are accumulating to suggest noninvasive markers (combining a noninvasive test plus ultrasound-based elastrography, for example) are powerful tools in assessing natural history of individuals with many chronic liver diseases including hepatitis B, providing indices of disease activity, progression and fibrosis regression after treatment. Convenience, lower cost, and ease of repeated measurements over time favor widespread acceptance of these tools in clinical practice.