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Hepatitis B Treatment

HBV Journal Review February 2015

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:

  • Quality of Care for Women with Hepatitis B Varies Dramatically Across U.S.
  • One-third of HBeAg-negative Women Experience “Flares” After Childbirth
  • Immunizing Newborns Is an Effective Tool in Preventing Cancer
  • Experts Warn: Don’t Delay Treatment in Patients with HBV Genotype C
  • Antivirals Help Patients with Cirrhosis, If Started Early Enough
  • Entecavir Effective at Clearing HBV’s cccDNA from Liver Cells
  • Older Age and a Weakened Immune System Can Cause HBV to Reactivate
  • Survey Shows Doctors Fail to Adequately Screen for Liver Cancer
  • Innovative Venues Increase Hepatitis B Screening Among Asian-Americans
  • Study Finds Waste Collectors at High Risk of Hepatitis B
  • Study Comparing Four Antivirals Finds All Appear Effective

Continue reading "HBV Journal Review February 2015" →

Hepatitis B Treatment

The Drug Discovery Process

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It takes talent, dedication, lots of  time, and a sizable investment to bring a safe and effective drug to market. The Drug Discovery Process YouTube video, compliments of PhRMAPress, introduces the long and arduous drug process from the identification of a compound in the lab, though clinical trials and the FDA approval process. It may sound simple, but this process may take up to 1,000 people, 12-15 years and up to 1.3 to 1.6 billion dollars to put a new drug in the hands of the patient.

Consider this process when following the progress of  hepatitis B drugs on the Hepatitis B Foundation Drug Watch page.  Compounds could remain in various stages for years. Note that the “preclinical” phase represents the drugs that are still in the lab and not yet ready for human clinical trials.

The Hepatitis B Foundation also maintains a webpage with the latest hepatitis B related clinical trials. Contact information is provided for each trial for those wishing to volunteer to participate.  Volunteers must meet the criteria for participation in a trial.

The future looks bright for a functional cure for hepatitis B. It may take a few more years to get the drug into the hands of the patient, but each step of the process is crucial in order to produce a drug that is both effective and safe.

 

 

 

Hepatitis B Diagnosis & Monitoring, Hepatitis B Prevention, Hepatitis B Treatment

HBV Journal Review – January 2015

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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:

  • Having Hepatitis B and a Family Member with Cancer Raises Cancer Risk Dramatically
  • VA Tests Only 21.8% of Its Patients for Hepatitis B, Missing Many at Risk of Infection
  • Research Shows Importance of HBV Screening Before Chemotherapy Begins
  • Younger Age and Low HBsAgLevels Benefit Patients Who Stop Antivirals
  • Doctors Debate Benefits of Interferon vs. Antiviral Treatment
  • New Study Finds Fibroscan Accuracy on Par with Liver Biopsies
  • Mild Kidney Problems and Bone Loss Linked to Antivirals
  • Hepatitis B Vaccine Effectiveness Challenged

Continue reading "HBV Journal Review – January 2015" →

Hepatitis B Treatment

Research at the HBF’s Baruch S. Blumberg Institute

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hbvvirus

Hepatitis C is now declared curable. Hepatitis B is still not, despite having been discovered nearly 50 years ago. An interview with Dr. Timothy Block of  the Hepatitis B Foundation and the Baruch S. Blumberg Institute. The future does look bright…

Perhaps this should not be a surprise, thinks Timothy Block, PhD, president and co-founder of the Hepatitis B Foundation (HBF) and its research arm, the Baruch S. Blumberg Institute. According to Block,there are two main reasons for the “cure deficit” between hepatitis B and C — funding and physiology.

He points out that commercial and federal investment in hepatitis C have been far greater than in hepatitis B. And that has clearly paid off in terms of finding a hepatitis C cure. “You get what you pay for,” he observes.

Physiologically, hepatitis B also presents unique challenges not found with hepatitis C — most notably cccDNA (or covalently closed circular DNA), the “mini- chromosome” produced by the hepatitis B virus. The cccDNA persists in the nucleus of the liver cell, where it can hide amidst the host’s own chromosomes, apparently out of reach of the cell’s own defense systems.

Acting like “an indestructible template,” cccDNA continues to produce virus particles throughout the life of the infected liver cell, even in people being treated with antiviral agents.

Hepatitis C, on the other hand, doesn’t enter the cell’s nucleus, so it’s possible to cure a person by stopping this virus from replicating long enough for the liver cells to regenerate.

But remember that people who have been “cured” of hepatitis C can still get re-infected,” Block cautions. The hepatitis C drugs apparently do not trigger an immune response that protects against re-infection.

In contrast, some people can be cured of hepatitis B, either naturally or through drug therapy. These individuals do seem to have long-term protective immunity. “And that’s what we are aiming for,” he declares.

Why We Need a Cure for Hepatitis B 

It can be argued that the approved antiviral agents are very successful in keeping the virus under control. So do we really need a cure? Definitely yes, Block replies emphatically.

Current antiviral drugs are effective, but need to be taken lifelong and are recommended for use in only about half of the infected population. And even after 10 years of use, the antivirals reduce HBV-related diseases by only about 50 to 60 percent. The drugs can also lead to the development of resistant hepatitis B strains (drug resistance).

For those who benefit from treatment, the antiviral drugs have been transformational and prove that medical intervention can be effective. However, there are millions who do not benefit and are still left vulnerable.

Clearly, new approaches to a “functional cure” are needed, which Block defines as “returning the risk of death due to hepatitis B to the level of someone who has a resolved infection.” And the person should not need to take any drugs to stay at this low-risk level.

Targeted Strategy for a Cure

The HBF/Blumberg Institute scientists, with their research partners from Drexel University College of Medicine, both located in the HBF’s Pennsylvania Biotechnology Center, are developing two types of therapies: direct-acting antivirals and innate host defense activators. The first type inhibits virus-host interactions and viral gene products; the second recruits the host’s immune system to attack and eliminate cccDNA and infected liver cells.

For each of these approaches, the researchers have identified key steps to target in the hepatitis B infection cycle, from virus entry into the liver cell, to cccDNA replication, to formation of virus particles.

For many of these steps, “Our scientists have developed assays that can be used to screen for new drugs. We are a recognized leader in designing and developing these assays and, for a time, had the only cccDNA- dependent cell lines,” notes Block. Almost 100 different cell lines for assays have been developed that can be used to screen for drugs that activate the innate host defense pathways.

For drug screening, cell lines are incubated with potential drug candidates to try and find new therapeutic drugs for future hepatitis B treatment. The strategic goal is to discover new drugs that complement existing therapies, but also enable the immune system to provide long-lasting antiviral protection, even when the person is no longer on drug therapy.

The strategic goal is to discover new drugs that complement existing therapies, but also enable the immune system to provide long-lasting antiviral protection, even when the person is no longer on drug therapy.

Several compounds in development already show some effectiveness in animal models. “We have a capsid inhibitor, a pregenomic RNA capsid inhibitor (JT Guo), an HBsAg inhibitor (A Cuconati), a cccDNA repressor (H Guo, A Cuconati, JT Guo), and an activator of innate host defense pathways (J Chang and JT Guo),” Block reports.

He is particularly excited about their stimulator of interferon genes (STING) agonist, which was very effective in mouse models. The research group is now working on a human STING agonist, although an appropriate assay for this compound still needs to be developed.

What the Future Holds 

“The Hepatitis B Foundation and its Blumberg Institute have contributed
to some of the most important work in studying the phases of the virus lifecycle that has led to the currently available drugs. Our researchers continue to be at the forefront in developing a promising pipeline for hepatitis B drug discovery,” says Block.

“I am absolutely confident that a cure is possible” he asserts. “After all, enough people with hepatitis B resolve their infections, either medically or spontaneously — even some people with chronic infections. So we know it’s possible.”

 

 

Hepatitis B Treatment, Liver Cancer

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" →

Uncategorized

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" →

Hepatitis B Treatment

Arrowhead’s HBV Candidate Requires Further Dose Escalation

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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…

Posted by Dirk Haussecker at Wednesday, October 08, 2014 

Uncategorized

HBV Journal Review – October 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:

  • 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 Treatment

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. 

Hepatitis B Treatment

HBV Journal Review – August 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:

  • Health Concerns Grow as Researchers Uncover the Risks of “Occult”
  • Are Current Hepatitis B Tests Missing Some Infections?
  • First Case of Tenofovir Resistance Found in Patient with Prior Entecavir Resistance
  • Even Specialists Fail to Treat Hepatitis in Patients Who Qualify for Treatment
  • No Benefit Found from Antiviral Treatment after Liver Cancer Surgery
  • Another Study Confirms Success of Sequential Antiviral and Interferon Treatment
  • Snapshot of Hepatitis B in the United States
  • Metformin Safe and Effective in Cirrhotic Patients with Diabetes Type 2

HBV Journal Review

August 1, 2014
Volume 11, Issue 8
by Christine M. Kukka

Health Concerns Grow as Researchers Uncover the Risks of “Occult” Hepatitis B
Researchers studying the health effects of “occult” hepatitis B are finding that this infection that can “hide” from conventional lab tests carries a higher risk of liver cancer and poses a risk to the general population when undiagnosed.

This type of hepatitis B occurs when a mutation in the virus’ outer coat, made up of the hepatitis B surface antigen (HBsAg), makes it impossible for common lab tests that look for that protein to identify an active HBV infection. The HBsAg lab test is commonly used to identify hepatitis B in patients and even blood supplies.

When lab tests fail to identity HBV infection, people can unknowingly spread the infection to their partners, family members and newborns. And when occult HBV infection goes untreated, a patient’s risk of liver cancer is 3.7-fold higher than in patients with “regular” or non-occult hepatitis B, according to a recent report in the August issue of the Journal of Hepatology.

HBsAg has three proteins and in the case of occult HBV, the immune system attacks one of the three surface proteins–the same protein that lab tests look for when screening blood for HBsAg.

Most vaccines contain this exact same HBsAg protein in order to spur production of surface antibodies to fight off an actual infection. In most cases, the vaccine is very effective, but when occult hepatitis B occurs, the vaccine-induced antibodies are powerless against the remaining two surface proteins and viral reproduction and infection can continue.

This concern has grown recently as scientists find a number of children born to HBV-infected mothers, who were immunized at birth, have developed “occult” hepatitis B. Additionally, people with occult hepatitis B can transmit the mutated, “occult” version of HBV to partners and close contacts (even if they’re vaccinated), adding to the spread of this hard-to-identify viral hepatitis infection.

Because of the unique genetic make-up of this mutated HBsAg and how it interacts with liver cells, this mutation appears to cause more rapid liver damage and cancer.

Scientists suggest that drug resistance, especially to the antiviral lamivudine (Epivir-HBV), may contribute to development of this mutation.

“Recent studies have reported that (surface mutations) tend to (emerge) with the drug resistance-associated mutations in lamivudine-treated patients, and that the (mutations) …. play a supportive role in the replication of lamivudine-resistant viruses,” Italian researchers wrote in the report.

“Therefore it appears of the utmost importance that patients with chronic hepatitis B are screened for the presence of (surface antigen) mutant infection,” they recommended. “The detection of these specific HBV variants may indeed be useful for the identification of those patients requiring a preventive and appropriate treatment and a more intensive follow-up strategy for early detection of liver cancer.”

Source: www.journal-of-hepatology.eu/article/S0168-8278(14)00304-3/fulltext

Are Current Hepatitis B Tests Missing Some Infections?
When do hepatitis B tests miss true infections?A number of confounding factors, ranging from “occult” hepatitis B increase (see above article), failure of lab tests to pick up extremely low levels of HBsAg, immunizations, and the rapidly changing progression of HBV infection can all conspire to mask the infection from conventional laboratory tests.

Read the HBV Journal Review in its entirety 

Baruch S. Blumberg Institute